Novel, full 3D scintillation dosimetry using a static plenoptic camera.

PubMed

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-08-01

Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm(3) EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle(3) was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions.

Novel, full 3D scintillation dosimetry using a static plenoptic camera

PubMed Central

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-01-01

Purpose: Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm3 EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. Results: The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle3 was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Conclusions: Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions. PMID:25086549

Genistein aglycone effect on bone loss is not enhanced by supplemental calcium and vitamin D3: a dose ranging experimental study.

PubMed

Bitto, A; Marini, H; Burnett, B P; Polito, F; Levy, R M; Irrera, N; Minutoli, L; Adamo, E B; Squadrito, F; Altavilla, D

2011-07-15

Genistein aglycone (GEN) has a favorable effect on bone loss. We investigated the effects of GEN alone or in combination with supplemental calcium and vitamin D(3) in an animal model of bone loss to evaluate if there was additional benefit. Ovariectomized (OVX) and SHAM-OVX rats were used. OVX were divided into 12 groups and randomized to receive: GEN at 27, 54, 200, 500 or 1000 mg (human equivalent dose (HED)/day/ip injection alone or with calcium carbonate (Ca) (360 mg/kg/day/gavages) and vitamin D(3) (D(3)) (50 IU/kg/day/gavages) or Ca/D(3) without GEN or untreated for 6 weeks. SHAM-OVX were randomized into 7 groups and treated with: Ca and D(3) alone or in combination with GEN (same doses as OVX), or left untreated. Bone mineral density (BMD), bone-alkaline phosphatase (b-ALP), collagen C-telopeptides (CTX), osteoprotegerin (OPG) and soluble receptor activator of NFκB ligand (sRANKL) were assessed. Femurs were excised and tested for breaking strength and histology. Uterine weight was analyzed to assess GEN's estrogenic effects on the SHAM-OVX. The most effective dose of GEN, independent of Ca/D(3) supplementation, was 54 mg/day. Higher doses yielded no further improvement in bone biomarkers, histology or strength. Only 1000 mg/day HED of genistein produced statistically significant changes in uterine weight of the SHAM-OVX. This study suggests that 54 mg/day of GEN is the threshold dose for efficacy. In addition, supplemental calcium and vitamin D(3), beyond normal dietary intake do not enhance the effects of genistein on improving measures of bone loss. This observation has implications regarding the use of calcium and vitamin D(3) supplementation. Copyright © 2011 Elsevier GmbH. All rights reserved.

3D conditional generative adversarial networks for high-quality PET image estimation at low dose.

PubMed

Wang, Yan; Yu, Biting; Wang, Lei; Zu, Chen; Lalush, David S; Lin, Weili; Wu, Xi; Zhou, Jiliu; Shen, Dinggang; Zhou, Luping

2018-07-01

Positron emission tomography (PET) is a widely used imaging modality, providing insight into both the biochemical and physiological processes of human body. Usually, a full dose radioactive tracer is required to obtain high-quality PET images for clinical needs. This inevitably raises concerns about potential health hazards. On the other hand, dose reduction may cause the increased noise in the reconstructed PET images, which impacts the image quality to a certain extent. In this paper, in order to reduce the radiation exposure while maintaining the high quality of PET images, we propose a novel method based on 3D conditional generative adversarial networks (3D c-GANs) to estimate the high-quality full-dose PET images from low-dose ones. Generative adversarial networks (GANs) include a generator network and a discriminator network which are trained simultaneously with the goal of one beating the other. Similar to GANs, in the proposed 3D c-GANs, we condition the model on an input low-dose PET image and generate a corresponding output full-dose PET image. Specifically, to render the same underlying information between the low-dose and full-dose PET images, a 3D U-net-like deep architecture which can combine hierarchical features by using skip connection is designed as the generator network to synthesize the full-dose image. In order to guarantee the synthesized PET image to be close to the real one, we take into account of the estimation error loss in addition to the discriminator feedback to train the generator network. Furthermore, a concatenated 3D c-GANs based progressive refinement scheme is also proposed to further improve the quality of estimated images. Validation was done on a real human brain dataset including both the normal subjects and the subjects diagnosed as mild cognitive impairment (MCI). Experimental results show that our proposed 3D c-GANs method outperforms the benchmark methods and achieves much better performance than the state-of-the-art methods in both qualitative and quantitative measures. Copyright © 2018 Elsevier Inc. All rights reserved.

Opposing Effects of Dopamine D1- and D2-Like Agonists on Intracranial Self-Stimulation in Male Rats

PubMed Central

Lazenka, Matthew F.; Legakis, Luke P.; Negus, S. Stevens

2016-01-01

Dopamine acts through dopamine type 1 receptors (comprised of D1 and D5 subtypes) and dopamine type 2 receptors (comprised of D2, D3 and D4 subtypes). Intracranial self-stimulation (ICSS) is one experimental procedure that can be used to evaluate abuse-related effects of drugs targeting dopamine receptors. This study evaluated effects of dopamine receptor ligands on ICSS in rats using experimental procedures that have been used previously to examine abused indirect dopamine agonists such as cocaine and amphetamine. Male Sprague-Dawley rats responded under a fixed-ratio 1 schedule for electrical stimulation of the medial forebrain bundle, and frequency of stimulation varied from 56–158 Hz in 0.05 log increments during each experimental session. Drug potency and time course were determined for the D1 ligands A77636, SKF82958, SKF38393, fenoldopam and SCH39166 and the D2/3 ligands sumanirole, apomorphine, quinpirole, PD128907, pramipexole, aripiprazole, eticolopride and PG01037. The high-efficacy D1 agonists A77636 and SKF82958 produced dose-dependent, time-dependent, and abuse-related facilitation of ICSS. Lower efficacy D1 ligands and all D2/3 ligands failed to facilitate ICSS at any dose or pretreatment time. A mixture of SKF82958 and quinpirole produced a mixture of effects produced by each drug alone. Quinpirole also failed to facilitate ICSS after regimens of repeated treatment with either quinpirole or cocaine. These studies provide more evidence for divergent effects of dopamine D1- and D2-family agonists on ICSS procedure in rats and suggest that ICSS may be a useful complement to other approaches for preclinical abuse potential assessment, in part because of the reproducibility of results. PMID:26987070

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

PubMed

Seed, T M; Fritz, T E; Tolle, D V; Jackson, W E

2002-01-01

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation. Published by Elsevier Science Ltd on behalf of COSPAR.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crijns, W; Vandenbroucke, D; Leblans, P

Purpose: Computed Radiography (CR) dosimetry could offer film dosimetry resolution and flexibility but with reusability and instantaneous processing. For an experimental CR-plate, designed for radiotherapy (Zeff=18), CR’s typical out-of-field over-response to low energy photons was previously reduced to 8%. The present work assesses the impact of the residual over-response when open-fields are combined or when intensity modulated fields are used. Methods: Agfa Healthcare’s experimental CRplate was scanned and erased 4min after each irradiation using a flying-spot CR-15-X-engine based reader, which was adapted for radiotherapy dosimetry. A CR-plate specific calibration and uniformity correction was used.For open-fields two abutting half beams (5×10cm{supmore » 2}) captured out-offield and in-field doses in a single image. Additionally, both half beams were measured individually as well as a 3×18Gy open-field SBRT-lung treatment. For intensity modulated fields standard test patterns (Chair and Pyramid) and a clinical 5×5Gy rectal VMAT plan were captured. All measurements were compared to the corresponding dose calculations. Results: For open-fields the out-of-field overdose was clearly larger than the in-field overdose (10% vs. 4%). The sum of the individual measurements corresponded well with the combined measurement (dose difference, ΔD<−2.2%). The SBRT case had no overdose in the high dose region; ΔD=−5.6%±3.3%, the deviation was attributed to CR-fading effects (−0.3%/min) which were not corrected for.Compared to open-fields, intensity modulated deliveries had a further increased over-response out-offield (ΔD=+58% to +125% [Chair] +43% [Pyramid]), due to the increased amount of low energy photons for IMRT. However, this effect was not measured in-field where even decreased dose signals were observed (ΔD=−0.3% to +2.25% [Chair], −4.5% to −0.1% [Pyramid]). The rectal VMAT treatment had a dose difference +2.4%±6.0%. The in-field deviations were attributed to a residual non-uniformity. Conclusion: The experimental CRplate’s out-of-field over-response does not propagate in in-field overresponse errors when static or dynamic (IMRT/VMAT) abutting fields are used.« less

SU-F-T-74: Experimental Validation of Monaco Electron Monte Carlo Dose Calculation for Small Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varadhan; Way, S; Arentsen, L

2016-06-15

Purpose: To verify experimentally the accuracy of Monaco (Elekta) electron Monte Carlo (eMC) algorithm to calculate small field size depth doses, monitor units and isodose distributions. Methods: Beam modeling of eMC algorithm was performed for electron energies of 6, 9, 12 15 and 18 Mev for a Elekta Infinity Linac and all available ( 6, 10, 14 20 and 25 cone) applicator sizes. Electron cutouts of incrementally smaller field sizes (20, 40, 60 and 80% blocked from open cone) were fabricated. Dose calculation was performed using a grid size smaller than one-tenth of the R{sub 80–20} electron distal falloff distancemore » and number of particle histories was set at 500,000 per cm{sup 2}. Percent depth dose scans and beam profiles at dmax, d{sub 90} and d{sub 80} depths were measured for each cutout and energy with Wellhoffer (IBA) Blue Phantom{sup 2} scanning system and compared against eMC calculated doses. Results: The measured dose and output factors of incrementally reduced cutout sizes (to 3cm diameter) agreed with eMC calculated doses within ± 2.5%. The profile comparisons at dmax, d{sub 90} and d{sub 80} depths and percent depth doses at reduced field sizes agreed within 2.5% or 2mm. Conclusion: Our results indicate that the Monaco eMC algorithm can accurately predict depth doses, isodose distributions, and monitor units in homogeneous water phantom for field sizes as small as 3.0 cm diameter for energies in the 6 to 18 MeV range at 100 cm SSD. Consequently, the old rule of thumb to approximate limiting cutout size for an electron field determined by the lateral scatter equilibrium (E (MeV)/2.5 in centimeters of water) does not apply to Monaco eMC algorithm.« less

Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats.

PubMed

Thomsen, Morgane; Barrett, Andrew C; Butler, Paul; Negus, S Stevens; Caine, S Barak

2017-07-01

Dopamine D 3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D 2 - and D 3 -preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. Acutely, the D 2 agonist R -(-)-norpropylapomorphine (NPA) and antagonist L-741,626 [3-[[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1 H -indole] produced leftward and rightward shifts in cocaine dose-effect curves, respectively, whereas the partial agonist terguride had no effect. All three drugs dose-dependently decreased food-maintained responding. Chronically, the effects of R -(-)-norpropylapomorphine and L-741,626 on cocaine self-administration showed marked tolerance, whereas suppression of food-reinforced behavior persisted. Acute effects of the D 3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. Chronically, the D 3 agonist PF-592,379 [5-[(2 R ,5 S )-5-methyl-4-propylmorpholin-2-yl]pyridin-2-amine] increased cocaine choice, whereas an intermediate dose of the D 3 antagonist PG01037 [ N -[( E )-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide] produced a therapeutically desirable decrease in cocaine choice early in treatment; however, tolerance to this effect developed, and lower and higher doses were ineffective. D 3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. Thus, D 2 -and D 3 -preferring ligands showed distinct profiles, consistent with different pharmacological actions. In addition, these results highlight the role of acute versus chronic treatment as a determinant of test drug effects. With the possible exception of the D 3 antagonist PG01037, no ligand was promising in terms of cocaine addiction treatment. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

[Experimental study on the impact of photodynamic therapy on the normal vocal cord injury].

PubMed

Liu, Haiyan; Huang, Yongwang; Wang, Shanshan; Li, Yingxin; Yin, Huijuan; Gao, Xiaowei

2015-12-01

To investigate the reactive characteristics of normal vocal cord tissues to photodynamic therapy (PDT) and the damage effects of different concentration of photosensitizer and different light on normal rabbit vocal cord. Making the preliminary research of PDT in clinical treatment of chronic inflammation of the vocal cords and precancerous lesions. Twenty-five healthy Japanese big ear experimental rabbits were randomly divided into 5 groups: low work rate low dose group A (100 mW, 10%5-ALA), high work rate low dose group B (200 mW, 10%5-ALA), high work rate high dose group C (200 mW, 20%5-ALA), low work rate high dose group D (100 mW, 20%5-ALA) and normal control group E. The issue damage and wound recovery were observed in 1 d, 3 d, 7 d, 14 d, 28 d after intervention. A severe inflammation reaction was observed in group A, B, C, D after intervened with PDT compared to normal group. The reaction of group A was lighter, and the reaction of group C was the most serious. The content of collagenous fiber, hyaluronic acid and fibronectin in vocal fold lamina layer was significantly higher than that in normal group (P<0.05). Different degrees of fiber proliferation were observed in all groups. The content of each component of vocal fold lamina layer tended to be normal slightly higher level in 28 d. Observation by electron microscope showed that there were no significant differences in A, B, C, D, E in 28 d after intervention. Recoverable damage repair process can be detected in rabbit vocal after intervened with PDT, which began in 7 d and basically completed in 28 d. In a certain concentration (10%-20%) and dose range (100-200 mW). The higher of photodynamic dose, the more serious of the damage. And the damage was basically reversible.

Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.

PubMed

Scott, Jeffrey F; Das, Lopa M; Ahsanuddin, Sayeeda; Qiu, Yuqi; Binko, Amy M; Traylor, Zachary P; Debanne, Sara M; Cooper, Kevin D; Boxer, Rebecca; Lu, Kurt Q

2017-10-01

The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D 3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of UVR. Compared with placebo, participants receiving vitamin D 3 (200,000 international units) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D 3 levels after treatment (P = 0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (P = 0.005), and a sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D 3 levels had significant expression of proinflammatory genes. Together the data may have broad implications for the immunotherapeutic properties of vitamin D in skin homeostasis, and implicate arginase-1 upregulation as a previously unreported mechanism by which vitamin D exerts anti-inflammatory effects in humans. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Poster - Thurs Eve-09: Evaluation of a commercial 2D ion-chamber array for intensity modulated radiation therapy dose measurements.

PubMed

Mei, X; Bracken, G; Kerr, A

2008-07-01

Experimental verification of calculated dose from a treatment planning system is often essential for quality assurance (QA) of intensity modulated radiation therapy (IMRT). Film dosimetry and single ion chamber measurements are commonly used for IMRT QA. Film dosimetry has very good spatial resolution, but is labor intensive and absolute dose is not reliable. Ion chamber measurements are still required for absolute dose after measurements using films. Dosimeters based on 2D detector arrays that can measure 2D dose in real-time are gaining wider use. These devices provide a much easier and reliable tool for IMRT QA. We report the evaluation of a commercial 2D ion chamber array, including its basic performance characteristics, such as linearity, reproducibility and uniformity of relative ion chamber sensitivities, and comparisons between measured 2D dose and calculated dose with a commercial treatment planning system. Our analysis shows this matrix has excellent linearity and reproducibility, but relative sensitivities are tilted such that the +Y region is over sensitive, while the -Y region is under sensitive. Despite this behavior, our results show good agreement between measured 2D dose profiles and Eclipse planned data for IMRT test plans and a few verification plans for clinical breast field-in-field plans. The gamma values (3% or 3 mm distance-to-agreement) are all less than 1 except for one or two pixels at the field edge This device provides a fast and reliable stand-alone dosimeter for IMRT QA. © 2008 American Association of Physicists in Medicine.

Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.

PubMed

Ramos, Carlos Alberto F; Sá, Rita de Cássia da S; Alves, Mateus F; Benedito, Rubens B; de Sousa, Damião P; Diniz, Margareth de Fátima F M; Araújo, Maria Salete T; de Almeida, Reinaldo N

2015-01-01

The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.

Different contributions of dopamine D1 and D2 receptor activity to alcohol potentiation of brain stimulation reward in C57BL/6J and DBA/2J mice.

PubMed

Fish, Eric W; DiBerto, Jeffrey F; Krouse, Michael C; Robinson, J Elliott; Malanga, C J

2014-08-01

C57BL/6J (C57) and DBA/2J (DBA) mice respond differently to drugs that affect dopamine systems, including alcohol. The current study compared effects of D1 and D2 receptor agonists and antagonists, and the interaction between D1/D2 antagonists and alcohol, on intracranial self-stimulation in male C57 and DBA mice to determine the role of dopamine receptors in the effects of alcohol on brain stimulation reward (BSR). In the initial strain comparison, dose effects on BSR thresholds and maximum operant response rates were determined for the D1 receptor agonist SKF-82958 (±-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.1-0.56 mg/kg) and antagonist SCH 23390 (+-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrochloride; 0.003-0.056 mg/kg), and the D2 receptor agonist quinpirole (0.1-3.0 mg/kg) and antagonist raclopride (0.01-0.56 mg/kg). For the alcohol interaction, SCH 23390 (0.003 mg/kg) or raclopride (0.03 mg/kg) was given before alcohol (0.6-2.4 g/kg p.o.). D1 antagonism dose-dependently elevated and SKF-82958 dose-dependently lowered BSR threshold in both strains; DBA mice were more sensitive to SKF-82958 effects. D2 antagonism dose-dependently elevated BSR threshold only in C57 mice. Low doses of quinpirole elevated BSR threshold equally in both strains, whereas higher doses of quinpirole lowered BSR threshold only in C57 mice. SCH 23390, but not raclopride, prevented lowering of BSR threshold by alcohol in DBA mice. Conversely, raclopride, but not SCH 23390, prevented alcohol potentiation of BSR in C57 mice. These results extend C57 and DBA strain differences to D1/D2 sensitivity of BSR, and suggest differential involvement of D1 and D2 receptors in the acute rewarding effects of alcohol in these two mouse strains. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

PubMed

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect is negligible (<0.2%). It is also small (0.9% average, 2.2% maximum) when the target excursion increased to 2-3 cm. Only with large motion and increased period (60 s) was a significant interplay effect observed, with D99% ranging from 16% low to 17% high. The interplay effect was statistically significantly lower for the three- and five-fraction statistical simulations. Overall, the gradient effect dominates the clinical situation. A novel method was used to reconstruct the volumetric dose to a moving tumor during lung SBRT VMAT deliveries. With the studied planning and treatment technique for realistic motion periods, regardless of the amplitude, the interplay has nearly no impact on the near-minimum dose. The interplay effect was observed, for study purposes only, with the period comparable to the VMAT delivery time.

Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats.

PubMed

Long, Hu; Liao, Lina; Gao, Meiya; Ma, Wenqiang; Zhou, Yang; Jian, Fan; Wang, Yan; Lai, Wenli

2015-08-01

Calcitonin-related gene peptide (CGRP) plays an important role in orofacial inflammatory pain. The aim of this study was to determine whether periodontal CGRP contributes to orofacial pain induced by experimental tooth movement in rats. Male Sprague-Dawley rats were used in this study. Closed coil springs were used to deliver forces. Rats were euthanized on 0d, 1d, 3d, 5d, 7d, and 14d following experimental tooth movement. Then, alveolar bones were obtained for immunostaining of periodontal tissues against CGRP. Two hours prior to euthanasia on each day, orofacial pain levels were assessed through rat grimace scale. CGRP and olcegepant (CGRP receptor antagonist) were injected into periodontal tissues to verify the roles of periodontal CGRP in orofacial pain induced by experimental tooth movement. Periodontal CGRP expression levels and orofacial pain levels were elevated on 1d, 3d, 5d, and 7d following experimental tooth movement. The two indices were significantly correlated with each other and fitted into a dose-response model. Periodontal administration of CGRP could elevate periodontal CGRP expressions and exacerbate orofacial pain. Moreover, olcegepant administration could decrease periodontal CGRP expressions and alleviate orofacial pain. Therefore, periodontal CGRP plays an important role in pain transmission and modulation following experimental tooth movement. We suggest that it may participate in a positive feedback aiming to amplify orofacial pain signals. Copyright © 2015 Elsevier B.V. All rights reserved.

Three dimensional dose distribution comparison of simple and complex acquisition trajectories in dedicated breast CT

PubMed Central

Shah, Jainil P.; Mann, Steve D.; McKinley, Randolph L.; Tornai, Martin P.

2015-01-01

Purpose: A novel breast CT system capable of arbitrary 3D trajectories has been developed to address cone beam sampling insufficiency as well as to image further into the patient’s chest wall. The purpose of this study was to characterize any trajectory-related differences in 3D x-ray dose distribution in a pendant target when imaged with different orbits. Methods: Two acquisition trajectories were evaluated: circular azimuthal (no-tilt) and sinusoidal (saddle) orbit with ±15° tilts around a pendant breast, using Monte Carlo simulations as well as physical measurements. Simulations were performed with tungsten (W) filtration of a W-anode source; the simulated source flux was normalized to the measured exposure of a W-anode source. A water-filled cylindrical phantom was divided into 1 cm3 voxels, and the cumulative energy deposited was tracked in each voxel. Energy deposited per voxel was converted to dose, yielding the 3D distributed dose volumes. Additionally, three cylindrical phantoms of different diameters (10, 12.5, and 15 cm) and an anthropomorphic breast phantom, initially filled with water (mimicking pure fibroglandular tissue) and then with a 75% methanol-25% water mixture (mimicking 50–50 fibroglandular-adipose tissues), were used to simulate the pendant breast geometry and scanned on the physical system. Ionization chamber calibrated radiochromic film was used to determine the dose delivered in a 2D plane through the center of the volume for a fully 3D CT scan using the different orbits. Results: Measured experimental results for the same exposure indicated that the mean dose measured throughout the central slice for different diameters ranged from 3.93 to 5.28 mGy, with the lowest average dose measured on the largest cylinder with water mimicking a homogeneously fibroglandular breast. These results align well with the cylinder phantom Monte Carlo studies which also showed a marginal difference in dose delivered by a saddle trajectory in the central slice. Regardless of phantom material or filled fluid density, dose delivered by the saddle scan was negligibly different than the simple circular, no-tilt scans. The average dose measured in the breast phantom was marginally higher for saddle than the circular no tilt scan at 3.82 and 3.87 mGy, respectively. Conclusions: Not only does nontraditional 3D-trajectory CT scanning yield more complete sampling of the breast volume but also has comparable dose deposition throughout the breast and anterior chest volume, as verified by Monte Carlo simulation and physical measurements. PMID:26233179

Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

PubMed Central

Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2014-01-01

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

Effect of titanium dental implants on proton therapy delivered for head tumors: experimental validation using an anthropomorphic head phantom

NASA Astrophysics Data System (ADS)

Oancea, C.; Shipulin, K.; Mytsin, G.; Molokanov, A.; Niculae, D.; Ambrožová, I.; Davídková, M.

2017-03-01

A dosimetric experiment was performed at the Medico-Technical Complex in the Joint Institute for Nuclear Research, Dubna, to investigate the effects of metallic dental implants in the treatment of head and neck tumours with proton therapy. The goal of the study was to evaluate the 2D dose distributions of different clinical treatment plans measured in an anthropomorphic phantom, and compare them to predictions from a treatment planning system. The anthropomorphic phantom was sliced into horizontal segments. Two grade 4 Titanium implants were inserted between 2 slices, corresponding to a maxillary area. GafChromic EBT2 films were placed between the segments containing the implants to measure the 2D delivered dose. Two different targets were designed: the first target includes the dental implants in the isocentre, and in the second target, the proton beam is delivered through the implants, which are located at the entrance region of the Bragg curve. The experimental results were compared to the treatment plans made using our custom 3D Treatment Planning System, named RayTreat. To quantitatively determine differences in the isodose distributions (measured and calculated), the gamma index (3 mm, 3%) was calculated for each target for the matrix value in the region of high isodose (> 90%): for the experimental setup, which includes the implants in the SOBP region, the result obtained was 84.3%. When the implants were localised in the entrance region of the Bragg curve, the result obtained was 86.4%. In conclusion, the uncertainties introduced by the clinically planned dose distribution are beyond reasonable limits. The linear energy transfer spectra in close proximity to the implants were investigated using solid state nuclear track detectors (TED). Scattered particles outside the target were detected.

Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields

NASA Astrophysics Data System (ADS)

Diego Azcona, Juan; Barbés, Benigno; Wang, Lilie; Burguete, Javier

2016-01-01

This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac’s head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.

On the experimental validation of model-based dose calculation algorithms for 192Ir HDR brachytherapy treatment planning

NASA Astrophysics Data System (ADS)

Pappas, Eleftherios P.; Zoros, Emmanouil; Moutsatsos, Argyris; Peppa, Vasiliki; Zourari, Kyveli; Karaiskos, Pantelis; Papagiannis, Panagiotis

2017-05-01

There is an acknowledged need for the design and implementation of physical phantoms appropriate for the experimental validation of model-based dose calculation algorithms (MBDCA) introduced recently in 192Ir brachytherapy treatment planning systems (TPS), and this work investigates whether it can be met. A PMMA phantom was prepared to accommodate material inhomogeneities (air and Teflon), four plastic brachytherapy catheters, as well as 84 LiF TLD dosimeters (MTS-100M 1  ×  1  ×  1 mm3 microcubes), two radiochromic films (Gafchromic EBT3) and a plastic 3D dosimeter (PRESAGE). An irradiation plan consisting of 53 source dwell positions was prepared on phantom CT images using a commercially available TPS and taking into account the calibration dose range of each detector. Irradiation was performed using an 192Ir high dose rate (HDR) source. Dose to medium in medium, Dmm , was calculated using the MBDCA option of the same TPS as well as Monte Carlo (MC) simulation with the MCNP code and a benchmarked methodology. Measured and calculated dose distributions were spatially registered and compared. The total standard (k  =  1) spatial uncertainties for TLD, film and PRESAGE were: 0.71, 1.58 and 2.55 mm. Corresponding percentage total dosimetric uncertainties were: 5.4-6.4, 2.5-6.4 and 4.85, owing mainly to the absorbed dose sensitivity correction and the relative energy dependence correction (position dependent) for TLD, the film sensitivity calibration (dose dependent) and the dependencies of PRESAGE sensitivity. Results imply a LiF over-response due to a relative intrinsic energy dependence between 192Ir and megavoltage calibration energies, and a dose rate dependence of PRESAGE sensitivity at low dose rates (<1 Gy min-1). Calculations were experimentally validated within uncertainties except for MBDCA results for points in the phantom periphery and dose levels  <20%. Experimental MBDCA validation is laborious, yet feasible. Further work is required for the full characterization of dosimeter response for 192Ir and the reduction of experimental uncertainties.

Extending Three-Dimensional Weighted Cone Beam Filtered Backprojection (CB-FBP) Algorithm for Image Reconstruction in Volumetric CT at Low Helical Pitches

PubMed Central

Hsieh, Jiang; Nilsen, Roy A.; McOlash, Scott M.

2006-01-01

A three-dimensional (3D) weighted helical cone beam filtered backprojection (CB-FBP) algorithm (namely, original 3D weighted helical CB-FBP algorithm) has already been proposed to reconstruct images from the projection data acquired along a helical trajectory in angular ranges up to [0, 2 π]. However, an overscan is usually employed in the clinic to reconstruct tomographic images with superior noise characteristics at the most challenging anatomic structures, such as head and spine, extremity imaging, and CT angiography as well. To obtain the most achievable noise characteristics or dose efficiency in a helical overscan, we extended the 3D weighted helical CB-FBP algorithm to handle helical pitches that are smaller than 1: 1 (namely extended 3D weighted helical CB-FBP algorithm). By decomposing a helical over scan with an angular range of [0, 2π + Δβ] into a union of full scans corresponding to an angular range of [0, 2π], the extended 3D weighted function is a summation of all 3D weighting functions corresponding to each full scan. An experimental evaluation shows that the extended 3D weighted helical CB-FBP algorithm can improve noise characteristics or dose efficiency of the 3D weighted helical CB-FBP algorithm at a helical pitch smaller than 1: 1, while its reconstruction accuracy and computational efficiency are maintained. It is believed that, such an efficient CB reconstruction algorithm that can provide superior noise characteristics or dose efficiency at low helical pitches may find its extensive applications in CT medical imaging. PMID:23165031

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Jainil P., E-mail: jainil.shah@duke.edu; Mann, Steve D.; McKinley, Randolph L.

Purpose: A novel breast CT system capable of arbitrary 3D trajectories has been developed to address cone beam sampling insufficiency as well as to image further into the patient’s chest wall. The purpose of this study was to characterize any trajectory-related differences in 3D x-ray dose distribution in a pendant target when imaged with different orbits. Methods: Two acquisition trajectories were evaluated: circular azimuthal (no-tilt) and sinusoidal (saddle) orbit with ±15° tilts around a pendant breast, using Monte Carlo simulations as well as physical measurements. Simulations were performed with tungsten (W) filtration of a W-anode source; the simulated source fluxmore » was normalized to the measured exposure of a W-anode source. A water-filled cylindrical phantom was divided into 1 cm{sup 3} voxels, and the cumulative energy deposited was tracked in each voxel. Energy deposited per voxel was converted to dose, yielding the 3D distributed dose volumes. Additionally, three cylindrical phantoms of different diameters (10, 12.5, and 15 cm) and an anthropomorphic breast phantom, initially filled with water (mimicking pure fibroglandular tissue) and then with a 75% methanol-25% water mixture (mimicking 50–50 fibroglandular-adipose tissues), were used to simulate the pendant breast geometry and scanned on the physical system. Ionization chamber calibrated radiochromic film was used to determine the dose delivered in a 2D plane through the center of the volume for a fully 3D CT scan using the different orbits. Results: Measured experimental results for the same exposure indicated that the mean dose measured throughout the central slice for different diameters ranged from 3.93 to 5.28 mGy, with the lowest average dose measured on the largest cylinder with water mimicking a homogeneously fibroglandular breast. These results align well with the cylinder phantom Monte Carlo studies which also showed a marginal difference in dose delivered by a saddle trajectory in the central slice. Regardless of phantom material or filled fluid density, dose delivered by the saddle scan was negligibly different than the simple circular, no-tilt scans. The average dose measured in the breast phantom was marginally higher for saddle than the circular no tilt scan at 3.82 and 3.87 mGy, respectively. Conclusions: Not only does nontraditional 3D-trajectory CT scanning yield more complete sampling of the breast volume but also has comparable dose deposition throughout the breast and anterior chest volume, as verified by Monte Carlo simulation and physical measurements.« less

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy.

PubMed

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C; Lomax, Antony J; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

NASA Astrophysics Data System (ADS)

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C.; Lomax, Antony J.; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6× layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with > 5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Design and implementation of a robust and cost-effective double-scattering system at a horizontal proton beamline

NASA Astrophysics Data System (ADS)

Helmbrecht, S.; Baumann, M.; Enghardt, W.; Fiedler, F.; Krause, M.; Lühr, A.

2016-11-01

Purpose: particle therapy has the potential to improve radiooncology. With more and more facilities coming into operation, also the interest for research at proton beams increases. Though many centers provide beam at an experimental room, some of them do not feature a device for radiation field shaping, a so called nozzle. Therefore, a robust and cost-effective double-scattering system for horizontal proton beamlines has been designed and implemented. Materials and methods: the nozzle is based on the double scattering technique. Two lead scatterers, an aluminum ridge-filter and two brass collimators were optimized in a simulation study to form a laterally homogeneous 10 cm × 10 cm field with a spread-out Bragg-peak (SOBP). The parts were mainly manufactured using 3D printing techniques and the system was set up at OncoRay's experimental beamline. Measurement of the radiation field were carried out using a water phantom. Results: high levels of dose homogeneity were found in lateral (dose variation ΔD/D < ±2%) as well as in beam direction (ΔD/D < ± 3% in the SOBP). The system has already been used for radiobiology and physical experiments. Conclusion: the presented setup allows for creating clinically realistic extended radiation fields at fixed horizontal proton beamlines and is ready to use for internal and external users. The excellent performance combined with the simplistic design let it appear as a valuable option for proton therapy centers intending to foster their experimental portfolio.

[Effect of Jianpi Yangzheng Xiaozheng Recipe on Apoptosis and Autophagy of Subcutaneous Transplanted Tumor in Nude Mice: an Experimental Study on Mechanism].

PubMed

Wu, Jian; Liu, Shen-lin; Zhang, Xing-xing; Chen, Min; Zou, Xi

2015-09-01

To observe the effect of Jianpi Yangzheng Xiaozheng Recipe (JYXR) on the tumor inhibition rate of subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice, and to study its molecular mechanism of apoptosis and autophagy. Gastric cancer cell line MGC-803 was subcutaneously inoculated to nude mice for preparing transplanted gastric cancer models. Totally 32 BALB/c nude mice were randomly divided into 4 groups according to random digit table, i.e., the negative control group, the positive control group, the high dose JYXR group, the low dose JYXR group, 8 in each group. Normal saline was administered to mice in the negative control group by gastrogavage. 5-fluorouracil (5-Fu) at 2. 5 mg/kg was administered to mice in the positive control group by gastrogavage. JYXR at 85 and 43 g/kg was administered to mice in the high dose JYXR group and the low dose JYXR group by gastrogavage, once per day for 10 successive days. The effect of JYXR on the tumor inhibition rate of subcutaneous transplanted tumor was observed. Effects of JYXR on gene expression levels of Bax, Bcl-2, Fas, Cyclin D1, Cyclin D2, and Cyclin D3 in transplanted tumor were observed by real-time PCR. Effects of JYXR on protein expression levels of Procaspase-3, Procaspase-8, Procaspase-9, cleaved-PARP, Beclin-1, and LC3B were detected using Western blot. (1) Compared with the negative control group, the tumor weight was obviously reduced in the rest three groups (P <0. 05). The tumor weight was higher in the high dose JYXR group and the low dose JYXR group than in the positive control group (P <0. 05). (2) Results of RT-PCR indicated that, compared with the negative control group, expression levels of Bax were up-regulated, but expression levels of Bcl-2, Cyclin D1, Cyclin D2, and Cyclin D3 were down-regulated in the positive control group and JYXR groups (P <0. 05). The expression level of Fas was up-regulated in the positive control group and the high dose JYXR group (P <0. 05). Compared with the positive control group, expression levels of Fas, and Bax were all down-regulated, but expression levels of Bcl-2, Cyclin D2, and Cyclin D3 were all up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0. 05). The expression level of Cyclin D1 was down-regulated in the high dose JYXR group, but it was up-regulated in the low dose JYXR group ( both P <0. 05). (3) Results of Western blot showed, compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, and Procaspase-9 were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B II were up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0.05). Compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, Procaspase-9, and LC3B II were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B I were up-regulated in the positive control group (all P <0. 05). JYXR showed significant inhibition on subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice. Its mechanism might be associated with activating apoptosis and autophagy correlated factors.

RAIN-Droplet: A Novel 3-D in vitro Angiogenesis Model

PubMed Central

Zeitlin, Benjamin D.; Dong, Zhihong; Nör, Jacques E.

2012-01-01

Angiogenesis is fundamentally required for the initialization, development and metastatic spread of cancer. A rapidly expanding number of new experimental, chemical modulators of endothelial cell function have been described for the therapeutic inhibition of angiogenesis in cancer. Despite this expansion there has been very limited parallel growth of in vitro angiogenesis models or experimental tools. Here we present the Responsive Angiogenic Implanted Network (RAIN)-Droplet model and novel angiogenesis assay using an endothelial cell culture model of microvascular endothelial cells encapsulated in a spontaneously self-assembling, toroidal hydrogel droplet uniquely yielding discrete, pre-formed, angiogenic networks that may be embedded in 3-D matrices. On embedding, radial growth of capillary-like sprouts and cell invasion was observed. The sprouts formed as both outgrowths from endothelial cells on the surface of the droplets but also, uniquely, from the pre-formed network structures within the droplet. We demonstrate proof-of-principle for the utility of the model showing significant inhibition of sprout formation (p<0.001) in the presence of bevacizumab, an anti-angiogenic antibody. Using the RAIN-Droplet assay we also demonstrate a novel dose dependent pro-angiogenic function for the characteristically anti-angiogenic multi-kinase inhibitor sorafenib. Exposure of endothelial cells in 3-D culture to low, non-lethal doses (<1 μM) of sorafenib after initiation of sprouting resulted in the formation of significantly (p<0.05) more endothelial sprouts compared to controls over a 48-hour period. Higher doses of sorafenib (5 μM) resulted in a significant (p<0.05) reduction of sprouting over the same time period. The RAIN-Droplet model is a highly versatile and simply constructed 3-D focal sprouting approach well suited for the study of vascular morphogenesis and for preclinical testing of drugs. Furthermore, the RAIN-Droplet model has facilitated the discovery of a novel pro-angiogenic capacity for sorafenib which may impact the clinical application and dosing regimen of that drug. PMID:22565576

MO-FG-CAMPUS-TeP1-01: An Efficient Method of 3D Patient Dose Reconstruction Based On EPID Measurements for Pre-Treatment Patient Specific QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, R; Lee, C; Calvary Mater Newcastle, Newcastle

Purpose: To demonstrate an efficient and clinically relevant patient specific QA method by reconstructing 3D patient dose from 2D EPID images for IMRT plans. Also to determine the usefulness of 2D QA metrics when assessing 3D patient dose deviations. Methods: Using the method developed by King et al (Med Phys 39(5),2839–2847), EPID images of IMRT fields were acquired in air and converted to dose at 10 cm depth (SAD setup) in a flat virtual water phantom. Each EPID measured dose map was then divided by the corresponding treatment planning system (TPS) dose map calculated with an identical setup, to derivemore » a 2D “error matrix”. For each field, the error matrix was used to adjust the doses along the respective ray lines in the original patient 3D dose. All field doses were combined to derive a reconstructed 3D patient dose for quantitative analysis. A software tool was developed to efficiently implement the entire process and was tested with a variety of IMRT plans for 2D (virtual flat phantom) and 3D (in-patient) QA analysis. Results: The method was tested on 60 IMRT plans. The mean (± standard deviation) 2D gamma (2%,2mm) pass rate (2D-GPR) was 97.4±3.0% and the mean 2D gamma index (2D-GI) was 0.35±0.06. The 3D PTV mean dose deviation was 1.8±0.8%. The analysis showed very weak correlations between both the 2D-GPR and 2D-GI when compared with PTV mean dose deviations (R2=0.3561 and 0.3632 respectively). Conclusion: Our method efficiently calculates 3D patient dose from 2D EPID images, utilising all of the advantages of an EPID-based dosimetry system. In this study, the 2D QA metrics did not predict the 3D patient dose deviation. This tool allows reporting of the 3D volumetric dose parameters thus providing more clinically relevant patient specific QA.« less

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

NASA Astrophysics Data System (ADS)

Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

2013-11-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats.

PubMed

Martín-Lacave, I; Ramos, F; Utrilla, J C; Conde, E; Hevia, A; Fernández, R; Moreno, A M; Fernández-Santos, J M; Galera-Davidson, H

1998-02-01

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI.

PubMed

Papagiannis, P; Karaiskos, P; Kozicki, M; Rosiak, J M; Sakelliou, L; Sandilos, P; Seimenis, I; Torrens, M

2005-05-07

This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.

Methodology to reduce 6D patient positional shifts into a 3D linear shift and its verification in frameless stereotactic radiotherapy

NASA Astrophysics Data System (ADS)

Sarkar, Biplab; Ray, Jyotirmoy; Ganesh, Tharmarnadar; Manikandan, Arjunan; Munshi, Anusheel; Rathinamuthu, Sasikumar; Kaur, Harpreet; Anbazhagan, Satheeshkumar; Giri, Upendra K.; Roy, Soumya; Jassal, Kanan; Kalyan Mohanti, Bidhu

2018-04-01

The aim of this article is to derive and verify a mathematical formulation for the reduction of the six-dimensional (6D) positional inaccuracies of patients (lateral, longitudinal, vertical, pitch, roll and yaw) to three-dimensional (3D) linear shifts. The formulation was mathematically and experimentally tested and verified for 169 stereotactic radiotherapy patients. The mathematical verification involves the comparison of any (one) of the calculated rotational coordinates with the corresponding value from the 6D shifts obtained by cone beam computed tomography (CBCT). The experimental verification involves three sets of measurements using an ArcCHECK phantom, when (i) the phantom was not moved (neutral position: 0MES), (ii) the position of the phantom shifted by 6D shifts obtained from CBCT (6DMES) from neutral position and (iii) the phantom shifted from its neutral position by 3D shifts reduced from 6D shifts (3DMES). Dose volume histogram and statistical comparisons were made between ≤ft< TPSCAL{\\text -}0MES \\right> and ≤ft< 3DMES{\\text -6DMES} \\right> . The mathematical verification was performed by a comparison of the calculated and measured yaw (γ°) rotation values, which gave a straight line, Y  =  1X with a goodness of fit as R 2  =  0.9982. The verification, based on measurements, gave a planning target volume receiving 100% of the dose (V100%) as 99.1  ±  1.9%, 96.3  ±  1.8%, 74.3  ±  1.9% and 72.6  ±  2.8% for the calculated treatment planning system values TPSCAL, 0MES, 3DMES and 6DMES, respectively. The statistical significance (p-values: paired sample t-test) of V100% were found to be 0.03 for the paired sample ≤ft< 3DMES{\\text -6DMES} \\right> and 0.01 for ≤ft< 0MES{\\text -TPSCAL} \\right> . In this paper, a mathematical method to reduce 6D shifts to 3D shifts is presented. The mathematical method is verified by using well-matched values between the measured and calculated γ°. Measurements done on the ArcCHECK phantom also proved that the proposed methodology is correct. The post-correction of the table position condition introduces a minimal spatial dose delivery error in the frameless stereotactic system, using a 6D motion enabled robotic couch. This formulation enables the reduction of 6D positional inaccuracies to 3D linear shifts, and hence allows the treatment of patients with frameless stereotactic radiosurgery by using only a 3D linear motion enabled couch.

Poster - 40: Treatment Verification of a 3D-printed Eye Phantom for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunning, Chelsea; Lindsay, Clay; Unick, Nick

Purpose: Ocular melanoma is a form of eye cancer which is often treated using proton therapy. The benefit of the steep proton dose gradient can only be leveraged for accurate patient eye alignment. A treatment-planning program was written to plan on a 3D-printed anatomical eye-phantom, which was then irradiated to demonstrate the feasibility of verifying in vivo dosimetry for proton therapy using PET imaging. Methods: A 3D CAD eye model with critical organs was designed and voxelized into the Monte-Carlo transport code FLUKA. Proton dose and PET isotope production were simulated for a treatment plan of a test tumour, generatedmore » by a 2D treatment-planning program developed using NumPy and proton range tables. Next, a plastic eye-phantom was 3D-printed from the CAD model, irradiated at the TRIUMF Proton Therapy facility, and imaged using a PET scanner. Results: The treatment-planning program prediction of the range setting and modulator wheel was verified in FLUKA to treat the tumour with at least 90% dose coverage for both tissue and plastic. An axial isotope distribution of the PET isotopes was simulated in FLUKA and converted to PET scan counts. Meanwhile, the 3D-printed eye-phantom successfully yielded a PET signal. Conclusions: The 2D treatment-planning program can predict required parameters to sufficiently treat an eye tumour, which was experimentally verified using commercial 3D-printing hardware to manufacture eye-phantoms. Comparison between the simulated and measured PET isotope distribution could provide a more realistic test of eye alignment, and a variation of the method using radiographic film is being developed.« less

3D printer generated thorax phantom with mobile tumor for radiation dosimetry

NASA Astrophysics Data System (ADS)

Mayer, Rulon; Liacouras, Peter; Thomas, Andrew; Kang, Minglei; Lin, Liyong; Simone, Charles B.

2015-07-01

This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches a patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor's trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between the measured and intended doses.

3D printer generated thorax phantom with mobile tumor for radiation dosimetry.

PubMed

Mayer, Rulon; Liacouras, Peter; Thomas, Andrew; Kang, Minglei; Lin, Liyong; Simone, Charles B

2015-07-01

This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches a patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor's trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between the measured and intended doses.

3D printer generated thorax phantom with mobile tumor for radiation dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Rulon; Liacouras, Peter; Thomas, Andrew

2015-07-15

This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches amore » patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor’s trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between the measured and intended doses.« less

SU-F-BRA-11: An Experimental Commissioning Test of Brachytherapy MBDCA Dosimetry, Based On a Commercial Radiochromic Gel/optical CT System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pappas, E; Karaiskos, P; Zourari, K

2015-06-15

Purpose: To implement a 3D dose verification procedure of Model-Based Dose Calculation Algorithms (MBDCAs) for {sup 192}Ir HDR brachytherapy, based on a novel Ferrous Xylenol-orange gel (FXG) and optical CT read-out. Methods: The TruView gel was employed for absolute dosimetry in conjunction with cone-beam optical CT read-out with the VISTA scanner (both from Modus Medical Inc, London, ON, Canada). A multi-catheter skin flap was attached to a cylindrical PETE jar (d=9.6cm, h=16cm) filled with FXG, which served as both the dosimeter and the water equivalent phantom of bounded dimensions. X- ray CT image series of the jar with flap attachedmore » was imported to Oncentra Brachy v.4.5. A treatment plan consisting of 8 catheters and 56 dwell positions was generated, and Oncentra-ACE MBDCA as well as TG43 dose results were exported for further evaluation. The irradiation was carried out with a microSelecton v2 source. The FXG dose-response, measured via an electron irradiation of a second dosimeter from the same batch, was linear (R2>0.999) at least up to 12Gy. A MCNP6 input file was prepared from the DICOM-RT plan data using BrachyGuide to facilitate Monte Carlo (MC) simulation dosimetry in the actual experimental geometry. Agreement between experimental (reference) and calculated dose distributions was evaluated using the 3D gamma index (GI) method with criteria (5%-2mm applied locally) determined from uncertainty analysis. Results: The TG-43 GI failed, as expected, in the majority of voxels away from the flap (pass rate 59% for D>0.8Gy, corresponding to 10% of prescribed dose). ACE performed significantly better (corresponding pass rate 92%). The GI evaluation for the MC data (corresponding pass rate 97%) failed mainly at low dose points of increased uncertainty. Conclusion: FXG gel/optical CT is an efficient method for level-2 commissioning of brachytherapy MBDCAs. Target dosimetry is not affected from uncertainty introduced by TG43 assumptions in 192Ir skin brachytherapy. Research co-financed by the ESF and Greek funds through the Operational Program Education and Lifelong Learning Investing in Knowledge Society of the NSRF. Research Funding Program: Aristeia. Modus Medical Devices Inc. provided a TruView dosimeter batch and Nucletron, and Elekta company, provided access to Oncentra Brachy v4.5, for research purposes.« less

Methodology to reduce 6D patient positional shifts into a 3D linear shift and its verification in frameless stereotactic radiotherapy.

PubMed

Sarkar, Biplab; Ray, Jyotirmoy; Ganesh, Tharmarnadar; Manikandan, Arjunan; Munshi, Anusheel; Rathinamuthu, Sasikumar; Kaur, Harpreet; Anbazhagan, Satheeshkumar; Giri, Upendra K; Roy, Soumya; Jassal, Kanan; Mohanti, Bidhu Kalyan

2018-03-22

The aim of this article is to derive and verify a mathematical formulation for the reduction of the six-dimensional (6D) positional inaccuracies of patients (lateral, longitudinal, vertical, pitch, roll and yaw) to three-dimensional (3D) linear shifts. The formulation was mathematically and experimentally tested and verified for 169 stereotactic radiotherapy patients. The mathematical verification involves the comparison of any (one) of the calculated rotational coordinates with the corresponding value from the 6D shifts obtained by cone beam computed tomography (CBCT). The experimental verification involves three sets of measurements using an ArcCHECK phantom, when (i) the phantom was not moved (neutral position: 0MES), (ii) the position of the phantom shifted by 6D shifts obtained from CBCT (6DMES) from neutral position and (iii) the phantom shifted from its neutral position by 3D shifts reduced from 6D shifts (3DMES). Dose volume histogram and statistical comparisons were made between [Formula: see text] and [Formula: see text]. The mathematical verification was performed by a comparison of the calculated and measured yaw (γ°) rotation values, which gave a straight line, Y  =  1X with a goodness of fit as R 2   =  0.9982. The verification, based on measurements, gave a planning target volume receiving 100% of the dose (V100%) as 99.1  ±  1.9%, 96.3  ±  1.8%, 74.3  ±  1.9% and 72.6  ±  2.8% for the calculated treatment planning system values TPSCAL, 0MES, 3DMES and 6DMES, respectively. The statistical significance (p-values: paired sample t-test) of V100% were found to be 0.03 for the paired sample [Formula: see text] and 0.01 for [Formula: see text]. In this paper, a mathematical method to reduce 6D shifts to 3D shifts is presented. The mathematical method is verified by using well-matched values between the measured and calculated γ°. Measurements done on the ArcCHECK phantom also proved that the proposed methodology is correct. The post-correction of the table position condition introduces a minimal spatial dose delivery error in the frameless stereotactic system, using a 6D motion enabled robotic couch. This formulation enables the reduction of 6D positional inaccuracies to 3D linear shifts, and hence allows the treatment of patients with frameless stereotactic radiosurgery by using only a 3D linear motion enabled couch.

An assessment of a 3D EPID-based dosimetry system using conventional two- and three-dimensional detectors for VMAT.

PubMed

Stevens, S; Dvorak, P; Spevacek, V; Pilarova, K; Bray-Parry, M; Gesner, J; Richmond, A

2018-01-01

To provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT. A 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions. Fluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition. 3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-J-110: Dosimetric Analysis of Respiratory Motion Based On Four-Dimensional Dose Accumulation in Liver Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2015-06-15

Purpose: Respiratory motion in thoracic and abdominal region could lead to significant underdosing of target and increased dose to healthy tissues. The aim of this study is to evaluate the dosimetric effect of respiratory motion in conventional 3D dose by comparing 4D deformable dose in liver stereotactic body radiotherapy (SBRT). Methods: Five patients who had previously treated liver SBRT were included in this study. Four-dimensional computed tomography (4DCT) images with 10 phases for all patients were acquired on multi-slice CT scanner (Siemens, Somatom definition). Conventional 3D planning was performed using the average intensity projection (AIP) images. 4D dose accumulation wasmore » calculated by summation of dose distribution for all phase images of 4DCT using deformable image registration (DIR) . The target volume and normal organs dose were evaluated with the 4D dose and compared with those from 3D dose. And also, Index of achievement (IOA) which assesses the consistency between planned dose and prescription dose was used to compare target dose distribution between 3D and 4D dose. Results: Although the 3D dose calculation considered the moving target coverage, significant differences of various dosimetric parameters between 4D and 3D dose were observed in normal organs and PTV. The conventional 3D dose overestimated dose to PTV, however, there was no significant difference for GTV. The average difference of IOA which become ‘1’ in an ideal case was 3.2% in PTV. The average difference of liver and duodenum was 5% and 16% respectively. Conclusion: 4D dose accumulation which can provide dosimetric effect of respiratory motion has a possibility to predict the more accurate delivered dose to target and normal organs and improve treatment accuracy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning (MSIP) of Korea.« less

[Antitumor effect of baicalin on rat brain glioma].

PubMed

Hu, Yong-zhen; Wang, Dian-hong; Luan, Yu; Gong, Hai-dong

2013-01-01

To investigate the therapeutic mechanism of baicalin on rat brain glioma. Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed. Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas. Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression.

CT-image-based conformal brachytherapy of breast cancer. The significance of semi-3-D and 3-D treatment planning.

PubMed

Polgár, C; Major, T; Somogyi, A; Takácsi-Nagy, Z; Mangel, L C; Forrai, G; Sulyok, Z; Fodor, J; Németh, G

2000-03-01

To compare the conventional 2-D, the simulator-guided semi-3-D and the recently developed CT-guided 3-D brachytherapy treatment planning in the interstitial radiotherapy of breast cancer. In 103 patients with T1-2, N0-1 breast cancer the tumor bed was clipped during breast conserving surgery. Fifty-two of them received boost brachytherapy after 46 to 50 Gy teletherapy and 51 patients were treated with brachytherapy alone via flexible implant tubes. Single, double and triple plane implant was used in 6, 89 and 8 cases, respectively. The dose of boost brachytherapy and sole brachytherapy prescribed to dose reference points was 3 times 4.75 Gy and 7 times 5.2 Gy, respectively. The positions of dose reference points varied according to the level (2-D, semi-3-D and 3-D) of treatment planning performed. The treatment planning was based on the 3-D reconstruction of the surgical clips, implant tubes and skin points. In all cases the implantations were planned with a semi-3-D technique aided by simulator. In 10 cases a recently developed CT-guided 3-D planning system was used. The semi-3-D and 3-D treatment plans were compared to hypothetical 2-D plans using dose-volume histograms and dose non-uniformity ratios. The values of mean central dose, mean skin dose, minimal clip dose, proportion of underdosaged clips and mean target surface dose were evaluated. The accuracy of tumor bed localization and the conformity of planning target volume and treated volume were also analyzed in each technique. With the help of conformal semi-3-D and 3-D brachytherapy planning we could define reference dose points, active source positions and dwell times individually. This technique decreased the mean skin dose with 22.2% and reduced the possibility of geographical miss. We could achieve the best conformity between the planning target volume and the treated volume with the CT-image based 3-D treatment planning, at the cost of worse dose homogeneity. The mean treated volume was reduced by 25.1% with semi-3-D planning, however, it was increased by 16.2% with 3-D planning, compared to the 2-D planning. The application of clips into the tumor bed and the conformal (semi-3-D and 3-D) planning help to avoid geographical miss. CT is suitable for 3-D brachytherapy planning. Better local control with less side effects might be achieved with these new techniques. Conformal 3-D brachytherapy calls for new treatment planning concepts, taking the irregular 3-D shape of the target volume into account. The routine clinical application of image-based 3-D brachytherapy is a real aim in the very close future.

Comparative evaluation of two-dimensional radiography and three dimensional computed tomography based dose-volume parameters for high-dose-rate intracavitary brachytherapy of cervical cancer: a prospective study.

PubMed

Madan, Renu; Pathy, Sushmita; Subramani, Vellaiyan; Sharma, Seema; Mohanti, Bidhu Kalyan; Chander, Subhash; Thulkar, Sanjay; Kumar, Lalit; Dadhwal, Vatsla

2014-01-01

Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

Characterization of Al2O3 optically stimulated luminescence films for 2D dosimetry using a 6 MV photon beam

NASA Astrophysics Data System (ADS)

Ahmed, M. F.; Shrestha, N.; Schnell, E.; Ahmad, S.; Akselrod, M. S.; Yukihara, E. G.

2016-11-01

This work evaluates the dosimetric properties of newly developed optically stimulated luminescence (OSL) films, fabricated with either Al2O3:C or Al2O3:C,Mg, using a prototype laser scanning reader, a developed image reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing OSL films (Al2O3:C and Al2O3:C,Mg) and a radiochromic film (Gafchromic EBT3) were irradiated using a 6 MV photon beam using different doses, field sizes, with and without wedge filter. Dependence on film orientation of the OSL system was also tested. Diode-array (MapCHECK) and ionization chamber measurements were performed for comparison. The OSLD film doses agreed with the MapCHECK and ionization chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system background and minimum detectable dose (MDD) were  <0.5 mGy, and the dose response was approximately linear from the MDD up to a few grays (the linearity correction was  <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose profiles agreed with those obtained using EBT3 films (analyzed using the triple channel method) in the high dose regions of the images. In the low dose regions, the dose profiles from the OSLD films were more reproducible than those from the EBT3 films. We also demonstrated that the OSL film data are independent on scan orientation and field size over the investigated range. The results demonstrate the potential of OSLD films for 2D dosimetry, particularly for the characterization of small fields, due to their wide dynamic range, linear response, resolution and dosimetric properties. The negligible background and potential simple calibration make these OSLD films suitable for remote audits. The characterization presented here may motivate further commercial development of a 2D dosimetry system based on the OSL from Al2O3:C or Al2O3:C,Mg.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, D; Kang, S; Kim, D

Purpose: The dose difference between three-dimensional dose (3D dose) and 4D dose which considers motion due to respiratory can be varied according to geometrical relationship between planning target volume (PTV) and organ at risk (OAR). The purpose of the study is to investigate the dose difference between 3D and 4D dose using overlap volume histogram (OVH) which is an indicator that quantify geometrical relationship between a PTV and an OAR. Methods: Five liver cancer patients who previously treated stereotactic body radiotherapy (SBRT) were investigated. Four-dimensional computed tomography (4DCT) images were acquired for all patients. ITV-based treatment planning was performed. 3Dmore » dose was calculated on the end-exhale phase image as a reference phase image. 4D dose accumulation was implemented from all phase images using dose warping technique used deformable image registration (DIR) algorithm (Horn and Schunck optical flow) in DIRART. In this study OVH was used to quantify geometrical relationship between a PTV and an OAR. OVH between a PTV and a selected OAR was generated for each patient case and compared for all cases. The dose difference between 3D and 4D dose for normal organ was calculated and compared for all cases according to OVH. Results: The 3D and 4D dose difference for OAR was analyzed using dose-volume histogram (DVH). On the basis of a specific point which corresponds to 10% of OAR volume overlapped with expanded PTV, mean dose difference was 34.56% in minimum OVH distance case and 13.36% in maximum OVH distance case. As the OVH distance increased, mean dose difference between 4D and 3D dose was decreased. Conclusion: The tendency of dose difference variation was verified according to OVH. OVH is seems to be indicator that has a potential to predict the dose difference between 4D and 3D dose. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning.« less

Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations.

PubMed

Paniagua, Natalia; Lopez, Rebeca; Muñoz, Natalia; Tames, Miriam; Mojica, Elisa; Arana-Arri, Eunate; Mintegi, Santiago; Benito, Javier

2017-12-01

To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED). We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting. During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05). Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. clinicaltrialsregister.eu: 2013-003145-42. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.

PubMed

Poulsen, Per Rugaard; Eley, John; Langner, Ulrich; Simone, Charles B; Langen, Katja

2018-01-01

To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS). A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage. One time was static and 2 used 4-second, 3-cm peak-to-peak sinusoidal motion with delivery started at maximum inhalation and maximum exhalation. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3-mm gamma pass rate was calculated using the motion-convolved static dose as the reference. Simulations were first validated with the experiments and then used to extend the study to 0- to 5-cm motion magnitude, 2- to 6-second motion periods, patient-measured liver tumor motion, and 1- to 6-fraction treatments. The effect of the proposed method was evaluated for the 5 clinical cases using 4-dimensional (4D) dose reconstruction in the planning 4D computed tomography scan. The target homogeneity index, HI = (D 2 - D 98 )/D mean , of a single-fraction delivery is reported, where D 2 and D 98 is the dose delivered to 2% and 98% of the target, respectively, and D mean is the mean dose. The gamma pass rates were 59.6% ± 9.7% with no repainting, 76.5% ± 10.8% with 8 repaintings, and 92.4% ± 3.8% with the new repainting scheme. Simulations reproduced the experimental gamma pass rates with a 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had gamma pass rates similar to those of 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the 5 clinical cases was 14.2% with no repainting, 13.7% with 8 repaintings, 12.0% with the new repainting scheme, and 11.6% for the 4D dose without interplay effects. A novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations, and dose reconstructions. This strategy could allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, J; Lee, C; Tee, S

2014-06-15

Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as wellmore » as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.14±0.70 Gy, - 0.11±0.51 Gy, and 0.00±0.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.« less

D-T Neutron Skyshine Experiments at JAERI/FNS

NASA Astrophysics Data System (ADS)

Nishitani, Takeo; Ochiai, Kentaro; Yoshida, Shigeo; Tanaka, Ryohei; Wakisaka, Masashi; Nakao, Makoto; Sato, Satoshi; Yamauchi, Michinori; Hori, Jun-Ichi; Takahashi, Akito; Kaneko, Jun-Ichi; Sawamura, Teruko

The D-T neutron skyshine experiments have been carried out at the Fusion Neutronics Source (FNS) of JAERI with the neutron yield of ˜1.7×1011n/s. The concrete thickness of the roof and the wall of a FNS target room are 1.15 and 2 m, respectively. The FNS skyshine port with a size of 0.9 × 0.9 m2 was open during the experimental period.The radiation dose rate outside the target room was measured as far as about 550 m away from the D-T target point with a spherical rem-counter. The highest neutron dose was about 0.5 μSv/hr at a distance of 30 m from the D-T target point and the dose rate was attenuated to 0.002 μSv/hr at a distance of 550 m. The measured neutron dose distribution was analyzed with Monte Carlo code MCNP-4B and a simple line source model. The MCNP calculation overestimates the neutron dose in the distance range larger than 250 m. The neutron spectra were evaluated with a 3He detector with different thickness of polyethylene neutron moderators. Secondary gamma-rays were measured with high purity Ge detectors and NaI scintillation detectors.

Statistical model based iterative reconstruction (MBIR) in clinical CT systems: experimental assessment of noise performance.

PubMed

Li, Ke; Tang, Jie; Chen, Guang-Hong

2014-04-01

To reduce radiation dose in CT imaging, the statistical model based iterative reconstruction (MBIR) method has been introduced for clinical use. Based on the principle of MBIR and its nonlinear nature, the noise performance of MBIR is expected to be different from that of the well-understood filtered backprojection (FBP) reconstruction method. The purpose of this work is to experimentally assess the unique noise characteristics of MBIR using a state-of-the-art clinical CT system. Three physical phantoms, including a water cylinder and two pediatric head phantoms, were scanned in axial scanning mode using a 64-slice CT scanner (Discovery CT750 HD, GE Healthcare, Waukesha, WI) at seven different mAs levels (5, 12.5, 25, 50, 100, 200, 300). At each mAs level, each phantom was repeatedly scanned 50 times to generate an image ensemble for noise analysis. Both the FBP method with a standard kernel and the MBIR method (Veo(®), GE Healthcare, Waukesha, WI) were used for CT image reconstruction. Three-dimensional (3D) noise power spectrum (NPS), two-dimensional (2D) NPS, and zero-dimensional NPS (noise variance) were assessed both globally and locally. Noise magnitude, noise spatial correlation, noise spatial uniformity and their dose dependence were examined for the two reconstruction methods. (1) At each dose level and at each frequency, the magnitude of the NPS of MBIR was smaller than that of FBP. (2) While the shape of the NPS of FBP was dose-independent, the shape of the NPS of MBIR was strongly dose-dependent; lower dose lead to a "redder" NPS with a lower mean frequency value. (3) The noise standard deviation (σ) of MBIR and dose were found to be related through a power law of σ ∝ (dose)(-β) with the component β ≈ 0.25, which violated the classical σ ∝ (dose)(-0.5) power law in FBP. (4) With MBIR, noise reduction was most prominent for thin image slices. (5) MBIR lead to better noise spatial uniformity when compared with FBP. (6) A composite image generated from two MBIR images acquired at two different dose levels (D1 and D2) demonstrated lower noise than that of an image acquired at a dose level of D1+D2. The noise characteristics of the MBIR method are significantly different from those of the FBP method. The well known tradeoff relationship between CT image noise and radiation dose has been modified by MBIR to establish a more gradual dependence of noise on dose. Additionally, some other CT noise properties that had been well understood based on the linear system theory have also been altered by MBIR. Clinical CT scan protocols that had been optimized based on the classical CT noise properties need to be carefully re-evaluated for systems equipped with MBIR in order to maximize the method's potential clinical benefits in dose reduction and/or in CT image quality improvement. © 2014 American Association of Physicists in Medicine.

Statistical model based iterative reconstruction (MBIR) in clinical CT systems: Experimental assessment of noise performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ke; Tang, Jie; Chen, Guang-Hong, E-mail: gchen7@wisc.edu

Purpose: To reduce radiation dose in CT imaging, the statistical model based iterative reconstruction (MBIR) method has been introduced for clinical use. Based on the principle of MBIR and its nonlinear nature, the noise performance of MBIR is expected to be different from that of the well-understood filtered backprojection (FBP) reconstruction method. The purpose of this work is to experimentally assess the unique noise characteristics of MBIR using a state-of-the-art clinical CT system. Methods: Three physical phantoms, including a water cylinder and two pediatric head phantoms, were scanned in axial scanning mode using a 64-slice CT scanner (Discovery CT750 HD,more » GE Healthcare, Waukesha, WI) at seven different mAs levels (5, 12.5, 25, 50, 100, 200, 300). At each mAs level, each phantom was repeatedly scanned 50 times to generate an image ensemble for noise analysis. Both the FBP method with a standard kernel and the MBIR method (Veo{sup ®}, GE Healthcare, Waukesha, WI) were used for CT image reconstruction. Three-dimensional (3D) noise power spectrum (NPS), two-dimensional (2D) NPS, and zero-dimensional NPS (noise variance) were assessed both globally and locally. Noise magnitude, noise spatial correlation, noise spatial uniformity and their dose dependence were examined for the two reconstruction methods. Results: (1) At each dose level and at each frequency, the magnitude of the NPS of MBIR was smaller than that of FBP. (2) While the shape of the NPS of FBP was dose-independent, the shape of the NPS of MBIR was strongly dose-dependent; lower dose lead to a “redder” NPS with a lower mean frequency value. (3) The noise standard deviation (σ) of MBIR and dose were found to be related through a power law of σ ∝ (dose){sup −β} with the component β ≈ 0.25, which violated the classical σ ∝ (dose){sup −0.5} power law in FBP. (4) With MBIR, noise reduction was most prominent for thin image slices. (5) MBIR lead to better noise spatial uniformity when compared with FBP. (6) A composite image generated from two MBIR images acquired at two different dose levels (D1 and D2) demonstrated lower noise than that of an image acquired at a dose level of D1+D2. Conclusions: The noise characteristics of the MBIR method are significantly different from those of the FBP method. The well known tradeoff relationship between CT image noise and radiation dose has been modified by MBIR to establish a more gradual dependence of noise on dose. Additionally, some other CT noise properties that had been well understood based on the linear system theory have also been altered by MBIR. Clinical CT scan protocols that had been optimized based on the classical CT noise properties need to be carefully re-evaluated for systems equipped with MBIR in order to maximize the method's potential clinical benefits in dose reduction and/or in CT image quality improvement.« less

FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties

NASA Astrophysics Data System (ADS)

De Deene, Y.; Skyt, P. S.; Hil, R.; Booth, J. T.

2015-02-01

Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software. A new three dimensional anthropomorphically shaped flexible dosimeter, further called ‘FlexyDos3D’, has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision. The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence. The first authors Y De Deene and P S Skyt made an equivalent contribution to the experimental work presented in this paper.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PubMed

Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D

2013-03-01

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

The calcitonin/calcitonin gene related peptide-alpha gene is not required for 1alpha,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis.

PubMed

Becklund, Bryan R; James, Bradley J; Gagel, Robert F; DeLuca, Hector F

2009-08-15

The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), can suppress disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Calcium appears to be a critical component of 1,25(OH)(2)D(3)-mediated suppression of EAE, as complete disease prevention only occurs with a concomitant increase in serum calcium levels. Calcitonin (CT) is a peptide hormone released in response to acute increases in serum calcium, which led us to explore its importance in 1,25(OH)(2)D(3)-mediated suppression of EAE. Previously, we discovered that co-administration of pharmacological doses of CT enhanced the suppressive effect of 1,25(OH)(2)D(3) on EAE, suggesting CT may play a role in 1,25(OH)(2)D(3)-mediated suppression of EAE. To determine the importance of CT in EAE we have utilized a mouse strain in which the gene encoding CT and its alternative splice product, calcitonin gene related peptide-alpha (CGRP), have been deleted. Deletion of the CT/CGRP gene had no effect on EAE progression. Furthermore, treatment with 1,25(OH)(2)D(3) suppressed EAE in CT/CGRP knock-out mice equal to that in wild type mice. Therefore, we conclude that CT is not necessary for 1,25(OH)(2)D(3)-mediated suppression of EAE.

Total body irradiation with a compensator fabricated using a 3D optical scanner and a 3D printer

NASA Astrophysics Data System (ADS)

Park, So-Yeon; Kim, Jung-in; Joo, Yoon Ha; Lee, Jung Chan; Park, Jong Min

2017-05-01

We propose bilateral total body irradiation (TBI) utilizing a 3D printer and a 3D optical scanner. We acquired surface information of an anthropomorphic phantom with the 3D scanner and fabricated the 3D compensator with the 3D printer, which could continuously compensate for the lateral missing tissue of an entire body from the beam’s eye view. To test the system’s performance, we measured doses with optically stimulated luminescent dosimeters (OSLDs) as well as EBT3 films with the anthropomorphic phantom during TBI without a compensator, conventional bilateral TBI, and TBI with the 3D compensator (3D TBI). The 3D TBI showed the most uniform dose delivery to the phantom. From the OSLD measurements of the 3D TBI, the deviations between the measured doses and the prescription dose ranged from  -6.7% to 2.4% inside the phantom and from  -2.3% to 0.6% on the phantom’s surface. From the EBT3 film measurements, the prescription dose could be delivered to the entire body of the phantom within  ±10% accuracy, except for the chest region, where tissue heterogeneity is extreme. The 3D TBI doses were much more uniform than those of the other irradiation techniques, especially in the anterior-to-posterior direction. The 3D TBI was advantageous, owing to its uniform dose delivery as well as its efficient treatment procedure.

Epinephrine doses delivered from auto-injectors stored at excessively high temperatures.

PubMed

Rachid, Ousama; Simons, F Estelle R; Rawas-Qalaji, Mutasem; Lewis, Stephen; Simons, Keith J

2016-01-01

Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25 °C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures. We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70 °C. Twenty-five in-date EAIs were stored constantly or cyclically at 70 °C (excessive heat) or 25 °C (controls) for 5 d or 10 d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV. Control EAIs ejected a volume of 0.300 ± 0.006 mL containing 103.7 ± 3.3% of labeled dose (LD). After 5 d or 10 d of constant storage at 70 °C and activation at 70 °C, EAIs ejected a volume of 0.367 ± 0.008 mL containing 96.8 ± 3.8% LD and 0.373 ± 0.007 mL containing 77.7 ± 3.3% LD, respectively. After 5 d of cyclic storage at 70 °C and cooling to 25 °C before activation, EAIs ejected a volume of 0.311 ± 0.008 mL containing 87.2 ± 1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine. EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.

Experimental Clostridium perfringens type D enterotoxemia in goats.

PubMed

Uzal, F A; Kelly, W R

1998-03-01

The effects of intraduodenal administration of Clostridium perfringens cultures and culture products in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species. Five conventionally reared, 11-16-week-old Angora goat kids were dosed intraduodenally with whole cultures of C. perfringens type D; five similar animals were dosed with C. perfringens type D filtered culture supernatant; and a third group of five kids was dosed with C. perfringens type D washed cells. Two kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. All five kids inoculated with whole culture and three of five dosed with culture supernatant and with washed cells developed central nervous system signs. Diarrhea was observed in two of five kids inoculated with whole culture, in all five of those dosed with culture supernatant, and in three of five of those that received washed cells. The most striking postmortem findings consisted of lung edema, necrotizing pseudomembranous colitis, and cerebral vasogenic edema. The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease.

Does prolonged cyanide exposure have a diabetogenic effect?

PubMed

Soto-Blanco, B; Sousa, A B; Manzano, H; Guerra, J L; Górniak, S L

2001-04-01

Cyanide exposure through cassava consumption has been associated with the development of malnutrition-related diabetes mellitus (MRDM). However, there are few experimental reproductions of this disease. In the present study 42 rats received 0, 9.0 or 12.0 mg KCN/kg bw/d for 15 d, 26 pigs were dosed with 0, 2.0, 4.0 or 6.0 mg KCN/kg for 74 d, and 34 goats received 0, 0.3, 0.6, 1.2 or 3.0 mg KCN/kg for 5 mo. At the end of each experimental period, plasma samples were obtained for glucose and thiocyanate measurement, and the pancreas was collected for histopathologic study. No significant differences in plasma glucose concentrations occurred between groups. The pancreas had no pathology. Chronic cyanide exposure did not promote diabetogenic effects in rats, swine or goats, suggesting that cyanide is not responsible for MRDM in humans.

Preliminary investigations on the determination of three-dimensional dose distributions using scintillator blocks and optical tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroll, Florian; Karsch, Leonhard; Pawelke, Jörg

2013-08-15

Purpose: Clinical QA in teletherapy as well as the characterization of experimental radiation sources for future medical applications requires effective methods for measuring three-dimensional (3D) dose distributions generated in a water-equivalent medium. Current dosimeters based on ionization chambers, diodes, thermoluminescence detectors, radiochromic films, or polymer gels exhibit various drawbacks: High quality 3D dose determination is either very sophisticated and expensive or requires high amounts of effort and time for the preparation or read out. New detectors based on scintillator blocks in combination with optical tomography are studied, since they have the potential to facilitate the desired cost-effective, transportable, and long-termmore » stable dosimetry system that is able to determine 3D dose distributions with high spatial resolution in a short time.Methods: A portable detector prototype was set up based on a plastic scintillator block and four digital cameras. During irradiation the scintillator emits light, which is detected by the fixed cameras. The light distribution is then reconstructed by optical tomography, using maximum-likelihood expectation maximization. The result of the reconstruction approximates the 3D dose distribution. First performance tests of the prototype using laser light were carried out. Irradiation experiments were performed with ionizing radiation, i.e., bremsstrahlung (6 to 21 MV), electrons (6 to 21 MeV), and protons (68 MeV), provided by clinical and research accelerators.Results: Laser experiments show that the current imaging properties differ from the design specifications: The imaging scale of the optical systems is position dependent, ranging from 0.185 mm/pixel to 0.225 mm/pixel. Nevertheless, the developed dosimetry method is proven to be functional for electron and proton beams. Induced radiation doses of 50 mGy or more made 3D dose reconstructions possible. Taking the imaging properties into account, determined dose profiles are in agreement with reference measurements. An inherent drawback of the scintillator is the nonlinear light output for high stopping-power radiation due to the quenching effect. It impacts the depth dose curves measured with the dosimeter. For single Bragg peak distributions this leads to a peak to plateau ratio of 2.8 instead of 4.5 for the reference ionization chamber measurement. Furthermore, the transmission of the clinical bremsstrahlung beams through the scintillator leads to the saturation of one camera, making dose reconstructions in that case presently not feasible.Conclusions: It is shown that distributions of scintillation light generated by proton or electron beams can be reconstructed by the dosimetry system within minutes. The quenching apparent for proton irradiation, and the yet not precisely determined position dependency of the imaging scale, require further investigation and corrections. Upgrading the prototype with larger or inorganic scintillators would increase the detectable proton and electron energy range. The presented results show that the determination of 3D dose distributions using scintillator blocks and optical tomography is a promising dosimetry method.« less

Preliminary investigations on the determination of three-dimensional dose distributions using scintillator blocks and optical tomography.

PubMed

Kroll, Florian; Pawelke, Jörg; Karsch, Leonhard

2013-08-01

Clinical QA in teletherapy as well as the characterization of experimental radiation sources for future medical applications requires effective methods for measuring three-dimensional (3D) dose distributions generated in a water-equivalent medium. Current dosimeters based on ionization chambers, diodes, thermoluminescence detectors, radiochromic films, or polymer gels exhibit various drawbacks: High quality 3D dose determination is either very sophisticated and expensive or requires high amounts of effort and time for the preparation or read out. New detectors based on scintillator blocks in combination with optical tomography are studied, since they have the potential to facilitate the desired cost-effective, transportable, and long-term stable dosimetry system that is able to determine 3D dose distributions with high spatial resolution in a short time. A portable detector prototype was set up based on a plastic scintillator block and four digital cameras. During irradiation the scintillator emits light, which is detected by the fixed cameras. The light distribution is then reconstructed by optical tomography, using maximum-likelihood expectation maximization. The result of the reconstruction approximates the 3D dose distribution. First performance tests of the prototype using laser light were carried out. Irradiation experiments were performed with ionizing radiation, i.e., bremsstrahlung (6 to 21 MV), electrons (6 to 21 MeV), and protons (68 MeV), provided by clinical and research accelerators. Laser experiments show that the current imaging properties differ from the design specifications: The imaging scale of the optical systems is position dependent, ranging from 0.185 mm/pixel to 0.225 mm/pixel. Nevertheless, the developed dosimetry method is proven to be functional for electron and proton beams. Induced radiation doses of 50 mGy or more made 3D dose reconstructions possible. Taking the imaging properties into account, determined dose profiles are in agreement with reference measurements. An inherent drawback of the scintillator is the nonlinear light output for high stopping-power radiation due to the quenching effect. It impacts the depth dose curves measured with the dosimeter. For single Bragg peak distributions this leads to a peak to plateau ratio of 2.8 instead of 4.5 for the reference ionization chamber measurement. Furthermore, the transmission of the clinical bremsstrahlung beams through the scintillator leads to the saturation of one camera, making dose reconstructions in that case presently not feasible. It is shown that distributions of scintillation light generated by proton or electron beams can be reconstructed by the dosimetry system within minutes. The quenching apparent for proton irradiation, and the yet not precisely determined position dependency of the imaging scale, require further investigation and corrections. Upgrading the prototype with larger or inorganic scintillators would increase the detectable proton and electron energy range. The presented results show that the determination of 3D dose distributions using scintillator blocks and optical tomography is a promising dosimetry method.

Evaluation of low-dose limits in 3D-2D rigid registration for surgical guidance

NASA Astrophysics Data System (ADS)

Uneri, A.; Wang, A. S.; Otake, Y.; Kleinszig, G.; Vogt, S.; Khanna, A. J.; Gallia, G. L.; Gokaslan, Z. L.; Siewerdsen, J. H.

2014-09-01

An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image + guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image + guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

I-125 ROPES eye plaque dosimetry: Validation of a commercial 3D ophthalmic brachytherapy treatment planning system and independent dose calculation software with GafChromic{sup ®} EBT3 films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poder, Joel; Corde, Stéphanie

Purpose: The purpose of this study was to measure the dose distributions for different Radiation Oncology Physics and Engineering Services, Australia (ROPES) type eye plaques loaded with I-125 (model 6711) seeds using GafChromic{sup ®} EBT3 films, in order to verify the dose distributions in the Plaque Simulator™ (PS) ophthalmic 3D treatment planning system. The brachytherapy module of RADCALC{sup ®} was used to independently check the dose distributions calculated by PS. Correction factors were derived from the measured data to be used in PS to account for the effect of the stainless steel ROPES plaque backing on the 3D dose distribution.Methods:more » Using GafChromic{sup ®} EBT3 films inserted in a specially designed Solid Water™ eye ball phantom, dose distributions were measured three-dimensionally both along and perpendicular to I-125 (model 6711) loaded ROPES eye plaque's central axis (CAX) with 2 mm depth increments. Each measurement was performed in full scatter conditions both with and without the stainless steel plaque backing attached to the eye plaque, to assess its effect on the dose distributions. Results were compared to the dose distributions calculated by Plaque Simulator™ and checked independently with RADCALC{sup ®}.Results: The EBT3 film measurements without the stainless steel backing were found to agree with PS and RADCALC{sup ®} to within 2% and 4%, respectively, on the plaque CAX. Also, RADCALC{sup ®} was found to agree with PS to within 2%. The CAX depth doses measured using EBT3 film with the stainless steel backing were observed to result in a 4% decrease relative to when the backing was not present. Within experimental uncertainty, the 4% decrease was found to be constant with depth and independent of plaque size. Using a constant dose correction factor of T= 0.96 in PS, where the calculated dose for the full water scattering medium is reduced by 4% in every voxel in the dose grid, the effect of the plaque backing was accurately modeled in the planning system. Off-axis profiles were also modeled in PS by taking into account the three-dimensional model of the plaque backing.Conclusions: The doses calculated by PS and RADCALC{sup ®} for uniformly loaded ROPES plaques in full and uniform scattering conditions were validated by the EBT3 film measurements. The stainless steel plaque backing was observed to decrease the measured dose by 4%. Through the introduction of a scalar correction factor (0.96) in PS, the dose homogeneity effect of the stainless steel plaque backing was found to agree with the measured EBT3 film measurements.« less

I-125 ROPES eye plaque dosimetry: validation of a commercial 3D ophthalmic brachytherapy treatment planning system and independent dose calculation software with GafChromic® EBT3 films.

PubMed

Poder, Joel; Corde, Stéphanie

2013-12-01

The purpose of this study was to measure the dose distributions for different Radiation Oncology Physics and Engineering Services, Australia (ROPES) type eye plaques loaded with I-125 (model 6711) seeds using GafChromic(®) EBT3 films, in order to verify the dose distributions in the Plaque Simulator™ (PS) ophthalmic 3D treatment planning system. The brachytherapy module of RADCALC(®) was used to independently check the dose distributions calculated by PS. Correction factors were derived from the measured data to be used in PS to account for the effect of the stainless steel ROPES plaque backing on the 3D dose distribution. Using GafChromic(®) EBT3 films inserted in a specially designed Solid Water™ eye ball phantom, dose distributions were measured three-dimensionally both along and perpendicular to I-125 (model 6711) loaded ROPES eye plaque's central axis (CAX) with 2 mm depth increments. Each measurement was performed in full scatter conditions both with and without the stainless steel plaque backing attached to the eye plaque, to assess its effect on the dose distributions. Results were compared to the dose distributions calculated by Plaque Simulator™ and checked independently with RADCALC(®). The EBT3 film measurements without the stainless steel backing were found to agree with PS and RADCALC(®) to within 2% and 4%, respectively, on the plaque CAX. Also, RADCALC(®) was found to agree with PS to within 2%. The CAX depth doses measured using EBT3 film with the stainless steel backing were observed to result in a 4% decrease relative to when the backing was not present. Within experimental uncertainty, the 4% decrease was found to be constant with depth and independent of plaque size. Using a constant dose correction factor of T = 0.96 in PS, where the calculated dose for the full water scattering medium is reduced by 4% in every voxel in the dose grid, the effect of the plaque backing was accurately modeled in the planning system. Off-axis profiles were also modeled in PS by taking into account the three-dimensional model of the plaque backing. The doses calculated by PS and RADCALC(®) for uniformly loaded ROPES plaques in full and uniform scattering conditions were validated by the EBT3 film measurements. The stainless steel plaque backing was observed to decrease the measured dose by 4%. Through the introduction of a scalar correction factor (0.96) in PS, the dose homogeneity effect of the stainless steel plaque backing was found to agree with the measured EBT3 film measurements.

Sirolimus and everolimus clearance in maintenance kidney and liver transplant recipients: Diagnostic efficiency of the concentration/dose ratio for the prediction of trough steady-state concentrations

PubMed Central

Bouzas, Lorena; Hermida, Jesús

2010-01-01

Objectives Therapeutic monitoring of sirolimus and everolimus is necessary in order to minimize adverse side-effects and to ensure effective immunosuppression. A sirolimus-dosing model using the concentration/dose ratio has been previously proposed for kidney transplant patients, and the aim of our study was the evaluation of this single model for the prediction of trough sirolimus and everolimus concentrations. Methods Trough steady-state sirolimus concentrations were determined in several blood samples from each of 7 kidney and 9 liver maintenance transplant recipients, and everolimus concentrations from 20 kidney, 17 liver, and 3 kidney/liver maintenance transplant recipients. Predicted sirolimus and everolimus concentrations (Css), corresponding to the doses (D), were calculated using the measured concentrations (Css0) and corresponding doses (D0) on starting the study: Css = (Css0)(D)/D0. Results The diagnostic efficiency of the predicting model for the correct classification as subtherapeutic, therapeutic, and supratherapeutic values with respect to the experimentally obtained concentrations was 91.3% for sirolimus and 81.4% for everolimus in the kidney transplant patients. In the liver transplant patients the efficiency was 69.2% for sirolimus and 72.6% for everolimus, and in the kidney/liver transplant recipients the efficiency for everolimus was 67.9%. Conclusions The model has an acceptable diagnostic efficiency (>80%) for the prediction of sirolimus and everolimus concentrations in kidney transplant recipients, but not in liver transplant recipients. However, considering the wide ranges found for the prediction error of sirolimus and everolimus concentrations, the clinical relevance of this dosing model is weak. PMID:19943816

Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9–14 Years: A Randomized Trial

PubMed Central

Puthanakit, Thanyawee; Cheng-Hsun, Chiu; Ren-Bin, Tang; Schwarz, Tino; Pellegrino, Angelo; Esposito, Susanna; Frenette, Louise; McNeil, Shelly; Durando, Paolo; Rheault, Paul; Giaquinto, Carlo; Horn, Michael; Petry, Karl Ulrich; Peters, Klaus; Azhar, Toma; Hillemanns, Peter; De Simoni, Stephanie; Friel, Damien; Pemmaraju, Suryakiran; Hezareh, Marjan; Thomas, Florence; Descamps, Dominique; Folschweiller, Nicolas; Struyf, Frank

2017-01-01

Abstract Background. We previously reported the noninferiority 1 month after the last dose of 2-dose human papillomavirus 16/18 AS04-adjuvanted (AS04-HPV-16/18) vaccine schedules at months 0 and 6 (2D_M0,6) and months 0 and 12 (2D_M0,12) in girls aged 9–14 years compared with a 3-dose schedule at months 0, 1, and 6 (3D_M0,1,6) in women aged 15–25 years. Here, we report the results at study end (month 36 [M36]). Methods. Girls were randomized 1:1 and received 2 vaccine doses either 6 months (2D_M0,6) or 12 months apart (2D_M0,12); women received 3 doses at months 0, 1, and 6 (3D_M0,1,6). Endpoints included noninferiority of HPV-16/18 antibodies for 2D_M0,6 versus 3D_M0,1,6; 2D_M0,12 versus 3D_M0,1,6; and 2D_M0,12 versus 2D_M0,6; and assessment of neutralizing antibodies, T cells, B cells, and safety. Results. At M36, the 2D_M0,6 and 2D_M0,12 schedules remained noninferior to the 3D_M0,1,6 schedule in terms of seroconversion rates and 3D/2D geometric mean titers for anti-HPV-16 and anti-HPV-18. All schedules elicited sustained immune responses up to M36. Conclusions. Both 2-dose schedules in young girls remained noninferior to the 3-dose schedule in women up to study conclusion at M36. The AS04-HPV-16/18 vaccine administered as a 2-dose schedule was immunogenic and well tolerated in young girls. PMID:28591778

Expression of porcine fusion protein IRF7/3(5D) efficiently controls foot-and-mouth disease virus replication

USDA-ARS?s Scientific Manuscript database

Several studies have demonstrated that administration of type I, II, or III interferons (IFN) delivered using a replication defective human adenovirus 5 (Ad5) vector is effective to control Foot-and-Mouth Disease (FMD) in cattle and swine during experimental infections. However, high doses are requi...

Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

PubMed

Verheijen, Marcha; Schrooders, Yannick; Gmuender, Hans; Nudischer, Ramona; Clayton, Olivia; Hynes, James; Niederer, Steven; Cordes, Henrik; Kuepfer, Lars; Kleinjans, Jos; Caiment, Florian

2018-05-24

Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death. We present an in vitro experimental design aimed at detecting DOX-induced cardiotoxicity by obtaining a global view of the induced molecular mechanisms through RNA-sequencing. To better reflect the in vivo situation, human 3D cardiac microtissues were exposed to physiologically-based pharmacokinetic (PBPK) relevant doses of DOX for 2 weeks. We analysed a therapeutic and a toxic dosing profile. Transcriptomics analysis revealed significant gene expression changes in pathways related to "striated muscle contraction" and "respiratory electron transport", thus suggesting mitochondrial dysfunction as an underlying mechanism for cardiotoxicity. Furthermore, expression changes in mitochondrial processes differed significantly between the doses. Therapeutic dose reflects processes resembling the phenotype of delayed chronic cardiotoxicity, while toxic doses resembled acute cardiotoxicity. Overall, these results demonstrate the capability of our innovative in vitro approach to detect the three known mechanisms of DOX leading to toxicity, thus suggesting its potential relevance for reflecting the patient situation. Our study also demonstrated the importance of applying physiologically relevant doses during toxicological research, since mechanisms of acute and chronic toxicity differ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

PubMed Central

Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

2014-01-01

The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

PubMed

Narula, Neeraj; Cooray, Mohan; Anglin, Rebecca; Muqtadir, Zack; Narula, Alisha; Marshall, John K

2017-02-01

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

Effects of 3-nitrooxypropanol on methane emission, digestion, and energy and nitrogen balance of lactating dairy cows.

PubMed

Reynolds, C K; Humphries, D J; Kirton, P; Kindermann, M; Duval, S; Steinberg, W

2014-01-01

The objective was to measure effects of 3-nitrooxypropanol (3 NP) on methane production of lactating dairy cows and any associated changes in digestion and energy and N metabolism. Six Holstein-Friesian dairy cows in mid-lactation were fed twice daily a total mixed ration with maize silage as the primary forage source. Cows received 1 of 3 treatments using an experimental design based on two 3 × 3 Latin squares with 5-wk periods. Treatments were a control placebo or 500 or 2,500 mg/d of 3 NP delivered directly into the rumen, via the rumen fistula, in equal doses before each feeding. Measurements of methane production and energy and N balance were obtained during wk 5 of each period using respiration calorimeters and digestion trials. Measurements of rumen pH (48 h) and postprandial volatile fatty acid and ammonia concentrations were made at the end of wk 4. Daily methane production was reduced by 3 NP, but the effects were not dose dependent (reductions of 6.6 and 9.8% for 500 and 2,500 mg/d, respectively). Dosing 3 NP had a transitory inhibitory effect on methane production, which may have been due to the product leaving the rumen in liquid outflow or through absorption or metabolism. Changes in rumen concentrations of volatile fatty acids indicated that the pattern of rumen fermentation was affected by both doses of the product, with a decrease in acetate:propionate ratio observed, but that acetate production was inhibited by the higher dose. Dry matter, organic matter, acid detergent fiber, N, and energy digestibility were reduced at the higher dose of the product. The decrease in digestible energy supply was not completely countered by the decrease in methane excretion such that metabolizable energy supply, metabolizable energy concentration of the diet, and net energy balance (milk plus tissue energy) were reduced by the highest dose of 3 NP. Similarly, the decrease in N digestibility at the higher dose of the product was associated with a decrease in body N balance that was not observed for the lower dose. Milk yield and milk fat concentration and fatty acid composition were not affected but milk protein concentration was greater for the higher dose of 3 NP. Twice-daily rumen dosing of 3 NP reduced methane production by lactating dairy cows, but the dose of 2,500 mg/d reduced rumen acetate concentration, diet digestibility, and energy supply. Further research is warranted to determine the optimal dose and delivery method of the product. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Phase I and Pharmacokinetic Study of Cetuximab and Irinotecan in Children With Refractory Solid Tumors: A Study of the Pediatric Oncology Experimental Therapeutic Investigators' Consortium

PubMed Central

Trippett, Tanya M.; Herzog, Cynthia; Whitlock, James A.; Wolff, Johannes; Kuttesch, John; Bagatell, Rochelle; Hunger, Stephen P.; Boklan, Jessica; Smith, Amy A.; Arceci, Robert J.; Katzenstein, Howard M.; Harbison, Christopher; Zhou, Xiaofei; Lu, Haolan; Langer, Christiane; Weber, Martin; Gore, Lia

2009-01-01

Purpose To determine the dose of cetuximab that can be safely combined with irinotecan for treatment of pediatric and adolescent patients with refractory solid tumors. Patients and Methods This open-label, phase I study enrolled patients ages 1 to 18 years with advanced refractory solid tumors, including tumors of the CNS. Patient cohorts by age group (children, ages 1 to 12 years; adolescents, ages 13 to 18 years) received escalating weekly doses of cetuximab (75, 150, 250 mg/m2) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m2/d) for 5 days for 2 consecutive weeks every 21 days. The primary end points were establishing the maximum-tolerated dose (MTD), recommended phase II dose (RPIID), and pharmacokinetics of the combination. Preliminary safety and efficacy data were also collected. Results Twenty-seven children and 19 adolescents received a median of 7.1 and 6.0 weeks of cetuximab therapy, respectively. Cetuximab 250 mg/m2 weekly plus irinotecan 16 mg/m2/d (pediatric) or 20 mg/m2/d (adolescent) have been established as the MTD/RPIID. Dose-limiting toxicities included diarrhea and neutropenia. Mild to moderate (grade 1 to 2) acneiform rash occurred in a majority of patients; no grade 3 to 4 rashes were observed. Cetuximab demonstrated dose-dependent clearance in both children and adolescents, similar to that in adults. There were two confirmed partial responses, both in patients with CNS tumors. Stable disease was achieved in 18 patients overall, including 10 patients with CNS tumors (38.5%). Conclusion The cetuximab/irinotecan combination can be given safely to children and adolescents with cancer. Promising activity, particularly in CNS tumors, warrants phase II evaluation of this regimen. PMID:19770383

Breast Radiation Dose With CESM Compared With 2D FFDM and 3D Tomosynthesis Mammography.

PubMed

James, Judy R; Pavlicek, William; Hanson, James A; Boltz, Thomas F; Patel, Bhavika K

2017-02-01

We aimed to compare radiation dose received during contrast-enhanced spectral mammography (CESM) using high- and low-energy projections with radiation dose received during 2D full field digital mammography (FFDM) and 3D tomosynthesis on phantoms and patients with varying breast thickness and density. A single left craniocaudal projection was chosen to determine the doses for 6214 patients who underwent 2D FFDM, 3662 patients who underwent 3D tomosynthesis, and 173 patients who underwent CESM in this retrospective study. Dose measurements were also collected in phantoms with composition mimicking nondense and dense breast tissue. Average glandular dose (AGD) ± SD was 3.0 ± 1.1 mGy for CESM exposures at a mean breast thickness of 63 mm. At this thickness, the dose was 2.1 mGy from 2D FFDM and 2.5 mGy from 3D tomosynthesis. The nondense phantom had a mean AGD of 1.0 mGy with 2D FFDM, 1.3 mGy with 3D tomosynthesis, and 1.6 mGy with CESM. The dense breast phantom had a mean AGD of 1.3 mGy with 2D FFDM, 1.4 mGy with 3D tomosynthesis, and 2.1 mGy with CESM. At a compressed thickness of 4.5 cm, radiation exposure from CESM was approximately 25% higher in dense breast phantoms than in nondense breast phantoms. The dose in the dense phantom at a compressed thickness of 6 cm was approximately 42% higher than the dose in the nondense phantom at a compressed thickness of 4.5 cm. CESM was found to increase AGD at a mean breast thickness of 63 mm by approximately 0.9 mGy and 0.5 mGy compared with 2D FFDM and 3D tomosynthesis, respectively. Of note, CESM provides a standard image (similar to 2D FFDM) that is obtained using the low-energy projection. Overall, the AGD from CESM falls below the dose limit of 3 mGy set by Mammography Quality Standards Act regulations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matney, Jason; Park, Peter C.; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas

Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable imagemore » registration algorithms. The dose–volume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dose–volume histogram indices (mean ± SD) except the lung V5 (PSPT: +1.1% ± 0.9%; IMRT: +0.4% ± 1.2%) and maximum cord dose (PSPT: +1.5 ± 2.9 Gy; IMRT: 0.0 ± 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.« less

Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.

PubMed

Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E

2016-04-01

Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proton depth dose distribution: 3-D calculation of dose distributions from solar flare irradiation

NASA Astrophysics Data System (ADS)

Leavitt, Dennis D.

1990-11-01

Relative depth dose distribution to the head from 3 typical solar flare proton events were calculated for 3 different exposure geometries: (1) single directional radiation incident upon a fixed head; (2) single directional radiation incident upon head rotating axially (2-D rotation); and (3) omnidirectional radiation incident upon head (3-D rotation). Isodose distributions in the transverse plane intersecting isocenter are presented for each of the 3 solar flare events in all 3 exposure geometries. In all 3 calculation configurations the maximum predicted dose occurred on the surface of the head. The dose at the isocenter of the head relative to the surface dose for the 2-D and 3-D rotation geometries ranged from 2 to 19 percent, increasing with increasing energy of the event. The calculations suggest the superficially located organs (lens of the eye and skin) are at greatest risk for the proton events studied here.

Experimental validation of the TOPAS Monte Carlo system for passive scattering proton therapy

PubMed Central

Testa, M.; Schümann, J.; Lu, H.-M.; Shin, J.; Faddegon, B.; Perl, J.; Paganetti, H.

2013-01-01

Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. Methods: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS’ capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the nuclear interaction models used in the simulations. Results: SOBPs’ range and modulation width were reproduced, on average, with an accuracy of +1, −2 and ±3 mm, respectively. OF simulations reproduced measured data within ±3%. Simulated 2D dose-profiles show field flatness and average field radius within ±3% of measured profiles. The field symmetry resulted, on average in ±3% agreement with commissioned profiles. TOPAS accuracy in reproducing measured dose profiles downstream the half beam shifter is better than 2%. Dose rate function simulation reproduced the measurements within ∼2% showing that the four-dimensional modeling of the passively modulation system was implement correctly and millimeter accuracy can be achieved in reproducing measured data. For MLFCs simulations, 2% agreement was found between TOPAS and both sets of experimental measurements. The overall results show that TOPAS simulations are within the clinical accepted tolerances for all QA measurements performed at our institution. Conclusions: Our Monte Carlo simulations reproduced accurately the experimental data acquired through all the measurements performed in this study. Thus, TOPAS can reliably be applied to quality assurance for proton therapy and also as an input for commissioning of commercial treatment planning systems. This work also provides the basis for routine clinical dose calculations in patients for all passive scattering proton therapy centers using TOPAS. PMID:24320505

Comparison of 2D and 3D Imaging and Treatment Planning for Postoperative Vaginal Apex High-Dose Rate Brachytherapy for Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russo, James K.; Armeson, Kent E.; Richardson, Susan, E-mail: srichardson@radonc.wustl.edu

2012-05-01

Purpose: To evaluate bladder and rectal doses using two-dimensional (2D) and 3D treatment planning for vaginal cuff high-dose rate (HDR) in endometrial cancer. Methods and Materials: Ninety-one consecutive patients treated between 2000 and 2007 were evaluated. Seventy-one and 20 patients underwent 2D and 3D planning, respectively. Each patient received six fractions prescribed at 0.5 cm to the superior 3 cm of the vagina. International Commission on Radiation Units and Measurements (ICRU) doses were calculated for 2D patients. Maximum and 2-cc doses were calculated for 3D patients. Organ doses were normalized to prescription dose. Results: Bladder maximum doses were 178% ofmore » ICRU doses (p < 0.0001). Two-cubic centimeter doses were no different than ICRU doses (p = 0.22). Two-cubic centimeter doses were 59% of maximum doses (p < 0.0001). Rectal maximum doses were 137% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 87% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 64% of maximum doses (p < 0.0001). Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final bladder dose to within 10% for 44%, 59%, 83%, 82%, and 89% of patients by using the ICRU dose, and for 45%, 55%, 80%, 85%, and 85% of patients by using the maximum dose, and for 37%, 68%, 79%, 79%, and 84% of patients by using the 2-cc dose. Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final rectal dose to within 10% for 100%, 100%, 100%, 100%, and 100% of patients by using the ICRU dose, and for 60%, 65%, 70%, 75%, and 75% of patients by using the maximum dose, and for 68%, 95%, 84%, 84%, and 84% of patients by using the 2-cc dose. Conclusions: Doses to organs at risk vary depending on the calculation method. In some cases, final dose accuracy appears to plateau after the third fraction, indicating that simulation and planning may not be necessary in all fractions. A clinically relevant level of accuracy should be determined and further research conducted to address this issue.« less

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PubMed

Fröhlich, Georgina; Agoston, Péter; Lövey, József; Somogyi, András; Fodor, János; Polgár, Csaba; Major, Tibor

2010-07-01

To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

How precise can atoms of a nanocluster be located in 3D using a tilt series of scanning transmission electron microscopy images?

PubMed

Alania, M; De Backer, A; Lobato, I; Krause, F F; Van Dyck, D; Rosenauer, A; Van Aert, S

2017-10-01

In this paper, we investigate how precise atoms of a small nanocluster can ultimately be located in three dimensions (3D) from a tilt series of images acquired using annular dark field (ADF) scanning transmission electron microscopy (STEM). Therefore, we derive an expression for the statistical precision with which the 3D atomic position coordinates can be estimated in a quantitative analysis. Evaluating this statistical precision as a function of the microscope settings also allows us to derive the optimal experimental design. In this manner, the optimal angular tilt range, required electron dose, optimal detector angles, and number of projection images can be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsuta, Y; Tohoku University Graduate School of Medicine, Sendal, Miyagi; Kadoya, N

Purpose: In this study, we developed a system to calculate three dimensional (3D) dose that reflects dosimetric error caused by leaf miscalibration for head and neck and prostate volumetric modulated arc therapy (VMAT) without additional treatment planning system calculation on real time. Methods: An original system called clarkson dose calculation based dosimetric error calculation to calculate dosimetric error caused by leaf miscalibration was developed by MATLAB (Math Works, Natick, MA). Our program, first, calculates point doses at isocenter for baseline and modified VMAT plan, which generated by inducing MLC errors that enlarged aperture size of 1.0 mm with clarkson dosemore » calculation. Second, error incuced 3D dose was generated with transforming TPS baseline 3D dose using calculated point doses. Results: Mean computing time was less than 5 seconds. For seven head and neck and prostate plans, between our method and TPS calculated error incuced 3D dose, the 3D gamma passing rates (0.5%/2 mm, global) are 97.6±0.6% and 98.0±0.4%. The dose percentage change with dose volume histogram parameter of mean dose on target volume were 0.1±0.5% and 0.4±0.3%, and with generalized equivalent uniform dose on target volume were −0.2±0.5% and 0.2±0.3%. Conclusion: The erroneous 3D dose calculated by our method is useful to check dosimetric error caused by leaf miscalibration before pre treatment patient QA dosimetry checks.« less

Quantification of the kV X-ray imaging dose during real-time tumor tracking and from three- and four-dimensional cone-beam computed tomography in lung cancer patients using a Monte Carlo simulation.

PubMed

Nakamura, Mitsuhiro; Ishihara, Yoshitomo; Matsuo, Yukinori; Iizuka, Yusuke; Ueki, Nami; Iramina, Hiraku; Hirashima, Hideaki; Mizowaki, Takashi

2018-03-01

Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4-10.5 cGy and 33.5-58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs.

Quantification of the kV X-ray imaging dose during real-time tumor tracking and from three- and four-dimensional cone-beam computed tomography in lung cancer patients using a Monte Carlo simulation

PubMed Central

Nakamura, Mitsuhiro; Ishihara, Yoshitomo; Matsuo, Yukinori; Iizuka, Yusuke; Ueki, Nami; Iramina, Hiraku; Hirashima, Hideaki; Mizowaki, Takashi

2018-01-01

Abstract Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4–10.5 cGy and 33.5–58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs. PMID:29385514

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, You; Yin, Fang-Fang; Ren, Lei, E-mail: lei.ren@duke.edu

2015-08-15

Purpose: Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Methods: Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated onmore » the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the “gold-standard” on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔD{sub min}), maximum dose (ΔD{sub max}), and mean dose (ΔD{sub mean}), and the absolute deviations of prescription dose coverage (ΔV{sub 100%}) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Results: Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). Conclusions: MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.« less

A Mouse Model of Hypospadias Induced by Estradiol Benzoate.

PubMed

He, Hou-Guang; Han, Cong-Hui; Zhang, Wei

2015-12-01

We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p < 0.01). Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias.

Anatomical background and generalized detectability in tomosynthesis and cone-beam CT.

PubMed

Gang, G J; Tward, D J; Lee, J; Siewerdsen, J H

2010-05-01

Anatomical background presents a major impediment to detectability in 2D radiography as well as 3D tomosynthesis and cone-beam CT (CBCT). This article incorporates theoretical and experimental analysis of anatomical background "noise" in cascaded systems analysis of 2D and 3D imaging performance to yield "generalized" metrics of noise-equivalent quanta (NEQ) and detectability index as a function of the orbital extent of the (circular arc) source-detector orbit. A physical phantom was designed based on principles of fractal self-similarity to exhibit power-law spectral density (kappa/Fbeta) comparable to various anatomical sites (e.g., breast and lung). Background power spectra [S(B)(F)] were computed as a function of source-detector orbital extent, including tomosynthesis (approximately 10 degrees -180 degrees) and CBCT (180 degrees + fan to 360 degrees) under two acquisition schemes: (1) Constant angular separation between projections (variable dose) and (2) constant total number of projections (constant dose). The resulting S(B) was incorporated in the generalized NEQ, and detectability index was computed from 3D cascaded systems analysis for a variety of imaging tasks. The phantom yielded power-law spectra within the expected spatial frequency range, quantifying the dependence of clutter magnitude (kappa) and correlation (beta) with increasing tomosynthesis angle. Incorporation of S(B) in the 3D NEQ provided a useful framework for analyzing the tradeoffs among anatomical, quantum, and electronic noise with dose and orbital extent. Distinct implications are posed for breast and chest tomosynthesis imaging system design-applications varying significantly in kappa and beta, and imaging task and, therefore, in optimal selection of orbital extent, number of projections, and dose. For example, low-frequency tasks (e.g., soft-tissue masses or nodules) tend to benefit from larger orbital extent and more fully 3D tomographic imaging, whereas high-frequency tasks (e.g., microcalcifications) require careful, application-specific selection of orbital extent and number of projections to minimize negative effects of quantum and electronic noise. The complex tradeoffs among anatomical background, quantum noise, and electronic noise in projection imaging, tomosynthesis, and CBCT can be described by generalized cascaded systems analysis, providing a useful framework for system design and optimization.

MO-FG-BRA-01: 4D Monte Carlo Simulations for Verification of Dose Delivered to a Moving Anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gholampourkashi, S; Cygler, J E.; The Ottawa Hospital Cancer Centre, Ottawa, ON

Purpose: To validate 4D Monte Carlo (MC) simulations of dose delivery by an Elekta Agility linear accelerator to a moving phantom. Methods: Monte Carlo simulations were performed using the 4DdefDOSXYZnrc/EGSnrc user code which samples a new geometry for each incident particle and calculates the dose in a continuously moving anatomy. A Quasar respiratory motion phantom with a lung insert containing a 3 cm diameter tumor was used for dose measurements on an Elekta Agility linac with the phantom in stationary and moving states. Dose to the center of tumor was measured using calibrated EBT3 film and the RADPOS 4D dosimetrymore » system. A VMAT plan covering the tumor was created on the static CT scan of the phantom using Monaco V.5.10.02. A validated BEAMnrc model of our Elekta Agility linac was used for Monte Carlo simulations on stationary and moving anatomies. To compare the planned and delivered doses, linac log files recorded during measurements were used for the simulations. For 4D simulations, deformation vectors that modeled the rigid translation of the lung insert were generated as input to the 4DdefDOSXYZnrc code as well as the phantom motion trace recorded with RADPOS during the measurements. Results: Monte Carlo simulations and film measurements were found to agree within 2mm/2% for 97.7% of points in the film in the static phantom and 95.5% in the moving phantom. Dose values based on film and RADPOS measurements are within 2% of each other and within 2σ of experimental uncertainties with respect to simulations. Conclusion: Our 4D Monte Carlo simulation using the defDOSXYZnrc code accurately calculates dose delivered to a moving anatomy. Future work will focus on more investigation of VMAT delivery on a moving phantom to improve the agreement between simulation and measurements, as well as establishing the accuracy of our method in a deforming anatomy. This work was supported by the Ontario Consortium of Adaptive Interventions in Radiation Oncology (OCAIRO), funded by the Ontario Research Fund Research Excellence program.« less

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy.

PubMed

Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert F; Gotthardt, Martin; Goldenberg, David M; Sharkey, Robert M; Slump, Cornelis H; van der Graaf, Winette Ta; Oyen, Wim Jg; Boerman, Otto C; Sgouros, George; Visser, Eric P

2015-12-01

Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a (177)Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after (177)Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for (177)Lu-based pretargeted RIT and simulated pretargeted RIT with (90)Y. 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with (90)Y instead of (177)Lu. 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

Anal wall sparing effect of an endorectal balloon in 3D conformal and intensity-modulated prostate radiotherapy.

PubMed

Smeenk, Robert Jan; van Lin, Emile N J Th; van Kollenburg, Peter; Kunze-Busch, Martina; Kaanders, Johannes H A M

2009-10-01

To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer. In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D(min)), maximum dose (D(max)), and mean dose (D(mean)) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from >or=20Gy to >or=70Gy (V(20)-V(70), respectively). In the 3D-CRT plans, an ERB significantly reduced D(mean), D(max), and V(30)-V(70). For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D(mean) was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy.

Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus (HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.

PubMed

Toh, Zheng Quan; Russell, Fiona M; Reyburn, Rita; Fong, James; Tuivaga, Evelyn; Ratu, Tupou; Nguyen, Cattram D; Devi, Rachel; Kama, Mike; Matanitobua, Silivia; Tabrizi, Sepehr N; Garland, Suzanne M; Sinha, Rohit; Frazer, Ian; Tikoduadua, Lisi; Kado, Joseph; Rafai, Eric; Mulholland, Edward K; Licciardi, Paul V

2017-04-01

The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles.

PubMed

Poppinga, D; Meyners, J; Delfs, B; Muru, A; Harder, D; Poppe, B; Looe, H K

2015-12-21

This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with enhanced electron density compared with the surrounding water. In the cases of the scintillation detector and the small ionization chamber, the negative curve portions of K(x) practically vanish. It is planned to use the measured functions K(x) and K(r) to deconvolve clinical narrow-beam signal profiles and to correct the output factor values obtained with various high-resolution detectors.

SU-F-T-508: A Collimator-Based 3-Dimensional Grid Therapy Technique in a Small Animal Radiation Research Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, J; Kong, V; Zhang, H

Purpose: Three dimensional (3D) Grid Therapy using MLC-based inverse-planning has been proposed to achieve the features of both conformal radiotherapy and spatially fractionated radiotherapy, which may deliver very high dose in a single fraction to portions of a large tumor with relatively low normal tissue dose. However, the technique requires relatively long delivery time. This study aims to develop a collimator-based 3D grid therapy technique. Here we report the development of the technique in a small animal radiation research platform. Methods: Similar as in the MLC-based technique, 9 non-coplanar beams in special channeling directions were used for the 3D gridmore » therapy technique. Two specially designed grid collimators were fabricated, and one of them was selectively used to match the corresponding gantry/couch angles so that the grid opening of all 9 beams are met in the 3D space in the target. A stack of EBT3 films were used as 3D dosimetry to demonstrate the 3D grid-like dose distribution in the target. Three 1-mm beams were delivered to the stack of films in the area outside the target for alignment when all the films were scanned to reconstruct the 3D dosimtric image. Results: 3D film dosimetry showed a lattice-like dose distribution in the 3D target as well as in the axial, sagittal and coronal planes. The dose outside the target also showed a grid like dose distribution, and the average dose gradually decreased with the distance to the target. The peak to valley ratio was approximately 5:1. The delivery time was 7 minutes for 18 Gy peak dose, comparing to 6 minutes to deliver a 18-Gy 3D conformal plan. Conclusion: We have demonstrated the feasibility of the collimator-based 3D grid therapy technique which can significantly reduce delivery time comparing to MLC-based inverse planning technique.« less

Potential dosimetric benefit of dose-warping based 4D planning compared to conventional 3D planning in liver stereotactic body radiotherapy (SBRT)

NASA Astrophysics Data System (ADS)

Yeo, U. J.; Taylor, M. L.; Kron, T.; Pham, D.; Siva, S.; Franich, R. D.

2013-06-01

Respiratory motion induces dosimetric uncertainties for thoracic and abdominal cancer radiotherapy (RT) due to deforming and moving anatomy. This study investigates the extent of dosimetric differences between conventional 3D treatment planning and path-integrated 4D treatment planning in liver stereotactic body radiotherapy (SBRT). Respiratory-correlated 4DCT image sets with 10 phases were acquired for patients with liver tumours. Path-integrated 4D dose accumulation was performed using dose-warping techniques based on deformable image registration. Dose-volume histogram analysis demonstrated that the 3D planning approach overestimated doses to targets by up to 24% and underestimated dose to normal liver by ~4.5%, compared to the 4D planning methodology. Therefore, 4D planning has the potential to quantify such issues of under- and/or over-dosage and improve treatment accuracy.

Monte Carlo study of LDR seed dosimetry with an application in a clinical brachytherapy breast implant.

PubMed

Furstoss, C; Reniers, B; Bertrand, M J; Poon, E; Carrier, J-F; Keller, B M; Pignol, J P; Beaulieu, L; Verhaegen, F

2009-05-01

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PubMed Central

Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

2014-01-01

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

SU-E-T-77: Comparison of 2D and 3D Gamma Analysis in Patient-Specific QA for Prostate VMAT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clemente, F; Perez, C

2014-06-01

Purpose: Patient-specific QA procedures for IMRT and VMAT are traditionally performed by comparing TPS calculations with measured single point values and plane dose distributions by means of gamma analysis. New QA devices permit us to calculate 3D dose distributions on patient anatomy as redundant secondary check and reconstruct it from measurements taken with 2D and 3D detector arrays. 3D dose calculations allow us to perform DVH-based comparisons with clinical relevance, as well as 3D gamma analysis. One of these systems (Compass, IBA Dosimetry) combines traditional 2D with new anatomical-based 3D gamma analysis. This work shows the ability of this systemmore » by comparing 2D and 3D gamma analysis in pre-treatment QA for several VMAT prostate plans. Methods: Compass is capable of calculating dose as secondary check from DICOM TPS data and reconstructing it from measurements taken by a 2D ion chamber array (MatriXX Evolution, IBA Dosimetry). Both 2D and 3D gamma tests are available to compare calculated and reconstructed dose in Compass with TPS RT Dose. Results: 15 VMAT prostate plans have been measured with Compass. Dose is reconstructed with Compass for these plans. 2D gamma comparisons can be done for any plane from dose matrix. Mean gamma passing rates for isocenter planes (axial, coronal, sagittal) are (99.7±0.2)%, (99.9±0.1)%, (99.9±0.1)% for reconstructed dose planes. 3D mean gamma passing rates are (98.5±1.7)% for PTVs, (99.1±1.5)% for rectum, (100.0±0.0)% for bladder, (99.6±0.7)% for femoral heads and (98.1±4.1)% for penile bulb. Conclusion: Compass is a powerful tool to perform a complete pre-treatment QA analysis, from 2D techniques to 3D DVH-based techniques with clinical relevance. All reported values for VMAT prostate plans are in good agreement with TPS values. This system permits us to ensure the accuracy in the delivery of VMAT treatments completing a full patient-specific QA program.« less

Development of a Spect-Based Three-Dimensional Treatment Planner for Radionuclide Therapy with Iodine -131.

NASA Astrophysics Data System (ADS)

Giap, Huan Bosco

Accurate calculation of absorbed dose to target tumors and normal tissues in the body is an important requirement for establishing fundamental dose-response relationships for radioimmunotherapy. Two major obstacles have been the difficulty in obtaining an accurate patient-specific 3-D activity map in-vivo and calculating the resulting absorbed dose. This study investigated a methodology for 3-D internal dosimetry, which integrates the 3-D biodistribution of the radionuclide acquired from SPECT with a dose-point kernel convolution technique to provide the 3-D distribution of absorbed dose. Accurate SPECT images were reconstructed with appropriate methods for noise filtering, attenuation correction, and Compton scatter correction. The SPECT images were converted into activity maps using a calibration phantom. The activity map was convolved with an ^{131}I dose-point kernel using a 3-D fast Fourier transform to yield a 3-D distribution of absorbed dose. The 3-D absorbed dose map was then processed to provide the absorbed dose distribution in regions of interest. This methodology can provide heterogeneous distributions of absorbed dose in volumes of any size and shape with nonuniform distributions of activity. Comparison of the activities quantitated by our SPECT methodology to true activities in an Alderson abdominal phantom (with spleen, liver, and spherical tumor) yielded errors of -16.3% to 4.4%. Volume quantitation errors ranged from -4.0 to 5.9% for volumes greater than 88 ml. The percentage differences of the average absorbed dose rates calculated by this methodology and the MIRD S-values were 9.1% for liver, 13.7% for spleen, and 0.9% for the tumor. Good agreement (percent differences were less than 8%) was found between the absorbed dose due to penetrating radiation calculated from this methodology and TLD measurement. More accurate estimates of the 3 -D distribution of absorbed dose can be used as a guide in specifying the minimum activity to be administered to patients to deliver a prescribed absorbed dose to tumor without exceeding the toxicity limits of normal tissues.

D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.

PubMed

Coffey, Todd; Gennings, Chris; Simmons, Jane Ellen; Herr, David W

2005-12-01

Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals. Optimal experimental conditions can be chosen that result in increased power to detect departures from additivity. Although these designs are used widely for linear models, optimal designs for nonlinear threshold models are less well known. In the present work, the use of D-optimal designs is demonstrated for nonlinear threshold models applied to a fixed-ratio mixture ray. For a fixed sample size, this design criterion selects the experimental doses and number of subjects per dose level that result in minimum variance of the model parameters and thus increased power to detect departures from additivity. An optimal design is illustrated for a 2:1 ratio (chlorpyrifos:carbaryl) mixture experiment. For this example, and in general, the optimal designs for the nonlinear threshold model depend on prior specification of the slope and dose threshold parameters. Use of a D-optimal criterion produces experimental designs with increased power, whereas standard nonoptimal designs with equally spaced dose groups may result in low power if the active range or threshold is missed.

A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michalski, Andrea; Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales; Atyeo, John, E-mail: john.atyeo@sydney.edu.au

2014-07-01

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. Allmore » patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D{sub 98%} > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D{sub 98%} > 95% and D{sub 2%} < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTV{sub boost} {sub eval} (0.079 ± 0.011) and breast minus the SIB volume (Breast{sub SIB}) (p < 0.001, 0.15 ± 0.03) compared with the PTV{sub boost} {sub eval} (0.085 ± 0.008, 0.088 ± 0.12) and Breast{sub SIB} (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11 Gy compared with 7.75 ± 2.54 Gy and 8.29 ± 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26 Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44 Gy and 3.91 ± 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung.« less

[C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

PubMed

Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

2016-11-01

Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients

PubMed Central

Deutsch, Eric; Haie-Meder, Christine; Bayar, Mohamed Amine; Mondini, Michele; Laporte, Mélanie; Mazeron, Renaud; Adam, Julien; Varga, Andrea; Vassal, Gilles; Magné, Nicolas; Chargari, Cyrus; Lanoy, Emilie; Pautier, Patricia; Levy, Antonin; Soria, Jean-Charles

2016-01-01

Purpose This phase I trial aimed to assess the safety and determine the recommended Phase II dose (RP2D) of Cidofovir combined with chemoradiotherapy in patients with stage IB2-IVA cervical cancer. Experimental design Incremental doses (1, 2.5, 5 and 6.5 mg/kg) of IV Cidofovir were administered weekly for two weeks, and then every 2 weeks from the start of chemoradiotherapy to the initiation of utero-vaginal brachytherapy. Biological expression of HPV was analyzed during treatment and tumor response was assessed according to RECIST v1.0 criteria. Results A total of 15 patients were treated with Cidofovir. Dose-limiting toxicities occurred in 2/6 patients at the 6.5 mg/kg dose level (G3 proteinuria, and G3 acute pyelonephritis with G3 febrile neutropenia). No toxicity occurred at the 5 mg/kg dose level, but only 3 patients received this dose due to trial interruption because of low accrual. The most frequent G3-4 adverse effects observed during the trial were: abdominal pain (n=3), infection (n=2), leuckoneutropenia (n=2), and others (n=6). No toxic death or major renal side effect occurred. The best response was that 8/9 evaluable patients achieved a complete response (89%). In the intention to treat population, the 2-year overall and progression-free survival rates were 93% and 76%, respectively. Biological monitoring of HPV-related markers (decreased p16 expression, and increased p53 and pRb levels) was possible on sequential tumor biopsy samples. The genomic alterations identified were PIK3CA (n=5; one also had a KRAS mutation), and HRAS (n=1) mutations. Conclusion Cidofovir at a dose of 5mg/kg combined with chemoradiotherapy appeared tolerable and yielded tumor regressions. Due to early trial interruption, the RP2D was not confirmed. PMID:27016411

How well are the optimal serum 25OHD concentrations reached in high-dose intermittent vitamin D therapy? a placebo-controlled study on comparison between 100 000 IU and 200 000 IU of oral D3 every 3 months in elderly women.

PubMed

Välimäki, Ville-Valtteri; Löyttyniemi, Eliisa; Pekkarinen, Tuula; Välimäki, Matti J

2016-06-01

Intermittent dosing may improve adherence to vitamin D therapy. Dosing regimen should maintain optimal serum 25-hydroxyvitamin D (25OHD) levels over all the year. We compared two dosing regimens, the primary outcome being the percentage of 25OHD measurements reaching the targets of 75 nmol/l or 50 nmol/l after baseline. Randomized, placebo-controlled parallel group comparison. Sixty women aged 75·0 ± 2·9 years. 100 000 IU (group 1D) or 200 000 IU (2D) of vitamin D3 or placebo orally every 3 months plus calcium 1 g daily for 1 year. Serum 25OHD, 1,25-dihydroxyvitamin D, PTH, sclerostin, ionized calcium, urinary calcium, renal function, bone turnover markers. Serum 25OHD increased, but the difference between two doses was of borderline significance (P = 0·0554; area under curve analysis). Immediate postadministrative increases were higher in the 2D vs 1D group (P < 0·05) after 3 and 6 months' dosing. In the 1D and 2D groups, 51·2% and 57·7% of all on-treatment measurements reached the target of 75 nmol/l. PTH levels differed marginally (P = 0·0759) due to tendency to lowering immediately after vitamin D boluses. Urinary calcium differed between the groups (P = 0·0193) due to increases 1 week after vitamin D dosing. The doses of 100 000 or 200 000 IU of oral cholecalciferol every 3 months were not capable of stabilizing 25OHD levels over the target of 75 nmol/l over the year. To improve the efficacy of high-dose vitamin D therapy, the interval between boluses has to be shortened instead of increasing their size. © 2016 John Wiley & Sons Ltd.

Intensity-Modulated Radiotherapy for Craniospinal Irradiation: Target Volume Considerations, Dose Constraints, and Competing Risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, William; Filion, Edith; Roberge, David

2007-09-01

Purpose: To report the results of an analysis of dose received to tissues and organs outside the target volume, in the setting of spinal axis irradiation for the treatment of medulloblastoma, using three treatment techniques. Methods and Materials: Treatment plans (total dose, 23.4 Gy) for a standard two-dimensional (2D) technique, a three-dimensional (3D) technique using a 3D imaging-based target volume, and an intensity-modulated radiotherapy (IMRT) technique, were compared for 3 patients in terms of dose-volume statistics for target coverage, as well as organ at risk (OAR) and overall tissue sparing. Results: Planning target volume coverage and dose homogeneity was superiormore » for the IMRT plans for V{sub 95%} (IMRT, 100%; 3D, 96%; 2D, 98%) and V{sub 107%} (IMRT, 3%; 3D, 38%; 2D, 37%). In terms of OAR sparing, the IMRT plan was better for all organs and whole-body contour when comparing V{sub 10Gy}, V{sub 15Gy}, and V{sub 20Gy}. The 3D plan was superior for V{sub 5Gy} and below. For the heart and liver in particular, the IMRT plans provided considerable sparing in terms of V{sub 10Gy} and above. In terms of the integral dose, the IMRT plans were superior for liver (IMRT, 21.9 J; 3D, 28.6 J; 2D, 38.6 J) and heart (IMRT, 9 J; 3D, 14.1J; 2D, 19.4 J), the 3D plan for the body contour (IMRT, 349 J; 3D, 337 J; 2D, 555 J). Conclusions: Intensity-modulated radiotherapy is a valid treatment option for spinal axis irradiation. We have shown that IMRT results in sparing of organs at risk without a significant increase in integral dose.« less

The effect of exposure duration on the subjective discomfort of aircraft cabin noise.

PubMed

Huang, Yu; Jiang, Weikang

2017-01-01

The time dependency for subjective responses to noise has been a controversial question over many years. For durations of up to 10 min, the discomfort produced by three levels of noise (ie 60, 70 and 80 dBA) was investigated in this experimental study to determine the relation of discomfort to the time duration of noise. The rate of increase in discomfort with increasing duration was 1.5 dB per doubling of exposure duration, whereas it is currently assumed to be 3 dB per doubling of exposure duration. The sound dose level (SDL) was proposed to predict the discomfort caused by noise of long duration. The combination of SDL and vibration dose value (VDV) provided more consistent estimates of the equivalent comfort contours between noise and vibration over durations from 2 to 32 s than the combination of sound exposure level and VDV or that of sound pressure level and r.m.s. acceleration. Practitioner Summary: The discomfort produced by noise of long duration can be well predicted from a new definition of sound dose level, where the discomfort increases at 1.5 dB per doubling of exposure duration.

Fluorescent nuclear track detectors for alpha radiation microdosimetry.

PubMed

Kouwenberg, J J M; Wolterbeek, H T; Denkova, A G; Bos, A J J

2018-06-07

While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues. Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival. The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (< 5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 - 51%). The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.

Effects of benthos, temperature, and dose on the fate of hexabromocyclododecane in experimental coastal ecosystems.

PubMed

Bradshaw, Clare; Strid, Anna; von Stedingk, Hans; Gustafsson, Kerstin

2015-06-01

The authors studied the fate of the brominated flame retardant hexabromocyclododecane (HBCDD) added in a particulate suspension to experimental ecosystems assembled from brackish (Baltic Sea) coastal bays. Two experiments examined how benthic macrofauna (over 21 d) and increased temperature (14 d) affected HBCDD concentrations and fractionation of α, β, and γ diastereomers in the water, sediment, and biota. A third experiment run over 3 seasons (231 d), studied the effect of HBCDD dose on the same endpoints. In all treatments of the 3 experiments, HBCDD partitioned mainly to the sediment, and this proportion increased with time. Presence of macrofauna tended to increase the HBCDD concentration in the sediment and decreased its concentration in the water. Increased temperature (+ 5°C) decreased the amount of HBCDD in sediment and water but not in the filter- and deposit-feeding infaunal bivalves (Macoma balthica). The partitioning between water, sediment, and biota was not concentration dependent. In all treatments, sediment became enriched in γ-HBCDD, M. balthica in α-HBCDD, and water in α- and β-HBCDD. Bioaccumulation of HBCDD in M. balthica was high in all experiments (log biota-sediment accumulation factor [BSAF] > 1.25), the α diastereomer contributing the most (log BSAF 2.1-5.2). There is a risk of trophic transfer of HBCDD from benthic to pelagic food webs, as well as secondary poisoning of marine consumers. © 2015 SETAC.

A Phase I First-in-Human Trial of Bardoxolone Methyl in Patients with Advanced Solid Tumors and Lymphomas

PubMed Central

Hong, David S.; Kurzrock, Razelle; Supko, Jeffrey G.; He, Xiaoying; Naing, Aung; Wheler, Jennifer; Lawrence, Donald; Eder, Joseph Paul; Meyer, Colin J.; Ferguson, Deborah A.; Mier, James; Konopleva, Marina; Konoplev, Sergej; Andreeff, Michael; Kufe, Donald; Lazarus, Hillard; Shapiro, Geoffrey I.; Dezube, Bruce J.

2015-01-01

Purpose Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Experimental Design Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2–related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. Results The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Conclusions Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. PMID:22634319

Impact of heterogeneity-corrected dose calculation using a grid-based Boltzmann solver on breast and cervix cancer brachytherapy.

PubMed

Hofbauer, Julia; Kirisits, Christian; Resch, Alexandra; Xu, Yingjie; Sturdza, Alina; Pötter, Richard; Nesvacil, Nicole

2016-04-01

To analyze the impact of heterogeneity-corrected dose calculation on dosimetric quality parameters in gynecological and breast brachytherapy using Acuros, a grid-based Boltzmann equation solver (GBBS), and to evaluate the shielding effects of different cervix brachytherapy applicators. Calculations with TG-43 and Acuros were based on computed tomography (CT) retrospectively, for 10 cases of accelerated partial breast irradiation and 9 cervix cancer cases treated with tandem-ring applicators. Phantom CT-scans of different applicators (plastic and titanium) were acquired. For breast cases the V20Gyαβ3 to lung, the D0.1cm(3) , D1cm(3) , D2cm(3) to rib, the D0.1cm(3) , D1cm(3) , D10cm(3) to skin, and Dmax for all structures were reported. For cervix cases, the D0.1cm(3) , D2cm(3) to bladder, rectum and sigmoid, and the D50, D90, D98, V100 for the CTVHR were reported. For the phantom study, surrogates for target and organ at risk were created for a similar dose volume histogram (DVH) analysis. Absorbed dose and equivalent dose to 2 Gy fractionation (EQD2) were used for comparison. Calculations with TG-43 overestimated the dose for all dosimetric indices investigated. For breast, a decrease of ~8% was found for D10cm(3) to the skin and 5% for D2cm(3) to rib, resulting in a difference ~ -1.5 Gy EQD2 for overall treatment. Smaller effects were found for cervix cases with the plastic applicator, with up to -2% (-0.2 Gy EQD2) per fraction for organs at risk and -0.5% (-0.3 Gy EQD2) per fraction for CTVHR. The shielding effect of the titanium applicator resulted in a decrease of 2% for D2cm(3) to the organ at risk versus 0.7% for plastic. Lower doses were reported when calculating with Acuros compared to TG-43. Differences in dose parameters were larger in breast cases. A lower impact on clinical dose parameters was found for the cervix cases. Applicator material causes systematic shielding effects that can be taken into account.

Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

PubMed

Liu, Haisong; Li, Jun; Pappas, Evangelos; Andrews, David; Evans, James; Werner-Wasik, Maria; Yu, Yan; Dicker, Adam; Shi, Wenyin

2016-09-08

An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the treatment delivery accuracy as well. © 2016 The Authors.

Acquisition, preprocessing, and reconstruction of ultralow dose volumetric CT scout for organ-based CT scan planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Zhye, E-mail: yin@ge.com; De Man, Bruno; Yao, Yangyang

Purpose: Traditionally, 2D radiographic preparatory scan images (scout scans) are used to plan diagnostic CT scans. However, a 3D CT volume with a full 3D organ segmentation map could provide superior information for customized scan planning and other purposes. A practical challenge is to design the volumetric scout acquisition and processing steps to provide good image quality (at least good enough to enable 3D organ segmentation) while delivering a radiation dose similar to that of the conventional 2D scout. Methods: The authors explored various acquisition methods, scan parameters, postprocessing methods, and reconstruction methods through simulation and cadaver data studies tomore » achieve an ultralow dose 3D scout while simultaneously reducing the noise and maintaining the edge strength around the target organ. Results: In a simulation study, the 3D scout with the proposed acquisition, preprocessing, and reconstruction strategy provided a similar level of organ segmentation capability as a traditional 240 mAs diagnostic scan, based on noise and normalized edge strength metrics. At the same time, the proposed approach delivers only 1.25% of the dose of a traditional scan. In a cadaver study, the authors’ pictorial-structures based organ localization algorithm successfully located the major abdominal-thoracic organs from the ultralow dose 3D scout obtained with the proposed strategy. Conclusions: The authors demonstrated that images with a similar degree of segmentation capability (interpretability) as conventional dose CT scans can be achieved with an ultralow dose 3D scout acquisition and suitable postprocessing. Furthermore, the authors applied these techniques to real cadaver CT scans with a CTDI dose level of less than 0.1 mGy and successfully generated a 3D organ localization map.« less

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

SU-F-T-580: New Tumor Modeling Using 3D Gel Dosimeter for Brain Stereoctactic Radiotherpy (SRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, K; Kim, M; Kwak, J

Purpose: The purpose of this study is to develop new tumor model using 3D printing with 3D dosimeter for brain stereoctactic radiotherpy (SRT). Methods: BANG{sup 3} polymer gel was prepared and the gel-filled glass vials were irradiated with a 6 MV photon beam to acquire the calibration curve that present the change of R2 (1/T{sub 2}) value with dose. Graded doses from 0 to 12 Gy with an interval of 2 Gy were delivered. A kit for calibration of gel dosimeter and an 2 tumor model phantoms with a spherical shape were produced using a 3D printer with a polylacticmore » acid after its 3D images were created using Autodesk software. 3D printed tumor phantoms and EBT3 films were irradiated to compare with treatment plan. After irradiation, vials for calibration and tumor model phantoms were scanned at 9.4T MRI. The spin-spin relaxation times (T{sub 2}) according to the each dose were calculated to evaluate the dose response. Acquired images were analyzed using an ImageJ. Scanned MRI images of tumor models were transferred treatment planning system and these were registered to the CT images. In all treatment plans, two arc plans (CW and CCW) were designed to deliver 50 Gy for 10 fractions. For first PTV, treatment plan was accurately designed that 95% of dose to cover 100% of PTV. But 2nd PTV was not intentionally cover 100% of PTV to evaluate the intensity of delivered tumor phantom with polymer gel. We compared the 3D dose distributions obtained from measurements with the 3D printed phantom and calculated with the TPS. Results: 3D printed phantom with a polymer gel was successfully produced. The dose distributions showed qualitatively good agreement among gel, film, and RTP data. Conclusion: A hybrid phantom represents a useful to validate the 3D dose distributions for patient-specific QA.« less

Clinical application of 3D-printed-step-bolus in post-total-mastectomy electron conformal therapy.

PubMed

Park, Kwangwoo; Park, Sungjin; Jeon, Mi-Jin; Choi, Jinhyun; Kim, Jun Won; Cho, Yoon Jin; Jang, Won-Seok; Keum, Yo Sup; Lee, Ik Jae

2017-04-11

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses.

Clinical application of 3D-printed-step-bolus in post-total-mastectomy electron conformal therapy

PubMed Central

Park, Kwangwoo; Park, Sungjin; Jeon, Mi-Jin; Choi, Jinhyun; Kim, Jun Won; Cho, Yoon Jin; Jang, Won-Seok; Keum, Yo Sup; Lee, Ik Jae

2017-01-01

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses. PMID:27784001

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

PubMed Central

Lim, Hyeon Woo; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong

2016-01-01

Purpose To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys. PMID:27730803

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments.

PubMed

Tyler, Madelaine K

2016-01-08

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ± 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ± 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ± 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI.

Semi-3D dosimetry of high dose rate brachytherapy using a novel Gafchromic EBT3 film-array water phantom

NASA Astrophysics Data System (ADS)

Palmer, A. L.; Nisbet, A.; Bradley, D. A.

2013-06-01

There is a need to modernise clinical brachytherapy dosimetry measurement beyond traditional point dose verification to enable appropriate quality control within 3D treatment environments. This is to keep pace with the 3D clinical and planning approaches which often include significant patient-specific optimisation away from 'standard loading patterns'. A multi-dimension measurement system is required to provide assurance of the complex 3D dose distributions, to verify equipment performance, and to enable quality audits. However, true 3D dose measurements around brachytherapy applicators are often impractical due to their complex shapes and the requirement for close measurement distances. A solution utilising an array of radiochromic film (Gafchromic EBT3) positioned within a water filled phantom is presented. A calibration function for the film has been determined over 0 to 90Gy dose range using three colour channel analysis (FilmQAPro software). Film measurements of the radial dose from a single HDR source agree with TPS and Monte Carlo calculations within 5 % up to 50 mm from the source. Film array measurements of the dose distribution around a cervix applicator agree with TPS calculations generally within 4 mm distance to agreement. The feasibility of film array measurements for semi-3D dosimetry in clinical HDR applications is demonstrated.

A model-based 3D patient-specific pre-treatment QA method for VMAT using the EPID

NASA Astrophysics Data System (ADS)

McCowan, P. M.; Asuni, G.; van Beek, T.; van Uytven, E.; Kujanpaa, K.; McCurdy, B. M. C.

2017-02-01

This study reports the development and validation of a model-based, 3D patient dose reconstruction method for pre-treatment quality assurance using EPID images. The method is also investigated for sensitivity to potential MLC delivery errors. Each cine-mode EPID image acquired during plan delivery was processed using a previously developed back-projection dose reconstruction model providing a 3D dose estimate on the CT simulation data. Validation was carried out using 24 SBRT-VMAT patient plans by comparing: (1) ion chamber point dose measurements in a solid water phantom, (2) the treatment planning system (TPS) predicted 3D dose to the EPID reconstructed 3D dose in a solid water phantom, and (3) the TPS predicted 3D dose to the EPID and our forward predicted reconstructed 3D dose in the patient (CT data). AAA and AcurosXB were used for TPS predictions. Dose distributions were compared using 3%/3 mm (95% tolerance) and 2%/2 mm (90% tolerance) γ-tests in the planning target volume (PTV) and 20% dose volumes. The average percentage point dose differences between the ion chamber and the EPID, AcurosXB, and AAA were 0.73  ±  1.25%, 0.38  ±  0.96% and 1.06  ±  1.34% respectively. For the patient (CT) dose comparisons, seven (3%/3 mm) and nine (2%/2 mm) plans failed the EPID versus AAA. All plans passed the EPID versus Acuros XB and the EPID versus forward model γ-comparisons. Four types of MLC sensitive errors (opening, shifting, stuck, and retracting), of varying magnitude (0.2, 0.5, 1.0, 2.0 mm), were introduced into six different SBRT-VMAT plans. γ-comparisons of the erroneous EPID dose and original predicted dose were carried out using the same criteria as above. For all plans, the sensitivity testing using a 3%/3 mm γ-test in the PTV successfully determined MLC errors on the order of 1.0 mm, except for the single leaf retraction-type error. A 2%/2 mm criteria produced similar results with two more additional detected errors.

A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

PubMed

Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve patients' symptoms quickly, and lower the chance of adverse reactions. It is effective and safe.

A method for modeling laterally asymmetric proton beamlets resulting from collimation

PubMed Central

Gelover, Edgar; Wang, Dongxu; Hill, Patrick M.; Flynn, Ryan T.; Gao, Mingcheng; Laub, Steve; Pankuch, Mark; Hyer, Daniel E.

2015-01-01

Purpose: To introduce a method to model the 3D dose distribution of laterally asymmetric proton beamlets resulting from collimation. The model enables rapid beamlet calculation for spot scanning (SS) delivery using a novel penumbra-reducing dynamic collimation system (DCS) with two pairs of trimmers oriented perpendicular to each other. Methods: Trimmed beamlet dose distributions in water were simulated with MCNPX and the collimating effects noted in the simulations were validated by experimental measurement. The simulated beamlets were modeled analytically using integral depth dose curves along with an asymmetric Gaussian function to represent fluence in the beam’s eye view (BEV). The BEV parameters consisted of Gaussian standard deviations (sigmas) along each primary axis (σx1,σx2,σy1,σy2) together with the spatial location of the maximum dose (μx,μy). Percent depth dose variation with trimmer position was accounted for with a depth-dependent correction function. Beamlet growth with depth was accounted for by combining the in-air divergence with Hong’s fit of the Highland approximation along each axis in the BEV. Results: The beamlet model showed excellent agreement with the Monte Carlo simulation data used as a benchmark. The overall passing rate for a 3D gamma test with 3%/3 mm passing criteria was 96.1% between the analytical model and Monte Carlo data in an example treatment plan. Conclusions: The analytical model is capable of accurately representing individual asymmetric beamlets resulting from use of the DCS. This method enables integration of the DCS into a treatment planning system to perform dose computation in patient datasets. The method could be generalized for use with any SS collimation system in which blades, leaves, or trimmers are used to laterally sharpen beamlets. PMID:25735287

TU-C-BRE-11: 3D EPID-Based in Vivo Dosimetry: A Major Step Forward Towards Optimal Quality and Safety in Radiation Oncology Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mijnheer, B; Mans, A; Olaciregui-Ruiz, I

Purpose: To develop a 3D in vivo dosimetry method that is able to substitute pre-treatment verification in an efficient way, and to terminate treatment delivery if the online measured 3D dose distribution deviates too much from the predicted dose distribution. Methods: A back-projection algorithm has been further developed and implemented to enable automatic 3D in vivo dose verification of IMRT/VMAT treatments using a-Si EPIDs. New software tools were clinically introduced to allow automated image acquisition, to periodically inspect the record-and-verify database, and to automatically run the EPID dosimetry software. The comparison of the EPID-reconstructed and planned dose distribution is donemore » offline to raise automatically alerts and to schedule actions when deviations are detected. Furthermore, a software package for online dose reconstruction was also developed. The RMS of the difference between the cumulative planned and reconstructed 3D dose distributions was used for triggering a halt of a linac. Results: The implementation of fully automated 3D EPID-based in vivo dosimetry was able to replace pre-treatment verification for more than 90% of the patient treatments. The process has been fully automated and integrated in our clinical workflow where over 3,500 IMRT/VMAT treatments are verified each year. By optimizing the dose reconstruction algorithm and the I/O performance, the delivered 3D dose distribution is verified in less than 200 ms per portal image, which includes the comparison between the reconstructed and planned dose distribution. In this way it was possible to generate a trigger that can stop the irradiation at less than 20 cGy after introducing large delivery errors. Conclusion: The automatic offline solution facilitated the large scale clinical implementation of 3D EPID-based in vivo dose verification of IMRT/VMAT treatments; the online approach has been successfully tested for various severe delivery errors.« less

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

The polyGeVero® software for fast and easy computation of 3D radiotherapy dosimetry data

NASA Astrophysics Data System (ADS)

Kozicki, Marek; Maras, Piotr

2015-01-01

The polyGeVero® software package was elaborated for calculations of 3D dosimetry data such as the polymer gel dosimetry. It comprises four workspaces designed for: i) calculating calibrations, ii) storing calibrations in a database, iii) calculating dose distribution 3D cubes, iv) comparing two datasets e.g. a measured one with a 3D dosimetry with a calculated one with the aid of a treatment planning system. To accomplish calculations the software was equipped with a number of tools such as the brachytherapy isotopes database, brachytherapy dose versus distance calculation based on the line approximation approach, automatic spatial alignment of two 3D dose cubes for comparison purposes, 3D gamma index, 3D gamma angle, 3D dose difference, Pearson's coefficient, histograms calculations, isodoses superimposition for two datasets, and profiles calculations in any desired direction. This communication is to briefly present the main functions of the software and report on the speed of calculations performed by polyGeVero®.

Configuration and validation of an analytical model predicting secondary neutron radiation in proton therapy using Monte Carlo simulations and experimental measurements.

PubMed

Farah, J; Bonfrate, A; De Marzi, L; De Oliveira, A; Delacroix, S; Martinetti, F; Trompier, F; Clairand, I

2015-05-01

This study focuses on the configuration and validation of an analytical model predicting leakage neutron doses in proton therapy. Using Monte Carlo (MC) calculations, a facility-specific analytical model was built to reproduce out-of-field neutron doses while separately accounting for the contribution of intra-nuclear cascade, evaporation, epithermal and thermal neutrons. This model was first trained to reproduce in-water neutron absorbed doses and in-air neutron ambient dose equivalents, H*(10), calculated using MCNPX. Its capacity in predicting out-of-field doses at any position not involved in the training phase was also checked. The model was next expanded to enable a full 3D mapping of H*(10) inside the treatment room, tested in a clinically relevant configuration and finally consolidated with experimental measurements. Following the literature approach, the work first proved that it is possible to build a facility-specific analytical model that efficiently reproduces in-water neutron doses and in-air H*(10) values with a maximum difference less than 25%. In addition, the analytical model succeeded in predicting out-of-field neutron doses in the lateral and vertical direction. Testing the analytical model in clinical configurations proved the need to separate the contribution of internal and external neutrons. The impact of modulation width on stray neutrons was found to be easily adjustable while beam collimation remains a challenging issue. Finally, the model performance agreed with experimental measurements with satisfactory results considering measurement and simulation uncertainties. Analytical models represent a promising solution that substitutes for time-consuming MC calculations when assessing doses to healthy organs. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vikraman, S; Karrthick, K; Rajesh, T

2014-06-15

Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated withmore » COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for patient specific quality assurance compared to 2D fluence verification.« less

Determination of effective doses in image-guided radiation therapy system

NASA Astrophysics Data System (ADS)

Pyone, Y. Y.; Suriyapee, S.; Sanghangthum, T.; Oonsiri, S.; Tawonwong, T.

2016-03-01

The organ and effective doses in image-guided radiotherapy system are determined in this study. For 2D imaging, incident air kerma (Ki) was measured by 6cc ionization chamber with Accu-Pro dosimeter. The entrance surface air kerma (ESAK) was calculated by multiplying Ki with backscatter factor. The effective dose was calculated by multiplying ESAK with conversion coefficient. For 3D imaging, computed tomography/cone-beam dose index (CTDI/CBDI) measurements were performed by using 100mm pencil ionization chamber with Accu-Pro dosimeter. The dose index in air and in CTDI phantom from planning CT and cone- beam CT were measured. Then, effective dose was calculated by ImPACT software. The effective doses from 2D conventional simulator for anteroposterior and lateral projections were 01 and 0.02mSv for head, 0.15 and 0.16mSv for thorax, 0.22 and 0.21mSv for pelvis, respectively. The effective doses from 3D, planning CT and CBCT, were 3.3 and 0.1mSv for head, 13 and 2.4mSv for thorax and 7.2 and 4.9mSv for pelvis, respectively. Based on 30 fractions of treatment course, total effective dose (3D CT, 2D setup verification and 6 times CBCT) of head, thorax and pelvis were 3.93, 27.71 and 37.03mSv, respectively. Therefore, IGRT should be administered with significant parameters to reduce the dose.

SU-F-T-635: Lung SBRT: Dosimetric and Treatment Time Comparison of Volumetric-Modulated Arc Therapy and Three-Dimensional Conformal Radiotherapy in Clinically Treated Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, J; Xu, Z; Baker, J

Purpose: To compare three-dimensional conformal radiotherapy (3D CRT) and volumetric-modulated arc therapy (VMAT) in lung stereotactic body radiation therapy (SBRT) Methods: A retrospective study of clinically treated lung SBRT cases treated between 2010 and 2015 at our hospital was performed. All treatment modalities were included in this evaluation (VMAT, 3D CRT, static IMRT, and dynamic conformal arc therapy). However, the majority of treatment modalities were either VMAT or 3D CRT. Treatment times of patients and dosimetric plan quality metrics were compared. Treatment times were calculated based on the time the therapist opened and closed the patient’s treatment plan. This treatmentmore » time closely approximates the utilization time of the treatment room. The dosimetric plan quality metrics evaluated include ICRU conformity index, the volume of 105% prescribed dose outside PTV, the ratio of volume of 50% prescribed dose to the volume of PTV, the percentage of maximum dose at 2 cm away from PTV to the prescribed dose, and the V20 (percentage of lung volume receiving 20 Gy or more). Results: Treatment time comparisons show that on average VMAT has shorter treatment times than 3D CRT. Dose conformity, defined by the ICRU conformity index, and high dose spillage, defined by the volume of 105% dose outside the PTV, is reduced when using VMAT compared to 3D CRT. V20 and intermediate dose spillage/fall-off metrics of VMAT and 3D are not significantly different. Conclusion: Clinically treated lung SBRT cases indicate VMAT is superior to 3D with regard to shorter treatment times, plan dose conformity, and plan high dose spillage.« less

A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.

2013-07-01

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumesmore » of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.« less

Effect of different oral oxytetracycline treatment regimes on selection of antimicrobial resistant coliforms in nursery pigs.

PubMed

Herrero-Fresno, Ana; Zachariasen, Camilla; Nørholm, Nanna; Holm, Anders; Christiansen, Lasse Engbo; Olsen, John Elmerdahl

2017-09-01

A major concern derived from using antimicrobials in pig production is the development of resistance. This study aimed to assess the impact of selected combinations of oral dose and duration of treatment with oxytetracycline (OTC) on selection of tetracycline resistant (TET-R) coliforms recovered from swine feces. The work encompassed two studies: 1) OTC 5mg/kg and 20mg/kg were administered to nursery pigs for 3 and 10days, respectively, under controlled experimental conditions, and 2) 10mg/kg, 20mg/kg and 30mg/kg OTC were given to a higher number of pigs for 6, 3 and 2days, respectively, under field conditions. Statistical modeling was applied to analyze trends in the proportion of TET-R coliforms. In the experimental study, no statistical difference in proportion of TET-R coliforms was observed between treatments at the end of the trial (day 18) and compared to day 0. In the field study, treatment had a significant effect on the proportion of TET-R bacteria two days after the end of treatment (2dAT) with the regimes "low dose-six days" and "medium dose-three days" yielding the highest and lowest proportions of TET-R strains, respectively. No indication of co-selection for ampicillin- and sulphonamide -R bacteria was observed for any treatment at 2dAT. By the end of the nursery period, the proportion of TET-R bacteria was not significantly different between treatments and compared to day 0. Our results suggest that similar resistance levels might be obtained by using different treatment regimes regardless of the combinations of oral dose-duration of treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Randomized trial of two doses of vitamin D3 in preterm infants <32 weeks: Dose impact on achieving desired serum 25(OH)D3 in a NICU population

PubMed Central

Anderson-Berry, Ann; Thoene, Melissa; Wagner, Julie; Lyden, Elizabeth; Jones, Glenville; Kaufmann, Martin; Hanson, Corrine

2017-01-01

Background Recommendations for vitamin D supplementation for preterm infants span a wide range of doses. Response to vitamin D supplementation and impact on outcomes in preterm infants is not well understood. Objective Evaluate serum 25(OH)D3 concentration changes after 4 weeks in response to two different doses of vitamin D3 supplementation in a population of premature infants and quantify the impact on NICU outcomes. Design 32 infants born at 24–32 weeks gestation were prospectively randomized to receive 400 or 800 IU/day vitamin D3 supplementation. Serum 25(OH)D3 levels were measured every 4 weeks. The Wilcoxon signed rank test was used to compare serum levels of 25(OH)D3 at 4 weeks and each subsequent time point. A p-value of <0.05 was considered statistically significant. Results Serum 25(OH)D3 levels at birth were 41.9 and 42.9 nmol/l for infants in the 400 IU group and 800 IU group, respectively (p = 0.86). Cord 25(OH)D3 concentrations significantly correlated with gestational age (r = 0.40, p = 0.04). After 4 weeks of D3 supplementation, median 25(OH)D3 levels increased in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day respectively, with significantly more improvement in the higher dose (p = 0.048). Infants in the 400 IU group were significantly more likely to have dual energy x-ray absorptiometry (DEXA) bone density measurements <10 percentile (56% vs 16%, p = 0.04). Conclusions Improvement in 25(OH)D3 levels at 4 weeks, bone density, and trends towards improvement in linear growth support consideration of a daily dose of 800 IU of vitamin D for infants <32 weeks cared for in the NICU. PMID:29016653

3D conformal planning using low segment multi-criteria IMRT optimization

PubMed Central

Khan, Fazal; Craft, David

2014-01-01

Purpose To evaluate automated multicriteria optimization (MCO) – designed for intensity modulated radiation therapy (IMRT), but invoked with limited segmentation – to efficiently produce high quality 3D conformal radiation therapy (3D-CRT) plans. Methods Ten patients previously planned with 3D-CRT to various disease sites (brain, breast, lung, abdomen, pelvis), were replanned with a low-segment inverse multicriteria optimized technique. The MCO-3D plans used the same beam geometry of the original 3D plans, but were limited to an energy of 6 MV. The MCO-3D plans were optimized using fluence-based MCO IMRT and then, after MCO navigation, segmented with a low number of segments. The 3D and MCO-3D plans were compared by evaluating mean dose for all structures, D95 (dose that 95% of the structure receives) and homogeneity indexes for targets, D1 and clinically appropriate dose volume objectives for individual organs at risk (OARs), monitor units (MUs), and physician preference. Results The MCO-3D plans reduced the OAR mean doses (41 out of a total of 45 OARs had a mean dose reduction, p<<0.01) and monitor units (seven out of ten plans have reduced MUs; the average reduction is 17%, p=0.08) while maintaining clinical standards on coverage and homogeneity of target volumes. All MCO-3D plans were preferred by physicians over their corresponding 3D plans. Conclusion High quality 3D plans can be produced using MCO-IMRT optimization, resulting in automated field-in-field type plans with good monitor unit efficiency. Adopting this technology in a clinic could improve plan quality, and streamline treatment plan production by utilizing a single system applicable to both IMRT and 3D planning. PMID:25413405

The influence of different levels of micronized insoluble fiber on broiler performance and litter moisture.

PubMed

Rezaei, M; Karimi Torshizi, M A; Rouzbehan, Y

2011-09-01

The effects of different levels of micronized insoluble fiber (MIF) on broiler performance and litter moisture were assessed in 320 one-day-old male broilers (Ross 308). Feed was supplemented with 0, 0.3, 0.4, or 0.5% MIF during both the starter (1 to 14 d) and grower (15 to 42 d) periods. Supplementation of MIF was associated with dose dependent increases in daily BW gain and feed conversion ratio throughout the experimental period (P < 0.01), whereas feed intake was not influenced by MIF concentration. As MIF content increased, the relative weight of digestive organs was not changed (P > 0.05). Supplementation of MIF resulted in dose dependent increases in the ileal villus height:crypt depth ratio and number of goblet cells (P < 0.05), and a dose dependent decrease in litter moisture beginning during the third week (P < 0.01). These findings indicate that inclusion of 0.5% MIF in feed resulted in the greatest improvements in broiler performance, intestinal morphology, and litter moisture.

3D delivered dose assessment using a 4DCT-based motion model

PubMed Central

Cai, Weixing; Hurwitz, Martina H.; Williams, Christopher L.; Dhou, Salam; Berbeco, Ross I.; Seco, Joao; Mishra, Pankaj; Lewis, John H.

2015-01-01

Purpose: The purpose of this work is to develop a clinically feasible method of calculating actual delivered dose distributions for patients who have significant respiratory motion during the course of stereotactic body radiation therapy (SBRT). Methods: A novel approach was proposed to calculate the actual delivered dose distribution for SBRT lung treatment. This approach can be specified in three steps. (1) At the treatment planning stage, a patient-specific motion model is created from planning 4DCT data. This model assumes that the displacement vector field (DVF) of any respiratory motion deformation can be described as a linear combination of some basis DVFs. (2) During the treatment procedure, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying “fluoroscopic” 3D images of the patient are reconstructed using the motion model. The DVF of each timepoint in the time-varying reconstruction is an optimized linear combination of basis DVFs such that the 2D projection of the 3D volume at this timepoint matches the projection image. (3) 3D dose distribution is computed for each timepoint in the set of 3D reconstructed fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach was first validated using two modified digital extended cardio-torso (XCAT) phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for routine 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms at all timepoints. The approach was also tested using one set of patient data, which demonstrated the application of our method in a clinical scenario. Results: For the first XCAT phantom that has a mostly regular breathing pattern, the errors in 95% volume dose (D95) are 0.11% and 0.83%, respectively for 3D fluoroscopic images reconstructed from kV and MV projections compared to the ground truth, which is clinically comparable to 4DCT (0.093%). For the second XCAT phantom that has an irregular breathing pattern, the errors are 0.81% and 1.75% for kV and MV reconstructions, both of which are better than that of 4DCT (4.01%). In the case of real patient, although it is impossible to obtain the actual delivered dose, the dose estimation is clinically reasonable and demonstrates differences between 4DCT and MV reconstruction-based dose estimates. Conclusions: With the availability of kV or MV projection images, the proposed approach is able to assess delivered doses for all respiratory phases during treatment. Compared to the planning dose based on 4DCT, the dose estimation using reconstructed 3D fluoroscopic images was as good as 4DCT for regular respiratory pattern and was a better dose estimation for the irregular respiratory pattern. PMID:26127043

3D delivered dose assessment using a 4DCT-based motion model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Weixing; Hurwitz, Martina H.; Williams, Christopher L.

Purpose: The purpose of this work is to develop a clinically feasible method of calculating actual delivered dose distributions for patients who have significant respiratory motion during the course of stereotactic body radiation therapy (SBRT). Methods: A novel approach was proposed to calculate the actual delivered dose distribution for SBRT lung treatment. This approach can be specified in three steps. (1) At the treatment planning stage, a patient-specific motion model is created from planning 4DCT data. This model assumes that the displacement vector field (DVF) of any respiratory motion deformation can be described as a linear combination of some basismore » DVFs. (2) During the treatment procedure, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying “fluoroscopic” 3D images of the patient are reconstructed using the motion model. The DVF of each timepoint in the time-varying reconstruction is an optimized linear combination of basis DVFs such that the 2D projection of the 3D volume at this timepoint matches the projection image. (3) 3D dose distribution is computed for each timepoint in the set of 3D reconstructed fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach was first validated using two modified digital extended cardio-torso (XCAT) phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for routine 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms at all timepoints. The approach was also tested using one set of patient data, which demonstrated the application of our method in a clinical scenario. Results: For the first XCAT phantom that has a mostly regular breathing pattern, the errors in 95% volume dose (D95) are 0.11% and 0.83%, respectively for 3D fluoroscopic images reconstructed from kV and MV projections compared to the ground truth, which is clinically comparable to 4DCT (0.093%). For the second XCAT phantom that has an irregular breathing pattern, the errors are 0.81% and 1.75% for kV and MV reconstructions, both of which are better than that of 4DCT (4.01%). In the case of real patient, although it is impossible to obtain the actual delivered dose, the dose estimation is clinically reasonable and demonstrates differences between 4DCT and MV reconstruction-based dose estimates. Conclusions: With the availability of kV or MV projection images, the proposed approach is able to assess delivered doses for all respiratory phases during treatment. Compared to the planning dose based on 4DCT, the dose estimation using reconstructed 3D fluoroscopic images was as good as 4DCT for regular respiratory pattern and was a better dose estimation for the irregular respiratory pattern.« less

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

PubMed

Bagatini, Pamela Brambilla; Xavier, Léder Leal; Bertoldi, Karine; Moysés, Felipe; Lovatel, Gisele; Neves, Laura Tartari; Barbosa, Sílvia; Saur, Lisiani; de Senna, Priscylla Nunes; Souto, André Arigony; Siqueira, Ionara Rodrigues; Achaval, Matilde

2017-01-01

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of temporal probability in 4D dose calculation for lung tumors.

PubMed

Rouabhi, Ouided; Ma, Mingyu; Bayouth, John; Xia, Junyi

2015-11-08

The purpose of this study was to evaluate the dosimetric uncertainty in 4D dose calculation using three temporal probability distributions: uniform distribution, sinusoidal distribution, and patient-specific distribution derived from the patient respiratory trace. Temporal probability, defined as the fraction of time a patient spends in each respiratory amplitude, was evaluated in nine lung cancer patients. Four-dimensional computed tomography (4D CT), along with deformable image registration, was used to compute 4D dose incorporating the patient's respiratory motion. First, the dose of each of 10 phase CTs was computed using the same planning parameters as those used in 3D treatment planning based on the breath-hold CT. Next, deformable image registration was used to deform the dose of each phase CT to the breath-hold CT using the deformation map between the phase CT and the breath-hold CT. Finally, the 4D dose was computed by summing the deformed phase doses using their corresponding temporal probabilities. In this study, 4D dose calculated from the patient-specific temporal probability distribution was used as the ground truth. The dosimetric evaluation matrix included: 1) 3D gamma analysis, 2) mean tumor dose (MTD), 3) mean lung dose (MLD), and 4) lung V20. For seven out of nine patients, both uniform and sinusoidal temporal probability dose distributions were found to have an average gamma passing rate > 95% for both the lung and PTV regions. Compared with 4D dose calculated using the patient respiratory trace, doses using uniform and sinusoidal distribution showed a percentage difference on average of -0.1% ± 0.6% and -0.2% ± 0.4% in MTD, -0.2% ± 1.9% and -0.2% ± 1.3% in MLD, 0.09% ± 2.8% and -0.07% ± 1.8% in lung V20, -0.1% ± 2.0% and 0.08% ± 1.34% in lung V10, 0.47% ± 1.8% and 0.19% ± 1.3% in lung V5, respectively. We concluded that four-dimensional dose computed using either a uniform or sinusoidal temporal probability distribution can approximate four-dimensional dose computed using the patient-specific respiratory trace.

Robust low-dose dynamic cerebral perfusion CT image restoration via coupled dictionary learning scheme.

PubMed

Tian, Xiumei; Zeng, Dong; Zhang, Shanli; Huang, Jing; Zhang, Hua; He, Ji; Lu, Lijun; Xi, Weiwen; Ma, Jianhua; Bian, Zhaoying

2016-11-22

Dynamic cerebral perfusion x-ray computed tomography (PCT) imaging has been advocated to quantitatively and qualitatively assess hemodynamic parameters in the diagnosis of acute stroke or chronic cerebrovascular diseases. However, the associated radiation dose is a significant concern to patients due to its dynamic scan protocol. To address this issue, in this paper we propose an image restoration method by utilizing coupled dictionary learning (CDL) scheme to yield clinically acceptable PCT images with low-dose data acquisition. Specifically, in the present CDL scheme, the 2D background information from the average of the baseline time frames of low-dose unenhanced CT images and the 3D enhancement information from normal-dose sequential cerebral PCT images are exploited to train the dictionary atoms respectively. After getting the two trained dictionaries, we couple them to represent the desired PCT images as spatio-temporal prior in objective function construction. Finally, the low-dose dynamic cerebral PCT images are restored by using a general DL image processing. To get a robust solution, the objective function is solved by using a modified dictionary learning based image restoration algorithm. The experimental results on clinical data show that the present method can yield more accurate kinetic enhanced details and diagnostic hemodynamic parameter maps than the state-of-the-art methods.

EXPERIMENTAL EVALUATION OF DOSIMETRIC CHARACTERIZATION OF GAFCHROMIC EBT3 AND EBT-XD FILMS FOR CLINICAL CARBON ION BEAMS.

PubMed

Yonai, Shunsuke; Arai, Chinatsu; Shimoyama, Kaoru; Fournier-Bidoz, Nathalie

2018-02-03

Radiochromic film is a very useful tool for 2D dosimetric measurements in radiotherapy because it is self-developing and has very high-spatial resolution. However, considerable care has to be taken in ion beam radiotherapy owing to the quenching effect of high-linear energy transfer (LET) radiation. In this study, the dose responses of GAFchromic EBT3 and EBT-XD films were experimentally investigated using the clinical carbon ion beam at the Heavy Ion Medical Accelerator in Chiba. Results showed that the relations between absorbed dose and net optical density could be expressed well using an equation proposed by Reinhardt (2015). The quenching effect was evaluated by determining their relative efficiencies for photon irradiation as a function of LET. A correction equation derived in this study allowed the absorbed dose to be determined in the small irradiation field used for carbon ion radiotherapy eye treatments. This study contributes to establishing an absolute dosimetry procedure for heavy ion beams using radiochromic film. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Real-time dose calculation and visualization for the proton therapy of ocular tumours

NASA Astrophysics Data System (ADS)

Pfeiffer, Karsten; Bendl, Rolf

2001-03-01

A new real-time dose calculation and visualization was developed as part of the new 3D treatment planning tool OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner Institut Berlin. The implementation resolves the common separation between parameter definition, dose calculation and evaluation and allows a direct examination of the expected dose distribution while adjusting the treatment parameters. The new tool allows the therapist to move the desired dose distribution under visual control in 3D to the appropriate place. The visualization of the resulting dose distribution as a 3D surface model, on any 2D slice or on the surface of specified ocular structures is done automatically when adapting parameters during the planning process. In addition, approximate dose volume histograms may be calculated with little extra time. The dose distribution is calculated and visualized in 200 ms with an accuracy of 6% for the 3D isodose surfaces and 8% for other objects. This paper discusses the advantages and limitations of this new approach.

Online 3D EPID-based dose verification: Proof of concept.

PubMed

Spreeuw, Hanno; Rozendaal, Roel; Olaciregui-Ruiz, Igor; González, Patrick; Mans, Anton; Mijnheer, Ben; van Herk, Marcel

2016-07-01

Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5-10 s irradiation time. A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.

Four-dimensional dose evaluation using deformable image registration in radiotherapy for liver cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoon Jung, Sang; Min Yoon, Sang; Ho Park, Sung

2013-01-15

Purpose: In order to evaluate the dosimetric impact of respiratory motion on the dose delivered to the target volume and critical organs during free-breathing radiotherapy, a four-dimensional dose was evaluated using deformable image registration (DIR). Methods: Four-dimensional computed tomography (4DCT) images were acquired for 11 patients who were treated for liver cancer. Internal target volume-based treatment planning and dose calculation (3D dose) were performed using the end-exhalation phase images. The four-dimensional dose (4D dose) was calculated based on DIR of all phase images from 4DCT to the planned image. Dosimetric parameters from the 4D dose, were calculated and compared withmore » those from the 3D dose. Results: There was no significant change of the dosimetric parameters for gross tumor volume (p > 0.05). The increase D{sub mean} and generalized equivalent uniform dose (gEUD) for liver were by 3.1%{+-} 3.3% (p= 0.003) and 2.8%{+-} 3.3% (p= 0.008), respectively, and for duodenum, they were decreased by 15.7%{+-} 11.2% (p= 0.003) and 15.1%{+-} 11.0% (p= 0.003), respectively. The D{sub max} and gEUD for stomach was decreased by 5.3%{+-} 5.8% (p= 0.003) and 9.7%{+-} 8.7% (p= 0.003), respectively. The D{sub max} and gEUD for right kidney was decreased by 11.2%{+-} 16.2% (p= 0.003) and 14.9%{+-} 16.8% (p= 0.005), respectively. For left kidney, D{sub max} and gEUD were decreased by 11.4%{+-} 11.0% (p= 0.003) and 12.8%{+-} 12.1% (p= 0.005), respectively. The NTCP values for duodenum and stomach were decreased by 8.4%{+-} 5.8% (p= 0.003) and 17.2%{+-} 13.7% (p= 0.003), respectively. Conclusions: The four-dimensional dose with a more realistic dose calculation accounting for respiratory motion revealed no significant difference in target coverage and potentially significant change in the physical and biological dosimetric parameters in normal organs during free-breathing treatment.« less

Review of Real-Time 3-Dimensional Image Guided Radiation Therapy on Standard-Equipped Cancer Radiation Therapy Systems: Are We at the Tipping Point for the Era of Real-Time Radiation Therapy?

PubMed

Keall, Paul J; Nguyen, Doan Trang; O'Brien, Ricky; Zhang, Pengpeng; Happersett, Laura; Bertholet, Jenny; Poulsen, Per R

2018-04-14

To review real-time 3-dimensional (3D) image guided radiation therapy (IGRT) on standard-equipped cancer radiation therapy systems, focusing on clinically implemented solutions. Three groups in 3 continents have clinically implemented novel real-time 3D IGRT solutions on standard-equipped linear accelerators. These technologies encompass kilovoltage, combined megavoltage-kilovoltage, and combined kilovoltage-optical imaging. The cancer sites treated span pelvic and abdominal tumors for which respiratory motion is present. For each method the 3D-measured motion during treatment is reported. After treatment, dose reconstruction was used to assess the treatment quality in the presence of motion with and without real-time 3D IGRT. The geometric accuracy was quantified through phantom experiments. A literature search was conducted to identify additional real-time 3D IGRT methods that could be clinically implemented in the near future. The real-time 3D IGRT methods were successfully clinically implemented and have been used to treat more than 200 patients. Systematic target position shifts were observed using all 3 methods. Dose reconstruction demonstrated that the delivered dose is closer to the planned dose with real-time 3D IGRT than without real-time 3D IGRT. In addition, compromised target dose coverage and variable normal tissue doses were found without real-time 3D IGRT. The geometric accuracy results with real-time 3D IGRT had a mean error of <0.5 mm and a standard deviation of <1.1 mm. Numerous additional articles exist that describe real-time 3D IGRT methods using standard-equipped radiation therapy systems that could also be clinically implemented. Multiple clinical implementations of real-time 3D IGRT on standard-equipped cancer radiation therapy systems have been demonstrated. Many more approaches that could be implemented were identified. These solutions provide a pathway for the broader adoption of methods to make radiation therapy more accurate, impacting tumor and normal tissue dose, margins, and ultimately patient outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

SlicerRT: radiation therapy research toolkit for 3D Slicer.

PubMed

Pinter, Csaba; Lasso, Andras; Wang, An; Jaffray, David; Fichtinger, Gabor

2012-10-01

Interest in adaptive radiation therapy research is constantly growing, but software tools available for researchers are mostly either expensive, closed proprietary applications, or free open-source packages with limited scope, extensibility, reliability, or user support. To address these limitations, we propose SlicerRT, a customizable, free, and open-source radiation therapy research toolkit. SlicerRT aspires to be an open-source toolkit for RT research, providing fast computations, convenient workflows for researchers, and a general image-guided therapy infrastructure to assist clinical translation of experimental therapeutic approaches. It is a medium into which RT researchers can integrate their methods and algorithms, and conduct comparative testing. SlicerRT was implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. SlicerRT provides functionality specifically designed for radiation therapy research, in addition to the powerful tools that 3D Slicer offers for visualization, registration, segmentation, and data management. The feature set of SlicerRT was defined through consensus discussions with a large pool of RT researchers, including both radiation oncologists and medical physicists. The development processes used were similar to those of 3D Slicer to ensure software quality. Standardized mechanisms of 3D Slicer were applied for documentation, distribution, and user support. The testing and validation environment was configured to automatically launch a regression test upon each software change and to perform comparison with ground truth results provided by other RT applications. Modules have been created for importing and loading DICOM-RT data, computing and displaying dose volume histograms, creating accumulated dose volumes, comparing dose volumes, and visualizing isodose lines and surfaces. The effectiveness of using 3D Slicer with the proposed SlicerRT extension for radiation therapy research was demonstrated on multiple use cases. A new open-source software toolkit has been developed for radiation therapy research. SlicerRT can import treatment plans from various sources into 3D Slicer for visualization, analysis, comparison, and processing. The provided algorithms are extensively tested and they are accessible through a convenient graphical user interface as well as a flexible application programming interface.

WE-D-BRA-03: Four-Dimensional Dose Reconstruction Through Retrospective Phase Determination Using Cine Images of Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, J; Jung, J; Yi, B

2015-06-15

Purpose: To test a method to reconstruct a four-dimensional (4D) dose distribution using the correlation of pre-calculated 4D electronic portal imaging device (EPID) images and measured cine-EPID images. Methods: 1. A phantom designed to simulate a tumor in lung (a polystyrene block with 3.0 cm diameter embedded in cork) was placed on a sinusoidally moving platform with 2 cm amplitude and 4 sec/cycle. Ten-phase 4D CT images were acquired for treatment planning and dose reconstruction. A 6MV photon beam was irradiated on the phantom with static (field size=5×8.5 cm{sup 2}) and dynamic fields (sliding windows, 10×10 cm{sup 2}, X1 MLCmore » closing in parallel with the tumor movement). 2. 4D and 3D doses were calculated forwardly on PTV (1 cm margin). 3. Dose images on EPID under the fields were calculated for 10 phases. 4. Cine EPID images were acquired during irradiation. 5. Their acquisition times were correlated to the phases of the phantom at which irradiation occurred by inter-comparing calculated “reference” EPID images with measured images (2D gamma comparison). For the dynamic beam, the tumor was hidden under MLCs during a portion of irradiation time; the correlation performed when the tumor was visible was extrapolated. 6. Dose for each phase was reconstructed on the 4D CT images and summed over all phases. The summation was compared with forwardly calculated 4D and 3D dose distributions. Monte Carlo methods were used for all calculations. Results: For the open and dynamic beams, the 4D reconstructed doses showed the pass rates of 92.7 % and 100 %, respectively, at the isocenter plane given 3% / 3 mm criteria. The better agreement of the dynamic beam was from its dose gradient which blurred the otherwise sharp difference between forward and reconstructed doses. This also contributed slightly better agreement in DVH of PTV. Conclusion: The feasibility of 4D reconstruction was demonstrated.« less

A Randomized Trial of Vitamin D3 Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

PubMed Central

Laing, E. M.; Hill Gallant, K. M.; Hall, D. B.; McCabe, G. P.; Hausman, D. B.; Martin, B. R.; Warden, S. J.; Peacock, M.; Weaver, C. M.

2013-01-01

Context: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. Objective: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Design: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. Results: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Conclusion: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children. PMID:24092833

Design and optimization of a novel 3D detector: The 3D-open-shell-electrode detector

NASA Astrophysics Data System (ADS)

Liu, Manwen; Tan, Jian; Li, Zheng

2018-04-01

A new type of three-dimensional (3D) detector, namely 3D-Open-Shell-Electrode Detector (3DOSED), is proposed in this study. In a 3DOSED, the trench electrode can be etched all the way through the detector thickness, totally eliminating the low electric field region existed in the conventional 3D-Trench-Electrode detector. Full 3D technology computer-aided design (TCAD) simulations have been done on this novel silicon detector structure. Through comparing of the simulation results of the detector, we can obtain the best design of the 3SOSED. In addition, simulation results show that, as compared to the conventional 3D detector, the proposed 3DOSED can improve not only detector charge collection efficiency but also its radiation hardness with regard to solving the trapping problem in the detector bulk. What is more, it has been shown that detector full depletion voltage is also slightly reduced, which can improve the utility aspects of the detector. When compared to the conventional 3D detector, we find that the proposed novel 3DOSED structure has better electric potential and electric field distributions, and better electrical properties such as detector full depletion voltage. In 3DOSED array, each pixel cell is isolated from each other by highly doped trenches, but also electrically and physically connected with each other through the remaining silicon bulk between broken electrodes.

Alpha particle and proton relative thermoluminescence efficiencies in LiF:Mg,Cu,P:is track structure theory up to the task?

PubMed

Horowitz, Y S; Siboni, D; Oster, L; Livingstone, J; Guatelli, S; Rosenfeld, A; Emfietzoglou, D; Bilski, P; Obryk, B

2012-07-01

Low-energy alpha particle and proton heavy charged particle (HCP) relative thermoluminescence (TL) efficiencies are calculated for the major dosimetric glow peak in LiF:Mg,Cu,P (MCP-N) in the framework of track structure theory (TST). The calculations employ previously published TRIPOS-E Monte Carlo track segment values of the radial dose in condensed phase LiF calculated at the Instituto National de Investigaciones Nucleares (Mexico) and experimentally measured normalised (60)Co gamma-induced TL dose-response functions, f(D), carried out at the Institute of Nuclear Physics (Poland). The motivation for the calculations is to test the validity of TST in a TL system in which f(D) is not supralinear (f(D) >1) and is not significantly dependent on photon energy contrary to the behaviour of the dose-response of composite peak 5 in the glow curve of LiF:Mg,Ti (TLD-100). The calculated HCP relative efficiencies in LiF:MCP-N are 23-87% lower than the experimentally measured values, indicating a weakness in the major premise of TST which exclusively relates HCP effects to the radiation action of the secondary electrons liberated by the HCP slowing down. However, an analysis of the uncertainties involved in the TST calculations and experiments (i.e. experimental measurement of f(D) at high levels of dose, sample light self-absorption and accuracy in the estimation of D(r), especially towards the end of the HCP track) indicate that these may be too large to enable a definite conclusion. More accurate estimation of sample light self-absorption, improved measurements of f(D) and full-track Monte Carlo calculations of D(r) incorporating improvements of the low-energy electron transport are indicated in order to reduce uncertainties and enable a final conclusion.

Calculation of Dose Deposition in 3D Voxels by Heavy Ions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.

2010-01-01

The biological response to high-LET radiation is very different from low-LET radiation, and can be partly attributed to the energy deposition by the radiation. Several experiments, notably detection of gamma-H2AX foci by immunofluorescence, has revealed important differences in the nature and in the spatial distribution of double-strand breaks (DSB) induced by low- and high-LET radiations. Many calculations, most of which are based on amorphous track models with radial dose, have been combined with chromosome models to calculate the number and distribution of DSB within nuclei and chromosome aberrations. In this work, the Monte-Carlo track structure simulation code RITRACKS have been used to calculate directly the energy deposition in voxels (3D pixels). A cubic volume of 5 micrometers of side was irradiated by 1) 450 (1)H+ ions of 300 MeV (LET is approximately 0.3 keV/micrometer) and 2) by 1 (56)Fe26+ ion of 1 GeV/amu (LET is approximately 150 keV/micrometer). In both cases, the dose deposited in the volume is approximately 1 Gy. All energy deposition events are recorded and dose is calculated in voxels of 20 micrometers of side. The voxels are then visualized in 3D by using a color scale to represent the intensity of the dose in a voxel. This simple approach has revealed several important points which may help understand experimental observations. In both simulations, voxels which receive low dose are the most numerous, and those corresponding to electron track ends received a dose which is in the higher range. The dose voxels are distributed randomly and scattered uniformly within the volume irradiated by low-LET radiation. The distribution of the voxels shows major differences for the (56)Fe26+ ion. The track structure can still be seen, and voxels with much higher dose are found in the region corresponding to the track "core". These high-dose voxels are not found in the low-LET irradiation simulation and may be responsible for DSB that are more difficult to repair. By applying a threshold on the dose visualization, voxels corresponding to electron track ends are evidenced and the spatial distribution of voxels is very similar to the distribution of DSB observed in gamma H2AX experiments, even if no chromosomes have been included in the simulation. Furthermore, this work has shown that a significant dose is deposited in voxels corresponding to electron track ends. Since some delta-rays from iron ion can travel several millimeters, they may also be of radiobiological importance.

SU-F-J-146: Experimental Validation of 6 MV Photon PDD in Parallel Magnetic Field Calculated by EGSnrc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghila, A; Steciw, S; Fallone, B

Purpose: Integrated linac-MR systems are uniquely suited for real time tumor tracking during radiation treatment. Understanding the magnetic field dose effects and incorporating them in treatment planning is paramount for linac-MR clinical implementation. We experimentally validated the EGSnrc dose calculations in the presence of a magnetic field parallel to the radiation beam travel. Methods: Two cylindrical bore electromagnets produced a 0.21 T magnetic field parallel to the central axis of a 6 MV photon beam. A parallel plate ion chamber was used to measure the PDD in a polystyrene phantom, placed inside the bore in two setups: phantom top surfacemore » coinciding with the magnet bore center (183 cm SSD), and with the magnet bore’s top surface (170 cm SSD). We measured the field of the magnet at several points and included the exact dimensions of the coils to generate a 3D magnetic field map in a finite element model. BEAMnrc and DOSXYZnrc simulated the PDD experiments in parallel magnetic field (i.e. 3D magnetic field included) and with no magnetic field. Results: With the phantom surface at the top of the electromagnet, the surface dose increased by 10% (compared to no-magnetic field), due to electrons being focused by the smaller fringe fields of the electromagnet. With the phantom surface at the bore center, the surface dose increased by 30% since extra 13 cm of air column was in relatively higher magnetic field (>0.13T) in the magnet bore. EGSnrc Monte Carlo code correctly calculated the radiation dose with and without the magnetic field, and all points passed the 2%, 2 mm Gamma criterion when the ion chamber’s entrance window and air cavity were included in the simulated phantom. Conclusion: A parallel magnetic field increases the surface and buildup dose during irradiation. The EGSnrc package can model these magnetic field dose effects accurately. Dr. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).« less

Fully 3D refraction correction dosimetry system.

PubMed

Manjappa, Rakesh; Makki, S Sharath; Kumar, Rajesh; Vasu, Ram Mohan; Kanhirodan, Rajan

2016-02-21

The irradiation of selective regions in a polymer gel dosimeter results in an increase in optical density and refractive index (RI) at those regions. An optical tomography-based dosimeter depends on rayline path through the dosimeter to estimate and reconstruct the dose distribution. The refraction of light passing through a dose region results in artefacts in the reconstructed images. These refraction errors are dependant on the scanning geometry and collection optics. We developed a fully 3D image reconstruction algorithm, algebraic reconstruction technique-refraction correction (ART-rc) that corrects for the refractive index mismatches present in a gel dosimeter scanner not only at the boundary, but also for any rayline refraction due to multiple dose regions inside the dosimeter. In this study, simulation and experimental studies have been carried out to reconstruct a 3D dose volume using 2D CCD measurements taken for various views. The study also focuses on the effectiveness of using different refractive-index matching media surrounding the gel dosimeter. Since the optical density is assumed to be low for a dosimeter, the filtered backprojection is routinely used for reconstruction. We carry out the reconstructions using conventional algebraic reconstruction (ART) and refractive index corrected ART (ART-rc) algorithms. The reconstructions based on FDK algorithm for cone-beam tomography has also been carried out for comparison. Line scanners and point detectors, are used to obtain reconstructions plane by plane. The rays passing through dose region with a RI mismatch does not reach the detector in the same plane depending on the angle of incidence and RI. In the fully 3D scanning setup using 2D array detectors, light rays that undergo refraction are still collected and hence can still be accounted for in the reconstruction algorithm. It is found that, for the central region of the dosimeter, the usable radius using ART-rc algorithm with water as RI matched medium is 71.8%, an increase of 6.4% compared to that achieved using conventional ART algorithm. Smaller diameter dosimeters are scanned with dry air scanning by using a wide-angle lens that collects refracted light. The images reconstructed using cone beam geometry is seen to deteriorate in some planes as those regions are not scanned. Refraction correction is important and needs to be taken in to consideration to achieve quantitatively accurate dose reconstructions. Refraction modeling is crucial in array based scanners as it is not possible to identify refracted rays in the sinogram space.

Dosimetric verification for intensity-modulated arc therapy plans by use of 2D diode array, radiochromic film and radiosensitive polymer gel.

PubMed

Hayashi, Naoki; Malmin, Ryan L; Watanabe, Yoichi

2014-05-01

Several tools are used for the dosimetric verification of intensity-modulated arc therapy (IMAT) treatment delivery. However, limited information is available for composite on-line evaluation of these tools. The purpose of this study was to evaluate the dosimetric verification of IMAT treatment plans using a 2D diode array detector (2D array), radiochromic film (RCF) and radiosensitive polymer gel dosimeter (RPGD). The specific verification plans were created for IMAT for two prostate cancer patients by use of the clinical treatment plans. Accordingly, the IMAT deliveries were performed with the 2D array on a gantry-mounting device, RCF in a cylindrical acrylic phantom, and the RPGD in two cylindrical phantoms. After the irradiation, the planar dose distributions from the 2D array and the RCFs, and the 3D dose distributions from the RPGD measurements were compared with the calculated dose distributions using the gamma analysis method (3% dose difference and 3-mm distance-to-agreement criterion), dose-dependent dose difference diagrams, dose difference histograms, and isodose distributions. The gamma passing rates of 2D array, RCFs and RPGD for one patient were 99.5%, 96.5% and 93.7%, respectively; the corresponding values for the second patient were 97.5%, 92.6% and 92.9%. Mean percentage differences between the RPGD measured and calculated doses in 3D volumes containing PTVs were -0.29 ± 7.1% and 0.97 ± 7.6% for the two patients, respectively. In conclusion, IMAT prostate plans can be delivered with high accuracy, although the 3D measurements indicated less satisfactory agreement with the treatment plans, mainly due to the dosimetric inaccuracy in low-dose regions of the RPGD measurements.

Estimate of the risk of radiation-induced cancers after linear-accelerator-based breast-cancer radiotherapy

NASA Astrophysics Data System (ADS)

Koh, Eui Kwan; Seo, Jungju; Baek, Tae Seong; Chung, Eun Ji; Yoon, Myonggeun; Lee, Hyun-ho

2013-07-01

The aim of this study is to assess and compare the excess absolute risks (EARs) of radiation-induced cancers following conformal (3D-CRT), fixed-field intensity-modulated (IMRT) and volumetric modulated arc (RapidArc) radiation therapy in patients with breast cancer. 3D-CRT, IMRT and RapidArc were planned for 10 breast cancer patients. The organ-specific EAR for cancer induction was estimated using the organ equivalent dose (OED) based on computed dose volume histograms (DVHs) and the secondary doses measured at various points from the field edge. The average secondary dose per Gy treatment dose from 3D-CRT, measured 10 to 50 cm from the field edge, ranged from 8.27 to 1.04 mGy. The secondary doses per Gy from IMRT and RapidArc, however, ranged between 5.86 and 0.54 mGy, indicating that IMRT and RapidArc are associated with smaller doses of secondary radiation than 3D-CRT. The organ specific EARs for out-of-field organs, such as the thyroid, liver and colon, were higher with 3D-CRT than with IMRT or RapidArc. In contrast, EARs for in-field organs were much lower with 3D-CRT than with IMRT or RapidArc. The overall estimate of EAR indicated that the radiation-induced cancer risk was 1.8-2.0 times lower with 3D-CRT than with IMRT or RapidArc. Comparisons of EARs during breast irradiation suggested that the predicted risk of secondary cancers was lower with 3D-CRT than with IMRT or RapidArc.

Effect of dietary supplementation on resistance to experimental infection with Haemonchus contortus in Creole kids.

PubMed

Bambou, J C; Archimède, H; Arquet, R; Mahieu, M; Alexandre, G; González-Garcia, E; Mandonnet, N

2011-06-10

The aim of the present study was to test the effect of dietary supplementation on resistance to experimental infection with Haemonchus contortus in Creole kids. One trial with three replicates involved a total of 154 female kids that were chosen from three successive cohorts of the Creole flock of INRA-Gardel in 2007. The kids were placed into four treatments according to the amount of concentrate they received: G0 (no concentrate and a quality Dichantium spp. hay ad libitum, HAY), G1 (HAY+100g commercial concentrate d(-1)), G2 (HAY+200 g commercial concentrate d(-1)), G3 (HAY+300 g commercial concentrate d(-1)). The G0-G3 groups were infected with a single dose of 10,000 H. contortus third stage larvae (L(3)) at Day 0 (D0). Each infected group was comprised of one half resistant and one half susceptible genetically indexed kids. The average breeding values on egg excretion at 11 months of age were distant of 0.70, 0.65, 0.61 and 0.61 genetic standard deviations in G0, G1, G2 and G3, respectively. The faecal egg count (FEC), packed cell volume (PCV), eosinophilia (EOSI) and dry matter intake (DMI) indices were monitored weekly until 42 days post-infection. Enzyme-linked immunosorbent assay was carried out on serum samples to determine the level of IgA anti-H. contortus L(3) crude extracts and adult excretion/secretion products (ESP). The 10,000 L(3) dose received by the kids induced a severe infection: 8000 eggs per gram at the FEC peak, a PCV less than 15% and mortality. Interestingly, the supplemented animals in G3 showed a higher level of EOSI but a lower level of IgA anti-L3 and IgA anti-ESP than non-supplemented animals (G0). Resistant and susceptible kids had significantly different FEC variations within the groups. Susceptible kids had a 1.6 times higher egg output than resistant kids in G0. This difference was not found in the supplemented groups. The results of this study showed that supplementary feeding improved resistance of Creole kids to H. contortus experimental infection. Copyright © 2011 Elsevier B.V. All rights reserved.

Prophylactic versus Therapeutic Fingolimod: Restoration of Presynaptic Defects in Mice Suffering from Experimental Autoimmune Encephalomyelitis

PubMed Central

Merega, Elisa; Di Prisco, Silvia; Padolecchia, Cristina; Grilli, Massimo; Milanese, Marco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Bonanno, Giambattista; Marchi, Mario

2017-01-01

Fingolimod, the first oral, disease-modifying therapy for MS, has been recently proposed to modulate glutamate transmission in the central nervous system (CNS) of mice suffering from Experimental Autoimmune Encephalomyelitis (EAE) and in MS patients. Our study aims at investigating whether oral fingolimod recovers presynaptic defects that occur at different stages of disease in the CNS of EAE mice. In vivo prophylactic (0.3 mg/kg for 14 days, from the 7th day post immunization, d.p.i, the drug dissolved in the drinking water) fingolimod significantly reduced the clinical symptoms and the anxiety-related behaviour in EAE mice. Spinal cord inflammation, demyelination and glial cell activation are markers of EAE progression. These signs were ameliorated following oral fingolimod administration. Glutamate exocytosis was shown to be impaired in cortical and spinal cord terminals isolated from EAE mice at 21 ± 1 d.p.i., while GABA alteration emerged only at the spinal cord level. Prophylactic fingolimod recovered these presynaptic defects, restoring altered glutamate and GABA release efficiency. The beneficial effect occurred in a dose-dependent, region-specific manner, since lower (0.1–0.03 mg/kg) doses restored, although to a different extent, synaptic defects in cortical but not spinal cord terminals. A delayed reduction of glutamate, but not of GABA, exocytosis was observed in hippocampal terminals of EAE mice at 35 d.p.i. Therapeutic (0.3 mg/kg, from 21 d.p.i. for 14 days) fingolimod restored glutamate exocytosis in the cortex and in the hippocampus of EAE mice at 35 ± 1 d.p.i. but not in the spinal cord, where also GABAergic defects remained unmodified. These results improve our knowledge of the molecular events accounting for the beneficial effects elicited by fingolimod in demyelinating disorders. PMID:28125677

The immunomodulatory effect of vitamin D in chickens is dose-dependent and influenced by calcium and phosphorus levels.

PubMed

Rodriguez-Lecompte, J C; Yitbarek, A; Cuperus, T; Echeverry, H; van Dijk, A

2016-11-01

Vitamin D requirement is estimated to be higher than recommended values for the first two weeks of a broiler chicken's life, and is heavily dependent on the concentrations of Ca and P in the diet. There are data indicating the beneficial effect of higher vitamin D levels on performance and overall health of the chickens. However, data on the role of higher vitamin D levels on the innate immune response of chickens are limited. Therefore, in the current study, we examined the effect of higher doses of vitamin D supplementation on the innate immune response in broiler chickens receiving optimal or calcium (Ca) and phosphorus (P) deficient diets. Three hundred Ross-308 male broiler chicks were randomly allocated into 60 cages with 5 birds per cage in a 3 × 2 factorial design with three levels of vitamin D and two levels of Ca/P with each experimental diet fed to 10 cages (10 replicates). Quantitative reverse transcription PCR (n = 5) was used to assess Toll-like receptor (TLR2b and 4), cytokine/chemokine (IL-12, IFN-γ, IL-10, IL-4, IL-13, IL-18, CxCLi2) and cathelicidin (CATH1, CATHB1, CATH3) transcription levels in peripheral blood mononuclear cells (PBMCs), spleen, and bursa of Fabricius. Vitamin D supplementation of the Ca and P deficient diet considerably augmented transcription of TLR2b, TLR4, CATH1, and CATHB1 and predominantly Th2 cytokines in spleen. Supplementation of the control diet with vitamin D downregulated TLR4 transcription, and dose-dependently increased CATH1, CATHB1, Th1, and Th2 cytokine transcription (Th2>Th1). All diets downregulated CATH3 transcription. In conclusion, vitamin D or its derivative 25-OH-D 3 both have a robust immunomodulatory property with a more favorable Th2 response, while at the same time enhancing observed Th2 cytokine responses under both optimal and lower Ca and P inclusion levels in the diets of broiler chickens. © 2016 Poultry Science Association Inc.

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments

PubMed Central

2016-01-01

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5–30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ±2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ±15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ±3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI. PACS numbers: 87.55.km, 87.56.Fc PMID:26894347

SU-F-T-364: Monte Carlo-Dose Verification of Volumetric Modulated Arc Therapy Plans Using AAPM TG-119 Test Patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onizuka, R; Araki, F; Ohno, T

2016-06-15

Purpose: To investigate the Monte Carlo (MC)-based dose verification for VMAT plans by a treatment planning system (TPS). Methods: The AAPM TG-119 test structure set was used for VMAT plans by the Pinnacle3 (convolution/superposition), using a Synergy radiation head of a 6 MV beam with the Agility MLC. The Synergy was simulated with the EGSnrc/BEAMnrc code, and VMAT dose distributions were calculated with the EGSnrc/DOSXYZnrc code by the same irradiation conditions as TPS. VMAT dose distributions of TPS and MC were compared with those of EBT3 film, by 2-D gamma analysis of ±3%/3 mm criteria with a threshold of 30%more » of prescribed doses. VMAT dose distributions between TPS and MC were also compared by DVHs and 3-D gamma analysis of ±3%/3 mm criteria with a threshold of 10%, and 3-D passing rates for PTVs and OARs were analyzed. Results: TPS dose distributions differed from those of film, especially for Head & neck. The dose difference between TPS and film results from calculation accuracy for complex motion of MLCs like tongue and groove effect. In contrast, MC dose distributions were in good agreement with those of film. This is because MC can model fully the MLC configuration and accurately reproduce the MLC motion between control points in VMAT plans. D95 of PTV for Prostate, Head & neck, C-shaped, and Multi Target was 97.2%, 98.1%, 101.6%, and 99.7% for TPS and 95.7%, 96.0%, 100.6%, and 99.1% for MC, respectively. Similarly, 3-D gamma passing rates of each PTV for TPS vs. MC were 100%, 89.5%, 99.7%, and 100%, respectively. 3-D passing rates of TPS reduced for complex VMAT fields like Head & neck because MLCs are not modeled completely for TPS. Conclusion: MC-calculated VMAT dose distributions is useful for the 3-D dose verification of VMAT plans by TPS.« less

Dosimetric aspects of breast radiotherapy with three-dimensional and intensity-modulated radiotherapy helical tomotherapy planning modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam; Service of Radiation Therapy, University of Wisconsin Aspirus Cancer Center, Wisconsin Rapids, WI; Yan, Yue, E-mail: yyan5@mdanderson.org

In this work, we investigated the dosimetric differences between the intensity-modulated radiotherapy (IMRT) plans and the three-dimensional (3D) helical plans based on the TomoTherapy system. A total of 15 patients with supine setup were randomly selected from the data base. For patients with lumpectomy planning target volume (PTV), regional lymph nodes were also included as part of the target. For dose sparing, the significant differences between the helical IMRT and helical 3D were only found in the heart and contralateral breast. For the dose to the heart, helical IMRT reduced the maximum point dose by 6.98 Gy compared to themore » helical 3D plan (p = 0.01). For contralateral breast, the helical IMRT plans significantly reduced the maximum point dose by 5.6 Gy compared to the helical 3D plan. However, compared to the helical 3D plan, the helical IMRT plan increased the volume for lower dose (13.08% increase in V{sub 5} {sub Gy}, p = 0.01). In general, there are no significant differences in dose sparing between helical IMRT and helical 3D plans.« less

An NGF mimetic, MIM-D3, stimulates conjunctival cell glycoconjugate secretion and demonstrates therapeutic efficacy in a rat model of dry eye.

PubMed

Jain, Pooja; Li, Ruihong; Lama, Teresa; Saragovi, H Uri; Cumberlidge, Garth; Meerovitch, Karen

2011-10-01

The aim of this study was to evaluate the efficacy of MIM-D3, a small molecule nerve growth factor (NGF) peptidomimetic, as a therapeutic agent in rats with scopolamine induced dry eye. NGF plays an important role in ocular surface maintenance and corneal wound healing and was recently shown to have mucin secretagogue activity in conjunctival cells. We investigated whether MIM-D3 increased glycoconjugate secretion in conjunctival cells in vitro and in rat tear fluids in vivo. Primary rat conjunctival cell cultures were treated with increasing concentrations of MIM-D3 and evaluated for glycoconjugate secretion, proliferation and MAPK1/2 activation. Glycoconjugates were quantitated in tear fluids from normal rats treated topically with increasing doses of MIM-D3 (0.4%, 1% and 2.5%). Dry eye was induced in rats by subcutaneous scopolamine treatment, administered by surgically implanted osmotic pumps for 14 or 28 days. Aqueous tear production, tear clearance, fluorescein corneal staining and tear break-up time (tBUT) were evaluated. Glycoconjugates and NGF were quantitated in the tear fluids by enzyme-linked lectin assay (ELLA) and enzyme-linked immunosorbant assay (ELISA), respectively. We found that 50 μM MIM-D3 statistically significantly induced a 1.3-fold increase in glycoconjugate secretion and a 2.3-fold increase in MAPK1/2 activation without increasing proliferation from conjunctival cell cultures. Application of 2.5% MIM-D3 in normal rat eyes statistically significantly increased tear glycoconjugate concentration by 2.3-fold. In the experimental dry eye model, application of 1% MIM-D3 to rat eyes for either 1 or 17 consecutive days, followed by 1 week of no dosing produced a statistically significant decrease in corneal staining (p < 0.001), a slight increase in tBUT, and increases in tear glycoconjugates (p < 0.05) compared to vehicle. Scopolamine treatment also caused a statistically significant increase of endogenous NGF in tears (p < 0.005). We concluded that the increase in glycoconjugate concentration by the 1% MIM-D3 dose may have improved the quality and stability of the tear film, and thereby improved healing on the ocular surface in dry eye. Therefore, MIM-D3 may have therapeutic potential as a topical agent for the treatment of dry eye. Copyright © 2011 Elsevier Ltd. All rights reserved.

Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab 2013;98(4):1498-507 [Epub 2013 Mar 5].

PubMed

Olumi, Aria F

2014-02-01

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. Vitamin D3 (400, 10000, or 40000 IU/d) was orally administered before radical prostatectomy. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P<.03) and were significantly higher in the 40000-IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites correlated positively with serum levels (P<.0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P<.05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P< .02). Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PubMed

Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

2013-04-01

The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

WE-F-16A-05: Use of 3D-Printers to Create a Tissue Equivalent 3D-Bolus for External Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burleson, S; Baker, J; Hsia, A

2014-06-15

Purpose: The purpose of this project is to demonstrate that a non-expensive 3D-printer can be used to manufacture a 3D-bolus for external beam therapy. The printed bolus then can be modeled in our treatment planning system to ensure accurate dose delivery to the patient. Methods: We developed a simple method to manufacture a patient-specific custom 3Dbolus. The bolus is designed using Eclipse Treatment Planning System, contoured onto the patients CT images. The bolus file is exported from Eclipse to 3D-printer software, and then printed using a 3D printer. Various tests were completed to determine the properties of the printing material.more » Percent depth dose curves in this material were measured with electron and photon beams for comparison to other materials. In order to test the validity of the 3D printed bolus for treatment planning, a custom bolus was printed and tested on the Rando phantom using film for a dose plane comparison. We compared the dose plane measured on the film to the same dose plane exported from our treatment planning system using Film QA software. The gamma-dose distribution tool was used in our film analysis. Results: We compared point measurements throughout the dose plane and were able to achieve greater than 95% passing rate at 3% dose difference and 3 mm distance to agreement, which is our departments acceptable gamma pixel parameters. Conclusion: The printed 3D bolus has proven to be accurately modeled in our treatment planning system, it is more conformal to the patient surface and more durable than other bolus currently used (wax, superflab etc.). It is also more convenient and less costly than comparable bolus from milling machine companies.« less

SU-G-BRA-12: Development of An Intra-Fractional Motion Tracking and Dose Reconstruction System for Adaptive Stereotactic Body Radiation Therapy in High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rezaeian, N Hassan; Chi, Y; Tian, Z

Purpose: A clinical trial on stereotactic body radiation therapy (SBRT) for high-risk prostate cancer is undergoing at our institution. In addition to escalating dose to the prostate, we have increased dose to intra-prostatic lesions. Intra-fractional prostate motion deteriorates well planned radiation dose, especially for the small intra-prostatic lesions. To solve this problem, we have developed a motion tracking and 4D dose-reconstruction system to facilitate adaptive re-planning. Methods: Patients in the clinical trial were treated with VMAT using four arcs and 10 FFF beam. KV triggered x-ray projections were taken every 3 sec during delivery to acquire 2D projections of 3Dmore » anatomy at the direction orthogonal to the therapeutic beam. Each patient had three implanted prostate markers. Our developed system first determined 2D projection locations of these markers and then 3D prostate translation and rotation via 2D/3D registration of the markers. Using delivery log files, our GPU-based Monte Carlo tool (goMC) reconstructed dose corresponding to each triggered image. The calculated 4D dose distributions were further aggregated to yield the delivered dose. Results: We first tested each module in our system. MC dose engine were commissioned to our treatment planning system with dose difference of <0.5%. For motion tracking, 1789 kV projections from 7 patients were acquired. The 2D marker location error was <1 mm. For 3D motion tracking, root mean square (RMS) errors along LR, AP, and CC directions were 0.26mm, 0.36mm, and 0.01mm respectively in simulation studies and 1.99mm, 1.37mm, and 0.22mm in phantom studies. We also tested the entire system workflow. Our system was able to reconstruct delivered dose. Conclusion: We have developed a functional intra-fractional motion tracking and 4D dose re-construction system to support our clinical trial on adaptive high-risk prostate cancer SBRT. Comprehensive evaluations have shown the capability and accuracy of our system.« less

Dynamically accumulated dose and 4D accumulated dose for moving tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

Vitamin D and type 2 diabetes.

PubMed

Lips, Paul; Eekhoff, Marelise; van Schoor, Natasja; Oosterwerff, Mirjam; de Jongh, Renate; Krul-Poel, Yvonne; Simsek, Suat

2017-10-01

Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance ("prediabetes") or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600-4000IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

TH-CD-BRA-02: 3D Remote Dosimetry for MRI-Guided Radiation Therapy: A Hybrid Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rankine, L; The University of North Carolina at Chapel Hill, Chapel Hill, NC; Mein, S

2016-06-15

Purpose: To validate the dosimetric accuracy of a commercially available MR-IGRT system using a combination of 3D dosimetry measurements (with PRESAGE(R) radiochromic plastic and optical-CT readout) and an in-house developed GPU-accelerated PENELOPE Monte-Carlo dose calculation system. Methods: {sup 60}Co IMRT subject to a 0.35T lateral magnetic field has recently been commissioned in our institution following AAPM’s TG-119 recommendations. We performed PRESAGE(R) sensitivity studies in 4ml cuvettes to verify linearity, MR-compatibility, and energy-independence. Using 10cm diameter PRESAGE(R), we delivered an open calibration field to examine the percent depth dose and a symmetrical 3-field plan with three adjacent regions of varying dosemore » to determine uniformity within the dosimeter under a magnetic field. After initial testing, TG-119 plans were created in the TPS and then delivered to 14.5cm 2kg PRESAGE(R) dosimeters. Dose readout was performed via optical-CT at a second institution specializing in remote 3D dosimetry. Absolute dose was measured using an IBA CC01 ion chamber and the institution standard patient-specific QA methods were used to validate plan delivery. Calculated TG-119 plans were then compared with an independent Monte Carlo dose calculation (gPENELOPE). Results: PRESAGE(R) responds linearly (R{sup 2}=0.9996) to {sup 60}Co irradiation, in the presence of a 0.35T magnetic field, with a sensitivity of 0.0305(±0.003)cm{sup −1}Gy{sup −1}, within 1% of a 6MV non-MR linac irradiation (R{sup 2}=0.9991) with a sensitivity of 0.0302(±0.003)cm{sup −1}Gy{sup −1}. Analysis of TG-119 clinical plans using 3D-gamma (3%/3mm, 10% threshold) give passing rates of: HN 99.1%, prostate 98.0%, C-shape 90.8%, and multi-target 98.5%. The TPS agreed with gPENELOPE with a mean gamma passing rate of 98.4±1.5% (2%/2mm) with the z-score distributions following a standard normal distribution. Conclusion: We demonstrate for the first time that 3D remote dosimetry using both experimental and computational methods is a feasible and reliable approach to commissioning MR-IMRT, which is particularly useful for less specialized clinics in adopting this new treatment modality.« less

SU-E-T-20: A Correlation Study of 2D and 3D Gamma Passing Rates for Prostate IMRT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, D; Sun Yat-sen University Cancer Center, Guangzhou, Guangdong; Wang, B

2015-06-15

Purpose: To investigate the correlation between the two-dimensional gamma passing rate (2D %GP) and three-dimensional gamma passing rate (3D %GP) in prostate IMRT quality assurance. Methods: Eleven prostate IMRT plans were randomly selected from the clinical database and were used to obtain dose distributions in the phantom and patient. Three types of delivery errors (MLC bank sag errors, central MLC errors and monitor unit errors) were intentionally introduced to modify the clinical plans through an in-house Matlab program. This resulted in 187 modified plans. The 2D %GP and 3D %GP were analyzed using different dose-difference and distance-toagreement (1%-1mm, 2%-2mm andmore » 3%-3mm) and 20% dose threshold. The 2D %GP and 3D %GP were then compared not only for the whole region, but also for the PTVs and critical structures using the statistical Pearson’s correlation coefficient (γ). Results: For different delivery errors, the average comparison of 2D %GP and 3D %GP showed different conclusions. The statistical correlation coefficients between 2D %GP and 3D %GP for the whole dose distribution showed that except for 3%/3mm criterion, 2D %GP and 3D %GP of 1%/1mm criterion and 2%/2mm criterion had strong correlations (Pearson’s γ value >0.8). Compared with the whole region, the correlations of 2D %GP and 3D %GP for PTV were better (the γ value for 1%/1mm, 2%/2mm and 3%/3mm criterion was 0.959, 0.931 and 0.855, respectively). However for the rectum, there was no correlation between 2D %GP and 3D %GP. Conclusion: For prostate IMRT, the correlation between 2D %GP and 3D %GP for the PTV is better than that for normal structures. The lower dose-difference and DTA criterion shows less difference between 2D %GP and 3D %GP. Other factors such as the dosimeter characteristics and TPS algorithm bias may also influence the correlation between 2D %GP and 3D %GP.« less

Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

PubMed Central

Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-01-01

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901

Methods and procedures for: A randomized double-blind study investigating dose-dependent longitudinal effects of vitamin D supplementation on bone health.

PubMed

Burt, Lauren A; Gaudet, Sharon; Kan, Michelle; Rose, Marianne S; Billington, Emma O; Boyd, Steven K; Hanley, David A

2018-04-01

The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD) concentration for bone health is still debated and some health practitioners are recommending doses well above the Canada/USA recommended Dietary Reference Intake (DRI). We designed a three-year randomized double-blind clinical trial investigating whether there are dose-dependent effects of vitamin D supplementation above the Dietary Reference Intake (DRI) on bone health. The primary aims of this study are to assess, whether supplementation of vitamin D 3 increases 1) volumetric bone mineral density measured by high-resolution peripheral quantitative computed tomography (HR-pQCT); 2) bone strength assessed by finite element analysis, and 3) areal bone mineral density by dual X-ray absorptiometry (DXA). Secondary aims are to understand whether vitamin D 3 supplementation improves parameters of bone microarchitecture, balance, physical function and quality of life. Participants are men and women aged 55-70 years, with women at least 5-years post-menopause. The intervention is daily vitamin D 3 supplementation doses of 400, 4000 or 10,000 IU. Participants not achieving adequate dietary calcium intake are provided with calcium supplementation, up to a maximum supplemental dose of 600 mg elemental calcium per day. Results from this three-year study will provide evidence whether daily vitamin D 3 supplementation with adequate calcium intake can affect bone density, bone microarchitecture and bone strength in men and women. Furthermore, the safety of high dose daily vitamin D 3 supplementation will be explored. Copyright © 2018 Elsevier Inc. All rights reserved.

TU-FG-201-06: Remote Dosimetric Auditing for Clinical Trials Using EPID Dosimetry: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miri, N; Legge, K; Greer, P

2016-06-15

Purpose: To perform a pilot study for remote dosimetric credentialing of intensity modulated radiation therapy (IMRT) based clinical trials. The study introduces a novel, time efficient and inexpensive dosimetry audit method for multi-center credentialing. The method employs electronic portal imaging device (EPID) to reconstruct delivered dose inside a virtual flat/cylindrical water phantom. Methods: Five centers, including different accelerator types and treatment planning systems (TPS), were asked to download two CT data sets of a Head and Neck (H&N) and Postprostatectomy (P-P) patients to produce benchmark plans. These were then transferred to virtual flat and cylindrical phantom data sets that weremore » also provided. In-air EPID images of the plans were then acquired, and the data sent to the central site for analysis. At the central site, these were converted to DICOM format, all images were used to reconstruct 2D and 3D dose distributions inside respectively the flat and cylindrical phantoms using inhouse EPID to dose conversion software. 2D dose was calculated for individual fields and 3D dose for the combined fields. The results were compared to corresponding TPS doses. Three gamma criteria were used, 3%3mm-3%/2mm–2%/2mm with a 10% dose threshold, to compare the calculated and prescribed dose. Results: All centers had a high pass rate for the criteria of 3%/3 mm. For 2D dose, the average of centers mean pass rate was 99.6% (SD: 0.3%) and 99.8% (SD: 0.3%) for respectively H&N and PP patients. For 3D dose, 3D gamma was used to compare the model dose with TPS combined dose. The mean pass rate was 97.7% (SD: 2.8%) and 98.3% (SD: 1.6%). Conclusion: Successful performance of the method for the pilot centers establishes the method for dosimetric multi-center credentialing. The results are promising and show a high level of gamma agreement and, the procedure is efficient, consistent and inexpensive. Funding has been provided from Department of Radiation Oncology, TROG Cancer Research and the University of Newcastle. Narges Miri is a recipient of a University of Newcastle postgraduate scholarship.« less

Dependence of Coronary 3-Dimensional Dose Maps on Coronary Topologies and Beam Set in Breast Radiation Therapy: A Study Based on CT Angiographies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, Alexandra, E-mail: alexandra.moignier@gmail.com; Broggio, David; Derreumaux, Sylvie

2014-05-01

Purpose: In left-side breast radiation therapy (RT), doses to the left main (LM) and left anterior descending (LAD) coronary arteries are usually assessed after delineation by prior anatomic knowledge on the treatment planning computed tomography (CT) scan. In this study, dose sensitivity due to interindividual coronary topology variation was assessed, and hot spots were located. Methods and Materials: Twenty-two detailed heart models, created from heart computed tomography angiographies, were fitted into a single representative female thorax. Two breast RT protocols were then simulated into a treatment planning system: the first protocol comprised tangential and tumoral bed beams (TGs{sub T}B) atmore » 50 + 16 Gy, the second protocol added internal mammary chain beams at 50 Gy to TGs{sub T}B (TGs{sub T}B{sub I}MC). For the heart, the LAD, and the LM, several dose indicators were calculated: dose-volume histograms, mean dose (D{sub mean}), minimal dose received by the most irradiated 2% of the volume (D{sub 2%}), and 3-dimensional (3D) dose maps. Variations of these indicators with anatomies were studied. Results: For the LM, the intermodel dispersion of D{sub mean} and D{sub 2%} was 10% and 11%, respectively, with TGs{sub T}B and 40% and 80%, respectively, with TGs{sub T}B{sub I}MC. For the LAD, these dispersions were 19% (D{sub mean}) and 49% (D{sub 2%}) with TGs{sub T}B and 35% (D{sub mean}) and 76% (D{sub 2%}) with TGs{sub T}B{sub I}MC. The 3D dose maps revealed that the internal mammary chain beams induced hot spots between 20 and 30 Gy on the LM and the proximal LAD for some coronary topologies. Without IMC beams, hot spots between 5 and 26 Gy are located on the middle and distal LAD. Conclusions: Coronary dose distributions with hot spot location and dose level can change significantly depending on coronary topology, as highlighted by 3D coronary dose maps. In clinical practice, coronary imaging may be required for a relevant coronary dose assessment, especially in cases of internal mammary chain irradiation.« less

Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster dose and 2-dose catch-up regimens in the second year of life.

PubMed

Odusanya, Olumuyiwa O; Kuyinu, Yetunde A; Kehinde, Omolara A; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Dobbelaere, Kurt; Rüggeberg, Jens U; Borys, Dorota; Schuerman, Lode

2014-01-01

In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ≥ 0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ≥ 8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ≥ 0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ≥8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D.

Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO.

PubMed

Girgis, Ragy R; Slifstein, Mark; D'Souza, Deepak; Lee, Yih; Periclou, Antonia; Ghahramani, Parviz; Laszlovszky, István; Durgam, Suresh; Adham, Nika; Nabulsi, Nabeel; Huang, Yiyun; Carson, Richard E; Kiss, Béla; Kapás, Margit; Abi-Dargham, Anissa; Rakhit, Ashok

2016-10-01

Second-generation antipsychotics occupy dopamine D2 receptors and act as antagonists or partial agonists at these receptors. While these drugs alleviate positive symptoms in patients with schizophrenia, they are less effective for treating cognitive deficits and negative symptoms. Dopamine D3 receptors are highly expressed in areas of the brain thought to play a role in the regulation of motivation and reward-related behavior. Consequently, the dopamine D3 receptor has become a target for treating negative symptoms in combination with D2 antagonism to treat positive symptoms in patients with schizophrenia. The purpose of this study was to determine the cariprazine receptor occupancies in brain for D2 and D3 receptors in patients with schizophrenia. Using [(11)C]-(+)-PHNO as a radioligand, positron emission tomography (PET) scans were performed in eight patients at baseline and postdose on days 1, 4, and 15. Plasma and cerebrospinal fluid (CSF) samples were analyzed for cariprazine concentrations. A monotonic dose-occupancy relationship was observed for both receptor types. After 2 weeks of treatment, near complete (∼100 %) occupancies were observed for both receptors at a dose of 12 mg/day. At the lowest cariprazine dose (1 mg/day), mean D3 and D2 receptor occupancies were 76 and 45 %, respectively, suggesting selectivity for D3 over D2 receptors at low doses. An exposure-response analysis found a ∼3-fold difference in EC50 (D3 = 3.84 nM and D2 = 13.03 nM) in plasma after 2 weeks of dosing. This PET imaging study in patients with schizophrenia demonstrated that cariprazine is a D3-preferring dual D3/D2 receptor partial agonist.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Li, Z; Zheng, D

Purpose: In the context of evaluating dosimetric impacts of a variety of uncertainties involved in HDR Tandem-and-Ovoid treatment, to study the correlations between conventional point doses and 3D volumetric doses. Methods: For 5 cervical cancer patients treated with HDR T&O, 150 plans were retrospectively created to study dosimetric impacts of the following uncertainties: (1) inter-fractional applicator displacement between two treatment fractions within a single insertion by applying Fraction#1 plan to Fraction#2 CT; (2) positional dwell error simulated from −5mm to 5mm in 1mm steps; (3) simulated temporal dwell error of 0.05s, 0.1s, 0.5s, and 1s. The original plans were basedmore » on point dose prescription, from which the volume covered by the prescription dose was generated as the pseudo target volume to study the 3D target dose effect. OARs were contoured. The point and volumetric dose errors were calculated by taking the differences between original and simulated plans. The correlations between the point and volumetric dose errors were analyzed. Results: For the most clinically relevant positional dwell uncertainty of 1mm, temporal uncertainty of 0.05s, and inter-fractional applicator displacement within the same insertion, the mean target D90 and V100 deviation were within 1%. Among these uncertainties, the applicator displacement showed the largest potential target coverage impact (2.6% on D90) as well as the OAR dose impact (2.5% and 3.4% on bladder D2cc and rectum D2cc). The Spearman correlation analysis shows a correlation coefficient of 0.43 with a p-value of 0.11 between target D90 coverage and H point dose. Conclusion: With the most clinically relevant positional and temporal dwell uncertainties and patient interfractional applicator displacement within the same insertion, the dose error is within clinical acceptable range. The lack of correlation between H point and 3D volumetric dose errors is a motivator for the use of 3D treatment planning in cervical HDR brachytherapy.« less

Epsiprantel, a new tapeworm remedy. Preliminary efficacy studies in dogs and cats.

PubMed

Manger, B R; Brewer, M D

1989-01-01

The anthelmintic potential of epsiprantel, 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b-octahydropyrazin [2,1-a] [2]benzapine, was revealed using the tapeworms Dipylidium caninum and Taenia taeniaeformis in the cat, and Taenia pisiformis and T. hydatigena in the dog. Subsequent controlled tests in cats demonstrated oral efficacy of 100% against D. caninum with a single dose of 2.5 mg/kg. Although consistently 100% effective against T. taeniaeformis at 5 mg/kg, a single worm was found in one cat treated at 7.5 mg/kg. In experimental infections of Taenia pisiformis in dogs, 100% activity was achieved from a single oral dose of 1 mg/kg. No adverse reaction or drug-associated toxicity were observed at dose levels used.

SU-D-213AB-05: Commissioning a CT Compatible LDR T&O Applicator Using Analytical Calculation with ID and 3D Dosimetry.

PubMed

Adamson, J; Newton, J; Steffey, B; Cai, J; Adamovics, J; Oldham, M; Chino, J; Craciunescu, O

2012-06-01

To determine the characteristics of a new commercially available CT-compatible LDR Tandem and Ovoid (T&O) applicator using 3D dosimetry. We characterized source attenuation through the asymmetric gold shielding in the buckets by measuring dose with diode and 3D dosimetry and compared to an analytical line integral calculation. For 3D dosimetry, a cylindrical PRESAGE dosimeter (9.5cm diameter, 9.2cm height) with a central 6mm channel bored for source placement was scanned with the Duke Large field of view Optical CT-Scanner (DLOS) before and after delivering a nominal 7.7Gy at a distance of 1 cm using a Cs-137 source loaded in the bucket. The optical CT scan time lasted approximately 15 minutes during which 720 projections were acquired at 0.5° increments, anda 3D dose distribution was reconstructed with a 0.5mm 3 isotropic voxel size. The 3D dose distribution was applied to a CT-based T&O implant to determine effect of ovoid shielding on the dose delivered to ICRU 38 Point A as well as D2cc of the bladder, rectum, bowel, and sigmoid. Dose transmission through the gold shielding at a radial distance of 1-3cm from midplane of the source was 86.6%, 86.1, and 87.0% for analytical calculation, diode, and 3D dosimetry, respectively. For the gold shielding of the bucket, dose transmission calculated using the 3D dosimetrymeasurement was found to be lowest at oblique angles from the bucket witha minimum of ∼51%. For the patient case, attenuation from the buckets leadto a decrease in average Point A dose of ∼4% and decrease in D2cc to bladder, rectum, sigmoid, and bowel of 2%, 15%, 2%, and 7%, respectively. The measured 3D dose distribution provided unique insight to the dosimetry and shielding characteristics of the investigated applicator, the technique for which can be applied to commissioning of other brachytherapy applicators. John Adamovics is the owner of Heuris Pharma LLC. Partially supported by NIH Grant R01 CA100835-01. © 2012 American Association of Physicists in Medicine.

SU-E-T-279: Realization of Three-Dimensional Conformal Dose Planning in Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Z; Jiang, S; Yang, Z

2014-06-01

Purpose: Successful clinical treatment in prostate brachytherapy is largely dependent on the effectiveness of pre-surgery dose planning. Conventional dose planning method could hardly arrive at a satisfy result. In this abstract, a three-dimensional conformal localized dose planning method is put forward to ensure the accuracy and effectiveness of pre-implantation dose planning. Methods: Using Monte Carlo method, the pre-calculated 3-D dose map for single source is obtained. As for multiple seeds dose distribution, the maps are combined linearly to acquire the 3-D distribution. The 3-D dose distribution is exhibited in the form of isodose surface together with reconstructed 3-D organs groupmore » real-timely. Then it is possible to observe the dose exposure to target volume and normal tissues intuitively, thus achieving maximum dose irradiation to treatment target and minimum healthy tissues damage. In addition, the exfoliation display of different isodose surfaces can be realized applying multi-values contour extraction algorithm based on voxels. The needles could be displayed in the system by tracking the position of the implanted seeds in real time to conduct block research in optimizing insertion trajectory. Results: This study extends dose planning from two-dimensional to three-dimensional, realizing the three-dimensional conformal irradiation, which could eliminate the limitations of 2-D images and two-dimensional dose planning. A software platform is developed using VC++ and Visualization Toolkit (VTK) to perform dose planning. The 3-D model reconstruction time is within three seconds (on a Intel Core i5 PC). Block research could be conducted to avoid inaccurate insertion into sensitive organs or internal obstructions. Experiments on eight prostate cancer cases prove that this study could make the dose planning results more reasonable. Conclusion: The three-dimensional conformal dose planning method could improve the rationality of dose planning by safely reducing the large target margin and avoiding dose dead zones for prostate cancer treatment. 1) National Natural Science Foundation of People's Republic of China (No. 51175373); 2) New Century Educational Talents Plan of Chinese Education Ministry (NCET-10-0625); 3) Scientific and Technological Major Project, Tianjin (No. 12ZCDZSY10600)« less

Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.

PubMed

Elshama, Said Said; Osman, Hosam-Eldin Hussein; El-Kenawy, Ayman El-Meghawry; Youseef, Hamdi Mohamed

2016-02-17

Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3; the third received a toxic dose of vitamin D3 with vitamin A; and the fourth received a toxic dose of vitamin D3 with vitamin K. Vitamin D3 toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3. Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.

A novel approach to EPID-based 3D volumetric dosimetry for IMRT and VMAT QA

NASA Astrophysics Data System (ADS)

Alhazmi, Abdulaziz; Gianoli, Chiara; Neppl, Sebastian; Martins, Juliana; Veloza, Stella; Podesta, Mark; Verhaegen, Frank; Reiner, Michael; Belka, Claus; Parodi, Katia

2018-06-01

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are relatively complex treatment delivery techniques and require quality assurance (QA) procedures. Pre-treatment dosimetric verification represents a fundamental QA procedure in daily clinical routine in radiation therapy. The purpose of this study is to develop an EPID-based approach to reconstruct a 3D dose distribution as imparted to a virtual cylindrical water phantom to be used for plan-specific pre-treatment dosimetric verification for IMRT and VMAT plans. For each depth, the planar 2D dose distributions acquired in air were back-projected and convolved by depth-specific scatter and attenuation kernels. The kernels were obtained by making use of scatter and attenuation models to iteratively estimate the parameters from a set of reference measurements. The derived parameters served as a look-up table for reconstruction of arbitrary measurements. The summation of the reconstructed 3D dose distributions resulted in the integrated 3D dose distribution of the treatment delivery. The accuracy of the proposed approach was validated in clinical IMRT and VMAT plans by means of gamma evaluation, comparing the reconstructed 3D dose distributions with Octavius measurement. The comparison was carried out using (3%, 3 mm) criteria scoring 99% and 96% passing rates for IMRT and VMAT, respectively. An accuracy comparable to the one of the commercial device for 3D volumetric dosimetry was demonstrated. In addition, five IMRT and five VMAT were validated against the 3D dose calculation performed by the TPS in a water phantom using the same passing rate criteria. The median passing rates within the ten treatment plans was 97.3%, whereas the lowest was 95%. Besides, the reconstructed 3D distribution is obtained without predictions relying on forward dose calculation and without external phantom or dosimetric devices. Thus, the approach provides a fully automated, fast and easy QA procedure for plan-specific pre-treatment dosimetric verification.

Low-Dose Contrast-Enhanced Breast CT Using Spectral Shaping Filters: An Experimental Study.

PubMed

Makeev, Andrey; Glick, Stephen J

2017-12-01

Iodinated contrast-enhanced X-ray imaging of the breast has been studied with various modalities, including full-field digital mammography (FFDM), digital breast tomosynthesis (DBT), and dedicated breast CT. Contrast imaging with breast CT has a number of advantages over FFDM and DBT, including the lack of breast compression, and generation of fully isotropic 3-D reconstructions. Nonetheless, for breast CT to be considered as a viable tool for routine clinical use, it would be desirable to reduce radiation dose. One approach for dose reduction in breast CT is spectral shaping using X-ray filters. In this paper, two high atomic number filter materials are studied, namely, gadolinium (Gd) and erbium (Er), and compared with Al and Cu filters currently used in breast CT systems. Task-based performance is assessed by imaging a cylindrical poly(methyl methacrylate) phantom with iodine inserts on a benchtop breast CT system that emulates clinical breast CT. To evaluate detectability, a channelized hoteling observer (CHO) is used with sums of Laguerre-Gauss channels. It was observed that spectral shaping using Er and Gd filters substantially increased the dose efficiency (defined as signal-to-noise ratio of the CHO divided by mean glandular dose) as compared with kilovolt peak and filter settings used in commercial and prototype breast CT systems. These experimental phantom study results are encouraging for reducing dose of breast CT, however, further evaluation involving patients is needed.

Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats.

PubMed

Pinski, J; Yano, T; Janaky, T; Nagy, A; Juhasz, A; Bokser, L; Groot, K; Schally, A V

1993-01-01

A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-D-Nal(2), D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Car)2)6, D-Ala10]LH-RH (T-140); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Ac)2)6, D-Ala10]LH-RH (T-148); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(For)2)6, D-Ala10]LH-RH (T-151) and [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2bu(For)2)6, D-Ala10]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 micrograms/rat and antagonist T-159 at a dose of only 0.75 micrograms/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 micrograms/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P < 0.01) decrease in LH levels for more than 6 h. Significant (P < 0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 micrograms sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 micrograms/rat sc.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3beta.

PubMed

Whittle, Brendan J R; Varga, Csaba; Pósa, Anikó; Molnár, Andor; Collin, Marika; Thiemermann, Christoph

2006-03-01

The effects of the inhibitors of glycogen synthase kinase-3beta (GSK-3beta), TDZD-8 and SB 415286, which can substantially reduce the systemic inflammation associated with endotoxic shock in vivo, have now been investigated on the acute colitis provoked by trinitrobenzene sulphonic acid (TNBS) in the rat. Administration of the GSK-3beta inhibitor TDZD-8 (0.1, 0.33 or 1.0 mg kg-1, s.c., b.i.d., for 3 days) caused a dose-dependent reduction in the colonic inflammation induced by intracolonic TNBS assessed after 3 days, both as the area of macroscopic involvement and as a score using 0-10 scale. Likewise, following administration of the GSK-3beta inhibitor SB 415286 (0.1, 0.33 or 1.0 mg kg-1, s.c., b.i.d., for 3 days), the extent and degree of the TNBS-provoked colonic inflammation was reduced. Administration of either TDZD-8 or SB 415286 reduced the fall in body weight following challenge with TNBS at each dose level studied. The increase in myeloperoxidase activity, an index of neutrophil infiltration into the TNBS-induced inflamed colon, was significantly inhibited by both TDZD-8 and SB 415286 at each dose level. The increase in the levels of the proinflammatory cytokine, TNF-alpha, in the inflamed colon was also significantly inhibited by either compound at the highest doses evaluated. The elevated levels of the transcription factor NF-kappaB subunit p65, as determined by Western blot in the nuclear extracts from the TNBS-provoked inflamed colonic tissue, were dose-dependently reduced by TDZD-8 or SB 415286 treatment. These findings demonstrate that two chemically distinct selective inhibitors of the activity of GSK-3beta reduce the inflammation and tissue injury in a rat model of acute colitis. The mechanisms underlying this anti-inflammatory action may be related to downregulation of NF-kappaB activity, involved in the generation of proinflammatory mediators.

Investigation of Presage 3D Dosimetry as a Method of Clinically Intuitive Quality Assurance and Comparison to a Semi-3D Delta4 System

NASA Astrophysics Data System (ADS)

Crockett, Ethan Van

The need for clinically intuitive metrics for patient-specific quality assurance in radiation therapy has been well-documented (Zhen, Nelms et al. 2011). A novel transform method has shown to be effective at converting full-density 3D dose measurements made in a phantom to dose values in the patient geometry, enabling comparisons using clinically intuitive metrics such as dose-volume histograms (Oldham et al. 2011). This work investigates the transform method and compares its calculated dose-volume histograms (DVHs) to DVH values calculated by a Delta4 QA device (Scandidos), marking the first comparison of a true 3D system to a semi-3D device using clinical metrics. Measurements were made using Presage 3D dosimeters, which were readout by an in-house optical-CT scanner. Three patient cases were chosen for the study: one head-and-neck VMAT treatment and two spine IMRT treatments. The transform method showed good agreement with the planned dose values for all three cases. Furthermore, the transformed DVHs adhered to the planned dose with more accuracy than the Delta4 DVHs. The similarity between the Delta4 DVHs and the transformed DVHs, however, was greater for one of the spine cases than it was for the head-and-neck case, implying that the accuracy of the Delta4 Anatomy software may vary from one treatment site to another. Overall, the transform method, which incorporates data from full-density 3D dose measurements, provides clinically intuitive results that are more accurate and consistent than the corresponding results from a semi-3D Delta 4 system.

Feasibility study on dosimetry verification of volumetric-modulated arc therapy-based total marrow irradiation.

PubMed

Liang, Yun; Kim, Gwe-Ya; Pawlicki, Todd; Mundt, Arno J; Mell, Loren K

2013-03-04

The purpose of this study was to develop dosimetry verification procedures for volumetric-modulated arc therapy (VMAT)-based total marrow irradiation (TMI). The VMAT based TMI plans were generated for three patients: one child and two adults. The planning target volume (PTV) was defined as bony skeleton, from head to mid-femur, with a 3 mm margin. The plan strategy similar to published studies was adopted. The PTV was divided into head and neck, chest, and pelvic regions, with separate plans each of which is composed of 2-3 arcs/fields. Multiple isocenters were evenly distributed along the patient's axial direction. The focus of this study is to establish a dosimetry quality assurance procedure involving both two-dimensional (2D) and three-dimensional (3D) volumetric verifications, which is desirable for a large PTV treated with multiple isocenters. The 2D dose verification was performed with film for gamma evaluation and absolute point dose was measured with ion chamber, with attention to the junction between neighboring plans regarding hot/cold spots. The 3D volumetric dose verification used commercial dose reconstruction software to reconstruct dose from electronic portal imaging devices (EPID) images. The gamma evaluation criteria in both 2D and 3D verification were 5% absolute point dose difference and 3 mm of distance to agreement. With film dosimetry, the overall average gamma passing rate was 98.2% and absolute dose difference was 3.9% in junction areas among the test patients; with volumetric portal dosimetry, the corresponding numbers were 90.7% and 2.4%. A dosimetry verification procedure involving both 2D and 3D was developed for VMAT-based TMI. The initial results are encouraging and warrant further investigation in clinical trials.

Fast 3D dosimetric verifications based on an electronic portal imaging device using a GPU calculation engine.

PubMed

Zhu, Jinhan; Chen, Lixin; Chen, Along; Luo, Guangwen; Deng, Xiaowu; Liu, Xiaowei

2015-04-11

To use a graphic processing unit (GPU) calculation engine to implement a fast 3D pre-treatment dosimetric verification procedure based on an electronic portal imaging device (EPID). The GPU algorithm includes the deconvolution and convolution method for the fluence-map calculations, the collapsed-cone convolution/superposition (CCCS) algorithm for the 3D dose calculations and the 3D gamma evaluation calculations. The results of the GPU-based CCCS algorithm were compared to those of Monte Carlo simulations. The planned and EPID-based reconstructed dose distributions in overridden-to-water phantoms and the original patients were compared for 6 MV and 10 MV photon beams in intensity-modulated radiation therapy (IMRT) treatment plans based on dose differences and gamma analysis. The total single-field dose computation time was less than 8 s, and the gamma evaluation for a 0.1-cm grid resolution was completed in approximately 1 s. The results of the GPU-based CCCS algorithm exhibited good agreement with those of the Monte Carlo simulations. The gamma analysis indicated good agreement between the planned and reconstructed dose distributions for the treatment plans. For the target volume, the differences in the mean dose were less than 1.8%, and the differences in the maximum dose were less than 2.5%. For the critical organs, minor differences were observed between the reconstructed and planned doses. The GPU calculation engine was used to boost the speed of 3D dose and gamma evaluation calculations, thus offering the possibility of true real-time 3D dosimetric verification.

Online 3D EPID-based dose verification: Proof of concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spreeuw, Hanno; Rozendaal, Roel, E-mail: r.rozenda

Purpose: Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of thismore » study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. Methods: The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. Results: The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5–10 s irradiation time. Conclusions: A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.« less

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xin; Li, Guangjun; Zhang, Yingjie

2013-01-01

To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMATmore » plans successfully achieved better target dose conformity, reduced the V{sub 20/30}, and mean dose of the left kidney, as well as the V{sub 20/30} of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V{sub 20} of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.« less

Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

PubMed

Mohiti-Asli, M; Ghanaatparast-Rashti, M

2015-06-15

An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

PubMed

Grills, Inga S; Yan, Di; Martinez, Alvaro A; Vicini, Frank A; Wong, John W; Kestin, Larry L

2003-11-01

To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

Temporal Lobe Toxicity Analysis After Proton Radiation Therapy for Skull Base Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pehlivan, Berrin; Ares, Carmen, E-mail: carmen.ares@psi.ch; Lomax, Antony J.

2012-08-01

Purpose: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. Methods and Materials: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1,more » 2, and 3 cc of brain volume (D{sub 0.5}, D{sub 1}, D{sub 2}, D{sub 3}) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. Results: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 {+-} 5 Gy (RBE) for no toxicity to 74 {+-} 5 Gy (RBE) for Grade 1 and to 76 {+-} 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of {>=}64 Gy (RBE) D{sub 3}, {>=}68 Gy (RBE) D{sub 2}, {>=}72 Gy (RBE) D{sub 1}, and {>=}73 Gy (RBE) D{sub 0.5}, respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. Conclusions: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.« less

Experimental verification of a commercial Monte Carlo-based dose calculation module for high-energy photon beams.

PubMed

Künzler, Thomas; Fotina, Irina; Stock, Markus; Georg, Dietmar

2009-12-21

The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (gamma) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% +/- 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 x 10 cm(2) field at the first density interface from tissue to lung equivalent material. Small fields (2 x 2 cm(2)) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% +/- 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D gamma-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for gamma(>1) was 4.7% +/- 3.7%, the average gamma(1%) value was 1.19 +/- 0.16 and the mean 2D gamma-value was 0.44 +/- 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

SU-E-T-790: Validation of 4D Measurement-Guided Dose Reconstruction (MGDR) with OCTAVIUS 4D System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, V; Leung, R; Wong, M

2015-06-15

Purpose: To validate the MGDR of OCTAVIUS 4D system (PTW, Freiburg, Germany) for quality assurance (QA) of volumetric-modulated arc radiotherapy (VMAT). Methods: 4D-MGDR measurements were divided into two parts: 1) square fields from 2×2 to 25×25 cm{sup 2} at 0°, 10° and 45° gantry, and 2) 8 VMAT plans (5 nasopharyngeal and 3 prostate) collapsed to gantry 40° in QA mode in Monaco v5.0 (Elekta, CMS, Maryland Heights, MO) were delivered on the OCTAVIUS 4D phantom with the OCTAVIUS 1500 detector plane perpendicular to either the incident beam to obtain the reconstructed dose (OCTA4D) or the 0° gantry axis tomore » obtain the raw doses (OCTA3D) in Verisoft 6.1 (PTW, Freiburg, Germany). Raw measurements of OCTA3D were limited to < 45° gantry to avoid >0.5% variation of detector angular response with respect to 0° gantry as determined previously. Reconstructed OCTA4D and raw OCTA3D doses for all plans were compared at the same detector plane using γ criteria of 2% (local dose)/2mm and 3%/3mm criteria. Results: At gantry 0° and 10°, the γ results for all OCTA4D on detector plane coinciding with OCTA3D were over 90% at 2%/2mm except for the largest field (25×25 cm{sup 2} ) showing >88%. For square field at 45° gantry, γ passing rate is > 90% for fields smaller than 15x 15cm2 but < 80% for field size of 20 x20 cm{sup 2} upward. For VMAT, γ results showed 94% and 99% passing rate at 2%/2mm and 3%/3mm, respectively. Conclusion: OCTAVIUS 4D system has compromised accuracy in reconstructing dose away from the central beam axis, possibly due to the off-axis softening correction and errors of the percent depth dose data necessary as input for MGDR. Good results in VMAT delivery suggested that the system is relatively reliable for VMAT with small segments.« less

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

PubMed

Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

2012-12-01

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures. © 2011 Blackwell Publishing Ltd.

Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capelle, Lisa; Warkentin, Heather; MacKenzie, Marc

Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT theremore » was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.« less

Vitamin D3 affects innate immune status of European sea bass (Dicentrarchus labrax L.).

PubMed

Dioguardi, M; Guardiola, F A; Vazzana, M; Cuesta, A; Esteban, M A; Cammarata, M

2017-08-01

The effects of vitamin D 3 dietary administration on certain innate immune parameters on the expression of immune-related genes in head-kidney (HK) and gut were investigated in European sea bass Dicentrarchus labrax. Vitamin D 3 (vD 3 ) was orally administered to fish in a commercial pellet food supplemented with 0 (control); 3750; 18,750; or 37,500 U kg -1 . Furthermore, gut histology was considered. This study showed a modulation in the activities examined in fish fed with the addition of vD 3 . After just 2 weeks of administration, diet supplementation with the vitamin resulted in increased phagocytic ability, while serum peroxidase content was increased in fish fed with all experimental diets after 4 weeks, no significant differences were observed in protease, anti-protease, natural haemolytic complement activities and total IgM level. At gene level, fbl and rbl transcripts were up-regulated in HK in fish fed with the highest concentration of vD 3 -supplemented diets after 4 weeks, while in the gut, an up-regulation of hep gene was observed in fish fed with the different doses of vD 3 . These results suggest that vD 3 may be of great interest for immunostimulatory purposes in fish farms.

A novel four-dimensional radiotherapy planning strategy from a tumor-tracking beam's eye view

NASA Astrophysics Data System (ADS)

Li, Guang; Cohen, Patrice; Xie, Huchen; Low, Daniel; Li, Diana; Rimner, Andreas

2012-11-01

To investigate the feasibility of four-dimensional radiotherapy (4DRT) planning from a tumor-tracking beam's eye view (ttBEV) with reliable gross tumor volume (GTV) delineation, realistic normal tissue representation, high planning accuracy and low clinical workload, we propose and validate a novel 4D conformal planning strategy based on a synthesized 3.5D computed tomographic (3.5DCT) image with a motion-compensated tumor. To recreate patient anatomy from a ttBEV in the moving tumor coordinate system for 4DRT planning (or 4D planning), the centers of delineated GTVs in all phase CT images of 4DCT were aligned, and then the aligned CTs were averaged to produce a new 3.5DCT image. This GTV-motion-compensated CT contains a motionless target (with motion artifacts minimized) and motion-blurred normal tissues (with a realistic temporal density average). Semi-automatic threshold-based segmentation of the tumor, lung and body was applied, while manual delineation was used for other organs at risk (OARs). To validate this 3.5DCT-based 4D planning strategy, five patients with peripheral lung lesions of small size (<5 cm3) and large motion range (1.2-3.5 cm) were retrospectively studied for stereotactic body radiotherapy (SBRT) using 3D conformal radiotherapy planning tools. The 3.5DCT-based 4D plan (3.5DCT plan) with 9-10 conformal beams was compared with the 4DCT-based 4D plan (4DCT plan). The 4DCT plan was derived from multiple 3D plans based on all phase CT images, each of which used the same conformal beam configuration but with an isocenter shift to aim at the moving tumor and a minor beam aperture and weighting adjustment to maintain plan conformality. The dose-volume histogram (DVH) of the 4DCT plan was created with two methods: one is an integrated DVH (iDVH4D), which is defined as the temporal average of all 3D-phase-plan DVHs, and the other (DVH4D) is based on the dose distribution in a reference phase CT image by dose warping from all phase plans using the displacement vector field (DVF) from a free-form deformable image registration (DIR). The DVH3.5D (for the 3.5DCT plan) was compared with both iDVH4D and DVH4D. To quantify the DVH difference between the 3.5DCT plan and the 4DCT plan, two methods were used: relative difference (%) of the areas underneath the DVH curves and the volumes receiving more than 20% (V20) and 50% (V50) of prescribed dose of these 4D plans. The volume of the delineated GTV from different phase CTs varied dramatically from 24% to 112% among the five patients, whereas the GTV from 3.5DCT deviated from the averaged GTV in 4DCT by only -6%±6%. For planning tumor volume (PTV) coverage, the difference between the DVH3.5D and iDVH4D was negligible (<1% area), whereas the DVH3.5D and DVH4D were quite different, due to DIR uncertainty (˜2 mm), which propagates to PTV dose coverage with a pronounced uncertainty for small tumors (0.3-4.0 cm3) in stereotactic plans with sharp dose falloff around PTV. For OARs, such as the lung, heart, cord and esophagus, the three DVH curves (DVH3.5D, DVH4D and iDVH4D) were found to be almost identical for the same patients, especially in high-dose regions. For the tumor-containing lung, the relative difference of the areas underneath the DVH curves was found to be small (5.3% area on average), of which 65% resulted from the low-dose region (D < 20%). The averaged V20 difference between the two 4D plans was 1.2% ± 0.8%. For the mean lung dose (MLD), the 3.5DCT plan differed from the 4DCT plan by -1.1%±1.3%. GTV-motion-compensated CT (3.5DCT) produces an accurate and reliable GTV delineation, which is close to the mean GTV from 4DCT. The 3.5DCT plan is equivalent to the 4DCT plan with <1% dose difference to the PTV and negligible dose difference in OARs. The 3.5DCT approach simplifies 4D planning and provides accurate dose calculation without a substantial increase of clinical workload for motion-tracking delivery to treat small peripheral lung tumors with large motion.

Dosimetric comparison between intensity-modulated with coplanar field and 3D conformal radiotherapy with noncoplanar field for postocular invasion tumor.

PubMed

Wenyong, Tu; Lu, Liu; Jun, Zeng; Weidong, Yin; Yun, Li

2010-01-01

This study presents a dosimetric optimization effort aiming to compare noncoplanar field (NCF) on 3 dimensions conformal radiotherapy (3D-CRT) and coplanar field (CF) on intensity-modulated radiotherapy (IMRT) planning for postocular invasion tumor. We performed a planning study on the computed tomography data of 8 consecutive patients with localized postocular invasion tumor. Four fields NCF 3D-CRT in the transverse plane with gantry angles of 0-10 degrees , 30-45 degrees , 240-270 degrees , and 310-335 degrees degrees were isocentered at the center of gravity of the target volume. The geometry of the beams was determined by beam's eye view. The same constraints were prepared with between CF IMRT optimization and NCF 3D-CRT treatment. The maximum point doses (D max) for the different optic pathway structures (OPS) with NCF 3D-CRT treatment should differ in no more than 3% from those with the NCF IMRT plan. Dose-volume histograms (DVHs) were obtained for all targets and organ at risk (OAR) with both treatment techniques. Plans with NCF 3D-CRT and CF IMRT constraints on target dose in homogeneity were computed, as well as the conformity index (CI) and homogeneity index (HI) in the target volume. The PTV coverage was optimal with both NCF 3D-CRT and CF IMRT plans in the 8 tumor sites. No difference was noted between the two techniques for the average D(max) and D(min) dose. NCF 3D-CRT and CF IMRT will yield similar results on CI. However, HI was a significant difference between NCF 3D-CRT and CF IMRT plan (p < 0.001). Physical endpoints for target showed the mean target dose to be low in the CF IMRT plan, caused by a large target dose in homogeneity (p < 0.001). The impact of NCF 3D-CRT versus CF IMRT set-up is very slight. NCF3D-CRT is one of the treatment options for postocular invasion tumor. However, constraints for OARs are needed. 2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-F-T-191: 4D Dose Reconstruction of Intensity Modulated Proton Therapy (IMPT) Based On Breathing Probability Density Function (PDF) From 4D Cone Beam Projection Images: A Study for Lung Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, J; Ding, X; Liang, J

2016-06-15

Purpose: With energy repainting in lung IMPT, the dose delivered is approximate to the convolution of dose in each phase with corresponding breathing PDF. This study is to compute breathing PDF weighted 4D dose in lung IMPT treatment and compare to its initial robust plan. Methods: Six lung patients were evaluated in this study. Amsterdam shroud image were generated from pre-treatment 4D cone-beam projections. Diaphragm motion curve was extract from the shroud image and the breathing PDF was generated. Each patient was planned to 60 Gy (12GyX5). In initial plans, ITV density on average CT was overridden with its maximummore » value for planning, using two IMPT beams with robust optimization (5mm uncertainty in patient position and 3.5% range uncertainty). The plan was applied to all 4D CT phases. The dose in each phase was deformed to a reference phase. 4D dose is reconstructed by summing all these doses based on corresponding weighting from the PDF. Plan parameters, including maximum dose (Dmax), ITV V100, homogeneity index (HI=D2/D98), R50 (50%IDL/ITV), and the lung-GTV’s V12.5 and V5 were compared between the reconstructed 4D dose to initial plans. Results: The Dmax is significantly less dose in the reconstructed 4D dose, 68.12±3.5Gy, vs. 70.1±4.3Gy in the initial plans (p=0.015). No significant difference is found for the ITV V100, HI, and R50, 92.2%±15.4% vs. 96.3%±2.5% (p=0.565), 1.033±0.016 vs. 1.038±0.017 (p=0.548), 19.2±12.1 vs. 18.1±11.6 (p=0.265), for the 4D dose and initial plans, respectively. The lung-GTV V12.5 and V5 are significantly high in the 4D dose, 13.9%±4.8% vs. 13.0%±4.6% (p=0.021) and 17.6%±5.4% vs. 16.9%±5.2% (p=0.011), respectively. Conclusion: 4D dose reconstruction based on phase PDF can be used to evaluate the dose received by the patient. A robust optimization based on the phase PDF may even further improve patient care.« less

An electron-beam dose deposition experiment: TIGER 1-D simulation code versus thermoluminescent dosimetry

NASA Astrophysics Data System (ADS)

Murrill, Steven R.; Tipton, Charles W.; Self, Charles T.

1991-03-01

The dose absorbed in an integrated circuit (IC) die exposed to a pulse of low-energy electrons is a strong function of both electron energy and surrounding packaging materials. This report describes an experiment designed to measure how well the Integrated TIGER Series one-dimensional (1-D) electron transport simulation program predicts dose correction factors for a state-of-the-art IC package and package/printed circuit board (PCB) combination. These derived factors are compared with data obtained experimentally using thermoluminescent dosimeters (TLD's) and the FX-45 flash x-ray machine (operated in electron-beam (e-beam) mode). The results of this experiment show that the TIGER 1-D simulation code can be used to accurately predict FX-45 e-beam dose deposition correction factors for reasonably complex IC packaging configurations.

Fast, high-resolution 3D dosimetry utilizing a novel optical-CT scanner incorporating tertiary telecentric collimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakhalkar, H. S.; Oldham, M.

2008-01-15

This study introduces a charge coupled device (CCD) area detector based optical-computed tomography (optical-CT) scanner for comprehensive verification of radiation dose distributions recorded in nonscattering radiochromic dosimeters. Defining characteristics include: (i) a very fast scanning time of {approx}5 min to acquire a complete three-dimensional (3D) dataset, (ii) improved image formation through the use of custom telecentric optics, which ensures accurate projection images and minimizes artifacts from scattered and stray-light sources, and (iii) high resolution (potentially 50 {mu}m) isotropic 3D dose readout. The performance of the CCD scanner for 3D dose readout was evaluated by comparison with independent 3D readout frommore » the single laser beam OCTOPUS-scanner for the same PRESAGE dosimeters. The OCTOPUS scanner was considered the 'gold standard' technique in light of prior studies demonstrating its accuracy. Additional comparisons were made against calculated dose distributions from the ECLIPSE treatment-planning system. Dose readout for the following treatments were investigated: (i) a single rectangular beam irradiation to investigate small field and very steep dose gradient dosimetry away from edge effects, (ii) a 2-field open beam parallel-opposed irradiation to investigate dosimetry along steep dose gradients, and (iii) a 7-field intensity modulated radiation therapy (IMRT) irradiation to investigate dosimetry for complex treatment delivery involving modulation of fluence and for dosimetry along moderate dose gradients. Dose profiles, dose-difference plots, and gamma maps were employed to evaluate quantitative estimates of agreement between independently measured and calculated dose distributions. Results indicated that dose readout from the CCD scanner was in agreement with independent gold-standard readout from the OCTOPUS-scanner as well as the calculated ECLIPSE dose distribution for all treatments, except in regions within a few millimeters of the edge of the dosimeter, where edge artifact is predominant. Agreement of line profiles was observed, even along steep dose gradients. Dose difference plots indicated that the CCD scanner dose readout differed from the OCTOPUSscanner readout and ECLIPSE calculations by {approx}10% along steep dose gradients and by {approx}5% along moderate dose gradients. Gamma maps (3% dose-difference and 3 mm distance-to-agreement acceptance criteria) revealed agreement, except for regions within 5 mm of the edge of the dosimeter where the edge artifact occurs. In summary, the data demonstrate feasibility of using the fast, high-resolution CCD scanner for comprehensive 3D dosimetry in all applications, except where dose readout is required close to the edges of the dosimeter. Further work is ongoing to reduce this artifact.« less

Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

NASA Technical Reports Server (NTRS)

Zimmer, J. Paul; Lewis, Sherry M.; Moyer, Jerry L.

1993-01-01

Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sayah, N; Weiss, E; Watkins, W

Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM);more » an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is recommended for dose mapping. Interpolative dose methods are sufficiently accurate for the majority of cases. J.V. Siebers receives funding support from Varian Medical Systems.« less

SU-F-BRE-04: Construction of 3D Printed Patient Specific Phantoms for Dosimetric Verification Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ehler, E; Higgins, P; Dusenbery, K

2014-06-15

Purpose: To validate a method to create per patient phantoms for dosimetric verification measurements. Methods: Using a RANDO phantom as a substitute for an actual patient, a model of the external features of the head and neck region of the phantom was created. A phantom was used instead of a human for two reasons: to allow for dosimetric measurements that would not be possible in-vivo and to avoid patient privacy issues. Using acrylonitrile butadiene styrene thermoplastic as the building material, a hollow replica was created using the 3D printer filled with a custom tissue equivalent mixture of paraffin wax, magnesiummore » oxide, and calcium carbonate. A traditional parallel-opposed head and neck plan was constructed. Measurements were performed with thermoluminescent dosimeters in both the RANDO phantom and in the 3D printed phantom. Calculated and measured dose was compared at 17 points phantoms including regions in high and low dose regions and at the field edges. On-board cone beam CT was used to localize both phantoms within 1mm and 1° prior to radiation. Results: The maximum difference in calculated dose between phantoms was 1.8% of the planned dose (180 cGy). The mean difference between calculated and measured dose in the anthropomorphic phantom and the 3D printed phantom was 1.9% ± 2.8% and −0.1% ± 4.9%, respectively. The difference between measured and calculated dose was determined in the RANDO and 3D printed phantoms. The differences between measured and calculated dose in each respective phantom was within 2% for 12 of 17 points. The overlap of the RANDO and 3D printed phantom was 0.956 (Jaccard Index). Conclusion: A custom phantom was created using a 3D printer. Dosimetric calculations and measurements showed good agreement between the dose in the RANDO phantom (patient substitute) and the 3D printed phantom.« less

Effective radiation dose of ProMax 3D cone-beam computerized tomography scanner with different dental protocols.

PubMed

Qu, Xing-min; Li, Gang; Ludlow, John B; Zhang, Zu-yan; Ma, Xu-chen

2010-12-01

The aim of this study was to compare effective doses resulting from different scan protocols for cone-beam computerized tomography (CBCT) using International Commission on Radiological Protection (ICRP) 1990 and 2007 calculations of dose. Average tissue-absorbed dose, equivalent dose, and effective dose for a ProMax 3D CBCT with different dental protocols were calculated using thermoluminescent dosimeter chips in a human equivalent phantom. Effective doses were derived using ICRP 1990 and the superseding 2007 recommendations. Effective doses (ICRP 2007) for default patient sizes from small to large ranged from 102 to 298 μSv. The coefficient of determination (R(2)) between tube current and effective dose (ICRP 2007) was 0.90. When scanning with lower resolution settings, the effective doses were reduced significantly (P < .05). ProMax 3D can provide a wide range of radiation dose levels. Reduction in radiation dose can be achieved when using lower settings of exposure parameters. Copyright © 2010 Mosby, Inc. All rights reserved.

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors.

PubMed

Simeonova, Anna; Abo-Madyan, Yasser; El-Haddad, Mostafa; Welzel, Grit; Polednik, Martin; Boggula, Ramesh; Wenz, Frederik; Lohr, Frank

2012-02-01

IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem. Planning-CT-datasets of 20 patients with Stage I-IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60 Gy to the CTV and 70 Gy to the GTV. For the 3D plans an energy of 18 MV photons was used. IMRT plans were calculated for 6 MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan. As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43 Gy vs. 49.1 Gy vs. 48.6 Gy; p<0.001) and CTV D(95) (53.2 Gy vs. 55.0 Gy vs. 55.4 Gy; p=0.001). The D(mean) of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5 Gy vs. 14.8 Gy vs. 15.8 Gy: p<0.05). The spinal cord dose limit of 50 Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart D(max) was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2 Gy vs. 36.8 Gy vs. 37.8 Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (~0.5-1 Gy). Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-202: Comparison of 4D-Measurement-Guided Dose Reconstructions (MGDR) with COMPASS and OCTAVIUS 4D System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leung, R; Wong, M; Lee, V

2015-06-15

Purpose: To cross-validate the MGDR of COMPASS (IBA dosimetry, GmbH, Germany) and OCTAVIUS 4D system (PTW, Freiburg, Germany). Methods: Volumetric-modulated arc plans (5 head-and-neck and 3 prostate) collapsed to 40° gantry on the OCTAVIUS 4D phantom in QA mode on Monaco v5.0 (Elekta, CMS, Maryland Heights, MO) were delivered on a Elekta Agility linac. This study was divided into two parts: (1) error-free measurements by gantry-mounted EvolutionXX 2D array were reconstructed in COMPASS (IBA dosimetry, GmbH, Germany), and by OCTAVIUS 1500 array in Versoft v6.1 (PTW, Freiburg, Germany) to obtain the 3D doses (COM4D and OCTA4D). COM4D and OCTA4D weremore » compared to the raw measurement (OCTA3D) at the same detector plane for which OCTAVIUS 1500 was perpendicular to 0° gantry axis while the plans were delivered at gantry 40°; (2) beam steering errors of energy (Hump=-2%) and symmetry (2T=+2%) were introduced during the delivery of 5 plans to compare the MGDR doses COM4D-Hump (COM4D-2T), OCTA4D-Hump (OCTA4D-2T), with raw doses OCTA3D-Hump (OCTA3D-2T) and with OCTA3D to assess the error reconstruction and detection ability of MGDR tools. All comparisons used Υ-criteria of 2%(local dose)/2mm and 3%/3mm. Results: Averaged Υ passing rates were 85% and 96% for COM4D,and 94% and 99% for OCTA4D at 2%/2mm and 3%/3mm criteria respectively. For error reconstruction, COM4D-Hump (COM4D-2T) showed 81% (93%) at 2%/2mm and 94% (98%) at 3%/3mm, while OCTA4D-Hump (OCTA4D-2T) showed 96% (96%) at 2%/2mm and 99% (99%) at 3%/3mm. For error detection, OCTA3D doses were compared to COM4D-Hump (COM4D-2T) showing Υ passing rates of 93% (93%) at 2%/2mm and 98% (98%), and to OCTA4D-Hump (OCTA4D -2T) showing 94% (99%) at 2%/2mm and 81% (96%) at 3%/3mm, respectively. Conclusion: OCTAVIUS MGDR showed better agreement to raw measurements in both error- and error-free comparisons. COMPASS MGDR deviated from the raw measurements possibly owing to beam modeling uncertainty.« less

Current status of 3D EPID-based in vivo dosimetry in The Netherlands Cancer Institute

NASA Astrophysics Data System (ADS)

Mijnheer, B.; Olaciregui-Ruiz, I.; Rozendaal, R.; Spreeuw, H.; van Herk, M.; Mans, A.

2015-01-01

3D in vivo dose verification using a-Si EPIDs is performed routinely in our institution for almost all RT treatments. The EPID-based 3D dose distribution is reconstructed using a back-projection algorithm and compared with the planned dose distribution using 3D gamma evaluation. Dose-reconstruction and gamma-evaluation software runs automatically, and deviations outside the alert criteria are immediately available and investigated, in combination with inspection of cone-beam CT scans. The implementation of our 3D EPID- based in vivo dosimetry approach was able to replace pre-treatment verification for more than 90% of the patient treatments. Clinically relevant deviations could be detected for approximately 1 out of 300 patient treatments (IMRT and VMAT). Most of these errors were patient related anatomical changes or deviations from the routine clinical procedure, and would not have been detected by pre-treatment verification. Moreover, 3D EPID-based in vivo dose verification is a fast and accurate tool to assure the safe delivery of RT treatments. It provides clinically more useful information and is less time consuming than pre-treatment verification measurements. Automated 3D in vivo dosimetry is therefore a prerequisite for large-scale implementation of patient-specific quality assurance of RT treatments.

WE-D-BRA-05: Pseudo In Vivo Patient Dosimetry Using a 3D-Printed Patient-Specific Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ger, R; Craft, DF; Burgett, EA

Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by anmore » ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between measured and calculated doses will improve.« less

Biological Activity of the Salvia officinalis L. (Lamiaceae) Essential Oil on Varroa destructor Infested Honeybees.

PubMed

Bendifallah, Leila; Belguendouz, Rachida; Hamoudi, Latifa; Arab, Karim

2018-06-06

The present work is conducted as part of the development and the valorization of bioactive natural substances from Algerian medicinal and aromatic spontaneous plants, a clean alternative method in biological control. For this purpose, the bio-acaricidal activity of Salvia officinalis (sage)essential oil (EO)was evaluated against the Varroa destructor , a major threat to the honey bee Apis mellifera ssp. intermissa . The aerial parts of S. officinalis L., 1753 were collected from the Chrea mountainous area in Northern Algeria. They were subjected to hydro distillation by a Clevenger apparatus type to obtain the EO, and screened for bio-acaricidal activity against Varroa destructor by the method of strips impregnated with the mixture EO and twin according to three doses. Pre-treatment results revealed infestation rates in the experimental site ranging from 3.76% to 21.22%. This showed the heterogeneity of infestations in hives according to the density of bees. This constituted a difficulty in monitoring the population dynamics of this parasite. After treatment, a difference in the acaricidal effect of Sage essential oil is noticed. It gives a mortality rate of 6.09% by the dose D1: 5%, 2.32% by the dose D2: 15%, and a low mortality rate of 0.9% by the dose D3: 20%. The chemical treatment carried out by Bayvarol gives a result close to that of the essential oil of Sage (9.97%).These results point to the fact that Sage essential oil treatments have a significant effect and good biological activity with regard to harmful species.

Dosimetric impact of different CT datasets for stereotactic treatment planning using 3D conformal radiotherapy or volumetric modulated arc therapy.

PubMed

Oechsner, Markus; Odersky, Leonhard; Berndt, Johannes; Combs, Stephanie Elisabeth; Wilkens, Jan Jakob; Duma, Marciana Nona

2015-12-01

The purpose of this study was to assess the impact on dose to the planning target volume (PTV) and organs at risk (OAR) by using four differently generated CT datasets for dose calculation in stereotactic body radiotherapy (SBRT) of lung and liver tumors. Additionally, dose differences between 3D conformal radiotherapy and volumetric modulated arc therapy (VMAT) plans calculated on these CT datasets were determined. Twenty SBRT patients, ten lung cases and ten liver cases, were retrospectively selected for this study. Treatment plans were optimized on average intensity projection (AIP) CTs using 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT). Afterwards, the plans were copied to the planning CTs (PCT), maximum intensity projection (MIP) and mid-ventilation (MidV) CT datasets and dose was recalculated keeping all beam parameters and monitor units unchanged. Ipsilateral lung and liver volumes and dosimetric parameters for PTV (Dmean, D2, D98, D95), ipsilateral lung and liver (Dmean, V30, V20, V10) were determined and statistically analysed using Wilcoxon test. Significant but small mean differences were found for PTV dose between the CTs (lung SBRT: ≤2.5 %; liver SBRT: ≤1.6 %). MIPs achieved the smallest lung and the largest liver volumes. OAR mean doses in MIP plans were distinctly smaller than in the other CT datasets. Furthermore, overlapping of tumors with the diaphragm results in underestimated ipsilateral lung dose in MIP plans. Best agreement was found between AIP and MidV (lung SBRT). Overall, differences in liver SBRT were smaller than in lung SBRT and VMAT plans achieved slightly smaller differences than 3D-CRT plans. Only small differences were found for PTV parameters between the four CT datasets. Larger differences occurred for the doses to organs at risk (ipsilateral lung, liver) especially for MIP plans. No relevant differences were observed between 3D-CRT or VMAT plans. MIP CTs are not appropriate for OAR dose assessment. PCT, AIP and MidV resulted in similar doses. If a 4DCT is acquired PCT can be omitted using AIP or MidV for treatment planning.

MAGAT gel and EBT2 film‐based dosimetry for evaluating source plugging‐based treatment plan in Gamma Knife stereotactic radiosurgery

PubMed Central

Vivekanandhan, S.; Kale, S.S.; Rath, G.K.; Senthilkumaran, S.; Thulkar, S.; Subramani, V.; Laviraj, M.A.; Bisht, R.K.; Mahapatra, A.K.

2012-01-01

This work illustrates a procedure to assess the overall accuracy associated with Gamma Knife treatment planning using plugging. The main role of source plugging or blocking is to create dose falloff in the junction between a target and a critical structure. We report the use of MAGAT gel dosimeter for verification of an experimental treatment plan based on plugging. The polymer gel contained in a head‐sized glass container simulated all major aspects of the treatment process of Gamma Knife radiosurgery. The 3D dose distribution recorded in the gel dosimeter was read using a 1.5T MRI scanner. Scanning protocol was: CPMG pulse sequence with 8 equidistant echoes, TR=7 s, echo step=14 ms, pixel size=0.5 mm x 0.5 mm, and slice thickness of 2 mm. Using a calibration relationship between absorbed dose and spin‐spin relaxation rate (R2), we converted R2 images to dose images. Volumetric dose comparison between treatment planning system (TPS) and gel measurement was accomplished using an in‐house MATLAB‐based program. The isodose overlay of the measured and computed dose distribution on axial planes was in close agreement. Gamma index analysis of 3D data showed more than 94% voxel pass rate for different tolerance criteria of 3%/2 mm, 3%/1 mm and 2%/2 mm. Film dosimetry with GAFCHROMIC EBT 2 film was also performed to compare the results with the calculated TPS dose. Gamma index analysis of film measurement for the same tolerance criteria used for gel measurement evaluation showed more than 95% voxel pass rate. Verification of gamma plan calculated dose on account of shield is not part of acceptance testing of Leksell Gamma Knife (LGK). Through this study we accomplished a volumetric comparison of dose distributions measured with a polymer gel dosimeter and Leksell GammaPlan (LGP) calculations for plans using plugging. We propose gel dosimeter as a quality assurance (QA) tool for verification of plug‐based planning. PACS number: 87.53.Ly, 87.55.‐x, 87.56.N‐ PMID:23149780

Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults.

PubMed

Pettersen, Jacqueline A

2017-04-01

Insufficiency of 25-hydroxyvitamin D [25(OH)D] has been associated with dementia and cognitive decline. However, the effects of vitamin D supplementation on cognition are unclear. It was hypothesized that high dose vitamin D3 supplementation would result in enhanced cognitive functioning, particularly among adults whose 25(OH)D levels were insufficient (<75nmol/L) at baseline. Healthy adults (n=82) from northern British Columbia, Canada (54° north latitude) with baseline 25(OH)D levels ≤100nmol/L were randomized and blinded to High Dose (4000IU/d) versus Low Dose (400IU/d) vitamin D3 (cholecalciferol) for 18weeks. Baseline and follow-up serum 25(OH)D and cognitive performance were assessed and the latter consisted of: Symbol Digit Modalities Test, verbal (phonemic) fluency, digit span, and the CANTAB® computerized battery. There were no significant baseline differences between Low (n=40) and High (n=42) dose groups. Serum 25(OH)D increased significantly more in the High Dose (from 67.2±20 to 130.6±26nmol/L) than the Low Dose group (60.5±22 to 85.9±16nmol/L), p=0.0001. Performance improved in the High Dose group on nonverbal (visual) memory, as assessed by the Pattern Recognition Memory task (PRM), from 84.1±14.9 to 88.3±13.2, p=0.043 (d=0.3) and Paired Associates Learning Task, (PAL) number of stages completed, from 4.86±0.35 to 4.95±0.22, p=0.044 (d=0.5), but not in the Low Dose Group. Mixed effects modeling controlling for age, education, sex and baseline performance revealed that the degree of improvement was comparatively greater in the High Dose Group for these tasks, approaching significance: PRM, p=0.11 (d=0.4), PAL, p=0.058 (d=0.4). Among those who had insufficient 25(OH)D (<75nmol/L) at baseline, the High Dose group (n=23) improved significantly (p=0.005, d=0.7) and to a comparatively greater degree on the PRM (p=0.025, d=0.6). Nonverbal (visual) memory seems to benefit from higher doses of vitamin D supplementation, particularly among those who are insufficient (<75nmol/L) at baseline, while verbal memory and other cognitive domains do not. These findings are consistent with recent cross-sectional and longitudinal studies, which have demonstrated significant positive associations between 25(OH)D levels and nonverbal, but not verbal, memory. While our findings require confirmation, they suggest that higher 25(OH)D is particularly important for higher level cognitive functioning, specifically nonverbal (visual) memory, which also utilizes executive functioning processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of patient-specific bolus created using three-dimensional printing technique in photon radiotherapy.

PubMed

Fujimoto, Koya; Shiinoki, Takehiro; Yuasa, Yuki; Hanazawa, Hideki; Shibuya, Keiko

2017-06-01

A commercially available bolus ("commercial-bolus") does not make complete contact with the irregularly shaped patient skin. This study aims to customise a patient-specific three-dimensional (3D) bolus using a 3D printing technique ("3D-bolus") and to evaluate its clinical feasibility for photon radiotherapy. The 3D-bolus was designed using a treatment planning system (TPS) in Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format, and converted to stereolithographic format for printing. To evaluate its physical characteristics, treatment plans were created for water-equivalent phantoms that were bolus-free, or had a flat-form printed 3D-bolus, a TPS-designed bolus ("virtual-bolus"), or a commercial-bolus. These plans were compared based on the percentage depth dose (PDD) and target-volume dose volume histogram (DVH) measurements. To evaluate the clinical feasibility, treatment plans were created for head phantoms that were bolus-free or had a 3D-bolus, a virtual-bolus, or a commercial-bolus. These plans were compared based on the target volume DVH. In the physical evaluation, the 3D-bolus provided effective dose coverage in the build-up region, which was equivalent to the commercial-bolus. With regard to the clinical feasibility, the air gaps were lesser with the 3D-bolus when compared to the commercial-bolus. Furthermore, the prescription dose could be delivered appropriately to the target volume. The 3D-bolus has potential use for air-gap reduction compared to the commercial-bolus and facilitates target-volume dose coverage and homogeneity improvement. A 3D-bolus produced using a 3D printing technique is comparable to a commercial-bolus applied to an irregular-shaped skin surface. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters

PubMed Central

Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail–which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were between 98% and 100%. Parameters of major influence on 4D VMAT dose simulation accuracy were the degree of temporal discretization of the dose delivery process (the higher, the better) and correct alignment of the assumed breathing phases at the beginning of the dose measurements and simulations. Given the high γ-passing rates between simulated motion-affected doses and dynamic measurements, we consider the simulations to provide a reliable basis for assessment of VMAT motion effects that–in the sense of 4D QA of VMAT treatment plans–allows to verify target coverage in hypofractioned VMAT-based radiotherapy of moving targets. Remaining differences between measurements and simulations motivate, however, further detailed studies. PMID:28231337

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters.

PubMed

Sothmann, Thilo; Gauer, Tobias; Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail-which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were between 98% and 100%. Parameters of major influence on 4D VMAT dose simulation accuracy were the degree of temporal discretization of the dose delivery process (the higher, the better) and correct alignment of the assumed breathing phases at the beginning of the dose measurements and simulations. Given the high γ-passing rates between simulated motion-affected doses and dynamic measurements, we consider the simulations to provide a reliable basis for assessment of VMAT motion effects that-in the sense of 4D QA of VMAT treatment plans-allows to verify target coverage in hypofractioned VMAT-based radiotherapy of moving targets. Remaining differences between measurements and simulations motivate, however, further detailed studies.

The Impact of Different Levels of Adaptive Iterative Dose Reduction 3D on Image Quality of 320-Row Coronary CT Angiography: A Clinical Trial

PubMed Central

Feger, Sarah; Rief, Matthias; Zimmermann, Elke; Martus, Peter; Schuijf, Joanne Désirée; Blobel, Jörg; Richter, Felicitas; Dewey, Marc

2015-01-01

Purpose The aim of this study was the systematic image quality evaluation of coronary CT angiography (CTA), reconstructed with the 3 different levels of adaptive iterative dose reduction (AIDR 3D) and compared to filtered back projection (FBP) with quantum denoising software (QDS). Methods Standard-dose CTA raw data of 30 patients with mean radiation dose of 3.2 ± 2.6 mSv were reconstructed using AIDR 3D mild, standard, strong and compared to FBP/QDS. Objective image quality comparison (signal, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contour sharpness) was performed using 21 measurement points per patient, including measurements in each coronary artery from proximal to distal. Results Objective image quality parameters improved with increasing levels of AIDR 3D. Noise was lowest in AIDR 3D strong (p≤0.001 at 20/21 measurement points; compared with FBP/QDS). Signal and contour sharpness analysis showed no significant difference between the reconstruction algorithms for most measurement points. Best coronary SNR and CNR were achieved with AIDR 3D strong. No loss of SNR or CNR in distal segments was seen with AIDR 3D as compared to FBP. Conclusions On standard-dose coronary CTA images, AIDR 3D strong showed higher objective image quality than FBP/QDS without reducing contour sharpness. Trial Registration Clinicaltrials.gov NCT00967876 PMID:25945924

SU-D-201-07: Exploring the Utility of 4D FDG-PET/CT Scans in Design of Radiation Therapy Planning Compared with 3D PET/CT: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

2015-06-15

Purpose: A method using four-dimensional(4D) PET/CT in design of radiation treatment planning was proposed and the target volume and radiation dose distribution changes relative to standard three-dimensional (3D) PET/CT were examined. Methods: A target deformable registration method was used by which the whole patient’s respiration process was considered and the effect of respiration motion was minimized when designing radiotherapy planning. The gross tumor volume of a non-small-cell lung cancer was contoured on the 4D FDG-PET/CT and 3D PET/CT scans by use of two different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; another technique using amore » constant threshold of standardized uptake value (SUV) greater than 2.5. The target volume and radiotherapy dose distribution between VOL3D and VOL4D were analyzed. Results: For all phases, the average automatic and manually GTV volume was 18.61 cm3 (range, 16.39–22.03 cm3) and 31.29 cm3 (range, 30.11–35.55 cm3), respectively. The automatic and manually volume of merged IGTV were 27.82 cm3 and 49.37 cm3, respectively. For the manual contour, compared to 3D plan the mean dose for the left, right, and total lung of 4D plan have an average decrease 21.55%, 15.17% and 15.86%, respectively. The maximum dose of spinal cord has an average decrease 2.35%. For the automatic contour, the mean dose for the left, right, and total lung have an average decrease 23.48%, 16.84% and 17.44%, respectively. The maximum dose of spinal cord has an average decrease 1.68%. Conclusion: In comparison to 3D PET/CT, 4D PET/CT may better define the extent of moving tumors and reduce the contouring tumor volume thereby optimize radiation treatment planning for lung tumors.« less

Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children

PubMed Central

Odusanya, Olumuyiwa O; Kuyinu, Yetunde A; Kehinde, Omolara A; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Dobbelaere, Kurt; Rüggeberg, Jens U; Borys, Dorota; Schuerman, Lode

2014-01-01

In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15–21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15–21 and 17–23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ≥0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ≥8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ≥0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ≥8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D. PMID:24356787

Safety, reactogenicity and immunogenicity of a booster dose of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children.

PubMed

Dicko, Alassane; Santara, Gaoussou; Mahamar, Almahamoudou; Sidibe, Youssoufa; Barry, Amadou; Dicko, Yahia; Diallo, Aminata; Dolo, Amagana; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Strezova, Ana; Borys, Dorota; Schuerman, Lode

2013-02-01

Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was previously shown to be immunogenic and well tolerated in Malian children. Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe, Asia and Latin America but are lacking for Africa. The present study evaluated further the safety, reactogenicity and immunogenicity of a fourth consecutive (booster) dose of PHiD-CV. Low incidences of AEs with grade 3 intensity (2.1% of subjects) were observed. There were no reports of large swelling reactions and serious adverse events. One month post-booster vaccination, for each vaccine pneumococcal serotype, at least 97.8% of subjects had antibody concentrations ≥ 0.2 μg/ml, and at least 97.1% of subjects had opsonophagocytic activity ≥ 8. From pre- to post-booster, a 12.3-fold increase in anti-protein D geometric mean concentration was observed. This phase III, open-label study was conducted in Ouelessebougou, Mali, between November 2009 and June 2010. The study population consisted of Malian children previously primed (3 doses) with PHiD-CV in study NCT00678301 receiving a fourth consecutive (booster) dose of PHiD-CV in the second year of life. The incidences of adverse events (AEs) with grade 3 intensity (primary objective) or of any intensity (secondary objective), and the immunogenicity (secondary objective) of the PHiD-CV booster dose were assessed. A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. (ClinicalTrials.gov identifier: NCT00985465).

Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.

PubMed

Ocampo-Pelland, Alanna S; Gastonguay, Marc R; Riggs, Matthew M

2017-08-01

Association of Vitamin D (D3 & D2) and its 25OHD metabolite (25OHD3 & 25OHD2) exposures with various diseases is an active research area. D3 and D2 dose-equivalency and each form's ability to raise 25OHD concentrations are not well-defined. The current work describes a population pharmacokinetic (PK) model for D2 and 25OHD2 and the use of a previously developed D3-25OHD3 PK model [1] for comparing D3 and D2-related exposures. Public-source D2 and 25OHD2 PK data in healthy or osteoporotic populations, including 17 studies representing 278 individuals (15 individual-level and 18 arm-level units), were selected using search criteria in PUBMED. Data included oral, single and multiple D2 doses (400-100,000 IU/d). Nonlinear mixed effects models were developed simultaneously for D2 and 25OHD2 PK (NONMEM v7.2) by considering 1- and 2-compartment models with linear or nonlinear clearance. Unit-level random effects and residual errors were weighted by arm sample size. Model simulations compared 25OHD exposures, following repeated D2 and D3 oral administration across typical dosing and baseline ranges. D2 parent and metabolite were each described by 2-compartment models with numerous parameter estimates shared with the D3-25OHD3 model [1]. Notably, parent D2 was eliminated (converted to 25OHD) through a first-order clearance whereas the previously published D3 model [1] included a saturable non-linear clearance. Similar to 25OHD3 PK model results [1], 25OHD2 was eliminated by a first-order clearance, which was almost twice as fast as the former. Simulations at lower baselines, following lower equivalent doses, indicated that D3 was more effective than D2 at raising 25OHD concentrations. Due to saturation of D3 clearance, however, at higher doses or baselines, the probability of D2 surpassing D3's ability to raise 25OHD concentrations increased substantially. Since 25OHD concentrations generally surpassed 75 nmol/L at these higher baselines by 3 months, there would be no expected clinical difference in the two forms.

Do we need 3D tube current modulation information for accurate organ dosimetry in chest CT? Protocols dose comparisons.

PubMed

Lopez-Rendon, Xochitl; Zhang, Guozhi; Coudyzer, Walter; Develter, Wim; Bosmans, Hilde; Zanca, Federica

2017-11-01

To compare the lung and breast dose associated with three chest protocols: standard, organ-based tube current modulation (OBTCM) and fast-speed scanning; and to estimate the error associated with organ dose when modelling the longitudinal (z-) TCM versus the 3D-TCM in Monte Carlo simulations (MC) for these three protocols. Five adult and three paediatric cadavers with different BMI were scanned. The CTDI vol of the OBTCM and the fast-speed protocols were matched to the patient-specific CTDI vol of the standard protocol. Lung and breast doses were estimated using MC with both z- and 3D-TCM simulated and compared between protocols. The fast-speed scanning protocol delivered the highest doses. A slight reduction for breast dose (up to 5.1%) was observed for two of the three female cadavers with the OBTCM in comparison to the standard. For both adult and paediatric, the implementation of the z-TCM data only for organ dose estimation resulted in 10.0% accuracy for the standard and fast-speed protocols, while relative dose differences were up to 15.3% for the OBTCM protocol. At identical CTDI vol values, the standard protocol delivered the lowest overall doses. Only for the OBTCM protocol is the 3D-TCM needed if an accurate (<10.0%) organ dosimetry is desired. • The z-TCM information is sufficient for accurate dosimetry for standard protocols. • The z-TCM information is sufficient for accurate dosimetry for fast-speed scanning protocols. • For organ-based TCM schemes, the 3D-TCM information is necessary for accurate dosimetry. • At identical CTDI vol , the fast-speed scanning protocol delivered the highest doses. • Lung dose was higher in XCare than standard protocol at identical CTDI vol .

A study on quantitative analysis of field size and dose by using gating system in 4D conformal radiation treatment

NASA Astrophysics Data System (ADS)

Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Chung, Woon-Kwan; Cho, Jae-Hwan; Lee, Hae-Kag

2012-10-01

This study evaluated the gating-based 4-D conformal radiation therapy (4D-CT) treatment planning by a comparison with the common 3-D conformal radiation therapy (3D-CT) treatment planning and examined the change in treatment field size and dose to the tumors and adjacent normal tissues because an unnecessary dose is also included in the 3-D treatment planning for the radiation treatment of tumors in the chest and abdomen. The 3D-CT and gating-based 4D-CT images were obtained from patients who had undergone radiation treatment for chest and abdomen tumors in the oncology department. After establishing a treatment plan, the CT treatment and planning system were used to measure the change in field size for analysis. A dose volume histogram (DVH) was used to calculate the appropriate dose to planning target volume (PTV) tumors and adjacent normal tissue. The difference in the treatment volume of the chest was 0.6 and 0.83 cm on the X- and Y-axis, respectively, for the gross tumor volume (GTV). Accordingly, the values in the 4D-CT treatment planning were smaller and the dose was more concentrated by 2.7% and 0.9% on the GTV and clinical target volume (CTV), respectively. The normal tissues in the surrounding normal tissues were reduced by 3.0%, 7.2%, 0.4%, 1.7%, 2.6% and 0.2% in the bronchus, chest wall, esophagus, heart, lung and spinal cord, respectively. The difference in the treatment volume of the abdomen was 0.72 cm on the X-axis and 0.51 cm on the Y-axis for the GTV; and 1.06 cm on the X-axis and 1.85 cm on the Y-axis for the PTV. Therefore, the values in the 4D-CT treatment planning were smaller. The dose was concentrated by 6.8% and 4.3% on the GTV and PTV, respectively, whereas the adjacent normal tissues in the cord, Lt. kidney, Rt. kidney, small bowels and whole liver were reduced by 3.2%, 4.2%, 1.5%, 6.2% and 12.7%, respectively. The treatment field size was smaller in volume in the case of the 4D-CT treatment planning. In the DVH, the 4D-CT treatment planning showed a higher dose concentration on the part to be treated than the 3D-CT treatment planning with a lower dose to the adjacent normal tissues. Overall, the gating-based 4D-CT treatment planning is believed to be more helpful than the 3D-CT treatment planning.

[Polymer Gel Dosimeter].

PubMed

Hayashi, Shin-Ichiro

2017-01-01

With rapid advances being made in radiotherapy treatment, three-dimensional (3D) dose measurement techniques of great precision are required more than ever before. It is expected that 3D polymer gel dosimeters will satisfy clinical needs for an effective detector that can measure the complex 3D dose distributions. Polymer gel dosimeters are devices that utilize the radiation-induced polymerization reactions of vinyl monomers in a gel to store information about radiation dose. The 3D absorbed dose distribution can be deduced from the resulting polymer distribution using several imaging modalities, such as MRI, X-ray and optical CTs. In this article, the fundamental characteristics of polymer gel dosimeter are reviewed and some challenging keys are also suggested for the widely spread in clinical use.

Estimates of Average Glandular Dose with Auto-modes of X-ray Exposures in Digital Breast Tomosynthesis.

PubMed

Kamal, Izdihar; Chelliah, Kanaga K; Mustafa, Nawal

2015-05-01

The aim of this research was to examine the average glandular dose (AGD) of radiation among different breast compositions of glandular and adipose tissue with auto-modes of exposure factor selection in digital breast tomosynthesis. This experimental study was carried out in the National Cancer Society, Kuala Lumpur, Malaysia, between February 2012 and February 2013 using a tomosynthesis digital mammography X-ray machine. The entrance surface air kerma and the half-value layer were determined using a 100H thermoluminescent dosimeter on 50% glandular and 50% adipose tissue (50/50) and 20% glandular and 80% adipose tissue (20/80) commercially available breast phantoms (Computerized Imaging Reference Systems, Inc., Norfolk, Virginia, USA) with auto-time, auto-filter and auto-kilovolt modes. The lowest AGD for the 20/80 phantom with auto-time was 2.28 milliGray (mGy) for two dimension (2D) and 2.48 mGy for three dimensional (3D) images. The lowest AGD for the 50/50 phantom with auto-time was 0.97 mGy for 2D and 1.0 mGy for 3D. The AGD values for both phantoms were lower against a high kilovolt peak and the use of auto-filter mode was more practical for quick acquisition while limiting the probability of operator error.

SU-E-T-472: A Multi-Dimensional Measurements Comparison to Analyze a 3D Patient Specific QA Tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashmeg, S; Jackson, J; Zhang, Y

Purpose: To quantitatively evaluate a 3D patient specific QA tool using 2D film and 3D Presage dosimetry. Methods: A brain IMRT case was delivered to Delta4, EBT2 film and Presage plastic dosimeter. The film was inserted in the solid water slabs at 7.5cm depth for measurement. The Presage dosimeter was inserted into a head phantom for 3D dose measurement. Delta4's Anatomy software was used to calculate the corresponding dose to the film in solid water slabs and to Presage in the head phantom. The results from Anatomy were compared to both calculated results from Eclipse and measured dose from filmmore » and Presage to evaluate its accuracy. Using RIT software, we compared the “Anatomy” dose to the EBT2 film measurement and the film measurement to ECLIPSE calculation. For 3D analysis, DICOM file of “Anatomy” was extracted and imported to CERR software, which was used to compare the Presage dose to both “Anatomy” calculation and ECLIPSE calculation. Gamma criteria of 3% - 3mm and 5% - 5mm was used for comparison. Results: Gamma passing rates of film vs “Anatomy”, “Anatomy” vs ECLIPSE and film vs ECLIPSE were 82.8%, 70.9% and 87.6% respectively when 3% - 3mm criteria is used. When the criteria is changed to 5% - 5mm, the passing rates became 87.8%, 76.3% and 90.8% respectively. For 3D analysis, Anatomy vs ECLIPSE showed gamma passing rate of 86.4% and 93.3% for 3% - 3mm and 5% - 5mm respectively. The rate is 77.0% for Presage vs ECLIPSE analysis. The Anatomy vs ECLIPSE were absolute dose comparison. However, film and Presage analysis were relative comparison Conclusion: The results show higher passing rate in 3D than 2D in “Anatomy” software. This could be due to the higher degrees of freedom in 3D than in 2D for gamma analysis.« less

Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Jian-Jian; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

2014-07-01

The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies includingmore » gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10 Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V{sub 10}) or 20 Gy (V{sub 20}) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V{sub 5} and D{sub 5}). The total mean monitor units (MUs) for V-MAT (621.0 ± 111.9) were 12.2% less than those for 3D-CRT (707.3 ± 130.9) and 46.5% less than those for IMRT (1161.4 ± 315.6) (p < 0.05). The average machine delivery time was 1.5 ± 0.2 minutes for the V-MAT plans, 7.0 ± 1.6 minutes for the 3D-CRT plans, and 11.5 ± 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms of MU and delivery time, V-MAT is significantly more efficient for APBI than for conventional 3D-CRT and static-beam IMRT.« less

Ultralow-dose CT of the craniofacial bone for navigated surgery using adaptive statistical iterative reconstruction and model-based iterative reconstruction: 2D and 3D image quality.

PubMed

Widmann, Gerlig; Schullian, Peter; Gassner, Eva-Maria; Hoermann, Romed; Bale, Reto; Puelacher, Wolfgang

2015-03-01

OBJECTIVE. The purpose of this article is to evaluate 2D and 3D image quality of high-resolution ultralow-dose CT images of the craniofacial bone for navigated surgery using adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) in comparison with standard filtered backprojection (FBP). MATERIALS AND METHODS. A formalin-fixed human cadaver head was scanned using a clinical reference protocol at a CT dose index volume of 30.48 mGy and a series of five ultralow-dose protocols at 3.48, 2.19, 0.82, 0.44, and 0.22 mGy using FBP and ASIR at 50% (ASIR-50), ASIR at 100% (ASIR-100), and MBIR. Blinded 2D axial and 3D volume-rendered images were compared with each other by three readers using top-down scoring. Scores were analyzed per protocol or dose and reconstruction. All images were compared with the FBP reference at 30.48 mGy. A nonparametric Mann-Whitney U test was used. Statistical significance was set at p < 0.05. RESULTS. For 2D images, the FBP reference at 30.48 mGy did not statistically significantly differ from ASIR-100 at 3.48 mGy, ASIR-100 at 2.19 mGy, and MBIR at 0.82 mGy. MBIR at 2.19 and 3.48 mGy scored statistically significantly better than the FBP reference (p = 0.032 and 0.001, respectively). For 3D images, the FBP reference at 30.48 mGy did not statistically significantly differ from all reconstructions at 3.48 mGy; FBP and ASIR-100 at 2.19 mGy; FBP, ASIR-100, and MBIR at 0.82 mGy; MBIR at 0.44 mGy; and MBIR at 0.22 mGy. CONCLUSION. MBIR (2D and 3D) and ASIR-100 (2D) may significantly improve subjective image quality of ultralow-dose images and may allow more than 90% dose reductions.

SU-E-T-154: Establishment and Implement of 3D Image Guided Brachytherapy Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, S; Zhao, S; Chen, Y

2014-06-01

Purpose: Cannot observe the dose intuitionally is a limitation of the existing 2D pre-implantation dose planning. Meanwhile, a navigation module is essential to improve the accuracy and efficiency of the implantation. Hence a 3D Image Guided Brachytherapy Planning System conducting dose planning and intra-operative navigation based on 3D multi-organs reconstruction is developed. Methods: Multi-organs including the tumor are reconstructed in one sweep of all the segmented images using the multiorgans reconstruction method. The reconstructed organs group establishs a three-dimensional visualized operative environment. The 3D dose maps of the three-dimentional conformal localized dose planning are calculated with Monte Carlo method whilemore » the corresponding isodose lines and isodose surfaces are displayed in a stereo view. The real-time intra-operative navigation is based on an electromagnetic tracking system (ETS) and the fusion between MRI and ultrasound images. Applying Least Square Method, the coordinate registration between 3D models and patient is realized by the ETS which is calibrated by a laser tracker. The system is validated by working on eight patients with prostate cancer. The navigation has passed the precision measurement in the laboratory. Results: The traditional marching cubes (MC) method reconstructs one organ at one time and assembles them together. Compared to MC, presented multi-organs reconstruction method has superiorities in reserving the integrality and connectivity of reconstructed organs. The 3D conformal localized dose planning, realizing the 'exfoliation display' of different isodose surfaces, helps make sure the dose distribution has encompassed the nidus and avoid the injury of healthy tissues. During the navigation, surgeons could observe the coordinate of instruments real-timely employing the ETS. After the calibration, accuracy error of the needle position is less than 2.5mm according to the experiments. Conclusion: The speed and quality of 3D reconstruction, the efficiency in dose planning and accuracy in navigation all can be improved simultaneously.« less

Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies

PubMed Central

Rouillon, Jérémy; Poupiot, Jérôme; Zocevic, Aleksandar; Amor, Fatima; Léger, Thibaut; Garcia, Camille; Camadro, Jean-Michel; Wong, Brenda; Pinilla, Robin; Cosette, Jérémie; Coenen-Stass, Anna M.L.; Mcclorey, Graham; Roberts, Thomas C.; Wood, Matthew J.A.; Servais, Laurent; Udd, Bjarne; Voit, Thomas; Richard, Isabelle; Svinartchouk, Fedor

2015-01-01

Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the myofibrillar structural protein myomesin-3 (MYOM3) are abnormally present in sera of Duchenne muscular dystrophy (DMD) patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels. In the LGMD model, where different doses of vector were used, MYOM3 restoration was dose-dependent. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders. PMID:26060189

Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

NASA Astrophysics Data System (ADS)

Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

2016-03-01

Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

PubMed

Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

2012-05-01

Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

Gastroprotective potential of Pentahydroxy flavone isolated from Madhuca indica J. F. Gmel. leaves against acetic acid-induced ulcer in rats: The role of oxido-inflammatory and prostaglandins markers.

PubMed

Mohod, Smeeta M; Kandhare, Amit D; Bodhankar, Subhash L

2016-04-22

Madhuca indica J. F. Gmel. (Sapotaceae) has shown antioxidant, anti-inflammatory, analgesic, anti-diabetic and hepatoprotective potential. It has been traditionally used as laxative, tonic, anti-burn, anti-earthworm, wound healing and headache. To investigate the efficacy and possible mechanism of Madhuca indica J. F. Gmel. leaves methanolic extract (MI-ALC) and its isolated chloroform fraction (D3) against experimental induced gastric ulcers. D3 was isolated from MI-ALC, well characterized (HPTLC, FT-IR, (1)H-NMR and LC-MS) and evaluated for its gastroprotective activity by using acetic acid induced ulcer in male Wistar rats (150-200g). D3 (2.5, 5 and 10mg/kg, p.o.) were administered for the period of 14 days. At the end of treatment, rats were sacrificed to collect the stomach sample for evaluation of antioxidant (SOD, GSH, and MDA) enzyme, oxido-inflammatory (TNF-α, IL-1, iNOs) and prostaglandins (COX-II) markers by using RT-PCR. The structure and molecular weight (MW) of the isolated compound (D3) were confirmed by 1D and 2D spectral data and characterized as 3,5,7,3',4'-Pentahydroxy flavone with MW C15H10O7. Administration of 3,5,7,3',4'-Pentahydroxy flavone (5 and 10mg/kg) significantly and dose-dependently inhibited (P<0.01 and P<0.001) acetic acid induced an alteration in the antioxidant enzyme. It also significantly and dose-dependently down-regulated gastric oxido-inflammatory and prostaglandins markers. Histopathological aberration induced in the stomach also attenuated by 3,5,7,3',4'-Pentahydroxy flavone treatment. Finding of present investigation suggests that MI-ALC possessed potent antiulcer activity due to the presence of 3,5,7,3',4'-Pentahydroxy flavone via its oxido-inflammatory and prostaglandins modulatory potential. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years.

PubMed

Puthanakit, Thanyawee; Huang, Li-Min; Chiu, Cheng-Hsun; Tang, Ren-Bin; Schwarz, Tino F; Esposito, Susanna; Frenette, Louise; Giaquinto, Carlo; McNeil, Shelly; Rheault, Paul; Durando, Paolo; Horn, Michael; Klar, Maximilian; Poncelet, Sylviane; De Simoni, Stéphanie; Friel, Damien; De Muynck, Benoit; Suryakiran, Pemmaraju V; Hezareh, Marjan; Descamps, Dominique; Thomas, Florence; Struyf, Frank

2016-08-15

This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years. Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety. Limits of noninferiority were predefined as <5% difference in seroconversion rate and <2-fold difference in geometric mean antibody titer ratio. One month after the last dose, both 2D regimens in girls aged 9-14 years were noninferior to 3D in women aged 15-25 years and 2D (M0,12) was noninferior to 2D (M0,6). Geometric mean antibody titer ratios (3D/2D) for HPV-16 and HPV-18 were 1.09 (95% confidence interval, .97-1.22) and 0.85 (.76-.95) for 2D (M0,6) versus 3D and 0.89 (.79-1.01) and 0.75 (.67-.85) for 2D (M0,12) versus 3D. The safety profile was clinically acceptable in all groups. The 2D regimens for the HPV-16/18 AS04-adjuvanted vaccine in girls aged 9-14 years (M0,6 or M0,12) elicited HPV-16/18 immune responses that were noninferior to 3D in women aged 15-25 years. NCT01381575. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Comparison of long-term (10 years) immunogenicity of two- and three-dose regimens of a combined hepatitis A and B vaccine in adolescents.

PubMed

Beran, Jiri; Kervyn, Diane; Wertzova, Veronika; Hobzova, Lenka; Tichy, Petr; Kuriyakose, Sherine; Leyssen, Maarten; Jacquet, Jeanne-Marie

2010-08-23

300 adolescents aged 12-15 years were randomised (1:1) into two groups to compare the long-term (10 years) immunogenicity profile of two doses of an Adult formulation [Group HAB_2D: 150; 0-6 months] vs. three doses of a Paediatric formulation [Group HAB_3D: 150; 0-1-6 months] of a combined hepatitis A and B (HAB) vaccine. At Year 10, anti-HAV seropositivity rate was 100% in both groups, while 85.9% and 85.1% subjects in the HAB_2D and HAB_3D groups, respectively, had anti-HBs antibody concentrations > or =10 mIU/mL. The anti-HAV antibody GMCs (HAB_2D: 429.3 mIU/mL; HAB_3D: 335.5 mIU/mL) and anti-HBs antibody GMCs (HAB_2D: 50.6 mIU/mL; HAB_3D: 60.1 mIU/mL) were similar in both groups. No vaccine-related serious adverse events were reported. Hence, with respect to long-term antibody persistence, the two-dose schedule of the combined HAB vaccine Adult formulation is an effective alternative to the conventional three-dose schedule of the Paediatric formulation in adolescents. Copyright 2010 Elsevier Ltd. All rights reserved.

A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors.

PubMed

Aghajanian, Carol; Bell-McGuinn, Katherine M; Burris, Howard A; Siu, Lillian L; Stayner, Lee-Ann; Wheler, Jennifer J; Hong, David S; Kurkjian, Carla; Pant, Shubham; Santiago-Walker, Ademi; Gauvin, Jennifer L; Antal, Joyce M; Opalinska, Joanna B; Morris, Shannon R; Infante, Jeffrey R

2018-04-03

Background We sought to determine the recommended phase II dose (RP2D) and schedule of GSK2141795, an oral pan-AKT kinase inhibitor. Patients and Methods Patients with solid tumors were enrolled in the dose-escalation phase. Pharmacokinetic (PK) analysis after a single dose (Cycle 0) informed dose escalation using accelerated dose titration. Once one grade 2 toxicity or dose-limiting toxicity was observed in Cycle 1, the accelerated dose titration was terminated and a 3 + 3 dose escalation was started. Continuous daily dosing was evaluated along with two intermittent regimens (7 days on/7 days off and 3 times per week). In the expansion phase at RP2D, patients with endometrial or prostate cancer, as well as those with select tumor types with a PIK3CA mutation, AKT mutation or PTEN loss, were enrolled. Patients were evaluated for adverse events (AEs), PK parameters, blood glucose and insulin levels, and tumor response. Results The RP2D of GSK2141795 for once-daily dosing is 75 mg. The most common (>10%) treatment-related AEs included diarrhea, fatigue, vomiting, and decreased appetite. Most AEs were low grade. The frequency of hyperglycemia increased with dose; however, at the RP2D, grade 3 hyperglycemia was only reported in 4% of patients and no grade 4 events were observed. PK characteristics were favorable, with a prolonged half-life and low peak-to-trough ratio. There were two partial responses at the RP2D in patients with either a PIK3CA mutation or PTEN loss. Conclusion GSK2141795 was safe and well-tolerated, with clinical activity seen as monotherapy at the RP2D of 75 mg daily. NCT00920257.

Beam Path Toxicities to Non-Target Structures During Intensity-Modulated Radiation Therapy for Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, David I.; Chambers, Mark S.; Fuller, Clifton D.

2008-11-01

Background: Intensity-modulated radiation therapy (IMRT) beams traverse nontarget normal structures not irradiated during three-dimensional conformal RT (3D-CRT) for head and neck cancer (HNC). This study estimates the doses and toxicities to nontarget structures during IMRT. Materials and Methods: Oropharyngeal cancer IMRT and 3D-CRT cases were reviewed. Dose-volume histograms (DVH) were used to evaluate radiation dose to the lip, cochlea, brainstem, occipital scalp, and segments of the mandible. Toxicity rates were compared for 3D-CRT, IMRT alone, or IMRT with concurrent cisplatin. Descriptive statistics and exploratory recursive partitioning analysis were used to estimate dose 'breakpoints' associated with observed toxicities. Results: A totalmore » of 160 patients were evaluated for toxicity; 60 had detailed DVH evaluation and 15 had 3D-CRT plan comparison. Comparing IMRT with 3D-CRT, there was significant (p {<=} 0.002) nonparametric differential dose to all clinically significant structures of interest. Thirty percent of IMRT patients had headaches and 40% had occipital scalp alopecia. A total of 76% and 38% of patients treated with IMRT alone had nausea and vomiting, compared with 99% and 68%, respectively, of those with concurrent cisplatin. IMRT had a markedly distinct toxicity profile than 3D-CRT. In recursive partitioning analysis, National Cancer Institute's Common Toxicity Criteria adverse effects 3.0 nausea and vomiting, scalp alopecia and anterior mucositis were associated with reconstructed mean brainstem dose >36 Gy, occipital scalp dose >30 Gy, and anterior mandible dose >34 Gy, respectively. Conclusions: Dose reduction to specified structures during IMRT implies an increased beam path dose to alternate nontarget structures that may result in clinical toxicities that were uncommon with previous, less conformal approaches. These findings have implications for IMRT treatment planning and research, toxicity assessment, and multidisciplinary patient management.« less

SU-D-213-05: Design, Evaluation and First Applications of a Off-Site State-Of-The-Art 3D Dosimetry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malcolm, J; Mein, S; McNiven, A

2015-06-15

Purpose: To design, construct and commission a prototype in-house three dimensional (3D) dose verification system for stereotatic body radiotherapy (SBRT) verification at an off-site partner institution. To investigate the potential of this system to achieve sufficient performance (1mm resolution, 3% noise, within 3% of true dose reading) for SBRT verification. Methods: The system was designed utilizing a parallel ray geometry instigated by precision telecentric lenses and an LED 630nm light source. Using a radiochromic dosimeter, a 3D dosimetric comparison with our gold-standard system and treatment planning software (Eclipse) was done for a four-field box treatment, under gamma passing criteria ofmore » 3%/3mm/10% dose threshold. Post off-site installation, deviations in the system’s dose readout performance was assessed by rescanning the four-field box irradiated dosimeter and using line-profiles to compare on-site and off-site mean and noise levels in four distinct dose regions. As a final step, an end-to-end test of the system was completed at the off-site location, including CT-simulation, irradiation of the dosimeter and a 3D dosimetric comparison of the planned (Pinnacle{sup 3}) to delivered dose for a spinal SBRT treatment(12 Gy per fraction). Results: The noise level in the high and medium dose regions of the four field box treatment was relatively 5% pre and post installation. This reflects the reduction in positional uncertainty through the new design. This At 1mm dose voxels, the gamma pass rates(3%,3mm) for our in-house gold standard system and the off-site system were comparable at 95.8% and 93.2% respectively. Conclusion: This work will describe the end-to-end process and results of designing, installing, and commissioning a state-of-the-art 3D dosimetry system created for verification of advanced radiation treatments including spinal radiosurgery.« less

Vitamin D Replacement in Children, Adolescents and Pregnant Women in the Middle East and North Africa

PubMed Central

Chakhtoura, M; El Ghandour, S; Shawwa, K; Akl, EA; Arabi, A; Mahfoud, Z; Habib, RH; Hoballah, H; El Hajj Fuleihan, G

2017-01-01

Introduction Hypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region. Objective To evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes. Methods This is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (< 800 IU), intermediate (800–2,000 IU) or high (> 2,000 IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3. Results We identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women. In children and adolescents, an intermediate vitamin D dose (1,901 IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% Confidence Interval (CI) 8.1;18.8) ng/ml, compared to placebo, favoring the intermediate dose (p < 0.001). The proportion of children and adolescents reaching a 25(OH)D level ≥ 20 ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12–16 weeks of gestation and continued until delivery, and six trials started supplementation at 20–28 weeks gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3–11.9) ng/ml (p <0.001) comparing the high dose (3,662 IU/d) to the intermediate dose (1,836 IU/d), and 12.3 (95% CI 6.4–18.2) ng/ml (p <0.001), comparing the high dose (3,399 IU/d) to the low dose (375 IU/d). Comparing the intermediate (1,832 IU/d) to the low dose (301 IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5–10.8) ng/ml (p < 0.001). The proportion of pregnant women reaching a 25(OH)D level ≥ 20 ng/ml was 80–90%, 73% and 27–43% in the high, intermediate, and low dose groups, respectively. The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high. Conclusion In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1,000–2,000 IU seems necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20 ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes. PMID:28403940

Evaluation of Sentinel Lymph Node Dose Distribution in 3D Conformal Radiotherapy Techniques in 67 pN0 Breast Cancer Patients.

PubMed

Witucki, Gerlo; Degregorio, Nikolaus; Rempen, Andreas; Schwentner, Lukas; Bottke, Dirk; Janni, Wolfgang; Ebner, Florian

2015-01-01

Introduction. The anatomic position of the sentinel lymph node is variable. The purpose of the following study was to assess the dose distribution delivered to the surgically marked sentinel lymph node site by 3D conformal radio therapy technique. Material and Method. We retrospectively analysed 70 radiotherapy (RT) treatment plans of consecutive primary breast cancer patients with a successful, disease-free, sentinel lymph node resection. Results. In our case series the SN clip volume received a mean dose of 40.7 Gy (min 28.8 Gy/max 47.6 Gy). Conclusion. By using surgical clip markers in combination with 3D CT images our data supports the pathway of tumouricidal doses in the SN bed. The target volume should be defined by surgical clip markers and 3D CT images to give accurate dose estimations.

A Dosimetry Study of Deuterium-Deuterium Neutron Generator-based In Vivo Neutron Activation Analysis.

PubMed

Sowers, Daniel; Liu, Yingzi; Mostafaei, Farshad; Blake, Scott; Nie, Linda H

2015-12-01

A neutron irradiation cavity for in vivo neutron activation analysis (IVNAA) to detect manganese, aluminum, and other potentially toxic elements in human hand bone has been designed and its dosimetric specifications measured. The neutron source is a customized deuterium-deuterium neutron generator that produces neutrons at 2.45 MeV by the fusion reaction 2H(d, n)3He at a calculated flux of 7 × 10(8) ± 30% s(-1). A moderator/reflector/shielding [5 cm high density polyethylene (HDPE), 5.3 cm graphite and 5.7 cm borated (HDPE)] assembly has been designed and built to maximize the thermal neutron flux inside the hand irradiation cavity and to reduce the extremity dose and effective dose to the human subject. Lead sheets are used to attenuate bremsstrahlung x rays and activation gammas. A Monte Carlo simulation (MCNP6) was used to model the system and calculate extremity dose. The extremity dose was measured with neutron and photon sensitive film badges and Fuji electronic pocket dosimeters (EPD). The neutron ambient dose outside the shielding was measured by Fuji NSN3, and the photon dose was measured by a Bicron MicroREM scintillator. Neutron extremity dose was calculated to be 32.3 mSv using MCNP6 simulations given a 10-min IVNAA measurement of manganese. Measurements by EPD and film badge indicate hand dose to be 31.7 ± 0.8 mSv for neutrons and 4.2 ± 0.2 mSv for photons for 10 min; whole body effective dose was calculated conservatively to be 0.052 mSv. Experimental values closely match values obtained from MCNP6 simulations. These are acceptable doses to apply the technology for a manganese toxicity study in a human population.

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Shen, J; Stoker, J

2015-06-15

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

A Quality Assurance Method that Utilizes 3D Dosimetry and Facilitates Clinical Interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oldham, Mark, E-mail: mark.oldham@duke.edu; Thomas, Andrew; O'Daniel, Jennifer

2012-10-01

Purpose: To demonstrate a new three-dimensional (3D) quality assurance (QA) method that provides comprehensive dosimetry verification and facilitates evaluation of the clinical significance of QA data acquired in a phantom. Also to apply the method to investigate the dosimetric efficacy of base-of-skull (BOS) intensity-modulated radiotherapy (IMRT) treatment. Methods and Materials: Two types of IMRT QA verification plans were created for 6 patients who received BOS IMRT. The first plan enabled conventional 2D planar IMRT QA using the Varian portal dosimetry system. The second plan enabled 3D verification using an anthropomorphic head phantom. In the latter, the 3D dose distribution wasmore » measured using the DLOS/Presage dosimetry system (DLOS = Duke Large-field-of-view Optical-CT System, Presage Heuris Pharma, Skillman, NJ), which yielded isotropic 2-mm data throughout the treated volume. In a novel step, measured 3D dose distributions were transformed back to the patient's CT to enable calculation of dose-volume histograms (DVH) and dose overlays. Measured and planned patient DVHs were compared to investigate clinical significance. Results: Close agreement between measured and calculated dose distributions was observed for all 6 cases. For gamma criteria of 3%, 2 mm, the mean passing rate for portal dosimetry was 96.8% (range, 92.0%-98.9%), compared to 94.9% (range, 90.1%-98.9%) for 3D. There was no clear correlation between 2D and 3D passing rates. Planned and measured dose distributions were evaluated on the patient's anatomy, using DVH and dose overlays. Minor deviations were detected, and the clinical significance of these are presented and discussed. Conclusions: Two advantages accrue to the methods presented here. First, treatment accuracy is evaluated throughout the whole treated volume, yielding comprehensive verification. Second, the clinical significance of any deviations can be assessed through the generation of DVH curves and dose overlays on the patient's anatomy. The latter step represents an important development that advances the clinical relevance of complex treatment QA.« less

Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1.

PubMed

Dauletbaev, N; Herscovitch, K; Das, M; Chen, H; Bernier, J; Matouk, E; Bérubé, J; Rousseau, S; Lands, L C

2015-10-01

There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms. © 2015 The British Pharmacological Society.

Preliminary study of the dosimetric characteristics of 3D-printed materials with megavoltage photons

NASA Astrophysics Data System (ADS)

Jeong, Seonghoon; Yoon, Myonggeun; Chung, Weon Kuu; Kim, Dong Wook

2015-07-01

These days, 3D-printers are on the rise in various fields including radiation therapy. This preliminary study aimed to estimate the dose characteristics of 3D-printer materials that could be used as compensators or immobilizers in radiation treatment. The cubes with length of 5 cm and different densities of 50%, 75% and 100% were printed by using a 3D-printer. Planning CT scans of the cubes were performed by using a CT simulator (Brilliance CT, Philips Medical System, Netherlands). Dose distributions behind the cube were calculated after a 6 MV photon beam had passed through the cube. The dose responses for the 3D-printed cube, air and water were measured by using EBT3 film and a 2D array detector. When the results of air case were normalized to 100, the dose calculated by the TPS and the measured doses to 50% and 75% cube were of the 96 ~ 99. The measured and the calculated doses to water and to 100% of the cube were 82 ~ 84. The HU values for the 50%, 75% and 100% density cases were -910, -860 and -10, respectively. The dose characteristics of the 50% and the 75% products were similar to that of air while the 100% product seemed to be similar to that of water. This information will provide guidelines for making an immobilization tool that can play the role of a compensator and for making a real human phantom that can exactly describe the inside of the human body. This study was necessary for Poly Lactic Acid (PLA) based 3D-printer users who are planning to make something related to radiation therapy.

Vitamin D Uptake in Patients Treated with a High-Dosed Purified Omega-3 Compound in a Randomized Clinical Trial Following an Acute Myocardial Infarction.

PubMed

Naesgaard, Patrycja A; Grundt, Heidi; Nordøy, Arne F; Staines, Harry; Nilsen, Dennis W T

2017-01-01

Fish is the natural dietary source of vitamin D. Reports on the influence of purified omega-3 fatty acids on its uptake are scarce. We investigated the impact of a purified high-dose omega-3 compound compared to corn oil on 25-hydroxyvitamin D [25(OH)D] levels following an acute myocardial infarction. 228 patients were randomized 1:1 to receive a daily dose of either 4 g omega-3 (OMACOR ® ) or an equal dose of corn oil, administered double-blindly for 12 months. Total omega-3 and omega-6 measurements were available in 40 randomly picked patients. There was no significant intergroup difference in 25(OH)D changes at 12 months follow-up ( p  = 0.12), but there was a minor statistical significant intragroup increase in 25(OH)D in both intervention arms ( p  < 0.001 for n-3 polyunsaturated fatty acids and p  = 0.013 for corn oil, respectively). A positive correlation was noted between 25(OH)D and omega-3 prior to inclusion; r  = 0.418, p  = 0.007, attenuated at 12 months by purified omega-3 intervention; r  = 0.021, p  = 0.93. No positive correlation was observed between omega-6 and 25(OH)D. Long-term treatment with a high dose of purified omega-3 as compared to corn oil did not improve serum concentrations of vitamin D. ClinicalTrials.gov, Identifier: NCT01422317.

Monte Carlo study of the influence of energy spectra, mesh size, high Z element on dose and PVDR based on 1-D and 3-D heterogeneous mouse head phantom for Microbeam Radiation Therapy.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Mao, Xiaoli

2017-12-01

To evaluate the influence of energy spectra, mesh sizes, high Z element on dose and PVDR in Microbeam Radiation Therapy (MRT) based on 1-D analogy-mouse-head-model (1-D MHM) and 3-D voxel-mouse-head-phantom (3-D VMHP) by Monte Carlo simulation. A Microbeam-Array-Source-Model was implemented into EGSnrc/DOSXYZnrc. The microbeam size is assumed to be 25μm, 50μm or 75μm in thickness and fixed 1mm in height with 200μmc-t-c. The influence of the energy spectra of ID17@ESRF and BMIT@CLS were investigated. The mesh size was optimized. PVDR in 1-D MHM and 3-D VMHP was compared with the homogeneous water phantom. The arc influence of 3-D VMHP filled with water (3-D VMHWP) was compared with the rectangle phantom. PVDR of the lower BMIT@CLS spectrum is 2.4times that of ID17@ESRF for lower valley dose. The optimized mesh is 5µm for 25µm, and 10µm for 50µm and 75µm microbeams with 200µmc-t-c. A 500μm skull layer could make PVDR difference up to 62.5% for 1-D MHM. However this influence is limited (<5%) for the farther homogeneous media (e.g. 600µm). The peak dose uniformity of 3-D VMHP at the same depth could be up to 8% for 1.85mm×1mm irradiation field, whereas that of 3-D VMHWP is<1%. The high Z element makes the dose uniformity enhance in target. The surface arc could affect the superficial PVDR (from 44% to 21% in 0.2mm depth), whereas this influence is limited for the more depth (<1%). An accurate MRT dose calculation algorithm should include the influence of 3-D heterogeneous media. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

Decreasing Temporal Lobe Dose With Five-Field Intensity-Modulated Radiotherapy for Treatment of Pituitary Macroadenomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parhar, Preeti K.; Duckworth, Tamara; Shah, Parinda

2010-10-01

Purpose: To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Methods and Materials: Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV)more » = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Results: Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving {>=}25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10{sup -7} for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Conclusions: Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.« less

Impact of Three Doses of Vitamin D3 on Serum 25(OH)D Deficiency and Insufficiency in At-Risk Schoolchildren.

PubMed

Sacheck, Jennifer M; Van Rompay, Maria I; Chomitz, Virginia R; Economos, Christina D; Eliasziw, Misha; Goodman, Elizabeth; Gordon, Catherine M; Holick, Michael F

2017-12-01

We investigated the daily dose of vitamin D needed to achieve serum 25-hydroxyvitamin D [25(OH)D] sufficiency among schoolchildren at risk for deficiency. The Daily D Health Study was a randomized double-blind vitamin D supplementation trial among racially/ethnically diverse schoolchildren (n = 685) in the northeastern United States. Children were supplemented with vitamin D3 at 600, 1000, or 2000 IU/d for 6 months. Measurements included serum 25(OH)D at baseline (October to December), 3 months (January to March), 6 months (April to June), and 12 months (6 months after supplementation). At baseline, mean ± standard deviation serum 25(OH)D level was 22.0 ± 6.8 ng/mL, with 5.5% severely vitamin D deficient (<12 ng/mL), 34.1% deficient (12 to 19 ng/mL), 49.0% insufficient (20 to 29 ng/mL), and 11.4% sufficient (≥30 ng/mL). The lowest levels of serum 25(OH)D were found among black (17.9 ± 6.7 ng/mL) and Asian children (18.9 ± 4.8 ng/mL), with no baseline differences by weight status. Serum 25(OH)D increased over 6 months in all three dose groups. The 2000 IU/d group achieved a higher mean serum 25(OH)D level than the other two dose groups (33.1 vs 26.3 and 27.5 ng/mL; P < 0.001), with 59.9% of this group attaining sufficiency at 3 months and only 5.3% remaining severely deficient/deficient at 6 months. All dose groups demonstrated a fall in 25(OH)D at 12 months. Children at risk for vitamin D deficiency benefited from daily sustained supplementation of 2000 IU/d compared with lower doses closer to the current recommended daily allowance for vitamin D intake. This benefit occurred over the winter months, when serum 25(OH)D level tend to fall. Copyright © 2017 Endocrine Society

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters.

PubMed

Bache, Steven T; Juang, Titania; Belley, Matthew D; Koontz, Bridget F; Adamovics, John; Yoshizumi, Terry T; Kirsch, David G; Oldham, Mark

2015-02-01

Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1-15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm(3)) optical computed tomography (optical-CT) dose read-out. Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.

Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

PubMed Central

Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Adamovics, John; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark

2015-01-01

Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm3) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT. PMID:25652497

Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bache, Steven T.; Juang, Titania; Belley, Matthew D.

Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm{sup 3}) opticalmore » computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiyagarajan, Rajesh; Vikraman, S; Karrthick, KP

Purpose: To evaluate the impact of dose calculation algorithm on the dose distribution of biologically optimized Volumatric Modulated Arc Therapy (VMAT) plans for Esophgeal cancer. Methods: Eighteen retrospectively treated patients with carcinoma esophagus were studied. VMAT plans were optimized using biological objectives in Monaco (5.0) TPS for 6MV photon beam (Elekta Infinity). These plans were calculated for final dose using Monte Carlo (MC), Collapsed Cone Convolution (CCC) & Pencil Beam Convolution (PBC) algorithms from Monaco and Oncentra Masterplan TPS. A dose grid of 2mm was used for all algorithms and 1% per plan uncertainty maintained for MC calculation. MC basedmore » calculations were considered as the reference for CCC & PBC. Dose volume histogram (DVH) indices (D95, D98, D50 etc) of Target (PTV) and critical structures were compared to study the impact of all three algorithms. Results: Beam models were consistent with measured data. The mean difference observed in reference with MC calculation for D98, D95, D50 & D2 of PTV were 0.37%, −0.21%, 1.51% & 1.18% respectively for CCC and 3.28%, 2.75%, 3.61% & 3.08% for PBC. Heart D25 mean difference was 4.94% & 11.21% for CCC and PBC respectively. Lung Dmean mean difference was 1.5% (CCC) and 4.1% (PBC). Spinal cord D2 mean difference was 2.35% (CCC) and 3.98% (PBC). Similar differences were observed for liver and kidneys. The overall mean difference found for target and critical structures was 0.71±1.52%, 2.71±3.10% for CCC and 3.18±1.55%, 6.61±5.1% for PBC respectively. Conclusion: We observed a significant overestimate of dose distribution by CCC and PBC as compared to MC. The dose prediction of CCC is closer (<3%) to MC than that of PBC. This can be attributed to poor performance of CCC and PBC in inhomogeneous regions around esophagus. CCC can be considered as an alternate in the absence of MC algorithm.« less

SU-F-BRF-13: Investigating the Feasibility of Accurate Dose Measurement in a Deforming Radiochromic Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juang, T; Adamovics, J; Oldham, M

Purpose: Presage-Def, a deformable radiochromic 3D dosimeter, has been previously shown to have potential for validating deformable image registration algorithms. This work extends this effort to investigate the feasibility of using Presage-Def to validate dose-accumulation algorithms in deforming structures. Methods: Two cylindrical Presage-Def dosimeters (8cm diameter, 4.5cm length) were irradiated in a water-bath with a simple 4-field box treatment. Isocentric dose was 20Gy. One dosimeter served as control (no deformation) while the other was laterally compressed during irradiation by 21%. Both dosimeters were imaged before and after irradiation with a fast (∼10 minutes for 1mm isotropic resolution), broad beam, highmore » resolution optical-CT scanner. Measured dose distributions were compared to corresponding distributions calculated by a commissioned Eclipse planning system. Accuracy in the control was evaluated with 3D gamma (3%/3mm). The dose distribution calculated for the compressed dosimeter in the irradiation geometry cannot be directly compared via profiles or 3D gamma to the measured distribution, which deforms with release from compression. Thus, accuracy under deformation was determined by comparing integral dose within the high dose region of the deformed dosimeter distribution versus calculated dose. Dose profiles were used to study temporal stability of measured dose distributions. Results: Good dose agreement was demonstrated in the control with a 3D gamma passing rate of 96.6%. For the dosimeter irradiated under compression, the measured integral dose in the high dose region (518.0Gy*cm3) was within 6% of the Eclipse-calculated integral dose (549.4Gy*cm3). Elevated signal was noted on the dosimeter edge in the direction of compression. Change in dosimeter signal over 1.5 hours was ≤2.7%, and the relative dose distribution remained stable over this period of time. Conclusion: Presage-Def is promising as a 3D dosimeter capable of accurately measuring dose in a deforming structure, and warrants further study to quantify comprehensive accuracy at different levels of deformation. This work was supported by NIH R01CA100835. John Adamovics is the president of Heuris Inc., which commercializes PRESAGE.« less

A method for modeling laterally asymmetric proton beamlets resulting from collimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gelover, Edgar; Wang, Dongxu; Flynn, Ryan T.

2015-03-15

Purpose: To introduce a method to model the 3D dose distribution of laterally asymmetric proton beamlets resulting from collimation. The model enables rapid beamlet calculation for spot scanning (SS) delivery using a novel penumbra-reducing dynamic collimation system (DCS) with two pairs of trimmers oriented perpendicular to each other. Methods: Trimmed beamlet dose distributions in water were simulated with MCNPX and the collimating effects noted in the simulations were validated by experimental measurement. The simulated beamlets were modeled analytically using integral depth dose curves along with an asymmetric Gaussian function to represent fluence in the beam’s eye view (BEV). The BEVmore » parameters consisted of Gaussian standard deviations (sigmas) along each primary axis (σ{sub x1},σ{sub x2},σ{sub y1},σ{sub y2}) together with the spatial location of the maximum dose (μ{sub x},μ{sub y}). Percent depth dose variation with trimmer position was accounted for with a depth-dependent correction function. Beamlet growth with depth was accounted for by combining the in-air divergence with Hong’s fit of the Highland approximation along each axis in the BEV. Results: The beamlet model showed excellent agreement with the Monte Carlo simulation data used as a benchmark. The overall passing rate for a 3D gamma test with 3%/3 mm passing criteria was 96.1% between the analytical model and Monte Carlo data in an example treatment plan. Conclusions: The analytical model is capable of accurately representing individual asymmetric beamlets resulting from use of the DCS. This method enables integration of the DCS into a treatment planning system to perform dose computation in patient datasets. The method could be generalized for use with any SS collimation system in which blades, leaves, or trimmers are used to laterally sharpen beamlets.« less

Out-of-field doses from pediatric craniospinal irradiations using 3D-CRT, IMRT, helical tomotherapy and electron-based therapy

NASA Astrophysics Data System (ADS)

De Saint-Hubert, Marijke; Verellen, Dirk; Poels, Kenneth; Crijns, Wouter; Magliona, Federica; Depuydt, Tom; Vanhavere, Filip; Struelens, Lara

2017-07-01

Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e. craniospinal irradiation (CSI). This is associated with the significant exposure of large volumes of healthy tissue and there is growing concern regarding treatment-associated side effects. The current study compares out-of-field organ doses in children receiving CSI through 3D-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, and includes radiation doses resulting from imaging performed during treatment. An extensive phantom study is performed, using an anthropomorphic phantom corresponding to a five year old child, in which organ absorbed doses are measured using thermoluminescent detectors. Additionally, the study evaluates and explores tools for calculating out-of-field patient doses using the treatment planning system (TPS) and analytical models. In our study, 3D-CRT resulted in very high doses to a limited number of organs, while it was able to spare organs such as the lungs and breast when compared to IMRT and HT. Both IMRT and HT spread the dose over more organs and were able to spare the heart, thyroid, bladder, uterus and testes when compared to 3D-CRT. The electron-based technique considerably decreased the out-of-field doses in deep-seated organs but could not avoid nearby out-of-field organs such as the lungs, ribs, adrenals, kidneys and uterus. The daily imaging dose is small compared to the treatment dose burden. The TPS error for out-of-field doses was most pronounced for organs further away from the target; nevertheless, no systematic underestimation was observed for any of the studied TPS systems. Finally, analytical modeling was most optimal for 3D-CRT although the number of organs that could be modeled was limited. To conclude, none of the techniques studied was capable of sparing all organs from out-of-field doses. Nevertheless, the electron-based technique showed the most promise for out-of-field organ dose reduction during CSI when compared to photon techniques.

Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on-treatment EPID images and a model-based forward-calculation algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Uytven, Eric, E-mail: eric.vanuytven@cancercare.mb.ca; Van Beek, Timothy; McCowan, Peter M.

2015-12-15

Purpose: Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model-based technique to compute full three-dimensional patient dose reconstructed from on-treatment EPID portal images (i.e., transmission images). Methods: EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back-projecting the primary source component of the EPID fluence upstream of themore » patient. Incident fluence is then recombined with predicted extra-focal fluence and used to calculate 3D patient dose via a collapsed-cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT). Results: Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build-up region). Conclusions: An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient data sets, as well as for dynamic IMRT and VMAT delivery techniques. Results indicate that the EPID dose reconstruction algorithm presented in this work is suitable for clinical implementation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venencia, C; Pino, M; Caussa, L

Purpose: The purpose of this work was to quantify the dosimetric impact of Monte Carlo (MC) dose calculation algorithm compared to Pencil Beam (PB) on Spine SBRT with HybridARC (HA) and sliding windows IMRT (dMLC) treatment modality. Methods: A 6MV beam (1000MU/min) produced by a Novalis TX (BrainLAB-Varian) equipped with HDMLC was used. HA uses 1 arc plus 8 IMRT beams (arc weight between 60–40%) and dIMRT 15 beams. Plans were calculated using iPlan v.4.5.3 (BrainLAB) and the treatment dose prescription was 27Gy in 3 fractions. Dose calculation was done by PB (4mm spatial resolution) with heterogeneity correction and MCmore » dose to water (4mm spatial resolution and 4% mean variance). PTV and spinal cord dose comparison were done. Study was done on 12 patients. IROC Spine Phantom was used to validate HA and quantify dose variation using PB and MC algorithm. Results: The difference between PB and MC for PTV D98%, D95%, Dmean, D2% were 2.6% [−5.1, 6.8], 0.1% [−4.2, 5.4], 0.9% [−1.5, 3.8] and 2.4% [−0.5, 8.3]. The difference between PB and MC for spinal cord Dmax, D1.2cc and D0.35cc were 5.3% [−6.4, 18.4], 9% [−7.0, 17.0] and 7.6% [−0.6, 14.8] respectively. IROC spine phantom shows PTV TLD dose variation of 0.98% for PB and 1.01% for MC. Axial and sagittal film plane gamma index (5%-3mm) was 95% and 97% for PB and 95% and 99% for MC. Conclusion: PB slightly underestimates the dose for the PTV. For the spinal cord PB underestimates the dose and dose differences could be as high as 18% which could have unexpected clinical impact. CI shows no variation between PB and MC for both treatment modalities Treatment modalities have no impact with the dose calculation algorithms used. Following the IROC pass-fail criteria, treatment acceptance requirement was fulfilled for PB and MC.« less

Effect of maternal vitamin A supplementation on retinol concentration in colostrum.

PubMed

Grilo, Evellyn C; Lima, Mayara S R; Cunha, Lahyana R F; Gurgel, Cristiane S S; Clemente, Heleni A; Dimenstein, Roberto

2015-01-01

To investigate the effect of vitamin A supplementation on the retinol concentration in colostrum under fasting and postprandial conditions. This was a quasi-experimental study, with before and after assessments, conducted with 33 patients treated at a public maternity hospital. Blood and colostrum samples were collected under fasting conditions in the immediate postpartum period. A second colostrum collection occurred two hours after the first meal of the day, at which time a mega dose of 200,000 IU of retinyl palmitate was administered. On the following day, the colostrum was collected again under fasting and postprandial conditions. Serum and colostrum retinol concentrations were determined by high performance liquid chromatography. The serum retinol concentration was 37.3 (16.8-62.2) μg/dL, indicating adequate nutritional status. The colostrum retinol concentration before supplementation was 46.8 (29.7-158.9) μg/dL in fasting and 67.3 (31.1-148.7) μg/dL in postprandial condition (p < 0.05), showing an increase of 43.8%. After supplementation, the values were 89.5 (32.9-264.2) μg/dL and 102.7 (37.3-378.3) μg/dL in fasting and postprandial conditions, respectively (p < 0.05), representing an increase of 14.7%. This study demonstrated that maternal supplementation with high doses of vitamin A in postpartum resulted in a significant increase of the retinol concentration in colostrum under fasting conditions, with an even greater increase after a meal. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors.

PubMed

Jimeno, Antonio; Gordon, Michael; Chugh, Rashmi; Messersmith, Wells; Mendelson, David; Dupont, Jakob; Stagg, Robert; Kapoun, Ann M; Xu, Lu; Uttamsingh, Shailaja; Brachmann, Rainer K; Smith, David C

2017-12-15

Purpose: Wnt signaling is implicated in tumor cell dedifferentiation and cancer stem cell function. Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands. This trial evaluated ipafricept in patients with solid tumors. Experimental design: A 3+3 design was used; ipafricept was given intravenously every 3 weeks. The objectives were determination of dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy. Results: 26 patients were treated in seven dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15, and 20 mg/kg). No further dose escalation was pursued as PK modeling indicated that the target efficacious dose was reached at 10 mg/kg, and fragility fractures occurred at 20 mg/kg. Most common related grade 1 and 2 adverse events (AEs; ≥20% of patients) were dysgeusia, decreased appetite, fatigue, and muscle spasms. Ipafricept-related grade 3 TEAEs included hypophosphatemia and weight decrease (1 subject each, 3.8%). Ipafricept half-life was ∼4 days and had low incidence of antidrug antibody formation (7.69%) with no impact on drug exposure. Six patients had β-C-terminal telopeptide (β-CTX) doubling from baseline, which was reversible. PD modulation of Wnt pathway genes in hair follicles occurred ≥2.5 mg/kg. Two desmoid tumor and a germ cell cancer patient experienced stable disease for >6 months. Conclusions: Ipafricept was well tolerated, with RP2D of 15 mg/kg Q3W. Prolonged SD was noted in desmoid tumor and germ cell cancer patients. Clin Cancer Res; 23(24); 7490-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Pharmacodynamics of Amphotericin B Deoxycholate, Amphotericin B Lipid Complex, and Liposomal Amphotericin B against Aspergillus fumigatus

PubMed Central

Al-Nakeeb, Zaid; Petraitis, Vidmantas; Goodwin, Joanne; Petraitiene, Ruta; Walsh, Thomas J.

2015-01-01

Amphotericin B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known about the pharmacodynamics of amphotericin B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAMB), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (LAMB) by using a neutropenic-rabbit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1→3)-β-d-glucan. Mathematical models were used to describe PK-PD relationships. The experimental findings were bridged to humans by Monte Carlo simulation. Each amphotericin B formulation induced a dose-dependent decline in study endpoints. Near-maximal antifungal activity was evident with DAMB at 1 mg/kg/day and ABLC and LAMB at 5 mg/kg/day. The bridging study suggested that the “average” patient receiving LAMB at 3 mg/kg/day was predicted to have complete suppression of galactomannan and (1→3)-β-d-glucan levels, but 20 to 30% of the patients still had a galactomannan index of >1 and (1→3)-β-d-glucan levels of >60 pg/ml. All formulations of amphotericin B induce a dose-dependent reduction in markers of lung injury and circulating fungus-related biomarkers. A clinical dosage of liposomal amphotericin B of 3 mg/kg/day is predicted to cause complete suppression of galactomannan and (1→3)-β-d-glucan levels in the majority of patients. PMID:25712363

Dynamic gamma knife radiosurgery

NASA Astrophysics Data System (ADS)

Luan, Shuang; Swanson, Nathan; Chen, Zhe; Ma, Lijun

2009-03-01

Gamma knife has been the treatment of choice for various brain tumors and functional disorders. Current gamma knife radiosurgery is planned in a 'ball-packing' approach and delivered in a 'step-and-shoot' manner, i.e. it aims to 'pack' the different sized spherical high-dose volumes (called 'shots') into a tumor volume. We have developed a dynamic scheme for gamma knife radiosurgery based on the concept of 'dose-painting' to take advantage of the new robotic patient positioning system on the latest Gamma Knife C™ and Perfexion™ units. In our scheme, the spherical high dose volume created by the gamma knife unit will be viewed as a 3D spherical 'paintbrush', and treatment planning reduces to finding the best route of this 'paintbrush' to 'paint' a 3D tumor volume. Under our dose-painting concept, gamma knife radiosurgery becomes dynamic, where the patient moves continuously under the robotic positioning system. We have implemented a fully automatic dynamic gamma knife radiosurgery treatment planning system, where the inverse planning problem is solved as a traveling salesman problem combined with constrained least-square optimizations. We have also carried out experimental studies of dynamic gamma knife radiosurgery and showed the following. (1) Dynamic gamma knife radiosurgery is ideally suited for fully automatic inverse planning, where high quality radiosurgery plans can be obtained in minutes of computation. (2) Dynamic radiosurgery plans are more conformal than step-and-shoot plans and can maintain a steep dose gradient (around 13% per mm) between the target tumor volume and the surrounding critical structures. (3) It is possible to prescribe multiple isodose lines with dynamic gamma knife radiosurgery, so that the treatment can cover the periphery of the target volume while escalating the dose for high tumor burden regions. (4) With dynamic gamma knife radiosurgery, one can obtain a family of plans representing a tradeoff between the delivery time and the dose distributions, thus giving the clinician one more dimension of flexibility of choosing a plan based on the clinical situations.

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia

PubMed Central

Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-01-01

Objective The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. Results A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0–2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. Conclusions The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment. PMID:29142459

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

PubMed

Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-10-01

The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.

Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

NASA Technical Reports Server (NTRS)

Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

2011-01-01

Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would otherwise die or be rendered reproductively inactive in 2-D culture.

Four-dimensional dose reconstruction through in vivo phase matching of cine images of electronic portal imaging device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Jihyung; Jung, Jae Won, E-mail: jungj@ecu.ed

Purpose: A method is proposed to reconstruct a four-dimensional (4D) dose distribution using phase matching of measured cine images to precalculated images of electronic portal imaging device (EPID). Methods: (1) A phantom, designed to simulate a tumor in lung (a polystyrene block with a 3 cm diameter embedded in cork), was placed on a sinusoidally moving platform with an amplitude of 1 cm and a period of 4 s. Ten-phase 4D computed tomography (CT) images of the phantom were acquired. A planning target volume (PTV) was created by adding a margin of 1 cm around the internal target volume ofmore » the tumor. (2) Three beams were designed, which included a static beam, a theoretical dynamic beam, and a planning-optimized dynamic beam (PODB). While the theoretical beam was made by manually programming a simplistic sliding leaf motion, the planning-optimized beam was obtained from treatment planning. From the three beams, three-dimensional (3D) doses on the phantom were calculated; 4D dose was calculated by means of the ten phase images (integrated over phases afterward); serving as “reference” images, phase-specific EPID dose images under the lung phantom were also calculated for each of the ten phases. (3) Cine EPID images were acquired while the beams were irradiated to the moving phantom. (4) Each cine image was phase-matched to a phase-specific CT image at which common irradiation occurred by intercomparing the cine image with the reference images. (5) Each cine image was used to reconstruct dose in the phase-matched CT image, and the reconstructed doses were summed over all phases. (6) The summation was compared with forwardly calculated 4D and 3D dose distributions. Accounting for realistic situations, intratreatment breathing irregularity was simulated by assuming an amplitude of 0.5 cm for the phantom during a portion of breathing trace in which the phase matching could not be performed. Intertreatment breathing irregularity between the time of treatment and the time of planning CT was considered by utilizing the same reduced amplitude when the phantom was irradiated. To examine the phase matching in a humanoid environment, the matching was also performed in a digital phantom (4D XCAT phantom). Results: For the static, the theoretical, and the planning-optimized dynamic beams, the 4D reconstructed doses showed agreement with the forwardly calculated 4D doses within the gamma pass rates of 92.7%, 100%, and 98.1%, respectively, at the isocenter plane given by 3%/3 mm criteria. Excellent agreement in dose volume histogram of PTV and lung-PTV was also found between the two 4D doses, while substantial differences were found between the 3D and the 4D doses. The significant breathing irregularities modeled in this study were found not to be noticeably affecting the reconstructed dose. The phase matching was performed equally well in a digital phantom. Conclusions: The method of retrospective phase determination of a moving object under irradiation provided successful 4D dose reconstruction. This method will provide accurate quality assurance and facilitate adaptive therapy when distinguishable objects such as well-defined tumors, diaphragm, and organs with markers (pancreas and liver) are covered by treatment beam apertures.« less

Four-dimensional dose reconstruction through in vivo phase matching of cine images of electronic portal imaging device.

PubMed

Yoon, Jihyung; Jung, Jae Won; Kim, Jong Oh; Yi, Byong Yong; Yeo, Inhwan

2016-07-01

A method is proposed to reconstruct a four-dimensional (4D) dose distribution using phase matching of measured cine images to precalculated images of electronic portal imaging device (EPID). (1) A phantom, designed to simulate a tumor in lung (a polystyrene block with a 3 cm diameter embedded in cork), was placed on a sinusoidally moving platform with an amplitude of 1 cm and a period of 4 s. Ten-phase 4D computed tomography (CT) images of the phantom were acquired. A planning target volume (PTV) was created by adding a margin of 1 cm around the internal target volume of the tumor. (2) Three beams were designed, which included a static beam, a theoretical dynamic beam, and a planning-optimized dynamic beam (PODB). While the theoretical beam was made by manually programming a simplistic sliding leaf motion, the planning-optimized beam was obtained from treatment planning. From the three beams, three-dimensional (3D) doses on the phantom were calculated; 4D dose was calculated by means of the ten phase images (integrated over phases afterward); serving as "reference" images, phase-specific EPID dose images under the lung phantom were also calculated for each of the ten phases. (3) Cine EPID images were acquired while the beams were irradiated to the moving phantom. (4) Each cine image was phase-matched to a phase-specific CT image at which common irradiation occurred by intercomparing the cine image with the reference images. (5) Each cine image was used to reconstruct dose in the phase-matched CT image, and the reconstructed doses were summed over all phases. (6) The summation was compared with forwardly calculated 4D and 3D dose distributions. Accounting for realistic situations, intratreatment breathing irregularity was simulated by assuming an amplitude of 0.5 cm for the phantom during a portion of breathing trace in which the phase matching could not be performed. Intertreatment breathing irregularity between the time of treatment and the time of planning CT was considered by utilizing the same reduced amplitude when the phantom was irradiated. To examine the phase matching in a humanoid environment, the matching was also performed in a digital phantom (4D XCAT phantom). For the static, the theoretical, and the planning-optimized dynamic beams, the 4D reconstructed doses showed agreement with the forwardly calculated 4D doses within the gamma pass rates of 92.7%, 100%, and 98.1%, respectively, at the isocenter plane given by 3%/3 mm criteria. Excellent agreement in dose volume histogram of PTV and lung-PTV was also found between the two 4D doses, while substantial differences were found between the 3D and the 4D doses. The significant breathing irregularities modeled in this study were found not to be noticeably affecting the reconstructed dose. The phase matching was performed equally well in a digital phantom. The method of retrospective phase determination of a moving object under irradiation provided successful 4D dose reconstruction. This method will provide accurate quality assurance and facilitate adaptive therapy when distinguishable objects such as well-defined tumors, diaphragm, and organs with markers (pancreas and liver) are covered by treatment beam apertures.

Experimental assessment of out-of-field dose components in high energy electron beams used in external beam radiotherapy.

PubMed

Alabdoaburas, Mohamad M; Mege, Jean-Pierre; Chavaudra, Jean; Bezin, Jérémi Vũ; Veres, Atilla; de Vathaire, Florent; Lefkopoulos, Dimitri; Diallo, Ibrahima

2015-11-08

The purpose of this work was to experimentally investigate the out-of-field dose in a water phantom, with several high energy electron beams used in external beam radiotherapy (RT). The study was carried out for 6, 9, 12, and 18 MeV electron beams, on three different linear accelerators, each equipped with a specific applicator. Measurements were performed in a water phantom, at different depths, for different applicator sizes, and off-axis distances up to 70 cm from beam central axis (CAX). Thermoluminescent powder dosimeters (TLD-700) were used. For given cases, TLD measurements were compared to EBT3 films and parallel-plane ionization chamber measurements. Also, out-of-field doses at 10 cm depth, with and without applicator, were evaluated. With the Siemens applicators, a peak dose appears at about 12-15 cm out of the field edge, at 1 cm depth, for all field sizes and energies. For the Siemens Primus, with a 10 × 10 cm(²) applicator, this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6, 9, 12 and 18 MeV electron beams, respectively. For the Siemens Oncor, with a 10 × 10 cm(²) applicator, this peak dose reaches 0.8%, 1%, 1.4%, and 1.6% of Dmax for 6, 9, 12, and 14 MeV, respectively, and these values increase with applicator size. For the Varian 2300C/D, the doses at 12.5 cm out of the field edge are 0.3%, 0.6%, 0.5%, and 1.1% of Dmax for 6, 9, 12, and 18 MeV, respectively, and increase with applicator size. No peak dose is evidenced for the Varian applicator for these energies. In summary, the out-of-field dose from electron beams increases with the beam energy and the applicator size, and decreases with the distance from the beam central axis and the depth in water. It also considerably depends on the applicator types. Our results can be of interest for the dose estimations delivered in healthy tissues outside the treatment field for the RT patient, as well as in studies exploring RT long-term effects.

Experimental assessment of out‐of‐field dose components in high energy electron beams used in external beam radiotherapy

PubMed Central

Alabdoaburas, Mohamad M.; Mege, Jean‐Pierre; Chavaudra, Jean; Bezin, Jérémi Vũ; Veres, Attila; de Vathaire, Florent; Lefkopoulos, Dimitri

2015-01-01

The purpose of this work was to experimentally investigate the out‐of‐field dose in a water phantom, with several high energy electron beams used in external beam radiotherapy (RT). The study was carried out for 6, 9, 12, and 18 MeV electron beams, on three different linear accelerators, each equipped with a specific applicator. Measurements were performed in a water phantom, at different depths, for different applicator sizes, and off‐axis distances up to 70 cm from beam central axis (CAX). Thermoluminescent powder dosimeters (TLD‐700) were used. For given cases, TLD measurements were compared to EBT3 films and parallel‐plane ionization chamber measurements. Also, out‐of‐field doses at 10 cm depth, with and without applicator, were evaluated. With the Siemens applicators, a peak dose appears at about 12–15 cm out of the field edge, at 1 cm depth, for all field sizes and energies. For the Siemens Primus, with a 10×10cm2 applicator, this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6, 9, 12 and 18 MeV electron beams, respectively. For the Siemens Oncor, with a 10×10cm2 applicator, this peak dose reaches 0.8%, 1%, 1.4%, and 1.6% of Dmax for 6, 9, 12, and 14 MeV, respectively, and these values increase with applicator size. For the Varian 2300C/D, the doses at 12.5 cm out of the field edge are 0.3%, 0.6%, 0.5%, and 1.1% of Dmax for 6, 9, 12, and 18 MeV, respectively, and increase with applicator size. No peak dose is evidenced for the Varian applicator for these energies. In summary, the out‐of‐field dose from electron beams increases with the beam energy and the applicator size, and decreases with the distance from the beam central axis and the depth in water. It also considerably depends on the applicator types. Our results can be of interest for the dose estimations delivered in healthy tissues outside the treatment field for the RT patient, as well as in studies exploring RT long‐term effects. PACS number(s): 87.53.Bn, 87.56.bd, 87.56.J‐ PMID:26699572

Everolimus with reduced-dose cyclosporine in de novo renal transplant recipients: Philippine experience.

PubMed

Li, J T; Danguilan, R A; Cabanayan-Casasola, C B; Talusan-Tomacruz, Y; Ona, E T

2008-09-01

The objective of this study was to describe the appropriate dose of everolimus to achieve target trough concentrations in standard-risk Filipino kidney transplant recipients. We reviewed all kidney transplant recipients from December 1, 2006 to June 15, 2007 who were given everolimus (1.5 mg/d) in combination with low-dose cyclosporine (5 mg/kg/d) and prednisone but without induction therapy for their immunosuppressive doses, trough levels, as well as hematologic and blood chemistry profiles. Target everolimus trough concentration was 3-8 ng/mL and C2 level was 1000-1400 ng/mL for the first 3 months. Among 148 patients who underwent transplantation during the study period, 26 comprised the study population but only 15 patients completed the 3-month follow-up and are the subject of this report. Their mean age was 33 years, average PRA 2%, and mean HLA mismatches 3. All were from living donors. At 7 days posttransplantation, all patients achieved or exceeded the target everolimus trough and cyclosporine C2 level. At 1 and 3 months posttransplantation the mean everolimus dose was 1.17 and 0.78 mg/d, respectively, whereas the cyclosporine dose was 195 and 148 mg/d, respectively. Three patients showed elevated alanine aminotransferase (ALT) and all patients had hypercholesterolemia after 1 month, which improved with everolimus dose reduction (half required statins). One patient experienced a Banff Grade IA acute rejection episode at 2 months posttransplantation with a serum creatinine value of 2 mg/dL after steroid pulsing. Most standard-risk Filipino kidney transplant recipients required a maintenance everolimus dose of 1 mg/d at 1 month. The cyclosporine dose requirement was also lower. A larger sample size is needed to provide a level of significance compared with other populations.

SU-E-T-602: Patient-Specific Online Dose Verification Based On Transmission Detector Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thoelking, J; Yuvaraj, S; Jens, F

Purpose: Intensity modulated radiotherapy requires a comprehensive quality assurance program in general and ideally independent verification of dose delivery. Since conventional 2D detector arrays allow only pre-treatment verification, there is a debate concerning the need of online dose verification. This study presents the clinical performance, including dosimetric plan verification in 2D as well as in 3D and the error detection abilities of a new transmission detector (TD) for online dose verification of 6MV photon beam. Methods: To validate the dosimetric performance of the new device, dose reconstruction based on TD measurements were compared to a conventional pre-treatment verification method (reference)more » and treatment planning system (TPS) for 18 IMRT and VMAT treatment plans. Furthermore, dose reconstruction inside the patient based on TD read-out was evaluated by comparing various dose volume indices and 3D gamma evaluations against independent dose computation and TPS. To investigate the sensitivity of the new device, different types of systematic and random errors for leaf positions and linac output were introduced in IMRT treatment sequences. Results: The 2D gamma index evaluation of transmission detector based dose reconstruction showed an excellent agreement for all IMRT and VMAT plans compared to reference measurements (99.3±1.2)% and TPS (99.1±0.7)%. Good agreement was also obtained for 3D dose reconstruction based on TD read-out compared to dose computation (mean gamma value of PTV = 0.27±0.04). Only a minimal dose underestimation within the target volume was observed when analyzing DVH indices (<1%). Positional errors in leaf banks larger than 1mm and errors in linac output larger than 2% could clearly identified with the TD. Conclusion: Since 2D and 3D evaluations for all IMRT and VMAT treatment plans were in excellent agreement with reference measurements and dose computation, the new TD is suitable to qualify for routine treatment plan verification. Funding Support, Disclosures, and Conflict of Interest: COIs: Frank Lohr: Elekta: research grant, travel grants, teaching honoraria IBA: research grant, travel grants, teaching honoraria, advisory board C-Rad: board honoraria, travel grants Frederik Wenz: Elekta: research grant, teaching honoraria, consultant, advisory board Zeiss: research grant, teaching honoraria, patent Hansjoerg Wertz: Elekta: research grant, teaching honoraria IBA: research grant.« less

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

PubMed

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Comparison of three-dimensional vs. conventional radiotherapy in saving optic tract in paranasal sinus tumors.

PubMed

Kamian, S; Kazemian, A; Esfahani, M; Mohammadi, E; Aghili, M

2010-01-01

To assess the possibility of delivering a homogeneous irradiation with respect to maximal tolerated dose to the optic pathway for paranasal sinus (PNS) tumors. Treatment planning with conformal three-dimensional (3D) and conventional two-dimensional (2D) was done on CT scans of 20 patients who had early or advanced PNS tumors. Four cases had been previously irradiated. Dose-volume histograms (DVH) for the planning target volume (PTV) and the visual pathway including globes, chiasma and optic nerves were compared between the 2 treatment plannings. The area under curve (AUC) in the DVH of the globes on the same side and contralateral side of tumor involvement was significantly higher in 2D planning (p <0.05), which caused higher integral dose to both globes. Also, the AUC in the DVH of chiasma was higher in 2D treatment planning (p=0.002). The integral dose to the contralateral optic nerve was significantly lower with 3D planning (p=0.007), but there was no significant difference for the optic nerve which was on the same side of tumor involvement (p >0.05). The AUC in the DVH of PTV was not significant (201.1 + or - 16.23 mm(3) in 2D planning vs. 201.15 + or - 15.09 mm(3) in 3D planning). The volume of PTV which received 90% of the prescribed dose was 96.9 + or - 4.41 cm(3) in 2D planning and 97.2 + or - 2.61 cm(3) in 3D planning (p >0.05). 3D conformal radiotherapy (RT) for PNS tumors enables the delivery of radiation to the tumor with respect to critical organs with a lower toxicity to the optic pathway.

Effects of D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of saw palmetto (Serenoa repens) on the sexual activity in male rats: A controlled, experimental study.

PubMed

Fernández, Lilia C; Mas, Rosa; Fernández, Julio; Mendoza, Sarahí; Gámez, Rafael; Pardo, Balia

2008-02-01

The etiology of benign prostatic hyperplasia (BPH) is not completely understood, but hormonal changes in aging men seem to be pivotal. Dihydrotestosterone, a potent, active metabolite of testosterone, is formed by the enzymatic action of prostate 5α-reductase and causes cell growth and hyperplasia. Consistent with this action, male sexual dysfunction has been clinically documented to be among the drug-related adverse events associated with 5α-reductase inhibitors. The lipidosterolic extract of saw palmetto (LESP) fruit (Serenoa repens) has been used to treat BPH. D-004, a lipid extract of Roystonea regia Royal palm fruit, has been found to prevent prostatic hyperplasia induced by testoste-rone in rodents and to competitively inhibit prostate 5α-reductase activity in vitro. The purpose of this study was to assess the effects of D-004 and LESP, administered as single or repeated doses, on the sexual activity in male rats. This controlled, experimental study was conducted at the Pharmacology Department, Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba. Adult male Wistar rats weighing 250 to 300 g were randomized into 5 groups: 2 groups treated orally with D-004 (400 and 800 mg/kg); 2 groups treated orally with LESP (400 and 800 mg/kg); and 1 control group orally administered a water vehicle. Sexual activity behavior (the number of mounts and intromissions, mount latency, and intromission latency) was assessed during 2 observation periods: 90 minutes after the initial dose and at the end of the 30-day treatment. Latency was defined as time elapsed between the first mount and intromission. A total of 50 rats (mean [SD] age, 10 [3] weeks; mean [SD] weight, 295 [10] g) were included in the experiment. There were no significant difterences in the mean number of mounts, intromissions, mount latency, or intromission latency in the groups treated with single or repeated doses of D-004 or LESP (400 and 800 mg/kg) compared with the controls. There was also no between-group difterence in mating behavior among the active treatment groups. All rats survived up to study completion, with normal behavior (weight gain, food intake, daily observations, without any sign of toxicity). There were no observable adverse events during the study. D-004 and LESP administered as a single dose or repeated doses for 30 days did not significantly affect male rat sexual activity behavior compared with a vehicle control group.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

Implications of free breathing motion assessed by 4D-computed tomography on the delivered dose in radiotherapy for esophageal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duma, Marciana Nona, E-mail: Marciana.Duma@mri.tum.de; Berndt, Johannes; Rondak, Ina-Christine

2015-01-01

The aim of this study was to assess the effect of breathing motion on the delivered dose in esophageal cancer 3-dimensional (3D)-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). We assessed 16 patients with esophageal cancer. All patients underwent 4D-computed tomography (4D-CT) for treatment planning. For each of the analyzed patients, 1 3D-CRT, 1 IMRT, and 1 VMAT (RapidArc—RA) plan were calculated. Each of the 3 initial plans was recalculated on the 4D-CT (for the maximum free inspiration and maximum free expiration) to assess the effect of breathing motion. We assessed the minimum dose (D{sub min})more » and mean dose (D{sub mean}) to the esophagus within the planning target volume, the volume changes of the lungs, the D{sub mean} and the total lung volume receiving at least 40 Gy (V{sub 40}), and the V{sub 30}, V{sub 20}, V{sub 10}, and V{sub 5}. For the heart we assessed the D{sub mean} and the V{sub 25}. Over all techniques and all patients the change in D{sub mean} as compared with the planned D{sub mean} (planning CT [PCT]) to the esophagus was 0.48% in maximum free inspiration (CT-insp) and 0.55% in maximum free expiration (CT-exp). The D{sub min} CT-insp change was 0.86% and CT-exp change was 0.89%. The D{sub mean} change of the lungs (heart) was in CT-insp 1.95% (2.89%) and 3.88% (2.38%) in CT-exp. In all, 4 patients had a clinically relevant change of the dose (≥ 5% D{sub mean} to the heart and the lungs) between inspiration and expiration. These patients had a very cranially or caudally situated tumor. There are no relevant differences in the delivered dose to the regions of interest among the 3 techniques. Breathing motion management could be considered to achieve a better sparing of the lungs or heart in patients with cranially or caudally situated tumors.« less

Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.

2010-09-15

Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences inmore » radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krayenbuehl, Jerome Dipl.Phys. E.T.H.; Oertel, Susanne; Davis, J. Bernard

Purpose: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. Methods and Materials: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coveragemore » were analyzed. Results: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring {>=}95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. Conclusion: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.« less

The effect of surgical titanium rods on proton therapy delivered for cervical bone tumors: experimental validation using an anthropomorphic phantom

NASA Astrophysics Data System (ADS)

Dietlicher, Isabelle; Casiraghi, Margherita; Ares, Carmen; Bolsi, Alessandra; Weber, Damien C.; Lomax, Antony J.; Albertini, Francesca

2014-12-01

To investigate the effect of metal implants in proton radiotherapy, dose distributions of different, clinically relevant treatment plans have been measured in an anthropomorphic phantom and compared to treatment planning predictions. The anthropomorphic phantom, which is sliced into four segments in the cranio-caudal direction, is composed of tissue equivalent materials and contains a titanium implant in a vertebral body in the cervical region. GafChromic® films were laid between the different segments to measure the 2D delivered dose. Three different four-field plans have then been applied: a Single-Field-Uniform-Dose (SFUD) plan, both with and without artifact correction implemented, and an Intensity-Modulated-Proton-Therapy (IMPT) plan with the artifacts corrected. For corrections, the artifacts were manually outlined and the Hounsfield Units manually set to an average value for soft tissue. Results show a surprisingly good agreement between prescribed and delivered dose distributions when artifacts have been corrected, with > 97% and 98% of points fulfilling the gamma criterion of 3%/3 mm for both SFUD and the IMPT plans, respectively. In contrast, without artifact corrections, up to 18% of measured points fail the gamma criterion of 3%/3 mm for the SFUD plan. These measurements indicate that correcting manually for the reconstruction artifacts resulting from metal implants substantially improves the accuracy of the calculated dose distribution.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

NASA Astrophysics Data System (ADS)

Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.

2015-09-01

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation.

PubMed

Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M

2015-09-07

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

Modulation of deprivation-induced food intake by D-phenylalanine.

PubMed

Bodnar, R J; Butler, P D

1983-09-01

D-phenylalanine has been shown to possess opiate-like effects upon pain perception. The present study examined whether it would have similar opiate-like effects upon food intake in deprived rats. The first experiment demonstrated that food intake of rats deprived for 24 h prior to injection was significantly reduced for 2 h following a 250 mg/kg dose of D-phenylalanine. However, intake over a 24 h period following injection was significantly increased following a 125 mg/kg dose of D-phenylalanine. The second experiment revealed that 0.3, 1.0, 3.0 and 10.0 mg/kg doses of naloxone dose-dependently reduced intake for 2 h in deprived rats when paired with a vehicle injection. However, the inhibitory actions of the two lower naloxone doses were significantly attenuated when paired with an injection of a 250 mg/kg dose of D-phenylalanine. These results are discussed in terms of whether D-phenylalanine possesses direct or indirect opiate-like effects upon ingestion.

Variations in energy spectra and water-to-material stopping-power ratios in three-dimensional conformal and intensity-modulated photon fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Si Young; Liu, H. Helen; Mohan, Radhe

Because of complex dose distributions and dose gradients that are created in three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), photon- and electron-energy spectra might change significantly with spatial locations and doses. This study examined variations in photon- and electron-energy spectra in 3D-CRT and IMRT photon fields. The effects of spectral variations on water-to-material stopping-power ratios used in Monte Carlo treatment planning systems and the responses of energy-dependent dosimeters, such as thermoluminescent dosimeters (TLDs) and radiographic films were further studied. The EGSnrc Monte Carlo code was used to simulate megavoltage 3D-CRT and IMRT photon fields. The photon- and electron-energymore » spectra were calculated in 3D water phantoms and anthropomorphic phantoms based on the fluence scored in voxel grids. We then obtained the water-to-material stopping-power ratios in the local voxels using the Spencer-Attix cavity theory. Changes in the responses of films and TLDs were estimated based on the calculated local energy spectra and published data on the dosimeter energy dependency. Results showed that the photon-energy spectra strongly depended on spatial positions and doses in both the 3D-CRT and IMRT fields. The relative fraction of low-energy photons (<100 keV) increased inversely with the photon dose in low-dose regions of the fields. A similar but smaller effect was observed for electrons in the phantoms. The maximum variation of the water-to-material stopping-power ratio over the range of calculated dose for both 3D-CRT and IMRT was negligible (<1.0%) for ICRU tissue, cortical bone, and soft bone and less than 3.6% for dry air and lung. Because of spectral softening at low doses, radiographic films in the phantoms could over-respond to dose by more than 30%, whereas the over-response of TLDs was less than 10%. Thus, spatial variations of the photon- and electron-energy spectra should be considered as important factors in 3D-CRT and IMRT dosimetry.« less

Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechukwu R.

2016-05-01

Purpose: The purpose of this study was to evaluate factors associated with tumor control in clival chordomas. Methods and Materials: A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm{sup 3} of GTV (D1cm{sup 3}), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTVmore » and D1cm{sup 3}. Results: After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm{sup 3} was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm{sup 3}, and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm{sup 3} and D1cm{sup 3} of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm{sup 3} stratified by D1cm{sup 3}). A D1cm{sup 3} of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm{sup 3} had 80% sensitivity for local control and 66.7% specificity. Conclusions: Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek maximal safe surgical resection, particularly to facilitate delivery of high-dose radiation therapy in proximity to critical structures. A D1cm{sup 3} ≥74.5 Gy (RBE) represents a proposed treatment planning objective.« less

Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl; Nesteruk, Marta; Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich

The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared formore » 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.« less

SU-F-19A-05: Experimental and Monte Carlo Characterization of the 1 Cm CivaString 103Pd Brachytherapy Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, J; Micka, J; Culberson, W

Purpose: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of the CivaString {sup 103}Pd brachytherapy source through measurements and Monte Carlo (MC) simulations. American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters were also determined for this source. Methods: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and simulated with the MCNP5 radiation transport code. Measured and simulated results were normalized to their respective mean values and compared. The TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function for this sourcemore » were determined from LiF:Mg,Ti thermoluminescent dosimeter (TLD) measurements and MC simulations. The impact of {sup 103}Pd well-loading variability on the in-water dose distribution was investigated using MC simulations by comparing the dose distribution for a source model with four wells of equal strength to that for a source model with strengths increased by 1% for two of the four wells. Results: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy showed that ≥95% of the normalized data were within 1.2% of the mean value. TLD measurements and MC simulations of the TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function agreed to within the experimental TLD uncertainties (k=2). MC simulations showed that a 1% variability in {sup 103}Pd well-loading resulted in changes of <0.1%, <0.1%, and <0.3% in the TG-43 dose-rate constant, radial dose distribution, and polar dose distribution, respectively. Conclusion: The CivaString source has a high degree of azimuthal symmetry as indicated by the NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy. TG-43 dosimetry parameters for this source were determined from TLD measurements and MC simulations. {sup 103}Pd well-loading variability results in minimal variations in the in-water dose distribution according to MC simulations. This work was partially supported by CivaTech Oncology, Inc. through an educational grant for Joshua Reed, John Micka, Wesley Culberson, and Larry DeWerd and through research support for Mark Rivard.« less

Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity.

PubMed

Farber, Nuri B; Nemmers, Brian; Noguchi, Kevin K

2006-09-15

Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor, most likely by producing disinhibtion in complex circuits, acutely produce psychosis and cognitive disturbances in humans, and neurotoxicity in rodents. Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals, therefore, may provide insights into the pathophysiology of psychotic disorders. Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks, suggesting involvement of these transmitter system(s). We studied the ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both after a one-time acute exposure and after chronic daily exposure. Here we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo neurotoxicity when given acutely. The protective effect with D2/D3 agonists is not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However, after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo neurotoxicity with longer durations producing greater protection. Understanding the changes that occur in the NRHypo circuit after chronic exposure to dopaminergic agents could provide important clues into the pathophysiology of psychotic disorders.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.

Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less

Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India.

PubMed

Lalwani, Sanjay; Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-09-01

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaeken, B.; Lelie, S.; Meijnders, P.

2010-12-15

Purpose: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. Methods: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibratedmore » against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of ''dose-normalized amplitudes'' A{sub D}. The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. Results: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U{sub r}(A{sub D})=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of {+-}4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm{sup -1} was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. Conclusions: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate their TBI dose protocol. Dose calculations based on a collapsed cone convolution dose algorithm modeled for regular treatments are accurate within 3% and can further be improved when the algorithm is modeled for TBI.« less

Efficient implementation of the 3D-DDA ray traversal algorithm on GPU and its application in radiation dose calculation.

PubMed

Xiao, Kai; Chen, Danny Z; Hu, X Sharon; Zhou, Bo

2012-12-01

The three-dimensional digital differential analyzer (3D-DDA) algorithm is a widely used ray traversal method, which is also at the core of many convolution∕superposition (C∕S) dose calculation approaches. However, porting existing C∕S dose calculation methods onto graphics processing unit (GPU) has brought challenges to retaining the efficiency of this algorithm. In particular, straightforward implementation of the original 3D-DDA algorithm inflicts a lot of branch divergence which conflicts with the GPU programming model and leads to suboptimal performance. In this paper, an efficient GPU implementation of the 3D-DDA algorithm is proposed, which effectively reduces such branch divergence and improves performance of the C∕S dose calculation programs running on GPU. The main idea of the proposed method is to convert a number of conditional statements in the original 3D-DDA algorithm into a set of simple operations (e.g., arithmetic, comparison, and logic) which are better supported by the GPU architecture. To verify and demonstrate the performance improvement, this ray traversal method was integrated into a GPU-based collapsed cone convolution∕superposition (CCCS) dose calculation program. The proposed method has been tested using a water phantom and various clinical cases on an NVIDIA GTX570 GPU. The CCCS dose calculation program based on the efficient 3D-DDA ray traversal implementation runs 1.42 ∼ 2.67× faster than the one based on the original 3D-DDA implementation, without losing any accuracy. The results show that the proposed method can effectively reduce branch divergence in the original 3D-DDA ray traversal algorithm and improve the performance of the CCCS program running on GPU. Considering the wide utilization of the 3D-DDA algorithm, various applications can benefit from this implementation method.

Effects of Isatis root polysaccharide in mice infected with H3N2 swine influenza virus.

PubMed

Wang, Xuebing; Xue, Yang; Li, Yongliang; Liu, Fang; Yan, Yanhua; Zhang, Hongying; Jin, Qianyue

2018-05-01

Isatis root polysaccharide (IRPS) has gained attention in the field of virology. However, very few studies have evaluated the effects of IRPS on H3N2 swine influenza virus (SIV). The antiviral activities of IRPS against SIV were investigated in vitro through three different modes and in vivo in an experimental mouse model of SIV infection. Mice were treated by oral gavage with various doses of IRPS before being experimentally infected with SIV A/swine/Henan/2010(H3N2). The antiviral effects of IRPS were evaluated by clinical signs, weight, histopathology, cytokine levels in lung homogenates and serum nitric oxide (NO) and IgG levels at 2, 5 and 9 d post-infection. IRPS demonstrated an inhibitory effect on SIV in Madin-Darby canine kidney cells. Additionally, IRPS significantly improved symptoms, reduced pathological changes and enhanced serum levels of NO and IgG in SIV-infected mice. Furthermore, detection of cytokines in lung homogenates showed IRPS could alter cytokine production to improve immune responses and systemic ability to repair inflammation. Moreover, IRPS extenuated the pulmonary inflammatory response. The results show that various concentrations of IRPS exert antiviral effects in vitro and in vivo. In an experimental mouse model of SIV infection, IRPS at a dose of 75 mg/kg was effective. Copyright © 2018. Published by Elsevier Ltd.

Three consecutive days of application of LED therapy is necessary to inhibit experimentally induced root resorption in rats: a microtomographic study.

PubMed

Higashi, Dayla Thyeme; Andrello, Avacir Casanova; Tondelli, Pedro Marcelo; de Oliveira Toginho Filho, Dari; de Paula Ramos, Solange

2017-01-01

Previous studies have suggested that phototherapy may modulate orthodontic tooth movement and the incidence of root resorption. We aimed to identify a minimal dose-response relationship to LED therapy with regard to orthodontic tooth movement (OTM) and root resorption in rats. Forty-eight male Wistar rats were divided into six groups with equal and random distribution: control (C) no intervention; three daily LED irradiation (CLED); submitted only to OTM (RR); OTM and LED irradiation on the first day (LED1); OTM and two LED irradiation on the first and second days (LED2); and OTM and three LED irradiation on the first, second, and third days (LED3). Orthodontic appliance was installed in groups RR, LED1, LED2, and LED3 to promote OTM. Animals from groups CLED, LED1, LED2, and LED3 received LED therapy (940 nm, 4 J, 4 J/cm2) according to each group of treatment. After 7 days, all the animals were sacrificed. The jaws were fixed and scanned with microtomography (micro-CT). The micro-CT images were reconstructed on 2D and 3D models. These models were used to identify and measure root resorption number and dimensions (diameter, depth, and volume). The distance between the first and second molars was used to verify tooth displacement. The results showed that LED3 group had significantly lower number of root resorption. The root resorption dimensions (diameter and depth) had no significant differences among the experimental groups. LED3 group had significant tooth displacement in relation to C and CLED groups. In conclusion, three daily LED therapy doses are required to inhibit root resorption after appliance of orthodontic forces.

Action spectrum conversion factors that change erythemally weighted to previtamin D3-weighted UV doses.

PubMed

Pope, Stanley J; Holick, Michael F; Mackin, Steven; Godar, Dianne E

2008-01-01

Many solar UV measurements, either terrestrial or personal, weight the raw data by the erythemal action spectrum. However, a problem arises when one tries to estimate the benefit of vitamin D(3) production based on erythemally weighted outdoor doses, like those measured by calibrated R-B meters or polysulphone badges, because the differences between action spectra give dissimilar values. While both action spectra peak in the UVB region, the erythemal action spectrum continues throughout the UVA region while the previtamin D(3) action spectrum stops near that boundary. When one uses the previtamin D(3) action spectrum to weight the solar spectra (D(eff)), one gets a different contribution in W m(-2) than what the erythemally weighted data predicts (E(eff)). Thus, to do proper benefit assessments, one must incorporate action spectrum conversion factors (ASCF) into the calculations to change erythemally weighted to previtamin D(3)-weighted doses. To date, all benefit assessments for vitamin D(3) production in human skin from outdoor exposures are overestimates because they did not account for the different contributions of each action spectrum with changing solar zenith angle and ozone and they did not account for body geometry. Here we describe how to normalize the ratios of the effective irradiances (D(eff)/E(eff)) to get ASCF that change erythemally weighted to previtamin D(3)-weighted doses. We also give the ASCF for each season of the year in the northern hemisphere every 5 degrees from 30 degrees N to 60 degrees N, based on ozone values. These ASCF, along with geometry conversion factors and other information, can give better vitamin D(3) estimates from erythemally weighted outdoor doses.

A revision of the gamma-evaluation concept for the comparison of dose distributions.

PubMed

Bakai, Annemarie; Alber, Markus; Nüsslin, Fridtjof

2003-11-07

A method for the quantitative four-dimensional (4D) evaluation of discrete dose data based on gradient-dependent local acceptance thresholds is presented. The method takes into account the local dose gradients of a reference distribution for critical appraisal of misalignment and collimation errors. These contribute to the maximum tolerable dose error at each evaluation point to which the local dose differences between comparison and reference data are compared. As shown, the presented concept is analogous to the gamma-concept of Low et al (1998a Med. Phys. 25 656-61) if extended to (3+1) dimensions. The pointwise dose comparisons of the reformulated concept are easier to perform and speed up the evaluation process considerably, especially for fine-grid evaluations of 3D dose distributions. The occurrences of false negative indications due to the discrete nature of the data are reduced with the method. The presented method was applied to film-measured, clinical data and compared with gamma-evaluations. 4D and 3D evaluations were performed. Comparisons prove that 4D evaluations have to be given priority, especially if complex treatment situations are verified, e.g., non-coplanar beam configurations.

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

PubMed

Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

2017-08-01

Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO.

PubMed

Tateno, Amane; Sakayori, Takeshi; Kim, Woo-Chan; Honjo, Kazuyoshi; Nakayama, Haruo; Arakawa, Ryosuke; Okubo, Yoshiro

2018-06-01

Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

PubMed Central

Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

2016-01-01

Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images. PMID:26980176

Z-Index Parameterization for Volumetric CT Image Reconstruction via 3-D Dictionary Learning.

PubMed

Bai, Ti; Yan, Hao; Jia, Xun; Jiang, Steve; Wang, Ge; Mou, Xuanqin

2017-12-01

Despite the rapid developments of X-ray cone-beam CT (CBCT), image noise still remains a major issue for the low dose CBCT. To suppress the noise effectively while retain the structures well for low dose CBCT image, in this paper, a sparse constraint based on the 3-D dictionary is incorporated into a regularized iterative reconstruction framework, defining the 3-D dictionary learning (3-DDL) method. In addition, by analyzing the sparsity level curve associated with different regularization parameters, a new adaptive parameter selection strategy is proposed to facilitate our 3-DDL method. To justify the proposed method, we first analyze the distributions of the representation coefficients associated with the 3-D dictionary and the conventional 2-D dictionary to compare their efficiencies in representing volumetric images. Then, multiple real data experiments are conducted for performance validation. Based on these results, we found: 1) the 3-D dictionary-based sparse coefficients have three orders narrower Laplacian distribution compared with the 2-D dictionary, suggesting the higher representation efficiencies of the 3-D dictionary; 2) the sparsity level curve demonstrates a clear Z-shape, and hence referred to as Z-curve, in this paper; 3) the parameter associated with the maximum curvature point of the Z-curve suggests a nice parameter choice, which could be adaptively located with the proposed Z-index parameterization (ZIP) method; 4) the proposed 3-DDL algorithm equipped with the ZIP method could deliver reconstructions with the lowest root mean squared errors and the highest structural similarity index compared with the competing methods; 5) similar noise performance as the regular dose FDK reconstruction regarding the standard deviation metric could be achieved with the proposed method using (1/2)/(1/4)/(1/8) dose level projections. The contrast-noise ratio is improved by ~2.5/3.5 times with respect to two different cases under the (1/8) dose level compared with the low dose FDK reconstruction. The proposed method is expected to reduce the radiation dose by a factor of 8 for CBCT, considering the voted strongly discriminated low contrast tissues.

Vitamin D3 Loading Is Superior to Conventional Supplementation After Weight Loss Surgery in Vitamin D-Deficient Morbidly Obese Patients: a Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Luger, Maria; Kruschitz, Renate; Kienbacher, Christian; Traussnigg, Stefan; Langer, Felix B; Prager, Gerhard; Schindler, Karin; Kallay, Enikö; Hoppichler, Friedrich; Trauner, Michael; Krebs, Michael; Marculescu, Rodrig; Ludvik, Bernhard

2017-05-01

Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients. In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D 3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit. Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14). Our findings indicate that a high vitamin D 3 loading dose, in the first month postoperatively, with subsequent maintenance dose is effective and safe in achieving higher vitamin D concentrations in OLGB patients. Unexpectedly, it is more effective in patients with significant liver fibrosis which is of potentially high clinical relevance and requires further investigation.

SU-E-T-21: A D-D Based Neutron Generator System for Boron Neutron Capture Therapy: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, M; Liu, Y; Nie, L

2015-06-15

Purpose: To investigate the feasibility of a deuterium-deuterium (DD) neutron generator for application in boron neutron capture therapy (BNCT) of brain cancer Methods: MCNP simulations were performed using a head phantom and a monoenergetic neutron source, which resembles the point source in a DD generator that emits 2.45-MeV neutrons. Source energies ranging from 5eV to 2.45MeV were simulated to determine the optimal treatment energy. The phantom consisted of soft tissue, brain tissue, skull, skin layer, and a brain tumor of 5 cm in diameter. Tumor depth was varied from 5–10 cm. Boron-10 concentrations of 10 ppm, 15 ppm, and 30more » ppm were used in the soft/brain tissues, skin, and tumor, respectively. The neutron flux required to deliver 60 Gy to the tumor as well as the normal tissue doses were determined. Results: Beam energies between 5eV and 10keV obtained doses with the highest dose ratios (3.3–25.9) between the tumor and the brain at various depths. The dose ratio with 2.45-MeV neutrons ranged from 0.8–6.6. To achieve the desired tumor dose in 40 minutes, the required neutron flux for a DD generator was between 8.8E10 and 5.2E11 n/s and the resulting brain dose was between 2.3 and 18 Gy, depending on the tumor depth. The skin and soft tissue doses were within acceptable tolerances. The boron-neutron interaction accounted for 54–58% of the total dose. Conclusion: This study shows that the DD neutron generator can be a feasible neutron source for BNCT. The required neutron flux for treatment is achievable with the current DD neutron technology. With a well-designed beam shaping assembly and treatment geometry, the neutron flux can be further improved and a 60-Gy prescription can be accurately delivered to the target while maintaining tolerable normal tissue doses. Further experimental studies will be developed and conducted to validate the simulation results.« less

Anti-inflammatory effect of vitamin D on gingivitis: a dose-response randomised control trial.

PubMed

Hiremath, Vishwanath P; Rao, C Bhasker; Naik, Vijaya; Prasad, Kakrala Veera

2013-01-01

To assess the anti-inflammatory effect of vitamin D on gingivitis at various doses. In this randomized controlled trial, daily oral vitamin D supplementation was given in doses of 2000 IU for group A, 1000 IU for group B, 500 IU for group C and a placebo for group D over a 3-month period. The changes in gingival scores were measured after the 1st, 2nd and 3rd months. The gingivitis score changed in direct proportion to the dose of vitamin D supplementation. In group A, the mean gingival scores were 2.4 (baseline), 1.7 after the first month, 0.8 after the second month and 0.3 after the third month. The group B mean baseline gingival score of 2.3 decreased to 2.0 in the first month, 1.1 after the second month and 0.5 after the third month. In group C, the baseline gingival scores were 2.2 and 1.9 after one month, 1.4 after two months and 0.8 by the last visit. Comparing baseline gingivitis scores with the later-visit score using the Wilcoxon paired test, the significant anti-inflammatory effect was seen in group A after one month, in group B at two months and in group C at three months after oral vitamin D supplementation (P < 0.0001). However, group D did not show a significant antiinflammatory effect. There is a dose-dependent anti-inflammatory effect of vitamin D on gingivitis. Vitamin D is a safe and effective anti-inflammatory agent in doses ranging from 500 IU to 2000 IU. Results are apparent earlier with the higher dose of 2000 IU.

Long term dose monitoring onboard the European Columbus module of the international space station (ISS) in the frame of DOSIS and DOSIS 3D project - results from the active instruments

NASA Astrophysics Data System (ADS)

Burmeister, Soenke; Berger, Thomas; Reitz, Guenther; Boehme, Matthias; Haumann, Lutz; Labrenz, Johannes

Besides the effects of the microgravity environment, and the psychological and psychosocial problems encountered in confined spaces, radiation is the main health detriment for long duration human space missions. The radiation environment encountered in space differs in nature from that on earth, consisting mostly of high energetic ions from protons up to iron, resulting in radiation levels far exceeding the ones encountered on earth for occupational radiation workers. Accurate knowledge of the physical characteristics of the space radiation field in dependence on the solar activity, the orbital parameters and the different shielding configurations of the International Space Station ISS is therefore needed. For the investigation of the spatial and temporal distribution of the radiation field inside the European COLUMBUS module the experiment DOSIS (Dose Distribution Inside the ISS) under the lead of DLR has been launched on July 15 (th) 2009 with STS-127 to the ISS. The experimental package was transferred from the Space Shuttle into COLUMBUS on July 18 (th) . It consists of a combination of passive detector packages (PDP) distributed at 11 locations inside the European Columbus Laboratory and two active radiation detectors (Dosimetry Telescopes = DOSTELs) with a DDPU (DOSTEL Data and Power Unit) in a Nomex pouch (DOSIS MAIN BOX) mounted at a fixed location beneath the European Physiology Module rack (EPM) inside COLUMBUS. The active components of the DOSIS experiment were operational from July 18 (th) 2009 to June 16 (th) 2011. After refurbishment the hardware has been reactivated on May 15 (th) 2012 as active part of the DOSIS 3D experiment and provides continuous data since this activation. The presentation will focus on the latest results from the two DOSTEL instruments as absorbed dose, dose equivalent and the related LET spectra gathered within the DOSIS (2009 - 2011) and DOSIS 3D (2012 - 2014) experiment. The CAU contributions to DOSIS and DOSIS 3D are financially supported by BMWi under Grants 50WB0826, 50WB1026 and 50WB1232

Cellular communication and “non-targeted effects”: Modelling approaches

NASA Astrophysics Data System (ADS)

Ballarini, Francesca; Facoetti, Angelica; Mariotti, Luca; Nano, Rosanna; Ottolenghi, Andrea

2009-10-01

During the last decade, a large number of experimental studies on the so-called "non-targeted effects", in particular bystander effects, outlined that cellular communication plays a significant role in the pathways leading to radiobiological damage. Although it is known that two main types of cellular communication (i.e. via gap junctions and/or molecular messengers diffusing in the extra-cellular environment, such as cytokines, NO etc.) play a major role, it is of utmost importance to better understand the underlying mechanisms, and how such mechanisms can be modulated by ionizing radiation. Though the "final" goal is of course to elucidate the in vivo scenario, in the meanwhile also in vitro studies can provide useful insights. In the present paper we will discuss key issues on the mechanisms underlying non-targeted effects and cell communication, for which theoretical models and simulation codes can be of great help. In this framework, we will present in detail three literature models, as well as an approach under development at the University of Pavia. More specifically, we will first focus on a version of the "State-Vector Model" including bystander-induced apoptosis of initiated cells, which was successfully fitted to in vitro data on neoplastic transformation supporting the hypothesis of a protective bystander effect mediated by apoptosis. The second analyzed model, focusing on the kinetics of bystander effects in 3D tissues, was successfully fitted to data on bystander damage in an artificial 3D skin system, indicating a signal range of the order of 0.7-1 mm. A third model for bystander effect, taking into account of spatial location, cell killing and repopulation, showed dose-response curves increasing approximately linearly at low dose rates but quickly flattening out for higher dose rates, also predicting an effect augmentation following dose fractionation. Concerning the Pavia approach, which can model the release, diffusion and depletion/degradation of candidate signals (e.g. cytokines) travelling in the extra-cellular environment, the good agreement with ad hoc experimental data obtained in our laboratory validated the adopted approach, which in the future can be applied also to other candidate signals. Although the available information is still not sufficient to decide whether the Linear No Threshold approach for low dose risk - including space radiation risk - has to be modified, these studies confirmed the need of a paradigm shift in (low-dose) radiobiology, where the DNA-centric vision needs to be integrated by a wider vision where cells constitute an organized population responding to external stimuli in a collective fashion, communicating by means of different molecular signals. Further studies, in particular in vivo (or at least in 3D tissues) and possibly combined with human epidemiological data, will be crucial to help solving such questions in the future.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Use of 3-D digital subtraction rotational angiography during cardiac catheterization of infants and adults with congenital heart diseases.

PubMed

Surendran, Sushitha; Waller, B Rush; Elijovich, Lucas; Agrawal, Vijaykumar; Kuhls-Gilcrist, Andrew; Johnson, Jason; Fagan, Thomas; Sathanandam, Shyam K

2017-10-01

To compare image quality, radiation and contrast doses required to obtain 3D-Digital subtraction rotational angiography (3D-DSRA) with 3D-Digital rotational angiography (3D-DRA) in infants (children ≤ 2 years of age) and adults with congenital heart diseases (ACHD). 3D-DRA can be performed with radiation doses comparable to bi-plane cine-angiography. However, 3D-DRA in infants requires a large contrast volume. The resolution of 3D-DRA performed in ACHD patients is limited by their soft tissue density. We hypothesized that the use of 3D-DSRA could help alleviate these concerns. Radiation (DAP) and contrast doses required to obtain 3D-DSRA was compared with 3D-DRA in 15 age-, size-, and intervention-matched infants and 15 ACHD patients. The diagnostic quality and utility of these two modalities were scored by 4 qualified independent observers. Both in infants and adults, the median contrast volume for 3D-DSRA was lower than 3D-DRA (0.98 vs. 1.81 mL/kg; P < 0.001 and 0.92 vs. 1.4 mL/kg; P < 0.001, respectively) with an increased DAP (median: 188 vs. 128 cGy cm 2 ; P = 0.068 and 659 vs. 427 cGy cm 2 ; P = 0.045, respectively). The diagnostic quality and utility scores for rotational-angiography, and 3D-reconstruction were superior for 3D-DSRA (score = 94 vs. 80%, P = 0.03 and 90 vs.79%, P = 0.01, respectively) and equivalent for multi-planar-reformation and 3D-roadmapping in ACHD patients compared with 3D-DRA. All scores for both modalities were equivalent for infants. 3D-DSRA can be acquired using lower contrast volume with a mildly higher radiation dose than 3D-DRA in infants and ACHD patients. The diagnostic quality and utility scores for 3D-DSRA were higher in ACHD patients and equivalent for infants compared with 3D-DRA. © 2017 Wiley Periodicals, Inc.

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy

PubMed Central

Mavroidis, P; Shi, C; Plataniotis, G A; Delichas, M G; Costa Ferreira, B; Rodriguez, S; Lind, B K; Papanikolaou, N

2011-01-01

Objectives The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P+) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P+ of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average ΔP+ of 27.0% for a Δ effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average ΔP+ of 23.8% for a Δ effective uniform dose of 11.6 Gy. Conclusion A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose–response relations of the irradiated tumours and normal tissues. The use of P – effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans. PMID:20858664

3D silicon shapes through bulk nano structuration by focused ion beam implantation and wet etching

NASA Astrophysics Data System (ADS)

Salhi, Billel; Troadec, David; Boukherroub, Rabah

2017-05-01

The work presented in this paper concerns the synthesis of silicon (Si) 2D and 3D nanostructures using the delayed effect, caused by implanted Ga ions, on the dissolution of Si in aqueous solutions of tetramethylammonium hydroxide (TMAH). The crystalline silicon substrates (100) are first cleaned and then hydrogenated by immersion in an aqueous solution of hydrofluoric acid. The ion implantation is then carried out by a focused ion beam by varying the dose and the exposure time. Chemical etching in aqueous solutions of TMAH at 80 °C leads to the selective dissolution of the Si planes not exposed to the ions. The preliminary results obtained in the laboratory made it possible to optimize the experimental conditions for the synthesis of 2D and 3D nanoobjects of controlled shape and size. Analysis by transmission electron microscopy and energy dispersive x-ray showed the amorphous nature of the nanostructures obtained and the presence of 5%-20% Ga in these nanoobjects. The first experiments of recrystallization by rapid thermal annealing allowed to reconstitute the crystal structure of these nanoobjects.

3D silicon shapes through bulk nano structuration by focused ion beam implantation and wet etching.

PubMed

Salhi, Billel; Troadec, David; Boukherroub, Rabah

2017-05-19

The work presented in this paper concerns the synthesis of silicon (Si) 2D and 3D nanostructures using the delayed effect, caused by implanted Ga ions, on the dissolution of Si in aqueous solutions of tetramethylammonium hydroxide (TMAH). The crystalline silicon substrates (100) are first cleaned and then hydrogenated by immersion in an aqueous solution of hydrofluoric acid. The ion implantation is then carried out by a focused ion beam by varying the dose and the exposure time. Chemical etching in aqueous solutions of TMAH at 80 °C leads to the selective dissolution of the Si planes not exposed to the ions. The preliminary results obtained in the laboratory made it possible to optimize the experimental conditions for the synthesis of 2D and 3D nanoobjects of controlled shape and size. Analysis by transmission electron microscopy and energy dispersive x-ray showed the amorphous nature of the nanostructures obtained and the presence of 5%-20% Ga in these nanoobjects. The first experiments of recrystallization by rapid thermal annealing allowed to reconstitute the crystal structure of these nanoobjects.

SU-F-T-565: Assessment of Dosimetric Accuracy for a 3D Gel-Based Dosimetry Service

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosen, B; Lam, K; Moran, J

Purpose: To assess the 3D dosimetric accuracy when using a mail-in service for square and stereotactic fields in a clinical environment. Methods: The 3D dosimetry mail-in service (3DDaaS), offered by Modus QA (London, ON), was used to measure dose distributions from a 6 MV beam of a Varian Clinac. Plastic jars filled with radiosensitive ClearView™ gel were received, CT scanned (for registration and density information), irradiated, and then mailed back to the manufacturer for optical CT readout. Three square field irradiations (2×2, 4×4, and 10×10 cm{sup 2}) were performed with jars immobilized in a water tank, and a composite small-fieldmore » stereotactic delivery was performed using an in-air holder. Dosimetric properties of the gel were quantified within the 25–50 Gy dose range using 3D optical attenuation (OA) distributions provided by the manufacturer. OA was normalized to 100% at the position of isocenter, which received 40Gy. Percentage depth dose, profiles, and 3D gamma distributions (3%/1mm criteria) were calculated to quantify feasibility for relative dosimetry. Results: Mean CT-measured density in the central (3×3×3) cm{sup 3} gel region was 40 ± 3 HU, indicating good homogeneity and near-water-equivalence. Measured and calculated central axis doses agreed to within ±3% in the 25–50 Gy dose range. For the square field irradiations, dose profiles agreed to within 1mm. Gamma analysis of the composite irradiation yielded 99.8%, 91.4%, and 79.1% passing rates for regions receiving at least 10, 5, and 2 Gy, respectively, indicating feasibility for use in high-dose regions. Absolute response varied by up to 16% between jars, indicating limitations for absolute dosimetry under the mail-in conditions. Conclusion: 3DDaaS is a novel near-water-equivalent dosimetry system accurate to within 3% dose and 1mm 3D spatial resolution, and is straightforward to use in a clinical setting. Future investigations are warranted to improve dosimeter response in low-dose regions. The authors would like to thank ModusQA (London, ON) for providing the gels and optical readouts used this work. This work was partially funded by NIH P01CA059827.« less

Poster — Thur Eve — 30: 4D VMAT dose calculation methodology to investigate the interplay effect: experimental validation using TrueBeam Developer Mode and Gafchromic film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teke, T; Milette, MP; Huang, V

2014-08-15

The interplay effect between the tumor motion and the radiation beam modulation during a VMAT treatment delivery alters the delivered dose distribution from the planned one. This work present and validate a method to accurately calculate the dose distribution in 4D taking into account the tumor motion, the field modulation and the treatment starting phase. A QUASAR™ respiratory motion phantom was 4D scanned with motion amplitude of 3 cm and with a 3 second period. A static scan was also acquired with the lung insert and the tumor contained in it centered. A VMAT plan with a 6XFFF beam wasmore » created on the averaged CT and delivered on a Varian TrueBeam and the trajectory log file was saved. From the trajectory log file 10 VMAT plans (one for each breathing phase) and a developer mode XML file were created. For the 10 VMAT plans, the tumor motion was modeled by moving the isocentre on the static scan, the plans were re-calculated and summed in the treatment planning system. In the developer mode, the tumor motion was simulated by moving the couch dynamically during the treatment. Gafchromic films were placed in the QUASAR phantom static and irradiated using the developer mode. Different treatment starting phase were investigated (no phase shift, maximum inhalation and maximum exhalation). Calculated and measured isodose lines and profiles are in very good agreement. For each starting phase, the dose distribution exhibit significant differences but are accurately calculated with the methodology presented in this work.« less

SU-E-T-300: Dosimetric Comparision of 4D Radiation Therapy and 3D Radiation Therapy for the Liver Tumor Based On 4D Medical Image

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

Purpose: The purpose of this work was to determine the dosimetric benefit to normal tissues by tracking liver tumor dose in four dimensional radiation therapy (4DRT) on ten phases of four dimensional computer tomagraphy(4DCT) images. Methods: Target tracking each phase with the beam aperture for ten liver cancer patients were converted to cumulative plan and compared to the 3D plan with a merged target volume based on 4DCT image in radiation treatment planning system (TPS). The change in normal tissue dose was evaluated in the plan by using the parameters V5, V10, V15, V20,V25, V30, V35 and V40 (volumes receivingmore » 5, 10, 15, 20, 25, 30, 35 and 40Gy, respectively) in the dose-volume histogram for the liver; mean dose for the following structures: liver, left kidney and right kidney; and maximum dose for the following structures: bowel, duodenum, esophagus, stomach and heart. Results: There was significant difference between 4D PTV(average 115.71cm3 )and ITV(169.86 cm3). When the planning objective is 95% volume of PTV covered by the prescription dose, the mean dose for the liver, left kidney and right kidney have an average decrease 23.13%, 49.51%, and 54.38%, respectively. The maximum dose for bowel, duodenum,esophagus, stomach and heart have an average decrease 16.77%, 28.07%, 24.28%, 4.89%, and 4.45%, respectively. Compared to 3D RT, radiation volume for the liver V5, V10, V15, V20, V25, V30, V35 and V40 by using the 4D plans have a significant decrease(P≤0.05). Conclusion: The 4D plan method creates plans that permit better sparing of the normal structures than the commonly used ITV method, which delivers the same dosimetric effects to the target.« less

Radiotherapy for Early Mediastinal Hodgkin Lymphoma According to the German Hodgkin Study Group (GHSG): The Roles of Intensity-Modulated Radiotherapy and Involved-Node Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koeck, Julia, E-mail: Julia_Koeck@gmx.net; Abo-Madyan, Yasser; Department of Radiation Oncology, Faculty of Medicine, Cairo University, Cairo

2012-05-01

Purpose: Cure rates of early Hodgkin lymphoma (HL) are high, and avoidance of late complications and second malignancies have become increasingly important. This comparative treatment planning study analyzes to what extent target volume reduction to involved-node (IN) and intensity-modulated (IM) radiotherapy (RT), compared with involved-field (IF) and three-dimensional (3D) RT, can reduce doses to organs at risk (OAR). Methods and Materials: Based on 20 computed tomography (CT) datasets of patients with early unfavorable mediastinal HL, we created treatment plans for 3D-RT and IMRT for both the IF and IN according to the guidelines of the German Hodgkin Study Group (GHSG).more » As OAR, we defined heart, lung, breasts, and spinal cord. Dose-volume histograms (DVHs) were evaluated for planning target volumes (PTVs) and OAR. Results: Average IF-PTV and IN-PTV were 1705 cm{sup 3} and 1015 cm{sup 3}, respectively. Mean doses to the PTVs were almost identical for all plans. For IF-PTV/IN-PTV, conformity was better with IMRT and homogeneity was better with 3D-RT. Mean doses to the heart (17.94/9.19 Gy for 3D-RT and 13.76/7.42 Gy for IMRT) and spinal cord (23.93/13.78 Gy for 3D-RT and 19.16/11.55 Gy for IMRT) were reduced by IMRT, whereas mean doses to lung (10.62/8.57 Gy for 3D-RT and 12.77/9.64 Gy for IMRT) and breasts (left 4.37/3.42 Gy for 3D-RT and 6.04/4.59 Gy for IMRT, and right 2.30/1.63 Gy for 3D-RT and 5.37/3.53 Gy for IMRT) were increased. Volume exposed to high doses was smaller for IMRT, whereas volume exposed to low doses was smaller for 3D-RT. Pronounced benefits of IMRT were observed for patients with lymph nodes anterior to the heart. IN-RT achieved substantially better values than IF-RT for almost all OAR parameters, i.e., dose reduction of 20% to 50%, regardless of radiation technique. Conclusions: Reduction of target volume to IN most effectively improves OAR sparing, but is still considered investigational. For the time being, IMRT should be considered for large PTVs especially when the anterior mediastinum is involved.« less

Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses.

PubMed

Moreso, F; Serón, D; Morales, J M; Cruzado, J M; Gil-Vernet, S; Pérez, J L; Fulladosa, X; Andrés, A; Grinyó, J M

1998-06-01

Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids doses efficiently prevents acute rejection in kidney transplants. However, this regimen has been associated with an increased incidence of cytomegalovirus (CMV) disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting that the combination of two powerful immunosuppressants carries the risk of overimmunosuppression. For this reason, we treated a group of patients with MMF 3 g/d combined with low cyclosporine and steroids doses. Eighty-two kidney transplants performed at two centers and enrolled in the European Mycophenolate Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF 2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all patients received cyclosporine and steroids at conventional doses. Fifteen kidney transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3 g/day combined with low cyclosporine and steroid doses (group D). Efficacy was evaluated as the incidence of biopsy proven acute rejection, and safety focused on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C had a high incidence of CMV disease (35.7%) when compared with the other groups (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%). Patients in group (C) displayed leukopenia mainly in the context of CMV disease, while patients of group (D) had leukopenia not related to CMV infection. All patients of group (D) who presented leukopenia recovered after MMF reduction dose, while in group (C) there were 5 out of 28 patients who required MMF withdrawal. We propose that a reasonable approach to take advantage of a powerful non-nephrotoxic immunosuppressant such as MMF, could be the administration of this drug at 3 g/d from the time of transplantation combined with low CsA and steroid doses.

Predictors of High-Grade Esophagitis after Definitive 3D Conformal Therapy, Intensity Modulated Radiation Therapy, or Proton Beam Therapy for Non-Small Cell Lung Cancer

PubMed Central

Gomez, Daniel R.; Tucker, Susan L.; Martel, Mary K.; Mohan, Radhe; Balter, Peter A.; Guerra, Jose Luis Lopez; Liu, Hongmei; Komaki, Ritsuko; Cox, James D.; Liao, Zhongxing

2014-01-01

Introduction We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional (3D) conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade ≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results Overall, 652 patients were included: 405 treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade ≥3 RE were 8%, 28%, and 6%, with a median time to onset of 42 days (range 11–93 days). A fit of the fractional-DVH LKB model demonstrated that the volume parameter n was significantly different (p=0.046) than 1, indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (p=0.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (p=0.105). Conclusions The fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT. PMID:22920974

Optimization of LOPA-based direct laser writing technique for fabrication of submicrometric polymer two- and three-dimensional structures

NASA Astrophysics Data System (ADS)

Do, Mai Trang; Li, Qinggele; Ledoux-Rak, Isabelle; Lai, Ngoc D.

2013-05-01

We demonstrate a novel and very simple method allowing very easy flexible fabrication of 2D and 3D submicrometric structures. By using a photosensitive polymer (SU8) possessing an ultralow one-photon absorption (LOPA) coefficient at the excition laser wavelength (532 nm) and a high numerical aperture (NA = 1.3, oil immersion) objective lens, various submicrometric structures with feature size as small as 150 nm have been successfully fabricated. We have further investigated the energy accumulation effect in LOPA direct laser writing when the structure lattice constant approaches the diffraction limit. In this case, a proximity correction, i.e., a compensation of the doses between different voxels, was applied, allowing to create uniform and submicrometric structures with a lattice constant as small as 400 nm. As compared to commonly used two-photon absorption microscopy, the LOPA method allows to simplify the experimental setup and also to minimize the photo-damaging or bleaching effect. The idea of using LOPA also opens a new and inexpensive way to optically address 3D structures, namely 3D fluorescence imaging and 3D data storage.

Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT using GATE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bretin, Florian; Bahri, Mohamed Ali; Luxen, André

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies involving microCT, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low-level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non-invasively using Monte Carlo simulationsmore » in GATE and to compare results to previously obtained experimental values. Methods: Tungsten X-ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half-value layers were simulated for spectra validation against experimentally measured values of the physical X-ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat. Results: Simulated half-value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%. Conclusions: Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup.« less

Radiation experiments on Cosmos 2044: K-7-41, parts A, B, C, D, E

NASA Technical Reports Server (NTRS)

Frank, A. L.; Benton, E. V.; Benton, E. R.; Dudkin, V. E.; Marenny, A. M.

1990-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 deg and attitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10(exp -4) and 3.05 x 10(exp -4)/sq cm/s/sr, of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(sub infinity)-H2O is greater than or equal to 4 keV/micron. Neutron measurements yielded 0.018 mrem/d in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra were compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 deg) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCRs, and higher LET particles, in the heavy particle fluxes.

Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): the influence of gender and genetics (CYP2D6, COMT, 5-HTT).

PubMed

Pardo-Lozano, Ricardo; Farré, Magí; Yubero-Lahoz, Samanta; O'Mathúna, Brian; Torrens, Marta; Mustata, Cristina; Pérez-Mañá, Clara; Langohr, Klaus; Cuyàs, Elisabet; Carbó, Marcel lí; de la Torre, Rafael

2012-01-01

The synthetic psychostimulant MDMA (± 3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role. ClinicalTrials.gov NCT01447472.

Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT)

PubMed Central

O’Mathúna, Brian; Torrens, Marta; Mustata, Cristina; Pérez-Mañá, Clara; Langohr, Klaus; Cuyàs, Elisabet; Carbó, Marcel·lí; de la Torre, Rafael

2012-01-01

The synthetic psychostimulant MDMA (±3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75–100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role. Trial Registration ClinicalTrials.gov NCT01447472 PMID:23112822

In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer.

PubMed

Hassouna, Ashraf H; Bahadur, Yasir A; Constantinescu, Camelia; El Sayed, Mohamed E; Naseem, Hussain; Naga, Adly F

2011-01-01

To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)-reconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri. Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT images-based volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum. The ICRU reference point and the volumes of 1, 2, and 5cm(3) received 3.6±0.9, 5.6±2.0, 5.1±1.7, 4.3±1.4 and 5.0±1.2, 5.3±1.3, 4.9±1.1, and 4.2±0.9 Gy for the bladder and rectum, respectively. The ratio of the 1cm(3) and the ICRU reference point dose to the diode dose was 1.8±0.7 and 1.2±0.5 for the bladder and 1.9±0.6 and 1.7±0.5 for the rectum, respectively. 3D image-based dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-D3) dilution in rats.

PubMed

Stimpson, Stephen A; Turner, Scott M; Clifton, Lisa G; Poole, James C; Mohammed, Hussein A; Shearer, Todd W; Waitt, Greg M; Hagerty, Laura L; Remlinger, Katja S; Hellerstein, Marc K; Evans, William J

2012-06-01

There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass.

Real-time advanced spinal surgery via visible patient model and augmented reality system.

PubMed

Wu, Jing-Ren; Wang, Min-Liang; Liu, Kai-Che; Hu, Ming-Hsien; Lee, Pei-Yuan

2014-03-01

This paper presents an advanced augmented reality system for spinal surgery assistance, and develops entry-point guidance prior to vertebroplasty spinal surgery. Based on image-based marker detection and tracking, the proposed camera-projector system superimposes pre-operative 3-D images onto patients. The patients' preoperative 3-D image model is registered by projecting it onto the patient such that the synthetic 3-D model merges with the real patient image, enabling the surgeon to see through the patients' anatomy. The proposed method is much simpler than heavy and computationally challenging navigation systems, and also reduces radiation exposure. The system is experimentally tested on a preoperative 3D model, dummy patient model and animal cadaver model. The feasibility and accuracy of the proposed system is verified on three patients undergoing spinal surgery in the operating theater. The results of these clinical trials are extremely promising, with surgeons reporting favorably on the reduced time of finding a suitable entry point and reduced radiation dose to patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Helical tomotherapy significantly reduces dose to normal tissues when compared to 3D-CRT for locally advanced rectal cancer.

PubMed

Jhaveri, Pavan M; Teh, Bin S; Paulino, Arnold C; Smiedala, Mindy J; Fahy, Bridget; Grant, Walter; McGary, John; Butler, E Brian

2009-10-01

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.

Method for dose-reduced 3D catheter tracking on a scanning-beam digital x-ray system using dynamic electronic collimation

NASA Astrophysics Data System (ADS)

Dunkerley, David A. P.; Funk, Tobias; Speidel, Michael A.

2016-03-01

Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy system capable of tomosynthesis-based 3D catheter tracking. This work proposes a method of dose-reduced 3D tracking using dynamic electronic collimation (DEC) of the SBDX scanning x-ray tube. Positions in the 2D focal spot array are selectively activated to create a regionof- interest (ROI) x-ray field around the tracked catheter. The ROI position is updated for each frame based on a motion vector calculated from the two most recent 3D tracking results. The technique was evaluated with SBDX data acquired as a catheter tip inside a chest phantom was pulled along a 3D trajectory. DEC scans were retrospectively generated from the detector images stored for each focal spot position. DEC imaging of a catheter tip in a volume measuring 11.4 cm across at isocenter required 340 active focal spots per frame, versus 4473 spots in full-FOV mode. The dose-area-product (DAP) and peak skin dose (PSD) for DEC versus full field-of-view (FOV) scanning were calculated using an SBDX Monte Carlo simulation code. DAP was reduced to 7.4% to 8.4% of the full-FOV value, consistent with the relative number of active focal spots (7.6%). For image sequences with a moving catheter, PSD was 33.6% to 34.8% of the full-FOV value. The root-mean-squared-deviation between DEC-based 3D tracking coordinates and full-FOV 3D tracking coordinates was less than 0.1 mm. The 3D distance between the tracked tip and the sheath centerline averaged 0.75 mm. Dynamic electronic collimation can reduce dose with minimal change in tracking performance.

MO-FG-CAMPUS-TeP1-04: Pseudo-In-Vivo Dose Verification of a New Mono-Isocentric Technique for the Treatment of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pappas, E P; Makris, D; Lahanas, V

2016-06-15

Purpose: To validate dose calculation and delivery accuracy of a recently introduced mono-isocentric technique for the treatment of multiple brain metastases in a realistic clinical case. Methods: Anonymized CT scans of a patient were used to model a hollow phantom that duplicates anatomy of the skull. A 3D printer was used to construct the phantom of a radiologically bone-equivalent material. The hollow phantom was subsequently filled with a polymer gel 3D dosimeter which also acted as a water-equivalent material. Irradiation plan consisted of 5 targets and was identical to the one delivered to the specific patient except for the prescriptionmore » dose which was optimized to match the gel dose-response characteristics. Dose delivery was performed using a single setup isocenter dynamic conformal arcs technique. Gel dose read-out was carried out by a 1.5 T MRI scanner. All steps of the corresponding patient’s treatment protocol were strictly followed providing an end-to-end quality assurance test. Pseudo-in-vivo measured 3D dose distribution and calculated one were compared in terms of spatial agreement, dose profiles, 3D gamma indices (5%/2mm, 20% dose threshold), DVHs and DVH metrics. Results: MR-identified polymerized areas and calculated high dose regions were found to agree within 1.5 mm for all targets, taking into account all sources of spatial uncertainties involved (i.e., set-up errors, MR-related geometric distortions and registration inaccuracies). Good dosimetric agreement was observed in the vast majority of the examined profiles. 3D gamma index passing rate reached 91%. DVH and corresponding metrics comparison resulted in a satisfying agreement between measured and calculated datasets within targets and selected organs-at-risk. Conclusion: A novel, pseudo-in-vivo QA test was implemented to validate spatial and dosimetric accuracy in treatment of multiple metastases. End-to-end testing demonstrated that our gel dosimetry phantom is suited for such QA procedures, allowing for 3D analysis of both targeting placement and dose.« less

Intraindividual comparison of image quality in MR urography at 1.5 and 3 tesla in an animal model.

PubMed

Regier, M; Nolte-Ernsting, C; Adam, G; Kemper, J

2008-10-01

Experimental evaluation of image quality of the upper urinary tract in MR urography (MRU) at 1.5 and 3 Tesla in a porcine model. In this study four healthy domestic pigs, weighing between 71 and 80 kg (mean 73.6 kg), were examined with a standard T1w 3D-GRE and a high-resolution (HR) T1w 3D-GRE sequence at 1.5 and 3 Tesla. Additionally, at 3 Tesla both sequences were performed with parallel imaging (SENSE factor 2). The MR urographic scans were performed after intravenous injection of gadolinium-DTPA (0.1 mmol/kg body weight (bw)) and low-dose furosemide (0.1 mg/kg bw). Image evaluation was performed by two independent radiologists blinded to sequence parameters and field strength. Image analysis included grading of image quality of the segmented collecting system based on a five-point grading scale regarding anatomical depiction and artifacts observed (1: the majority of the segment (>50%) was not depicted or was obscured by major artifacts; 5: the segment was visualized without artifacts and had sharply defined borders). Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were determined. Statistical analysis included kappa-statistics, Wilcoxon and paired student t-test. The mean scores for MR urographies at 1.5 Tesla were 2.83 for the 3D-GRE and 3.48 for the HR3D-GRE sequence. Significantly higher values were determined using the corresponding sequences at 3 Tesla, averaging 3.19 for the 3D-GRE (p = 0.047) and 3.92 for the HR3D-GRE (p = 0,023) sequence. Delineation of the pelvicaliceal system was rated significantly higher at 3 Tesla compared to 1.5 Tesla (3D-GRE: p = 0.015; HR3D-GRE: p = 0.006). At 3 Tesla the mean SNR and CNR were significantly higher (p < 0.05). A kappa of 0.67 indicated good interobserver agreement. In an experimental setup, MR urography at 3 Tesla allowed for significantly higher image quality and SNR compared to 1.5 Tesla, particularly for the visualization of the pelvicaliceal system.

SU-F-T-184: 3D Range-Modulator for Scanned Particle Therapy: Development, Monte Carlo Simulations and Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simeonov, Y; Penchev, P; Ringbaek, T Printz

2016-06-15

Purpose: Active raster scanning in particle therapy results in highly conformal dose distributions. Treatment time, however, is relatively high due to the large number of different iso-energy layers used. By using only one energy and the so called 3D range-modulator irradiation times of a few seconds only can be achieved, thus making delivery of homogeneous dose to moving targets (e.g. lung cancer) more reliable. Methods: A 3D range-modulator consisting of many pins with base area of 2.25 mm2 and different lengths was developed and manufactured with rapid prototyping technique. The form of the 3D range-modulator was optimised for a sphericalmore » target volume with 5 cm diameter placed at 25 cm in a water phantom. Monte Carlo simulations using the FLUKA package were carried out to evaluate the modulating effect of the 3D range-modulator and simulate the resulting dose distribution. The fine and complicated contour form of the 3D range-modulator was taken into account by a specially programmed user routine. Additionally FLUKA was extended with the capability of intensity modulated scanning. To verify the simulation results dose measurements were carried out at the Heidelberg Ion Therapy Center (HIT) with a 400.41 MeV 12C beam. Results: The high resolution measurements show that the 3D range-modulator is capable of producing homogeneous 3D conformal dose distributions, simultaneously reducing significantly irradiation time. Measured dose is in very good agreement with the previously conducted FLUKA simulations, where slight differences were traced back to minor manufacturing deviations from the perfect optimised form. Conclusion: Combined with the advantages of very short treatment time the 3D range-modulator could be an alternative to treat small to medium sized tumours (e.g. lung metastasis) with the same conformity as full raster-scanning treatment. Further simulations and measurements of more complex cases will be conducted to investigate the full potential of the 3D range-modulator.« less

Sci-Thur PM – Brachytherapy 06: 3D Printed Surface Applicators for High Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clarke, Scott; Yewondwossen, Mammo; Robar, James

Purpose: The purpose of this work is to develop a new applicator for administering high dose rate (HDR) brachytherapy using 3D printing technology. Primary advantages of using a 3D printed applicator will be to offer a more streamlined approach for therapists and patients while achieving better conformity, reproducibility, and patient specific applicators. Methods: A phantom study was conducted to measure the effectiveness of a 3D printed surface applicator by analyzing tumours on three locations of the body: the foot, nose, and scalp. The applicator was designed using Eclipse and further modified using Blender to create the catheter tunnels before beingmore » printed on a Lulzbot Taz 5 3D printer. A radiation plan was made using Oncentra Brachytherapy for a control treatment option using Freiburg Flaps and one with the novel method of a 3D printed applicator. A comparative analysis was made using D90, D100, V100, V150, and V200 Results: The 3D printed applicator showed comparable dose coverage with significant improvements on highly irregular surfaces when analyzed against a plan made using Freiburg Flaps. Although both plans exhibited complete tumour coverage, the 3D applicator showed improvements in D90 and V150 and the 3D applicator had a dose homogeneity index (DHI) of 0.99 compared to a DHI of 0.97 for the control. Therapist prep time also dropped significantly due to the lack of need for a thermoplastic mesh. Conclusions: 3D printed applicators for treatment of superficial sites proved to offer more patient convenience, less prep time, better conformity and tighter margins.« less

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

PubMed Central

Tommasino, Francesco; Friedrich, Thomas; Jakob, Burkhard; Meyer, Barbara; Durante, Marco; Scholz, Michael

2015-01-01

We present here an analysis of DSB induction and processing after irradiation with X-rays in an extended dose range based on the use of the γH2AX assay. The study was performed by quantitative flow cytometry measurements, since the use of foci counting would result in reasonable accuracy only in a limited dose range of a few Gy. The experimental data are complemented by a theoretical analysis based on the GLOBLE model. In fact, original aim of the study was to test GLOBLE predictions against new experimental data, in order to contribute to the validation of the model. Specifically, the γH2AX signal kinetics has been investigated up to 24 h after exposure to increasing photon doses between 2 and 500 Gy. The prolonged persistence of the signal at high doses strongly suggests dose dependence in DSB processing after low LET irradiation. Importantly, in the framework of our modelling analysis, this is related to a gradually increased fraction of DSB clustering at the micrometre scale. The parallel study of γH2AX dose response curves shows the onset of a pronounced saturation in two cell lines at a dose of about 20 Gy. This dose is much lower than expected according to model predictions based on the values usually adopted for the DSB induction yield (≈ 30 DSB/Gy) and for the γH2AX foci extension of approximately 2 Mbp around the DSB. We show and discuss how theoretical predictions and experimental findings can be in principle reconciled by combining an increased DSB induction yield with the assumption of a larger genomic extension for the single phosphorylated regions. As an alternative approach, we also considered in our model the possibility of a 3D spreading-mechanism of the H2AX phosphorylation around the induced DSB, and applied it to the analysis of both the aspects considered. Our results are found to be supportive for the basic assumptions on which GLOBLE is built. Apart from giving new insights into the H2AX phosphorylation process, experiments performed at high doses are of relevance in the context of radiation therapy, where hypo-fractionated schemes become increasingly popular. PMID:26067661

Experimental and calculated LET distributions in the Cosmos-2044 biosatellite orbit

NASA Technical Reports Server (NTRS)

Dudkin, V. E.; Karpov, O. N.; Akopova, A. B.; Magradze, N. V.; Moiseenko, A. A.; Benton, E. V.; Frank, A. L.; Watts, J. W. Jr

1992-01-01

During the flight of the Cosmos-2044 biosatellite, joint U.S.S.R.-U.S.A. investigations of different characteristics of cosmic radiation (CR) in the near-Earth environment were carried out. The U.S. dielectric track detectors CR-39 and Soviet BYa- and BR-type nuclear photo-emulsions were used as detectors. The present work shows some results of experimental measurements of linear energy transfer (LET) spectra of CR particles obtained with the use of these detectors, which were placed both inside and outside the satellite. The LET spectra measurement with plastic detectors is composed of two parts: the measurement of galactic cosmic rays (GCR) particles, and of short-range particles. The contributions of these components to the total LET distribution at various thicknesses of the shielding were analyzed and the results of these studies are presented. Calculated LET spectra in the Cosmos-2044 orbit were compared with experimental data. On the basis of experimental and calculated values of the LET spectra, absorbed and equivalent CR doses were calculated. In the shielding range of 1-1.5 g cm-2, outside the spacecraft, the photo-emulsions yielded 10.3 mrad d-1 and 27.5 mrem d-1 (LET > or = 2 MeV cm-1) while the CR-39 yielded averages of 1.43 mrad d-1 and 13.4 mrem d-1 (LET > or = 40 MeV cm-1). Inside the spacecraft (> or = 10 g cm-2) the photo-emulsions yielded 8.9 mrad d-1 and 14.5 mrem d-1.

25-Hydroxyvitamin D response to graded vitamin D₃ supplementation among obese adults.

PubMed

Drincic, Andjela; Fuller, Eileen; Heaney, Robert P; Armas, Laura A G

2013-12-01

Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D₃ (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind study of 3 doses of oral vitamin D₃ (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

PubMed Central

Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

2013-01-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

Independent calculation-based verification of IMRT plans using a 3D dose-calculation engine.

PubMed

Arumugam, Sankar; Xing, Aitang; Goozee, Gary; Holloway, Lois

2013-01-01

Independent monitor unit verification of intensity-modulated radiation therapy (IMRT) plans requires detailed 3-dimensional (3D) dose verification. The aim of this study was to investigate using a 3D dose engine in a second commercial treatment planning system (TPS) for this task, facilitated by in-house software. Our department has XiO and Pinnacle TPSs, both with IMRT planning capability and modeled for an Elekta-Synergy 6MV photon beam. These systems allow the transfer of computed tomography (CT) data and RT structures between them but do not allow IMRT plans to be transferred. To provide this connectivity, an in-house computer programme was developed to convert radiation therapy prescription (RTP) files as generated by many planning systems into either XiO or Pinnacle IMRT file formats. Utilization of the technique and software was assessed by transferring 14 IMRT plans from XiO and Pinnacle onto the other system and performing 3D dose verification. The accuracy of the conversion process was checked by comparing the 3D dose matrices and dose volume histograms (DVHs) of structures for the recalculated plan on the same system. The developed software successfully transferred IMRT plans generated by 1 planning system into the other. Comparison of planning target volume (TV) DVHs for the original and recalculated plans showed good agreement; a maximum difference of 2% in mean dose, - 2.5% in D95, and 2.9% in V95 was observed. Similarly, a DVH comparison of organs at risk showed a maximum difference of +7.7% between the original and recalculated plans for structures in both high- and medium-dose regions. However, for structures in low-dose regions (less than 15% of prescription dose) a difference in mean dose up to +21.1% was observed between XiO and Pinnacle calculations. A dose matrix comparison of original and recalculated plans in XiO and Pinnacle TPSs was performed using gamma analysis with 3%/3mm criteria. The mean and standard deviation of pixels passing gamma tolerance for XiO-generated IMRT plans was 96.1 ± 1.3, 96.6 ± 1.2, and 96.0 ± 1.5 in axial, coronal, and sagittal planes respectively. Corresponding results for Pinnacle-generated IMRT plans were 97.1 ± 1.5, 96.4 ± 1.2, and 96.5 ± 1.3 in axial, coronal, and sagittal planes respectively. © 2013 American Association of Medical Dosimetrists.

Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via modeling and simulation analysis in a D2 receptor occupancy study.

PubMed

Lim, Hyeong-Seok; Kim, Su Jin; Noh, Yook-Hwan; Lee, Byung Chul; Jin, Seok-Joon; Park, Hyun Soo; Kim, Soohyeon; Jang, In-Jin; Kim, Sang Eun

2013-03-01

To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development. In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12, with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding potential to D(2) receptor in putamen and caudate nucleus over time were analyzed using NONMEM, and simulations for the profiles of D2RO over time on various regimens of haloperidol were conducted to find the optimal dosing regimens. One compartment model with a saturable binding compartment, and inhibitory E(max) model in the effect compartment best described the data. Plasma haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml, in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h is near the optimal dose. This study showed that sparse D2RO measurements in steady state pharmacodynamic design after multiple dosing could reveal the possibility of treatment effect of D(2) antagonist, and could identify the potential optimal doses for later clinical studies by modeling and simulation.

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: a pilot randomized study of high-dose vitamin D3 administration

PubMed Central

Alvarez, Jessica A.; Chong, Elizabeth Y.; Walker, Douglas I.; Chandler, Joshua D.; Michalski, Ellen S.; Grossmann, Ruth E.; Uppal, Karan; Li, Shuzhao; Frediani, Jennifer K.; Tirouvanziam, Rabindra; Tran, ViLinh T.; Tangpricha, Vin; Jones, Dean P.; Ziegler, Thomas R.

2017-01-01

Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways--predominantly representing amino acid pathways-- differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting. PMID:28403943

Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples

NASA Astrophysics Data System (ADS)

Furuta, T.; Maeyama, T.; Ishikawa, K. L.; Fukunishi, N.; Fukasaku, K.; Takagi, S.; Noda, S.; Himeno, R.; Hayashi, S.

2015-08-01

In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning.

Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples.

PubMed

Furuta, T; Maeyama, T; Ishikawa, K L; Fukunishi, N; Fukasaku, K; Takagi, S; Noda, S; Himeno, R; Hayashi, S

2015-08-21

In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning.

SU-E-T-14: Modeling of 3D Positron Emission Activity Distributions Induced by Proton Irradiation: A Semi-Empirical Method.

PubMed

Lopatiuk-Tirpak, O; Su, Z; Hsi, W; Zeidan, O; Meeks, S

2012-06-01

to present and validate a method for modeling three-dimensional positron emission (PE) activity distributions induced by proton beam irradiation for PET/CT delivery verification studies in homogeneous media. the method relies on modeling the 3D proton flux distribution by combining the analytical expression for the depth reduction of proton flux with the empirically obtained lateral distribution. The latter is extracted from the corresponding dose distribution under the assumption that the projectile energy is nearly constant in the lateral plane. The same assumption allows calculating the 3D induced activity distributions from proton flux distributions by parameterizing the energy-dependent activation cross-sections in terms of depth via the energy-range relation. Results of this modeling approach were validated against experimental PET/CT data from three phantom deliveries: unmodulated (pristine) beam, spread-out Bragg peak (SOBP) delivery without a range compensator, and SOBP with a range compensator. BANG3-Pro2 polymer gel was used as a phantom material because of its elemental soft-tissue equivalence. the agreement between modeled and measured activity distributions was evaluated using 3D gamma index analysis method, which, despite being traditionally reserved for dose distribution comparisons, is sufficiently general to be applied to other quantities. The evaluation criteria were dictated by limitations of PET imaging and were chosen to correspond to count rate uncertainty (6% value difference) and spatial resolution (4 mm distance to agreement). With these criteria and the threshold of 6%, the fraction of evaluated voxels passing the gamma evaluation was 97.9% for the pristine beam, 98.9% for the SOBP without compensator, and 98.5% for SOBP with compensator. results of gamma evaluation indicate that the activity distributions produced by the model are consistent with experimental data within the uncertainties of PET imaging for clinical proton beams deliveries. This work was supported by the Bankhead-Coley Florida Biomedical Research Program under Grant No. 1BD10-34212. © 2012 American Association of Physicists in Medicine.

Dietary Butyrate Helps to Restore the Intestinal Status of a Marine Teleost (Sparus aurata) Fed Extreme Diets Low in Fish Meal and Fish Oil

PubMed Central

Estensoro, Itziar; Ballester-Lozano, Gabriel; Benedito-Palos, Laura; Grammes, Fabian; Martos-Sitcha, Juan Antonio; Mydland, Liv-Torunn; Calduch-Giner, Josep Alvar; Fuentes, Juan; Karalazos, Vasileios; Ortiz, Álvaro; Øverland, Margareth; Pérez-Sánchez, Jaume

2016-01-01

There is a constant need to find feed additives that improve health and nutrition of farmed fish and lessen the intestinal inflammation induced by plant-based ingredients. The objective of this study was to evaluate the effects of adding an organic acid salt to alleviate some of the detrimental effects of extreme plant-ingredient substitution of fish meal (FM) and fish oil (FO) in gilthead sea bream diet. Three experiments were conducted. In a first trial (T1), the best dose (0.4%) of sodium butyrate (BP-70 ®NOREL) was chosen after a short (9-weeks) feeding period. In a second longer trial (T2) (8 months), four diets were used: a control diet containing 25% FM (T2-D1) and three experimental diets containing 5% FM (T2-D2, T2-D3, T2-D4). FO was the only added oil in D1, while a blend of plant oils replaced 58% and 84% of FO in T2-D2, and T2-D3 and T2-D4, respectively. The latter was supplemented with 0.4% BP-70. In a third trial (T3), two groups of fish were fed for 12 and 38 months with D1, D3 and D4 diets of T2. The effects of dietary changes were studied using histochemical, immunohistochemical, molecular and electrophysiological tools. The extreme diet (T2-D3) modified significantly the transcriptomic profile, especially at the anterior intestine, up-regulating the expression of inflammatory markers, in coincidence with a higher presence of granulocytes and lymphocytes in the submucosa, and changing genes involved in antioxidant defences, epithelial permeability and mucus production. Trans-epithelial electrical resistance (Rt) was also decreased (T3-D3). Most of these modifications were returned to control values with the addition of BP-70. None of the experimental diets modified the staining pattern of PCNA, FABP2 or ALPI. These results further confirm the potential of this additive to improve or reverse the detrimental effects of extreme fish diet formulations. PMID:27898676

Dietary Butyrate Helps to Restore the Intestinal Status of a Marine Teleost (Sparus aurata) Fed Extreme Diets Low in Fish Meal and Fish Oil.

PubMed

Estensoro, Itziar; Ballester-Lozano, Gabriel; Benedito-Palos, Laura; Grammes, Fabian; Martos-Sitcha, Juan Antonio; Mydland, Liv-Torunn; Calduch-Giner, Josep Alvar; Fuentes, Juan; Karalazos, Vasileios; Ortiz, Álvaro; Øverland, Margareth; Sitjà-Bobadilla, Ariadna; Pérez-Sánchez, Jaume

2016-01-01

There is a constant need to find feed additives that improve health and nutrition of farmed fish and lessen the intestinal inflammation induced by plant-based ingredients. The objective of this study was to evaluate the effects of adding an organic acid salt to alleviate some of the detrimental effects of extreme plant-ingredient substitution of fish meal (FM) and fish oil (FO) in gilthead sea bream diet. Three experiments were conducted. In a first trial (T1), the best dose (0.4%) of sodium butyrate (BP-70 ®NOREL) was chosen after a short (9-weeks) feeding period. In a second longer trial (T2) (8 months), four diets were used: a control diet containing 25% FM (T2-D1) and three experimental diets containing 5% FM (T2-D2, T2-D3, T2-D4). FO was the only added oil in D1, while a blend of plant oils replaced 58% and 84% of FO in T2-D2, and T2-D3 and T2-D4, respectively. The latter was supplemented with 0.4% BP-70. In a third trial (T3), two groups of fish were fed for 12 and 38 months with D1, D3 and D4 diets of T2. The effects of dietary changes were studied using histochemical, immunohistochemical, molecular and electrophysiological tools. The extreme diet (T2-D3) modified significantly the transcriptomic profile, especially at the anterior intestine, up-regulating the expression of inflammatory markers, in coincidence with a higher presence of granulocytes and lymphocytes in the submucosa, and changing genes involved in antioxidant defences, epithelial permeability and mucus production. Trans-epithelial electrical resistance (Rt) was also decreased (T3-D3). Most of these modifications were returned to control values with the addition of BP-70. None of the experimental diets modified the staining pattern of PCNA, FABP2 or ALPI. These results further confirm the potential of this additive to improve or reverse the detrimental effects of extreme fish diet formulations.

Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cucinotta, Francis A

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ)more » pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.« less

Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Neill, Peter; Anderson, Jennifer

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ)more » pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.« less

Dosimetric and radiobiologic comparison of 3D conformal versus intensity modulated planning techniques for prostate bed radiotherapy.

PubMed

Koontz, Bridget F; Das, Shiva; Temple, Kathy; Bynum, Sigrun; Catalano, Suzanne; Koontz, Jason I; Montana, Gustavo S; Oleson, James R

2009-01-01

Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively (p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% (p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.

Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial12

PubMed Central

Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Rahme, Maya; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Kassir, Mohamed-Faisal

2016-01-01

Background: It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). Objective: We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. Design: This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged ≥65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. Results: In total, 222 subjects (55% women) with a mean ± SD age and body mass index (BMI; in kg/m2) of 71 ± 4 y and 30 ± 4, respectively, completed the study. Subjects’ baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean ± SD serum 25(OH)D increased from 20 ± 7 to 26 ± 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 ± 8 to 36 ± 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. Conclusion: Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366. PMID:27413130

Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial.

PubMed

El-Hajj Fuleihan, Ghada; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Rahme, Maya; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Kassir, Mohamed-Faisal

2016-08-01

It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged ≥65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. In total, 222 subjects (55% women) with a mean ± SD age and body mass index (BMI; in kg/m(2)) of 71 ± 4 y and 30 ± 4, respectively, completed the study. Subjects' baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean ± SD serum 25(OH)D increased from 20 ± 7 to 26 ± 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 ± 8 to 36 ± 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366. © 2016 American Society for Nutrition.

Adaptive iterative dose reduction (AIDR) 3D in low dose CT abdomen-pelvis: Effects on image quality and radiation exposure

NASA Astrophysics Data System (ADS)

Ang, W. C.; Hashim, S.; Karim, M. K. A.; Bahruddin, N. A.; Salehhon, N.; Musa, Y.

2017-05-01

The widespread use of computed tomography (CT) has increased the medical radiation exposure and cancer risk. We aimed to evaluate the impact of AIDR 3D in CT abdomen-pelvic examinations based on image quality and radiation dose in low dose (LD) setting compared to standard dose (STD) with filtered back projection (FBP) reconstruction. We retrospectively reviewed the images of 40 patients who underwent CT abdomen-pelvic using a 80 slice CT scanner. Group 1 patients (n=20, mean age 41 ± 17 years) were performed at LD with AIDR 3D reconstruction and Group 2 patients (n=20, mean age 52 ± 21 years) were scanned with STD using FBP reconstruction. Objective image noise was assessed by region of interest (ROI) measurements in the liver and aorta as standard deviation (SD) of the attenuation value (Hounsfield Unit, HU) while subjective image quality was evaluated by two radiologists. Statistical analysis was used to compare the scan length, CT dose index volume (CTDIvol) and image quality of both patient groups. Although both groups have similar mean scan length, the CTDIvol significantly decreased by 38% in LD CT compared to STD CT (p<0.05). Objective and subjective image quality were statistically improved with AIDR 3D (p<0.05). In conclusion, AIDR 3D enables significant dose reduction of 38% with superior image quality in LD CT abdomen-pelvis.

Use of computer code for dose distribution studies in A 60CO industrial irradiator

NASA Astrophysics Data System (ADS)

Piña-Villalpando, G.; Sloan, D. P.

1995-09-01

This paper presents a benchmark comparison between calculated and experimental absorbed dose values tor a typical product, in a 60Co industrial irradiator, located at ININ, México. The irradiator is a two levels, two layers system with overlapping product configuration with activity around 300kCi. Experimental values were obtanied from routine dosimetry, using red acrylic pellets. Typical product was Petri dishes packages, apparent density 0.13 g/cm3; that product was chosen because uniform size, large quantity and low density. Minimum dose was fixed in 15 kGy. Calculated values were obtained from QAD-CGGP code. This code uses a point kernel technique, build-up factors fitting was done by geometrical progression and combinatorial geometry is used for system description. Main modifications for the code were related with source sumilation, using punctual sources instead of pencils and an energy and anisotropic emission spectrums were included. Results were, for maximum dose, calculated value (18.2 kGy) was 8% higher than experimental average value (16.8 kGy); for minimum dose, calculated value (13.8 kGy) was 3% higher than experimental average value (14.3 kGy).

The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific.

PubMed

Elmes, N J; Nasveld, P E; Kitchener, S J; Kocisko, D A; Edstein, M D

2008-11-01

Tafenoquine is being developed for radical cure and post-exposure prophylaxis of Plasmodium vivax malaria. In an open-label study, 1512 Australian Defence Force personnel received one of three tafenoquine 3 d regimens [400 mg once daily (od), 200 mg twice daily (bid), 200 mg od] or daily primaquine (22.5 mg) plus doxycycline (100 mg) over 14 d in Bougainville and in Timor-Leste for post-exposure prophylaxis. The relapse rate of subjects treated in Bougainville with tafenoquine (n=173) was 1.2% (200 mg bid x 3 d) and 2.3% (400 mg od x 3 d), while primaquine plus doxycycline (n=175) was 3.4%. For subjects treated in Timor-Leste with tafenoquine (n=636), the relapse rate was 4.9% (200 mg od x 3 d), 5.3% (200 mg bid x 3 d) and 11.0% (400 mg od x 3d), while primaquine plus doxycycline (n=289) was 10.0%. The most frequent adverse events reported across all groups were nausea, abdominal distress and diarrhoea. There was a dose-dependent reduction in adverse events with a reduced dose of tafenoquine, with the lowest dose (total 600 mg over 3 d) producing rates of adverse events equivalent to that of primaquine plus doxycycline. The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area. [Australian New Zealand Clinical Trials Registry Number 12607000588493].

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Efficacy of sulfonamides and Baycox(®) against Isospora suis in experimental infections of suckling piglets.

PubMed

Joachim, Anja; Mundt, Hans-Christian

2011-12-01

Sulfonamide treatment of piglets against neonatal coccidiosis has frequently been suggested in the literature. In order to evaluate the efficacy of sulfonamides against experimental Isospora suis infections in suckling piglets (oral infection with 1,500 sporulated oocysts of I. suis per piglet on the fourth day of life), two trials were conducted. In trial I, oral sulfadimidine (group Sulfa-Oral) was applied in doses of 100 mg/kg of body weight (BW) 1 day before infection and 75 mg/kg BW daily for the following 5 days, and sulfamethoxypyrimidine (SMP) was applied parenterally in daily doses of 75 mg/kg BW for the same time period. In trial II, SMP was applied parenterally in doses of 75 mg/kg BW (a) from the day of infection daily for 7 days (SMP-Standard), (b) for 2 days starting on the day of infection (SMP-Early), (c) for 3 days starting 2 days post-infection (d.p.i.; SMP-Middle), (d) for 2 days starting 5 d.p.i. (SMP-Late), and (e) every other day from the day of infection until 6 d.p.i. (SMP-Alternating), as well as (f) orally in doses of 75 mg/kg BW from the day of infection for 7 days (SMP-Oral). The sulfonamide-treated groups were compared to a toltrazuril-treated group (single oral treatment with Baycox® 5% suspension, 20 mg/kg BW 2 d.p.i.) and to a water-treated Control group. Each group consisted of seven to nine piglets. The parameters evaluated were oocyst excretion and fecal consistency/diarrhea from 4 to 15 d.p.i. Sulfa-Oral, SMP-Early, and SMP-Late had no significant effect in reduction of oocyst excretion and diarrhea, whereas treatment for 3-7 days with SMP reduced both parasite shedding and diarrhea significantly. Oral treatment with SMP was comparable to parenteral application. Baycox® in a single application had the most pronounced effect and completely suppressed oocyst excretion and diarrhea during the examination period. It could be shown that repeated application of sulfonamides, provided that the appropriate time period after infection is covered, can in principle be used to control piglet coccidiosis; however, the amount of work required is considerable, and the practicability is poor. Due to the short half-life of sulfonamides in pigs and the lack of predictability of the time point of infection, an efficient application of sulfonamides to control piglet coccidiosis under field conditions appears unlikely. Baycox®, on the other hand, applied once during the prepatent period of infection, had a lasting effect and can be used to most effectively control I. suis.

Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eley, John G.; Hogstrom, Kenneth R.; Matthews, Kenneth L.

2011-12-15

Purpose: The purpose of this work was to investigate the potential of discrete Gaussian edge feathering of the higher energy electron fields for improving abutment dosimetry in the planning volume when using an electron multileaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT). Methods: A discrete (five-step) Gaussian edge spread function was used to match dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a water phantom. Software was developed to define the leaf eMLC positions of an eMLC that most closely fit each electron field shape. The effect of 1D edge feathering of themore » higher energy field on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of the x-axis (parallel to leaf motion) and remained constant along the y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge feathering was computed and measured for one radially symmetric, 3D PTV in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of both axes. For the 3D PTV, the feathering scheme was evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the pencil beam dose algorithm in the Pinnacle{sup 3} treatment planning system. Dose verification measurements were made using a prototype eMLC (1-cm leaf width). Results: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1 cm) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced the standard deviation of dose in the 3D PTV by 33-28%, respectively. Conclusions: A five-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Öğretici, Akın, E-mail: akinogretici@gmail.com; Akbaş, Uğur; Köksal, Canan

The aim of this research was to investigate the fetal doses of pregnant patients undergoing conformal radiotherapy or intensity-modulated radiation therapy (IMRT) for breast cancers. An Alderson Rando phantom was chosen to simulate a pregnant patient with breast cancer who is receiving radiation therapy. This phantom was irradiated using the Varian Clinac DBX 600 system (Varian Medical System, Palo Alto, CA) linear accelerator, according to the standard treatment plans of both three-dimensional conformal radiation therapy (3-D CRT) and IMRT techniques. Thermoluminescent dosimeters were used to measure the irradiated phantom's virtually designated uterus area. Thermoluminescent dosimeter measurements (in the phantom) revealedmore » that the mean cumulative fetal dose for 3-D CRT is 1.39 cGy and for IMRT it is 8.48 cGy, for a pregnant breast cancer woman who received radiation treatment of 50 Gy. The fetal dose was confirmed to increase by 70% for 3-D CRT and 40% for IMRT, if it is closer to the irradiated field by 5 cm. The mean fetal dose from 3-D CRT is 1.39 cGy and IMRT is 8.48 cGy, consistent with theoretic calculations. The IMRT technique causes the fetal dose to be 5 times more than that of 3-D CRT. Theoretic knowledge concerning the increase in the peripheral doses as the measurements approached the beam was also practically proven.« less

Superior sulcus non-small cell lung carcinoma: A comparison of IMRT and 3D-RT dosimetry.

PubMed

Truntzer, Pierre; Antoni, Delphine; Santelmo, Nicola; Schumacher, Catherine; Falcoz, Pierre-Emmanuel; Quoix, Elisabeth; Massard, Gilbert; Noël, Georges

2016-01-01

A dosimetric study comparing intensity modulated radiotherapy (IMRT) by TomoTherapy to conformational 3D radiotherapy (3D-RT) in patients with superior sulcus non-small cell lung cancer (NSCLC). IMRT became the main technique in modern radiotherapy. However it was not currently used for lung cancers. Because of the need to increase the dose to control lung cancers but because of the critical organs surrounding the tumors, the gains obtainable with IMRT is not still demonstrated. A dosimetric comparison of the planned target and organs at risk parameters between IMRT and 3D-RT in eight patients who received preoperative or curative intent irradiation. In the patients who received at least 66 Gy, the mean V95% was significantly better with IMRT than 3D-RT (p = 0.043). IMRT delivered a lower D2% compared to 3D-RT (p = 0.043). The IH was significantly better with IMRT (p = 0.043). The lung V 5 Gy and V 13 Gy were significantly higher in IMRT than 3D-RT (p = 0.043), while the maximal dose (D max) to the spinal cord was significantly lower in IMRT (p = 0.043). The brachial plexus D max was significantly lower in IMRT than 3D-RT (p = 0.048). For patients treated with 46 Gy, no significant differences were found. Our study showed that IMRT is relevant for SS-NSCLC. In patients treated with a curative dose, it led to a reduction of the exposure of critical organs, allowing a better dose distribution in the tumor. For the patients treated with a preoperative schedule, our results provide a basis for future controlled trials to improve the histological complete response by increasing the radiation dose.

Anti-inflammatory effect of vitamin D on gingivitis: a dose response randomised controlled trial.

PubMed

Hiremath, Vishwanath P; Rao, C Bhasker; Naiak, Vijaya; Prasad, K V V

2013-01-01

In a randomized controlled trial, a daily Oral Vitamin D supplementation was given in dose of 2000 IU for Group A, 1000 IU for Group B , 500 IU for Group C and placebo for Group D over 3 months period to assess the anti-inflammatory effect of vitamin D on gingivitis at various doses. The changes in gingival scores were measured at the period of 1 st , 2 nd and 3 rd month. Gingivitis score changed in direct proportion to the dose of vitamin D supplementation. Group A mean gingival scores were 2.4 (baseline); 1.7 (1 st month), 0.8 (2 nd month) and 0.3 (3 rd month). The group B the mean baseline gingival score from 2.3 reduced to 2.0 (month), 1.1 (two months) and 0.5 (third month). Group C had baseline gingival scores of 2.2 and 1.9 (1 st month), 1.4 (2 nd month) and 0.8 (last visit). Comparing baseline gingivitis scores with later visit score by Wilcoxon paired test, the anti-inflammatory effect was significantly seen in group A after one month itself, group B at two months and group C at 3 rd month after oral vitamin D supplementation. However, Group D did not show any significant anti-inflammatory effect.

Trajectory modulated prone breast irradiation: a LINAC-based technique combining intensity modulated delivery and motion of the couch.

PubMed

Fahimian, Benjamin; Yu, Victoria; Horst, Kathleen; Xing, Lei; Hristov, Dimitre

2013-12-01

External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide-angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast. A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeam™ STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom. The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V50% and V100% parameters that have been correlated with EBRT toxicity. The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose-volume parameters correlated with toxicity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impact of bowel gas and body outline variations on total accumulated dose with intensity-modulated proton therapy in locally advanced cervical cancer patients.

PubMed

Berger, Thomas; Petersen, Jørgen Breede Baltzer; Lindegaard, Jacob Christian; Fokdal, Lars Ulrik; Tanderup, Kari

2017-11-01

Density changes occurring during fractionated radiotherapy in the pelvic region may degrade proton dose distributions. The aim of the study was to quantify the dosimetric impact of gas cavities and body outline variations. Seven patients with locally advanced cervical cancer (LACC) were analyzed through a total of 175 daily cone beam computed tomography (CBCT) scans. Four-beams intensity-modulated proton therapy (IMPT) dose plans were generated targeting the internal target volume (ITV) composed of: primary tumor, elective and pathological nodes. The planned dose was 45 Gy [Relative-Biological-Effectiveness-weighted (RBE)] in 25 fractions and simultaneously integrated boosts of pathologic lymph nodes were 55-57.5 Gy (RBE). In total, 475 modified CTs were generated to evaluate the effect of: 1/gas cavities, 2/outline variations and 3/the two combined. The anatomy of each fraction was simulated by propagating gas cavities contours and body outlines from each daily CBCT to the pCT. Hounsfield units corresponding to gas and fat were assigned to the propagated contours. D98 (least dose received by the hottest 98% of the volume) and D99.9 for targets and V43Gy(RBE) (volume receiving ≥43 Gy(RBE)) for organs at risk (OARs) were recalculated on each modified CT, and total dose was evaluated through dose volume histogram (DVH) addition across all fractions. Weight changes during radiotherapy were between -3.1% and 1.2%. Gas cavities and outline variations induced a median [range] dose degradation for ITV45 of 1.0% [0.5-3.5%] for D98 and 2.1% [0.8-6.4%] for D99.9. Outline variations had larger dosimetric impact than gas cavities. Worst nodal dose degradation was 2.0% for D98 and 2.3% for D99.9. The impact on bladder, bowel and rectum was limited with V43Gy(RBE) variations ≤3.5 cm 3 . Bowel gas cavities and outline variations had minor impact on accumulated dose in targets and OAR of four-field IMPT in a LACC population of moderate weight changes.

SU-E-J-80: Interplay Effect Between VMAT Intensity Modulation and Tumor Motion in Hypofractioned Lung Treatment, Investigated with 3D Pressage Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Touch, M; Duke University Medical Center, Durham, NC; Wu, Q

2014-06-01

Purpose: To demonstrate an embedded tissue equivalent presage dosimeter for measuring 3D doses in moving tumors and to study the interplay effect between the tumor motion and intensity modulation in hypofractioned Volumetric Modulated Arc Therapy(VMAT) lung treatment. Methods: Motion experiments were performed using cylindrical Presage dosimeters (5cm diameter by 7cm length) mounted inside the lung insert of a CIRS thorax phantom. Two different VMAT treatment plans were created and delivered in three different scenarios with the same prescribed dose of 18 Gy. Plan1, containing a 2 centimeter spherical CTV with an additional 2mm setup margin, was delivered on a stationarymore » phantom. Plan2 used the same CTV except expanded by 1 cm in the Sup-Inf direction to generate ITV and PTV respectively. The dosimeters were irradiated in static and variable motion scenarios on a Truebeam system. After irradiation, high resolution 3D dosimetry was performed using the Duke Large Field-of-view Optical-CT Scanner, and compared to the calculated dose from Eclipse. Results: In the control case (no motion), good agreement was observed between the planned and delivered dose distributions as indicated by 100% 3D Gamma (3% of maximum planned dose and 3mm DTA) passing rates in the CTV. In motion cases gamma passing rates was 99% in CTV. DVH comparisons also showed good agreement between the planned and delivered dose in CTV for both control and motion cases. However, differences of 15% and 5% in dose to PTV were observed in the motion and control cases respectively. Conclusion: With very high dose nature of a hypofraction treatment, significant effect was observed only motion is introduced to the target. This can be resulted from the motion of the moving target and the modulation of the MLC. 3D optical dosimetry can be of great advantage in hypofraction treatment dose validation studies.« less

[On the way to shortening tuberculosis treatments: clinical trials of the Unitat d' Investagació en Tuberculosi de Barcelona supported by the Centers for Disease Control and Prevention].

PubMed

Moreno, Antonio; Sánchez, Francesca; Nelson, Jeanne; Miró, José M; Caylà, Joan A

2010-01-01

New treatment guidelines are required to improve the tuberculosis control strategies that have been used for 30 years. Seven centers of the Barcelona Tuberculosis Research Unit (BTRU) (Unitat d'Investigació en Tuberculosi de Barcelona) are collaborating with the Division of Tuberculosis Elimination of the United States Centers for Disease Control and Prevention in a series of clinical trials on latent tuberculosis infection and tuberculosis disease. BTRU participation began in 2004 with Study 26, an evaluation of the efficacy and tolerability of rifapentine plus isoniazid administered once weekly for 3 months compared with the standard treatment for latent tuberculosis infection. The BTRU centers together enrolled 246 patients (3% of the total). General enrollment was completed in February, 2008. HIV-infected patient and child enrollment continues. Treatment with 12 doses instead of 270 doses is expected to be a clear success. However, the analysis will be completed in 2010. Study 28 (started in 2006), designed for the treatment of pulmonary tuberculosis, compared standard treatment with an experimental regimen substituting moxifloxacin for isoniazid. BTRU centers together enrolled 15 patients (3.5% of the total). The provisional results (presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, 2007) showed no difference between the sputum conversion rate of each regimen at week 8 of treatment. Study 29 is currently underway, in which rifapentine was introduced in the experimental regimen for active tuberculosis treatment. Copyright (c) 2009 SESPAS. Published by Elsevier Espana. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clemente, F; Perez, C

Purpose: Redundant treatment verifications in conformal and intensity-modulated radiation therapy techniques are traditionally performed with single point calculations. New solutions can replace these checks with 3D treatment plan verifications. This work describes a software tool (Mobius3D, Mobius Medical Systems) that uses a GPU-accelerated collapsed cone algorithm to perform 3D independent verifications of TPS calculations. Methods: Mobius3D comes with reference beam models for common linear accelerators. The system uses an independently developed collapsed cone algorithm updated with recent enhancements. 144 isotropically-spaced cones are used for each voxel for calculations. These complex calculations can be sped up by using GPUs. Mobius3D calculatemore » dose using DICOM information coming from TPS (CT, RT Struct, RT Plan RT Dose). DVH-metrics and 3D gamma tests can be used to compare both TPS and secondary calculations. 170 patients treated with all common techniques as 3DCFRT (including wedged), static and dynamic IMRT and VMAT have been successfully verified with this solution. Results: Calculation times are between 3–5 minutes for 3DCFRT treatments and 15–20 for most complex dMLC and VMAT plans. For all PTVs mean dose and 90% coverage differences are (1.12±0.97)% and (0.68±1.19)%, respectively. Mean dose discrepancies for all OARs is (0.64±1.00)%. 3D gamma (global, 3%/3 mm) analysis shows a mean passing rate of (97.8 ± 3.0)% for PTVs and (99.0±3.0)% for OARs. 3D gamma pasing rate for all voxels in CT has a mean value of (98.5±1.6)%. Conclusion: Mobius3D is a powerful tool to verify all modalities of radiation therapy treatments. Dose discrepancies calculated by this system are in good agreement with TPS. The use of reference beam data results in time savings and can be used to avoid the propagation of errors in original beam data into our QA system. GPU calculations permit enhanced collapsed cone calculations with reasonable calculation times.« less

SU-E-CAMPUS-T-05: Validation of High-Resolution 3D Patient QA for Proton Pencil Beam Scanning and IMPT by Polymer Gel Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardin, A; Avery, S; Ding, X

2014-06-15

Purpose: Validation of high-resolution 3D patient QA for proton pencil beam scanning and IMPT by polymer gel dosimetry. Methods: Four BANG3Pro polymer gel dosimeters (manufactured by MGS Research Inc, Madison, CT) were used for patient QA at the Robert's Proton Therapy Center (RPTC, Philadelphia, PA). All dosimeters were sealed in identical thin-wall Pyrex glass spheres. Each dosimeter contained a set of markers for 3D registration purposes. The dosimeters were mounted in a consistent and reproducible manner using a custom build holder. Two proton pencil beam scanning plans were designed using Varian Eclipse™ treatment planning system: 1) A two-field intensity modulatedmore » proton therapy (IMPT) plan and 2) one single field uniform dose (SFUD) plan. The IMPT fields were evaluated as a composite plan and individual fields, the SFUD plan was delivered as a single field plan.Laser CT scanning was performed using the manufacturer's OCTOPUS-IQ axial transmission laser CT scanner using a 1 mm slice thickness. 3D registration, analysis, and OD/cm to absorbed dose calibrations were perfomed using DICOM RT-Dose and CT files, and software developed by the manufacturer. 3D delta index, a metric equivalent to the gamma tool, was used for dose comparison. Results: Very good agreement with single IMPT fields and with SFUD was obtained. Composite IMPT fields had a less satisfactory agreement. The single fields had 3D delta index passing rates (3% dose difference, 3 mm DTA) of 98.98% and 94.91%. The composite 3D delta index passing rate was 80.80%. The SFUD passing rate was 93.77%. Required shifts of the dose distributions were less than 4 mm. Conclusion: A formulation of the BANG3Pro polymer gel dosimeter, suitable for 3D QA of proton patient plans is established and validated. Likewise, the mailed QA analysis service provided by the manufacturer is a practical option when required resources are unavailable. We fully disclose that the subject of this research regards a production of MGS Research, Inc.« less

A 3D isodose manipulation tool for interactive dose shaping

NASA Astrophysics Data System (ADS)

Kamerling, C. P.; Ziegenhein, P.; Heinrich, H.; Oelfke, U.

2014-03-01

The interactive dose shaping (IDS) planning paradigm aims to perform interactive local dose adaptations of an IMRT plan without compromising already established valuable dose features in real-time. In this work we introduce an interactive 3D isodose manipulation tool which enables local modifications of a dose distribution intuitively by direct manipulation of an isodose surface. We developed an in-house IMRT TPS framework employing an IDS engine as well as a 3D GUI for dose manipulation and visualization. In our software an initial dose distribution can be interactively modified through an isodose surface manipulation tool by intuitively clicking on an isodose surface. To guide the user interaction, the position of the modification is indicated by a sphere while the mouse cursor hovers the isodose surface. The sphere's radius controls the locality of the modification. The tool induces a dose modification as a direct change of dose in one or more voxels, which is incrementally obtained by fluence adjustments. A subsequent recovery step identifies voxels with violated dose features and aims to recover their original dose. We showed a proof of concept study for the proposed tool by adapting the dose distribution of a prostate case (9 beams, coplanar). Single dose modifications take less than 2 seconds on an actual desktop PC.

Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer

PubMed Central

Walsh, Christopher; Bonner, Jennifer J.; Johnson, Trevor N.; Neuhoff, Sibylle; Ghazaly, Essam A.; Gribben, John G.; Boddy, Alan V.

2016-01-01

Aims Use of the anti‐tumour antibiotic actinomycin D is associated with development of hepatotoxicity, particularly in young children. A paucity of actinomycin D pharmacokinetic data make it challenging to develop a sound rationale for defining dosing regimens in younger patients. The study aim was to develop a physiologically based pharmacokinetic (PBPK) model using a combination of data from the literature and generated from experimental analyses. Methods Assays to determine actinomycin D Log P, blood:plasma partition ratio and ABCB1 kinetics were conducted. These data were combined with physiochemical properties sourced from the literature to generate a compound file for use within the modelling‐simulation software Simcyp (version 14 release 1). For simulation, information was taken from two datasets, one from 117 patients under the age of 21 and one from 20 patients aged 16–48. Results The final model incorporated clinical renal and biliary clearance data and an additional systemic clearance value. The mean AUC0‐26h of simulated subjects was within 1.25‐fold of the observed AUC0‐26h (84 ng h ml−1 simulated vs. 93 ng h ml−1 observed). For the younger age ranges, AUC predictions were within two‐fold of observed values, with simulated data from six of the eight age/dose ranges falling within 15% of observed data. Simulated values for actinomycin D AUC0‐26h and clearance in infants aged 0–12 months ranged from 104 to 115 ng h ml−1 and 3.5–3.8 l h−1, respectively. Conclusions The model has potential utility for prediction of actinomycin D exposure in younger patients and may help guide future dosing. However, additional independent data from neonates and infants is needed for further validation. Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models. PMID:26727248

Direct-detection EPID dosimetry: investigation of a potential clinical configuration for IMRT verification.

PubMed

Vial, Philip; Gustafsson, Helen; Oliver, Lyn; Baldock, Clive; Greer, Peter B

2009-12-07

The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with d(max) solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with d(max) solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery.

WE-D-BRA-04: Online 3D EPID-Based Dose Verification for Optimum Patient Safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spreeuw, H; Rozendaal, R; Olaciregui-Ruiz, I

2015-06-15

Purpose: To develop an online 3D dose verification tool based on EPID transit dosimetry to ensure optimum patient safety in radiotherapy treatments. Methods: A new software package was developed which processes EPID portal images online using a back-projection algorithm for the 3D dose reconstruction. The package processes portal images faster than the acquisition rate of the portal imager (∼ 2.5 fps). After a portal image is acquired, the software seeks for “hot spots” in the reconstructed 3D dose distribution. A hot spot is in this study defined as a 4 cm{sup 3} cube where the average cumulative reconstructed dose exceedsmore » the average total planned dose by at least 20% and 50 cGy. If a hot spot is detected, an alert is generated resulting in a linac halt. The software has been tested by irradiating an Alderson phantom after introducing various types of serious delivery errors. Results: In our first experiment the Alderson phantom was irradiated with two arcs from a 6 MV VMAT H&N treatment having a large leaf position error or a large monitor unit error. For both arcs and both errors the linac was halted before dose delivery was completed. When no error was introduced, the linac was not halted. The complete processing of a single portal frame, including hot spot detection, takes about 220 ms on a dual hexacore Intel Xeon 25 X5650 CPU at 2.66 GHz. Conclusion: A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for various kinds of gross delivery errors. The detection of hot spots was proven to be effective for the timely detection of these errors. Current work is focused on hot spot detection criteria for various treatment sites and the introduction of a clinical pilot program with online verification of hypo-fractionated (lung) treatments.« less

SU-E-T-04: 3D Dose Based Patient Compensator QA Procedure for Proton Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, W; Reyhan, M; Zhang, M

2015-06-15

Purpose: In proton double-scattering radiotherapy, compensators are the essential patient specific devices to contour the distal dose distribution to the tumor target. Traditional compensator QA is limited to checking the drilled surface profiles against the plan. In our work, a compensator QA process was established that assess the entire compensator including its internal structure for patient 3D dose verification. Methods: The fabricated patient compensators were CT scanned. Through mathematical image processing and geometric transformations, the CT images of the proton compensator were combined with the patient simulation CT images into a new series of CT images, in which the imagedmore » compensator is placed at the planned location along the corresponding beam line. The new CT images were input into the Eclipse treatment planning system. The original plan was calculated to the combined CT image series without the plan compensator. The newly computed patient 3D dose from the combined patientcompensator images was verified against the original plan dose. Test plans include the compensators with defects intentionally created inside the fabricated compensators. Results: The calculated 3D dose with the combined compensator and patient CT images reflects the impact of the fabricated compensator to the patient. For the test cases in which no defects were created, the dose distributions were in agreement between our method and the corresponding original plans. For the compensator with the defects, the purposely changed material and a purposely created internal defect were successfully detected while not possible with just the traditional compensator profiles detection methods. Conclusion: We present here a 3D dose verification process to qualify the fabricated proton double-scattering compensator. Such compensator detection process assesses the patient 3D impact of the fabricated compensator surface profile as well as the compensator internal material and structure changes. This research receives funding support from CURA Medical Technologies.« less

High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

PubMed

Ganmaa, Davaasambuu; Munkhzul, Baatar; Fawzi, Wafaie; Spiegelman, Donna; Willett, Walter C; Bayasgalan, Purev; Baasansuren, Erkhembayar; Buyankhishig, Burneebaatar; Oyun-Erdene, Sereeter; Jolliffe, David A; Xenakis, Theodoros; Bromage, Sabri; Bloom, Barry R; Martineau, Adrian R

2017-09-01

Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. To determine the effect of high-dose vitamin D 3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D 3 . We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D 3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P < 0.001) but did not influence time to sputum culture conversion overall (adjusted hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive vitamin D 3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). Vitamin D 3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Gamma radiation effects on siloxane-based additive manufactured structures

NASA Astrophysics Data System (ADS)

Schmalzer, Andrew M.; Cady, Carl M.; Geller, Drew; Ortiz-Acosta, Denisse; Zocco, Adam T.; Stull, Jamie; Labouriau, Andrea

2017-01-01

Siloxane-basedadditive manufactured structures prepared by the direct ink write (DIW) technology were exposed to ionizing irradiation in order to gauge radiolysis effects on structure-property relationships. These well-defined 3-D structures were subjected to moderate doses of gamma irradiation in an inert atmosphere and characterized by a suite of experimental methods. Changes in thermal, chemical, microstructure, and mechanical properties were evaluated by DSC, TGA, FT-IR, mass spectroscopy, EPR, solvent swelling, SEM, and uniaxial compressive load techniques. Our results demonstrated that 3-D structures made from aromatic-free siloxane resins exhibited hardening after being exposed to gamma radiation. This effect was accompanied by gas evolution, decreasing in crystallization levels, decreasing in solvent swelling and damage to the microstructure. Furthermore, long-lived radiation-induced radicals were not detected by EPR methods. Our results are consistent with cross-link formation being the dominant degradation mechanism over chain scission reactions. On the other hand, 3-D structures made from high phenyl content siloxane resins showed little radiation damage as evidenced by low off gassing.

Calculation of dose distribution in compressible breast tissues using finite element modeling, Monte Carlo simulation and thermoluminescence dosimeters

NASA Astrophysics Data System (ADS)

Mohammadyari, Parvin; Faghihi, Reza; Mosleh-Shirazi, Mohammad Amin; Lotfi, Mehrzad; Rahim Hematiyan, Mohammad; Koontz, Craig; Meigooni, Ali S.

2015-12-01

Compression is a technique to immobilize the target or improve the dose distribution within the treatment volume during different irradiation techniques such as AccuBoost® brachytherapy. However, there is no systematic method for determination of dose distribution for uncompressed tissue after irradiation under compression. In this study, the mechanical behavior of breast tissue between compressed and uncompressed states was investigated. With that, a novel method was developed to determine the dose distribution in uncompressed tissue after irradiation of compressed breast tissue. Dosimetry was performed using two different methods, namely, Monte Carlo simulations using the MCNP5 code and measurements using thermoluminescent dosimeters (TLD). The displacement of the breast elements was simulated using a finite element model and calculated using ABAQUS software. From these results, the 3D dose distribution in uncompressed tissue was determined. The geometry of the model was constructed from magnetic resonance images of six different women volunteers. The mechanical properties were modeled by using the Mooney-Rivlin hyperelastic material model. Experimental dosimetry was performed by placing the TLD chips into the polyvinyl alcohol breast equivalent phantom. The results determined that the nodal displacements, due to the gravitational force and the 60 Newton compression forces (with 43% contraction in the loading direction and 37% expansion in the orthogonal direction) were determined. Finally, a comparison of the experimental data and the simulated data showed agreement within 11.5%  ±  5.9%.

Calculation of dose distribution in compressible breast tissues using finite element modeling, Monte Carlo simulation and thermoluminescence dosimeters.

PubMed

Mohammadyari, Parvin; Faghihi, Reza; Mosleh-Shirazi, Mohammad Amin; Lotfi, Mehrzad; Hematiyan, Mohammad Rahim; Koontz, Craig; Meigooni, Ali S

2015-12-07

Compression is a technique to immobilize the target or improve the dose distribution within the treatment volume during different irradiation techniques such as AccuBoost(®) brachytherapy. However, there is no systematic method for determination of dose distribution for uncompressed tissue after irradiation under compression. In this study, the mechanical behavior of breast tissue between compressed and uncompressed states was investigated. With that, a novel method was developed to determine the dose distribution in uncompressed tissue after irradiation of compressed breast tissue. Dosimetry was performed using two different methods, namely, Monte Carlo simulations using the MCNP5 code and measurements using thermoluminescent dosimeters (TLD). The displacement of the breast elements was simulated using a finite element model and calculated using ABAQUS software. From these results, the 3D dose distribution in uncompressed tissue was determined. The geometry of the model was constructed from magnetic resonance images of six different women volunteers. The mechanical properties were modeled by using the Mooney-Rivlin hyperelastic material model. Experimental dosimetry was performed by placing the TLD chips into the polyvinyl alcohol breast equivalent phantom. The results determined that the nodal displacements, due to the gravitational force and the 60 Newton compression forces (with 43% contraction in the loading direction and 37% expansion in the orthogonal direction) were determined. Finally, a comparison of the experimental data and the simulated data showed agreement within 11.5%  ±  5.9%.

Induced radioactivity in the forward shielding and semiconductor tracker of the ATLAS detector.

PubMed

Bĕdajánek, I; Linhart, V; Stekl, I; Pospísil, S; Kolros, A; Kovalenko, V

2005-01-01

The radioactivity induced in the forward shielding, copper collimator and semiconductor tracker modules of the ATLAS detector has been studied. The ATLAS detector is a long-term experiment which, during operation, will require to have service and access to all of its parts and components. The radioactivity induced in the forward shielding was calculated by Monte Carlo methods based on GEANT3 software tool. The results show that the equivalent dose rates on the outer surface of the forward shielding are very low (at most 0.038 microSv h(-1)). On the other hand, the equivalent dose rates are significantly higher on the inner surface of the forward shielding (up to 661 microSv h(-1)) and, especially, at the copper collimator close to the beampipe (up to 60 mSv h(-1)). The radioactivity induced in the semiconductor tracker modules was studied experimentally. The module was activated by neutrons in a training nuclear reactor and the delayed gamma ray spectra were measured. From these measurements, the equivalent dose rate on the surface of the semiconductor tracker module was estimated to be < 100 microSv h(-1) after 100 d of Large Hadron Collider (LHC) operation and 10 d of cooling.

Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.

PubMed

Jonker, Emile F F; Visser, Leonardus G

2017-09-01

The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P  < 0.03). This dose finding study demonstrates that priming with a single dose of rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice.

PubMed

Park, Jung-Hyun; Jung, Ji-Hye; Yang, Jin-Young; Kim, Hyun-Sook

2013-11-01

Type 1 diabetes is an endocrinologic disorder characterized by uncontrolled glucose regulation and oxidative stress. Olive leaves have been studied extensively for their antioxidant activity and capacity to improve immune function. We hypothesized that olive leaf powder supplementation will be effective in inhibiting the oxidative stress and immune dysregulation in streptozotocin (STZ)-induced diabetic mice. Mice were assigned to 1 of 5 groups: control (C), STZ-induced diabetes (D), and STZ-induced diabetes supplemented with very low dose (VLOL), low dose (LOL), or high dose of olive leaf powder (HOL). Blood glucose in the VLOL and LOL groups was lower than that in the D group (P < .05). Insulin levels were increased in all experimental groups in comparison with that in the D group, (P < .05). Superoxide dismutase, glutathione peroxidase, and catalase activities were shown to decrease in the D group, whereas these were increased in the VLOL and LOL groups. Nitric oxide levels decreased in the VLOL and LOL groups, as compared with the D group. The messenger RNA expression levels of inducible nitric oxide synthase were significantly decreased in the VLOL and HOL groups, and interferon-γ levels were significantly decreased in the liver of the VLOL, LOL, and HOL groups compared with the levels in the D group. Interleukin-17 levels were significantly decreased in the VLOL and HOL groups. Th1 and Th17 cytokine levels were increased in the D group but decreased in all the experimental groups. Th2 cytokine levels were increased in all olive leaf-supplemented groups compared with those in the D group. These results indicate a reduction in the levels of proinflammatory cytokines, suggesting that olive leaves have the potential to provide therapeutic inhibition of diabetic complications. © 2013.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richter, Daniel; TU Darmstadt, Darmstadt; Saito, Nami

2014-05-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporalmore » correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.« less

WE-AB-207B-05: Correlation of Normal Lung Density Changes with Dose After Stereotactic Body Radiotherapy (SBRT) for Early Stage Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Q; Devpura, S; Feghali, K

2016-06-15

Purpose: To investigate correlation of normal lung CT density changes with dose accuracy and outcome after SBRT for patients with early stage lung cancer. Methods: Dose distributions for patients originally planned and treated using a 1-D pencil beam-based (PB-1D) dose algorithm were retrospectively recomputed using algorithms: 3-D pencil beam (PB-3D), and model-based Methods: AAA, Acuros XB (AXB), and Monte Carlo (MC). Prescription dose was 12 Gy × 4 fractions. Planning CT images were rigidly registered to the followup CT datasets at 6–9 months after treatment. Corresponding dose distributions were mapped from the planning to followup CT images. Following the methodmore » of Palma et al .(1–2), Hounsfield Unit (HU) changes in lung density in individual, 5 Gy, dose bins from 5–45 Gy were assessed in the peri-tumor region, defined as a uniform, 3 cm expansion around the ITV(1). Results: There is a 10–15% displacement of the high dose region (40–45 Gy) with the model-based algorithms, relative to the PB method, due to the electron scattering of dose away from the tumor into normal lung tissue (Fig.1). Consequently, the high-dose lung region falls within the 40–45 Gy dose range, causing an increase in HU change in this region, as predicted by model-based algorithms (Fig.2). The patient with the highest HU change (∼110) had mild radiation pneumonitis, and the patient with HU change of ∼80–90 had shortness of breath. No evidence of pneumonitis was observed for the 3 patients with smaller CT density changes (<50 HU). Changes in CT densities, and dose-response correlation, as computed with model-based algorithms, are in excellent agreement with the findings of Palma et al. (1–2). Conclusion: Dose computed with PB (1D or 3D) algorithms was poorly correlated with clinically relevant CT density changes, as opposed to model-based algorithms. A larger cohort of patients is needed to confirm these results. This work was supported in part by a grant from Varian Medical Systems, Palo Alto, CA.« less

Development of a patient-specific 3D dose evaluation program for QA in radiation therapy

NASA Astrophysics Data System (ADS)

Lee, Suk; Chang, Kyung Hwan; Cao, Yuan Jie; Shim, Jang Bo; Yang, Dae Sik; Park, Young Je; Yoon, Won Sup; Kim, Chul Yong

2015-03-01

We present preliminary results for a 3-dimensional dose evaluation software system ( P DRESS, patient-specific 3-dimensional dose real evaluation system). Scanned computed tomography (CT) images obtained by using dosimetry were transferred to the radiation treatment planning system (ECLIPSE, VARIAN, Palo Alto, CA) where the intensity modulated radiation therapy (IMRT) nasopharynx plan was designed. We used a 10 MV photon beam (CLiX, VARIAN, Palo Alto, CA) to deliver the nasopharynx treatment plan. After irradiation, the TENOMAG dosimeter was scanned using a VISTA ™ scanner. The scanned data were reconstructed using VistaRecon software to obtain a 3D dose distribution of the optical density. An optical-CT scanner was used to readout the dose distribution in the gel dosimeter. Moreover, we developed the P DRESS by using Flatform, which were developed by our group, to display the 3D dose distribution by loading the DICOM RT data which are exported from the radiotherapy treatment plan (RTP) and the optical-CT reconstructed VFF file, into the independent P DRESS with an ioniz ation chamber and EBT film was used to compare the dose distribution calculated from the RTP with that measured by using a gel dosimeter. The agreement between the normalized EBT, the gel dosimeter and RTP data was evaluated using both qualitative and quantitative methods, such as the isodose distribution, dose difference, point value, and profile. The profiles showed good agreement between the RTP data and the gel dosimeter data, and the precision of the dose distribution was within ±3%. The results from this study showed significantly discrepancies between the dose distribution calculated from the treatment plan and the dose distribution measured by a TENOMAG gel and by scanning with an optical CT scanner. The 3D dose evaluation software system ( P DRESS, patient specific dose real evaluation system), which were developed in this study evaluates the accuracies of the three-dimensional dose distributions. Further applications of the system utility are expected to result from future studies.

Decomposition of 2,4-dichlorophenoxyacetic acid by ozonation, ionizing radiation as well as ozonation combined with ionizing radiation

NASA Astrophysics Data System (ADS)

Drzewicz, Przemyslaw; Trojanowicz, Marek; Zona, Robert; Solar, Sonja; Gehringer, Peter

2004-03-01

Electron beam (EB), ozone (O 3) and the combination EB/O 3 were used to study the oxidative decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) in local tap water. Using an EB treatment, a dose of 10 kGy was required for complete 2,4-D degradation, and a 90% conversion of organic chlorine into chloride ions. Using additionally 1.33 mmol dm -3 O 3 during irradiation, the same result was achieved with a dose of 2.7 kGy. The yields of products acetate and formate were almost doubled by the combined EB/O 3 treatment, compared to those obtained with the same dose by EB irradiation. Gamma radiolysis showed that the degradation dose was proportional to the initial concentration of 2,4-D in the range of 50-2260 μmol dm -3.

Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study

NASA Astrophysics Data System (ADS)

Wolfs, Cecile J. A.; Brás, Mariana G.; Schyns, Lotte E. J. R.; Nijsten, Sebastiaan M. J. J. G.; van Elmpt, Wouter; Scheib, Stefan G.; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

2017-08-01

The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study.

PubMed

Wolfs, Cecile J A; Brás, Mariana G; Schyns, Lotte E J R; Nijsten, Sebastiaan M J J G; van Elmpt, Wouter; Scheib, Stefan G; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

2017-07-12

The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95% ) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95% , which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

Actively triggered 4d cone-beam CT acquisition.

PubMed

Fast, Martin F; Wisotzky, Eric; Oelfke, Uwe; Nill, Simeon

2013-09-01

4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this "after-the-fact" binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor. The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective "Faraday" shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories. With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145 projections were acquired per respiratory phase resulting in a dose of ∼1.7-2.6 mGy per respiratory phase. Further dose savings and decreases in the scanning time are possible by acquiring only a subset of all respiratory phases, for example, peak-exhale and peak-inhale only scans. This study is the first experimental demonstration of a new 4d CBCT acquisition paradigm in which imaging dose is efficiently utilized by actively triggering only those projections that are desired for the reconstruction process.

SU-E-T-122: Anisotropic Analytical Algorithm (AAA) Vs. Acuros XB (AXB) in Stereotactic Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mynampati, D; Scripes, P Godoy; Kuo, H

2015-06-15

Purpose: To evaluate dosimetric differences between superposition beam model (AAA) and determinant photon transport solver (AXB) in lung SBRT and Cranial SRS dose computations. Methods: Ten Cranial SRS and ten Lung SBRT plans using Varian, AAA -11.0 were re-planned using Acuros -XB-11.0 with fixed MU. 6MV photon Beam model with HD120-MLC used for dose calculations. Four non-coplanar conformal arcs used to deliver 21Gy or 18Gy to SRS targets (0.4 to 6.2cc). 54Gy (3Fractions) or 50Gy (5Fractions) was planned for SBRT targets (7.3 to 13.9cc) using two VAMT non-coplanar arcs. Plan comparison parameters were dose to 1% PTV volume (D1), dosemore » to 99% PTV volume( D99), Target mean (Dmean), Conformity index (ratio of prescription isodose volume to PTV), Homogeneity Index [ (D2%-D98%)/Dmean] and R50 (ratio of 50% of prescription isodose volume to PTV). OAR parameters were Brain volume receiving 12Gy dose (V12Gy) and maximum dose (D0.03) to Brainstem for SRS. For lung SBRT, maximum dose to Heart and Cord, Mean lung dose (MLD) and volume of lung receiving 20Gy (V20Gy) were computed. PTV parameters compared by percentage difference between AXB and AAA parameters. OAR parameters and HI compared by absolute difference between two calculations. For analysis, paired t-test performed over the parameters. Results: Compared to AAA, AXB SRS plans have on average 3.2% lower D99, 6.5% lower CI and 3cc less Brain-V12. However, AXB SBRT plans have higher D1, R50 and Dmean by 3.15%, 1.63% and 2.5%. For SRS and SBRT, AXB plans have average HI 2 % and 4.4% higher than AAA plans. In both techniques, all other parameters vary within 1% or 1Gy. In both sets only two parameters have P>0.05. Conclusion: Even though t-test results signify difference between AXB and AAA plans, dose differences in dose estimations by both algorithms are clinically insignificant.« less

Convolutional auto-encoder for image denoising of ultra-low-dose CT.

PubMed

Nishio, Mizuho; Nagashima, Chihiro; Hirabayashi, Saori; Ohnishi, Akinori; Sasaki, Kaori; Sagawa, Tomoyuki; Hamada, Masayuki; Yamashita, Tatsuo

2017-08-01

The purpose of this study was to validate a patch-based image denoising method for ultra-low-dose CT images. Neural network with convolutional auto-encoder and pairs of standard-dose CT and ultra-low-dose CT image patches were used for image denoising. The performance of the proposed method was measured by using a chest phantom. Standard-dose and ultra-low-dose CT images of the chest phantom were acquired. The tube currents for standard-dose and ultra-low-dose CT were 300 and 10 mA, respectively. Ultra-low-dose CT images were denoised with our proposed method using neural network, large-scale nonlocal mean, and block-matching and 3D filtering. Five radiologists and three technologists assessed the denoised ultra-low-dose CT images visually and recorded their subjective impressions of streak artifacts, noise other than streak artifacts, visualization of pulmonary vessels, and overall image quality. For the streak artifacts, noise other than streak artifacts, and visualization of pulmonary vessels, the results of our proposed method were statistically better than those of block-matching and 3D filtering (p-values < 0.05). On the other hand, the difference in the overall image quality between our proposed method and block-matching and 3D filtering was not statistically significant (p-value = 0.07272). The p-values obtained between our proposed method and large-scale nonlocal mean were all less than 0.05. Neural network with convolutional auto-encoder could be trained using pairs of standard-dose and ultra-low-dose CT image patches. According to the visual assessment by radiologists and technologists, the performance of our proposed method was superior to that of large-scale nonlocal mean and block-matching and 3D filtering.

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

PubMed

Dougherty, Kelly A; Bertolaso, Chiara; Schall, Joan I; Smith-Whitley, Kim; Stallings, Virginia A

2015-07-01

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

Experimental and calculated LET distributions in the Cosmos-2044 biosatellite orbit

NASA Technical Reports Server (NTRS)

Watts, J. W., Jr.; Dudkin, V. E.; Karpov, O. N.; Potapov, Yu. V.; Akopova, A. B.; Magradze, N. V.; Moiseenko, A. A.; Benton, E. V.; Frank, A. L.

1995-01-01

During the flight of the Cosmos-2044 biosatellite, joint U.S.S.R.-U.S.A. investigations of different characteristics of cosmic radiation (CR) in the near-Earth environment were carried out. The U.S. dielectric track detectors CR-39 and Soviet BYa- and BR-type nuclear photo-emulsions were used as detectors. The present work shows some results of experimental measurements of linear energy transfer (LET) spectra of CR particles obtained with the use of these detectors, which were placed both inside and outside the satellite. The LET spectra measurements with plastic detectors is composed of two parts: the measurement of galactic cosmos rays (GCR) particles, and of short-range particles. The contributions of these components to the total LET distribution at various thicknesses of the shielding were analyzed and the results of these studies are presented. Calculated LET spectra in the Cosmos-2044 orbit were compared with experimental data. On the basis of experimental and calculated values of the LET spectra, absorbed and equivalent CR doses were calculated. In the shielding range of 1-1.5 g cm(exp -2), outside the spacecraft, the photo-emulsions yielded 10.3 mrad d(exp -1) and 13.4 mrem d(exp -1) (LET greater than or equal to 40 MeV cm(exp -1)). Inside the spacecraft (greater than or equal to 10 g cm(exp -2) the photo-emulsions yielded 8.9 mrad d(exp -1) and 14.5 mrem d(exp -1).

Effects of a Multi-Ingredient Energy Supplement on Cognitive Performance and Cerebral-Cortical Activation.

PubMed

Daou, Marcos; Sassi, Julia Montagner; Miller, Matthew W; Gonzalez, Adam M

2018-03-13

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η 2 p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η 2 p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.

PubMed

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart D mean ), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRT DIBH decreased the Heart D mean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRT FB . IMRT further lowered mean LAD dose by 18%. Heart D mean was lower with 3DCRT DIBH over IMRT DIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V 20 of ipsilateral lung were lower with 3DCRT DIBH over IMRT DIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRT DIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.

Monte Carlo evaluation of RapidArc™ oropharynx treatment planning strategies for sparing of midline structures

NASA Astrophysics Data System (ADS)

Bush, K.; Zavgorodni, S.; Gagne, I.; Townson, R.; Ansbacher, W.; Beckham, W.

2010-08-01

The aim of the study was to perform the Monte Carlo (MC) evaluation of RapidArc™ (Varian Medical Systems, Palo Alto, CA) dose calculations for four oropharynx midline sparing planning strategies. Six patients with squamous cell cancer of the oropharynx were each planned with four RapidArc head and neck treatment strategies consisting of single and double photon arcs. In each case, RTOG0522 protocol objectives were used during planning optimization. Dose calculations performed with the analytical anisotropic algorithm (AAA) are compared against BEAMnrc/DOSXYZnrc dose calculations for the 24-plan dataset. Mean dose and dose-to-98%-of-structure-volume (D98%) were used as metrics in the evaluation of dose to planning target volumes (PTVs). Mean dose and dose-to-2%-of-structure-volume (D2%) were used to evaluate dose differences within organs at risk (OAR). Differences in the conformity index (CI) and the homogeneity index (HI) as well as 3D dose distributions were also observed. AAA calculated PTV mean dose, D98%, and HIs showed very good agreement with MC dose calculations within the 0.8% MC (statistical) calculation uncertainty. Regional node volume (PTV-80%) mean dose and D98% were found to be overestimated (1.3%, σ = 0.8% and 2.3%, σ = 0.8%, respectively) by the AAA with respect to MC calculations. Mean dose and D2% to OAR were also observed to be consistently overestimated by the AAA. Increasing dose calculation differences were found in planning strategies exhibiting a higher overall fluence modulation. From the plan dataset, the largest local dose differences were observed in heavily shielded regions and within the esophageal and sinus cavities. AAA dose calculations as implemented in RapidArc™ demonstrate excellent agreement with MC calculations in unshielded regions containing moderate inhomogeneities. Acceptable agreement is achieved in regions of increased MLC shielding. Differences in dose are attributed to inaccuracies in the AAA-modulated fluence modeling, modeling of material inhomogeneities and dose deposition within low-density materials. The use of MC dose calculations leads to the same general conclusion as using AAA that a two arc delivery with limited collimator opening can provide the greatest amount of midline sparing compared to the other techniques investigated.

IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC: A direct comparison of PET-based treatment planning.

PubMed

Fleckenstein, Jochen; Kremp, Katharina; Kremp, Stephanie; Palm, Jan; Rübe, Christian

2016-02-01

The potential of intensity-modulated radiation therapy (IMRT) as opposed to three-dimensional conformal radiotherapy (3D-CRT) is analyzed for two different concepts of fluorodeoxyglucose positron emission tomography (FDG PET)-based target volume delineation in locally advanced non-small cell lung cancer (LA-NSCLC): involved-field radiotherapy (IF-RT) vs. elective nodal irradiation (ENI). Treatment planning was performed for 41 patients with LA-NSCLC, using four different planning approaches (3D-CRT-IF, 3D-CRT-ENI, IMRT-IF, IMRT-ENI). ENI included a boost irradiation after 50 Gy. For each plan, maximum dose escalation was calculated based on prespecified normal tissue constraints. The maximum prescription dose (PD), tumor control probability (TCP), conformal indices (CI), and normal tissue complication probabilities (NTCP) were analyzed. IMRT resulted in statistically significant higher prescription doses for both target volume concepts as compared with 3D-CRT (ENI: 68.4 vs. 60.9 Gy, p < 0.001; IF: 74.3 vs. 70.1 Gy, p < 0.03). With IMRT-IF, a PD of at least 66 Gy was achieved for 95 % of all plans. For IF as compared with ENI, there was a considerable theoretical increase in TCP (IMRT: 27.3 vs. 17.7 %, p < 0.00001; 3D-CRT: 20.2 vs. 9.9 %, p < 0.00001). The esophageal NTCP showed a particularly good sparing with IMRT vs. 3D-CRT (ENI: 12.3 vs. 30.9 % p < 0.0001; IF: 15.9 vs. 24.1 %; p < 0.001). The IMRT technique and IF target volume delineation allow a significant dose escalation and an increase in TCP. IMRT results in an improved sparing of OARs as compared with 3D-CRT at equivalent dose levels.

Development of a four-dimensional Monte Carlo dose calculation system for real-time tumor-tracking irradiation with a gimbaled X-ray head.

PubMed

Ishihara, Yoshitomo; Nakamura, Mitsuhiro; Miyabe, Yuki; Mukumoto, Nobutaka; Matsuo, Yukinori; Sawada, Akira; Kokubo, Masaki; Mizowaki, Takashi; Hiraoka, Masahiro

2017-03-01

To develop a four-dimensional (4D) dose calculation system for real-time tumor tracking (RTTT) irradiation by the Vero4DRT. First, a 6-MV photon beam delivered by the Vero4DRT was simulated using EGSnrc. A moving phantom position was directly measured by a laser displacement gauge. The pan and tilt angles, monitor units, and the indexing time indicating the phantom position were also extracted from a log file. Next, phase space data at any angle were created from both the log file and particle data under the dynamic multileaf collimator. Irradiation both with and without RTTT, with the phantom moving, were simulated using several treatment field sizes. Each was compared with the corresponding measurement using films. Finally, dose calculation for each computed tomography dataset of 10 respiratory phases with the X-ray head rotated was performed to simulate the RTTT irradiation (4D plan) for lung, liver, and pancreatic cancer patients. Dose-volume histograms of the 4D plan were compared with those calculated on the single reference respiratory phase without the gimbal rotation [three-dimensional (3D) plan]. Differences between the simulated and measured doses were less than 3% for RTTT irradiation in most areas, except the high-dose gradient. For clinical cases, the target coverage in 4D plans was almost identical to that of the 3D plans. However, the doses to organs at risk in the 4D plans varied at intermediate- and low-dose levels. Our proposed system has acceptable accuracy for RTTT irradiation in the Vero4DRT and is capable of simulating clinical RTTT plans. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Long-term oral nutrition supplementation improves outcomes in malnourished patients with chronic kidney disease on hemodialysis.

PubMed

Sezer, Siren; Bal, Zeynep; Tutal, Emre; Uyar, Mehtap Erkmen; Acar, Nurhan Ozdemir

2014-11-01

There is no consensus on the type, time of initiation, or duration of use of enteral nutrition in patients with chronic kidney disease (CKD). This study aimed to compare the effects of a renal-specific oral nutrition supplement (RS-ONS) and a standard recommended nutrition regime on biochemical and nutrition markers in malnourished patients with CKD on hemodialysis. Sixty-two malnourished patients with CKD, divided into experimental (RS-ONS; n = 32; mean [SD] age, 62.0 [11.3] years; 55.2% female) and control (CON; n = 30; mean [SD] age, 57.2 [12.3] years; 31% female) groups, were evaluated for anthropometric, biochemical, and inflammatory parameters. Mean (SD) serum albumin levels were significantly increased in the RS-ONS group from 3.5 (0.3) g/dL at baseline to 3.7 (0.2) g/dL at 6 months (P = .028). Significantly fewer patients had serum albumin levels of <3.5 g/dL after month 6. Dry weight of patients significantly increased in the RS-ONS but decreased in the CON groups (P < .001 for each). Percent change from baseline revealed negative results for bioelectrical impedance analysis (P < .001) in the CON group. Malnutrition inflammation score at 6 months (P = .006) and erythropoietin (EPO) dose requirements were higher in the CON group (P = .012). Our findings indicate that consuming RS-ONS improves serum albumin and anthropometric measures, as well as reduces EPO dose, in patients with CKD. © 2014 American Society for Parenteral and Enteral Nutrition.

Experimental and theoretical studies of nuclear generation of ozone from oxygen and oxygen-sulfur hexafluoride mixtures

NASA Astrophysics Data System (ADS)

Elsayed-Ali, H. E.; Miley, G. H.

1986-08-01

A series of experimental measurements of the yield of O3 in nuclear-induced O2 and O2-SF6 discharges are reported. The discharges were created by bombardment with energetic particles from the 10B(n,α)7Li reaction. Continuous irradiation at dose rates of 1015-1017 eV cm-3 s-1 and pulsed irradiation (˜10 ms FWHM) at a peak dose rate of ˜1020 eV cm-3 s-1 were conducted. At the lower dose rates, the addition of SF6 generally increased the ozone yield due to the slowing of ozone destruction by negative oxygen and ozone ions. In contrast, at the high dose rates, the ozone concentration decreased due to SF6 suppression of atomic oxygen formation by ion-ion recombination. A numerical model was developed and tested against experimental conditions. This model indicates that the steady-state ozone concentration was limited by the reaction O-3+O3→2O2+O-2 with a rate coefficient of ˜1×10-12 cm3 s-1. In addition to dose rate effects, pressure and temperature effects on ozone production are discussed and methods for increasing the ozone yield are suggested.

Effect of rosuvastatin monotherapy and in combination with fenofibrate or omega-3 fatty acids on serum vitamin D levels.

PubMed

Makariou, Stefania E; Liberopoulos, Evangelos N; Agouridis, Aris P; Challa, Anna; Elisaf, Moses

2012-12-01

Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration. To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia. We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD. Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups. High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.

Comparison of Monte Carlo and analytical dose computations for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Yepes, Pablo; Adair, Antony; Grosshans, David; Mirkovic, Dragan; Poenisch, Falk; Titt, Uwe; Wang, Qianxia; Mohan, Radhe

2018-02-01

To evaluate the effect of approximations in clinical analytical calculations performed by a treatment planning system (TPS) on dosimetric indices in intensity modulated proton therapy. TPS calculated dose distributions were compared with dose distributions as estimated by Monte Carlo (MC) simulations, calculated with the fast dose calculator (FDC) a system previously benchmarked to full MC. This study analyzed a total of 525 patients for four treatment sites (brain, head-and-neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD and Mean Dose) and a gamma-index analysis were utilized to evaluate the differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels with a dose larger than 10% of the maximum dose had a median larger than 98% for all sites. The median difference for all dosimetric indices for target volumes was less than 2% for all cases. However, differences for target volumes as large as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the median absolute dose difference was smaller than 2 Gy for all indices and cohorts. However, absolute dose differences as large as 10 Gy were found for some small volume organs in brain and head-and-neck patients. This analysis concludes that for a fraction of the patients studied, TPS may overestimate the dose in the target by as much as 10%, while for some OARs the dose could be underestimated by as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more accurate dose computations to improve target coverage and sparing of OARs in proton therapy.

Two Pharmacodynamic Models for Assessing the Efficacy of Amoxicillin-Clavulanate against Experimental Respiratory Tract Infections Caused by Strains of Streptococcus pneumoniae

PubMed Central

Woodnutt, Gary; Berry, Valerie

1999-01-01

Two models of respiratory tract infection were used to investigate the pharmacodynamics of amoxicillin-clavulanate against Streptococcus pneumoniae. Eight strains of S. pneumoniae were used in a mouse model in which the animals were infected intranasally and were then treated with a range of doses and dose intervals. The time that the plasma amoxicillin concentration remained above the MIC (T>MIC) correlated well with bacterial killing, such that if T>MIC was below 20% there was no effect on bacterial numbers in the lungs. As T>MIC increased, the response, in terms of decreased bacterial load, improved and at T>MICs of greater than 35 to 40% of the dosing interval, bacteriological cure was maximal. On the basis of equivalent T>MICs, these data would suggest that in humans a dosage of 500 mg three times daily (t.i.d.) should have efficacy equal to that of a dosage of 875 mg twice daily (b.i.d.). This hypothesis was evaluated in a rat model in which amoxicillin-clavulanate was given by computer-controlled intravenous infusion to achieve concentrations that approximate the concentrations achieved in the plasma of humans following oral administration of 500/125 mg t.i.d. or 875/125 mg b.i.d. Infusions continued for 3 days and bacterial numbers in the lungs 2 h after the cessation of the infusion were significantly reduced (P < 0.01) by both treatments in strains of S. pneumoniae for which amoxicillin MICs were below 2 μg/ml. When tested against a strain of S. pneumoniae for which the amoxicillin MIC was 4 μg/ml, the simulated 500/125-mg dose was ineffective but the 875/125-mg dose demonstrated a small but significant (P < 0.01) reduction in bacterial numbers. These data confirm the findings in the mouse and indicate that amoxicillin-clavulanate administered at 875/125 mg b.i.d. would be as effective clinically as amoxicillin-clavulanate administered at 500/125 mg t.i.d. PMID:9869561

Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

PubMed

Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

2017-01-01

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

Experimental studies on the effect of (Lambda-Cyhalothrin) insecticide on lungs and the ameliorating effect of plant extracts (Ginseng (Panax Ginseng) and garlic (Allium sativum L.) on asthma development in albino rats.

PubMed

Mohi El-Din, Mouchira M; Mostafa, Amna M; Abd-Elkader, Aml

2014-04-16

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for agricultural and public health applications. This study was to determine the pathological alterations of LTC in lungs, which has not previously been studied, and the ameliorating effects of plant extracts (ginseng and garlic) on the development of asthma in albino rats. Four groups (gps) of albino rats, (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1 was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp 3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples were collected for hematological and histopathological examinations. Hematological findings showed that the animals in gps 2 and 3, which were treated for 21 days, showed a significant difference in RBC counts (P > .001), Hb (P > .007), PCV% (P > .004), (P > .008) in comparison with the control group. Signs of cough and nasal discharge were seen in gp 2, which became mild in gp 4. Grossly, the lungs showed congestion and consolidation in gp 2. Histopathologically, macroabscesses and interstitial alveolitis were seen in gp 2, which led to obstruction in the lumen of the bronchioles at 21 d p.i. Meanwhile, thickening in the interalveolar septa with mononuclear cells was seen in gps. 3 and 4 at 21d p.i. The study shows 3 gps of rats injected with LHC alone or combined with garlic and ginseng extract, each group were divided into two sacrificed (15 and 21 d p.i.). Lambda cyhalothrin causes bronchial obstruction in the lungs of the rats (15 and 21 d p.i), which decreased into mild to moderate interstitial inflammation in the rats given garlic and ginseng, respectively.

Experimental studies on the effect of (Lambda-Cyhalothrin) insecticide on lungs and the ameliorating effect of plant extracts (Ginseng (Panax Ginseng) and garlic (Allium sativum L.) on asthma development in albino rats

PubMed Central

2014-01-01

Background Lambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for agricultural and public health applications. This study was to determine the pathological alterations of LTC in lungs, which has not previously been studied, and the ameliorating effects of plant extracts (ginseng and garlic) on the development of asthma in albino rats. Methods Four groups (gps) of albino rats, (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1 was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp 3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples were collected for hematological and histopathological examinations. Results Hematological findings showed that the animals in gps 2 and 3, which were treated for 21 days, showed a significant difference in RBC counts (P > .001), Hb (P > .007), PCV% (P > .004), (P > .008) in comparison with the control group. Signs of cough and nasal discharge were seen in gp 2, which became mild in gp 4. Grossly, the lungs showed congestion and consolidation in gp 2. Histopathologically, macroabscesses and interstitial alveolitis were seen in gp 2, which led to obstruction in the lumen of the bronchioles at 21 d p.i. Meanwhile, thickening in the interalveolar septa with mononuclear cells was seen in gps. 3 and 4 at 21d p.i. Conclusions The study shows 3 gps of rats injected with LHC alone or combined with garlic and ginseng extract, each group were divided into two sacrificed (15 and 21 d p.i.). Lambda cyhalothrin causes bronchial obstruction in the lungs of the rats (15 and 21 d p.i), which decreased into mild to moderate interstitial inflammation in the rats given garlic and ginseng, respectively. PMID:24739272

SU-F-T-440: The Feasibility Research of Checking Cervical Cancer IMRT Pre- Treatment Dose Verification by Automated Treatment Planning Verification System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Yin, Y; Lin, X

Purpose: To assess the preliminary feasibility of automated treatment planning verification system in cervical cancer IMRT pre-treatment dose verification. Methods: The study selected randomly clinical IMRT treatment planning data for twenty patients with cervical cancer, all IMRT plans were divided into 7 fields to meet the dosimetric goals using a commercial treatment planning system(PianncleVersion 9.2and the EclipseVersion 13.5). The plans were exported to the Mobius 3D (M3D)server percentage differences of volume of a region of interest (ROI) and dose calculation of target region and organ at risk were evaluated, in order to validate the accuracy automated treatment planning verification system.more » Results: The difference of volume for Pinnacle to M3D was less than results for Eclipse to M3D in ROI, the biggest difference was 0.22± 0.69%, 3.5±1.89% for Pinnacle and Eclipse respectively. M3D showed slightly better agreement in dose of target and organ at risk compared with TPS. But after recalculating plans by M3D, dose difference for Pinnacle was less than Eclipse on average, results were within 3%. Conclusion: The method of utilizing the automated treatment planning system to validate the accuracy of plans is convenientbut the scope of differences still need more clinical patient cases to determine. At present, it should be used as a secondary check tool to improve safety in the clinical treatment planning.« less

Effects of D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of saw palmetto (Serenoa repens) on the sexual activity in male rats: A controlled, experimental study

PubMed Central

Fernández, Lilia C.; Mas, Rosa; Fernández, Julio; Mendoza, Sarahí; Gámez, Rafael; Pardo, Balia

2008-01-01

Background: The etiology of benign prostatic hyperplasia (BPH) is not completely understood, but hormonal changes in aging men seem to be pivotal. Dihydrotestosterone, a potent, active metabolite of testosterone, is formed by the enzymatic action of prostate 5α-reductase and causes cell growth and hyperplasia. Consistent with this action, male sexual dysfunction has been clinically documented to be among the drug-related adverse events associated with 5α-reductase inhibitors. The lipidosterolic extract of saw palmetto (LESP) fruit (Serenoa repens) has been used to treat BPH. D-004, a lipid extract of Roystonea regia Royal palm fruit, has been found to prevent prostatic hyperplasia induced by testoste-rone in rodents and to competitively inhibit prostate 5α-reductase activity in vitro. Objective: The purpose of this study was to assess the effects of D-004 and LESP, administered as single or repeated doses, on the sexual activity in male rats. Methods: This controlled, experimental study was conducted at the Pharmacology Department, Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba. Adult male Wistar rats weighing 250 to 300 g were randomized into 5 groups: 2 groups treated orally with D-004 (400 and 800 mg/kg); 2 groups treated orally with LESP (400 and 800 mg/kg); and 1 control group orally administered a water vehicle. Sexual activity behavior (the number of mounts and intromissions, mount latency, and intromission latency) was assessed during 2 observation periods: 90 minutes after the initial dose and at the end of the 30-day treatment. Latency was defined as time elapsed between the first mount and intromission. Results: A total of 50 rats (mean [SD] age, 10 [3] weeks; mean [SD] weight, 295 [10] g) were included in the experiment. There were no significant difterences in the mean number of mounts, intromissions, mount latency, or intromission latency in the groups treated with single or repeated doses of D-004 or LESP (400 and 800 mg/kg) compared with the controls. There was also no between-group difterence in mating behavior among the active treatment groups. All rats survived up to study completion, with normal behavior (weight gain, food intake, daily observations, without any sign of toxicity). There were no observable adverse events during the study. Conclusions: D-004 and LESP administered as a single dose or repeated doses for 30 days did not significantly affect male rat sexual activity behavior compared with a vehicle control group. PMID:24692784

Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults.

PubMed

Vaes, Anouk M M; Tieland, Michael; de Regt, Margot F; Wittwer, Jonas; van Loon, Luc J C; de Groot, Lisette C P G M

2018-06-01

Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D 2 or D 3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D 3 and assessed the dose which results in mean serum 25(OH)D 3 concentrations between 75 and 100 nmol/L. This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D 3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D 3 , 25(OH)D 3 , 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. Supplementation with 20 μg vitamin D 3 increased 25(OH)D 3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D 3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D 3 levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D 3 and 24,25(OH) 2 D 3 (R 2  = 0.83, P < 0.01), but not between 25(OH)D 3 and 1,25(OH) 2 D 3 (R 2  = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. Calcifediol supplementation rapidly and safely elevates serum 25(OH)D 3 concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D 3 concentrations to be maintained between 75 and 100 nmol/L. NCT01868945. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vikraman, S; Ramu, M; Karrthick, Kp

Purpose: The purpose of this study was to validate the advent of COMPASS 3D dosimetry as a routine pre treatment verification tool with commercially available CMS Monaco and Oncentra Masterplan planning system. Methods: Twenty esophagus patients were selected for this study. All these patients underwent radical VMAT treatment in Elekta Linac and plans were generated in Monaco v5.0 with MonteCarlo(MC) dose calculation algorithm. COMPASS 3D dosimetry comprises an advanced dose calculation algorithm of collapsed cone convolution(CCC). To validate CCC algorithm in COMPASS, The DICOM RT Plans generated using Monaco MC algorithm were transferred to Oncentra Masterplan v4.3 TPS. Only finalmore » dose calculations were performed using CCC algorithm with out optimization in Masterplan planning system. It is proven that MC algorithm is an accurate algorithm and obvious that there will be a difference with MC and CCC algorithms. Hence CCC in COMPASS should be validated with other commercially available CCC algorithm. To use the CCC as pretreatment verification tool with reference to MC generated treatment plans, CCC in OMP and CCC in COMPASS were validated using dose volume based indices such as D98, D95 for target volumes and OAR doses. Results: The point doses for open beams were observed <1% with reference to Monaco MC algorithms. Comparisons of CCC(OMP) Vs CCC(COMPASS) showed a mean difference of 1.82%±1.12SD and 1.65%±0.67SD for D98 and D95 respectively for Target coverage. Maximum point dose of −2.15%±0.60SD difference was observed in target volume. The mean lung dose of −2.68%±1.67SD was noticed between OMP and COMPASS. The maximum point doses for spinal cord were −1.82%±0.287SD. Conclusion: In this study, the accuracy of CCC algorithm in COMPASS 3D dosimetry was validated by compared with CCC algorithm in OMP TPS. Dose calculation in COMPASS is feasible within < 2% in comparison with commercially available TPS algorithms.« less

An iterative three-dimensional electron density imaging algorithm using uncollimated compton scattered x rays from a polyenergetic primary pencil beam.

PubMed

Van Uytven, Eric; Pistorius, Stephen; Gordon, Richard

2007-01-01

X-ray film-screen mammography is currently the gold standard for detecting breast cancer. However, one disadvantage is that it projects a three-dimensional (3D) object onto a two-dimensional (2D) image, reducing contrast between small lesions and layers of normal tissue. Another limitation is its reduced sensitivity in women with mammographically dense breasts. Computed tomography (CT) produces a 3D image yet has had a limited role in mammography due to its relatively high dose, low resolution, and low contrast. As a first step towards implementing quantitative 3D mammography, which may improve the ability to detect and specify breast tumors, we have developed an analytical technique that can use Compton scatter to obtain 3D information of an object from a single projection. Imaging material with a pencil beam of polychromatic x rays produces a characteristic scattered photon spectrum at each point on the detector plane. A comparable distribution may be calculated using a known incident x-ray energy spectrum, beam shape, and an initial estimate of the object's 3D mass attenuation and electron density. Our iterative minimization algorithm changes the initially arbitrary electron density voxel matrix to reduce regular differences between the analytically predicted and experimentally measured spectra at each point on the detector plane. The simulated electron density converges to that of the object as the differences are minimized. The reconstruction algorithm has been validated using simulated data produced by the EGSnrc Monte Carlo code system. We applied the imaging algorithm to a cylindrically symmetric breast tissue phantom containing multiple inhomogeneities. A preliminary ROC analysis scores greater than 0.96, which indicate that under the described simplifying conditions, this approach shows promise in identifying and localizing inhomogeneities which simulate 0.5 mm calcifications with an image voxel resolution of 0.25 cm and at a dose comparable to mammography.

The IROC Houston Quality Assurance Program: Potential benefits of 3D dosimetry

NASA Astrophysics Data System (ADS)

Followill, D. S.; Molineu, H. A.; Lafratta, R.; Ibbott, G. S.

2017-05-01

The IROC Houston QA Center has provided QA core support for NCI clinical trials by ensuring that radiation doses delivered to trial patients are accurate and comparable between participating institutions. Within its QA program, IROC Houston uses anthropomorphic QA phantoms to credential sites. It is these phantoms that have the highest potential to benefit from the use of 3D dosimeters. Credentialing is performed to verify that institutions that are using advanced technologies to deliver complex treatment plans that conform to targets. This makes it increasingly difficult to assure the intended calculated dose is being delivered correctly using current techniques that are 2D-based. A 3D dosimeter such as PRESAGE® is able to provide a complete 3D measured dosimetry dataset with one treatment plan delivery. In our preliminary studies, the 3D dosimeters in our H&N and spine phantoms were found to be appropriate for remote dosimetry for relative dose measurements. To implement 3D dosimetry in IROC Houston’s phantoms, the benefit of this significant change to its current infrastructure would have to be assessed and further work would be needed before bringing 3D dosimeters into the phantom dosimetry program.

Bioavailability and Safety of Vitamin D3 from Pizza Baked with Fortified Mozzarella Cheese: A Randomized Controlled Trial.

PubMed

Al-Khalidi, Banaz; Chiu, Winnie; Rousseau, Dérick; Vieth, Reinhold

2015-09-01

To assess the bioavailability and safety of vitamin D3 from fortified mozzarella cheese baked on pizza. In a randomized, double-blind trial, 96 apparently healthy, ethnically diverse adults were randomized to consume 200 IU or 28 000 IU vitamin D3 fortified mozzarella cheese with pizza once weekly for a total of 8 weeks. Blood and urine samples were collected at baseline (week 1) and final (week 10) visits for serum 25-hydroxyvitamin D and other biochemical measures. The primary outcome compared serum 25-hydroxyvitamin D between groups at 10 weeks. The secondary outcome evaluated the safety of vitamin D dosing protocol as measured by serum and urine calcium, phosphate, creatinine, and serum parathyroid hormone (PTH). Serum 25-hydroxyvitamin D increased by 5.1 ± 11 nmol/L in the low-dose group (n = 47; P = 0.003), and by 73 ± 22 nmol/L in the high-dose group (n = 49; P < 0.0001). None of the subjects in either group developed any adverse events during the supplementation protocol. Serum PTH significantly decreased in the high-dose group only (P < 0.05). Vitamin D3 is safe and bioavailable from fortified mozzarella cheese baked on pizza.

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, Justus; Newton, Joseph; Yang Yun

2012-07-15

Purpose: To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T and O) applicator using Monte Carlo calculation and 3D dosimetry. Methods: For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 Multiplication-Sign 10{sup 9} photon histories from a {supmore » 137}Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for {sup 137}Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE{sup Registered-Sign} dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5 Degree-Sign increments, and a 3D distribution was reconstructed with a (0.05 cm){sup 3} isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T and O implant plan. Results: The systematic difference in bucket angle relative to the nominal ovoid angle (105 Degree-Sign ) was 3.1 Degree-Sign -4.7 Degree-Sign . A systematic difference in bucket angle of 1 Degree-Sign , 5 Degree-Sign , and 10 Degree-Sign caused a 1%{+-} 0.1%, 1.7%{+-} 0.4%, and 2.6%{+-} 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D {gamma}-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9%{+-} 0.2%, 83.4%{+-} 0.7%, and 82.5%{+-} 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7%{+-} 0.8%, 65.6%{+-} 1.7%, and 57.5%{+-} 1.6%, respectively. For a clinical T and O plan, attenuation from the buckets leads to a decrease in average Point A dose of {approx}3.2% and decrease in D{sub 2cc} to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. Conclusions: Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.« less

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry.

PubMed

Adamson, Justus; Newton, Joseph; Yang, Yun; Steffey, Beverly; Cai, Jing; Adamovics, John; Oldham, Mark; Chino, Junzo; Craciunescu, Oana

2012-07-01

To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 10(9) photon histories from a (137)Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for (137)Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE(®) dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)(3) isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D γ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D(2cc) to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.

Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968)

PubMed Central

Joerger, M; Hess, D; Delmonte, A; Gallerani, E; Fasolo, A; Gianni, L; Cresta, S; Barbieri, P; Pace, S; Sessa, C

2015-01-01

Aims Namitecan is a new camptothecan compound undergoing early clinical development. This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development. Methods Plasma concentration–time data, neutrophils and thrombocytes were pooled from two phase 1 studies in 90 patients with advanced solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3 weeks (D1,8) (n = 34), once every 3 weeks (D1) (n = 29) and on 3 consecutive days (D1–3) (n = 27). A linear three compartment PK model was coupled to a semiphysiological PD-model for neutrophils and thrombocytes. Data simulations were used to interrogate various dosing regimens and give dosing recommendations. Results Clearance was estimated to be 0.15 l h–1, with a long terminal half-life of 48 h. Body surface area was not associated with clearance, supporting flat-dosing of namitecan. A significant and clinically relevant association was found between namitecan area under the concentration–time curve (AUC) and the percentage drop of neutrophils (r2 = 0.51, P < 10−4) or thrombocytes (r2 = 0.49, P < 10−4). With a target for haematological dose-limiting toxicity of <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for the once every 3 week regimen and 7 mg for the D1–3 regimen. Conclusion This is the first integrated population PK–PD analysis of the new hydrophilic topoisomerase I inhibitor namitecan, that is currently undergoing early clinical development. A distinct relationship was found between drug exposure and haematological toxicity, supporting flat-dosing once every 3 weeks as the most adequate dosing regimen. PMID:25580946

MO-B-BRB-03: 3D Dosimetry in the Clinic: Validating Special Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juang, T.

Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by themore » development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an irradiated volume can help understand interplay effects during TomoTherapy or VMAT. Titania Juang: Special techniques in the clinic and research Understand the potential for 3D dosimetry in validating dose accumulation in deformable systems, and Observe the benefits of high resolution measurements for precision therapy in SRS and in MicroSBRT for small animal irradiators Geoffrey S. Ibbott: 3D Dosimetry in end-to-end dosimetry QA Understand the potential for 3D dosimetry for end-to-end radiation therapy process validation in the in-house and external credentialing setting. Canadian Institutes of Health Research; L. Schreiner, Modus QA, London, ON, Canada; T. Juang, NIH R01CA100835.« less

MO-B-BRB-01: 3D Dosimetry in the Clinic: Background and Motivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreiner, L.

Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by themore » development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an irradiated volume can help understand interplay effects during TomoTherapy or VMAT. Titania Juang: Special techniques in the clinic and research Understand the potential for 3D dosimetry in validating dose accumulation in deformable systems, and Observe the benefits of high resolution measurements for precision therapy in SRS and in MicroSBRT for small animal irradiators Geoffrey S. Ibbott: 3D Dosimetry in end-to-end dosimetry QA Understand the potential for 3D dosimetry for end-to-end radiation therapy process validation in the in-house and external credentialing setting. Canadian Institutes of Health Research; L. Schreiner, Modus QA, London, ON, Canada; T. Juang, NIH R01CA100835.« less

MO-B-BRB-04: 3D Dosimetry in End-To-End Dosimetry QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ibbott, G.

Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by themore » development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an irradiated volume can help understand interplay effects during TomoTherapy or VMAT. Titania Juang: Special techniques in the clinic and research Understand the potential for 3D dosimetry in validating dose accumulation in deformable systems, and Observe the benefits of high resolution measurements for precision therapy in SRS and in MicroSBRT for small animal irradiators Geoffrey S. Ibbott: 3D Dosimetry in end-to-end dosimetry QA Understand the potential for 3D dosimetry for end-to-end radiation therapy process validation in the in-house and external credentialing setting. Canadian Institutes of Health Research; L. Schreiner, Modus QA, London, ON, Canada; T. Juang, NIH R01CA100835.« less

MO-B-BRB-02: 3D Dosimetry in the Clinic: IMRT Technique Validation in Sweden

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ceberg, S.

Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by themore » development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an irradiated volume can help understand interplay effects during TomoTherapy or VMAT. Titania Juang: Special techniques in the clinic and research Understand the potential for 3D dosimetry in validating dose accumulation in deformable systems, and Observe the benefits of high resolution measurements for precision therapy in SRS and in MicroSBRT for small animal irradiators Geoffrey S. Ibbott: 3D Dosimetry in end-to-end dosimetry QA Understand the potential for 3D dosimetry for end-to-end radiation therapy process validation in the in-house and external credentialing setting. Canadian Institutes of Health Research; L. Schreiner, Modus QA, London, ON, Canada; T. Juang, NIH R01CA100835.« less

Effect of Simvastatin Prodrug on Experimental Periodontitis.

PubMed

Bradley, Aaron D; Zhang, Yijia; Jia, Zhenshan; Zhao, Gang; Wang, Xiaobei; Pranke, Laura; Schmid, Marian J; Wang, Dong; Reinhardt, Richard A

2016-05-01

Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation. Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance. Ligature alone caused a mean bone loss of 1.01 ± 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 ± 0.05 mm, P <0.001), which was not statistically different from contralateral control (0.47 ± 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% ± 1.0% versus 5.7% ± 1.1%; P <0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2% ± 3.3% versus 46.3% ± 3.3%; P <0.001). The mPEG carrier alone did not have bone-sparing or anti-inflammatory properties. Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.

Ionization chamber-based reference dosimetry of intensity modulated radiation beams.

PubMed

Bouchard, Hugo; Seuntjens, Jan

2004-09-01

The present paper addresses reference dose measurements using thimble ionization chambers for quality assurance in IMRT fields. In these radiation fields, detector fluence perturbation effects invalidate the application of open-field dosimetry protocol data for the derivation of absorbed dose to water from ionization chamber measurements. We define a correction factor C(Q)IMRT to correct the absorbed dose to water calibration coefficient N(D, w)Q for fluence perturbation effects in individual segments of an IMRT delivery and developed a calculation method to evaluate the factor. The method consists of precalculating, using accurate Monte Carlo techniques, ionization chamber, type-dependent cavity air dose, and in-phantom dose to water at the reference point for zero-width pencil beams as a function of position of the pencil beams impinging on the phantom surface. These precalculated kernels are convolved with the IMRT fluence distribution to arrive at the dose-to-water-dose-to-cavity air ratio [D(a)w (IMRT)] for IMRT fields and with a 10x10 cm2 open-field fluence to arrive at the same ratio D(a)w (Q) for the 10x10 cm2 reference field. The correction factor C(Q)IMRT is then calculated as the ratio of D(a)w (IMRT) and D(a)w (Q). The calculation method was experimentally validated and the magnitude of chamber correction factors in reference dose measurements in single static and dynamic IMRT fields was studied. The results show that, for thimble-type ionization chambers the correction factor in a single, realistic dynamic IMRT field can be of the order of 10% or more. We therefore propose that for accurate reference dosimetry of complete n-beam IMRT deliveries, ionization chamber fluence perturbation correction factors must explicitly be taken into account.

Experiment K-7-41: Radiation Experiments on Cosmos 2044

NASA Technical Reports Server (NTRS)

Benton, E. V.; Benton, E. R.; Frank, A. L.; Dudkin, V. E.; Marenny, A. M.; Kovalev, E. E.

1994-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 degrees and altitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq. cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10-4 and 3.05 x 10(exp -4) cm(exp -2).s(exp -1).sr(exp -4) of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(infinity).H2O is greater than or equal to 4 keV/micro-m. Neutron measurements yielded 0.018 mremld in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra have been compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 degrees) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCR's, and higher LET particles, in the heavy particle fluxes.

SU-E-T-72: A Retrospective Correlation Analysis On Dose-Volume Control Points and Treatment Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, A; Nohadani, O; Refaat, T

2015-06-15

Purpose: To quantify correlation between dose-volume control points and treatment outcomes. Specifically, two outcomes are analyzed: occurrence of radiation induced dysphagia and target complications. The results inform the treatment planning process when competing dose-volume criteria requires relaxations. Methods: 32 patients, treated with whole-field sequential intensity modulated radiation therapy during 2009–2010 period, are considered for this study. Acute dysphagia that is categorized into 3 grades is observed on all patients. 3 patients are observed in grade 1, 17 patients in grade 2, and 12 patients in grade 3. Ordinal logistic regression is employed to establish correlations between grades of dysphagia andmore » dose to cervico-thoracic esophagus. Particularly, minimum (Dmin), mean (Dmean), and maximum (Dmax) dose control points are analyzed. Additionally, target complication, which includes local-regional recurrence and/or distant metastasis, is observed on 4 patients. Binary logistic regression is used to quantify correlation between target complication and four dose control points. Namely, ICRU recommended dose control points, D2, D50, D95, and D98 are analyzed. Results: For correlation with dysphagia, Dmin on cervico-thoracic esophagus is statistically significant (p-value = 0.005). Additionally, Dmean on cervico-thoracic esophagus is also significant in association with dysphagia (p-value = 0.012). However, no correlation was observed between Dmax and dysphagia (p-value = 0.263). For target complications, D50 on the target is a statistically significant dose control point (p-value = 0.032). No correlations were observed between treatment complications and D2 (p-value = 0.866), D95 (p-value = 0.750), and D98 (p-value = 0.710) on the target. Conclusion: Significant correlations are observed between radiation induced dysphagia and Dmean (and Dmin) to cervico-thoracic esophagus. Additionally, correlation between target complications and median dose to target (D50) is observed. Quantification of these correlations can inform treatment planners when any competing objectives requires relaxation of target D50 or Dmean (or Dmin) to cervico-thoracic esophagus.« less

Dose distribution of secondary radiation in a water phantom for a proton pencil beam-EURADOS WG9 intercomparison exercise.

PubMed

Stolarczyk, L; Trinkl, S; Romero-Expósito, M; Mojżeszek, N; Ambrozova, I; Domingo, C; Davídková, M; Farah, J; Kłodowska, M; Knežević, Ž; Liszka, M; Majer, M; Miljanić, S; Ploc, O; Schwarz, M; Harrison, R M; Olko, P

2018-04-19

Systematic 3D mapping of out-of-field doses induced by a therapeutic proton pencil scanning beam in a 300  ×  300  ×  600 mm 3 water phantom was performed using a set of thermoluminescence detectors (TLDs): MTS-7 ( 7 LiF:Mg,Ti), MTS-6 ( 6 LiF:Mg,Ti), MTS-N ( nat LiF:Mg,Ti) and TLD-700 ( 7 LiF:Mg,Ti), radiophotoluminescent (RPL) detectors GD-352M and GD-302M, and polyallyldiglycol carbonate (PADC)-based (C 12 H 18 O 7 ) track-etched detectors. Neutron and gamma-ray doses, as well as linear energy transfer distributions, were experimentally determined at 200 points within the phantom. In parallel, the Geant4 Monte Carlo code was applied to calculate neutron and gamma radiation spectra at the position of each detector. For the cubic proton target volume of 100  ×  100  ×  100 mm 3 (spread out Bragg peak with a modulation of 100 mm) the scattered photon doses along the main axis of the phantom perpendicular to the primary beam were approximately 0.5 mGy Gy -1 at a distance of 100 mm and 0.02 mGy Gy -1 at 300 mm from the center of the target. For the neutrons, the corresponding values of dose equivalent were found to be ~0.7 and ~0.06 mSv Gy -1 , respectively. The measured neutron doses were comparable with the out-of-field neutron doses from a similar experiment with 20 MV x-rays, whereas photon doses for the scanning proton beam were up to three orders of magnitude lower.

Dose distribution of secondary radiation in a water phantom for a proton pencil beam—EURADOS WG9 intercomparison exercise

NASA Astrophysics Data System (ADS)

Stolarczyk, L.; Trinkl, S.; Romero-Expósito, M.; Mojżeszek, N.; Ambrozova, I.; Domingo, C.; Davídková, M.; Farah, J.; Kłodowska, M.; Knežević, Ž.; Liszka, M.; Majer, M.; Miljanić, S.; Ploc, O.; Schwarz, M.; Harrison, R. M.; Olko, P.

2018-04-01

Systematic 3D mapping of out-of-field doses induced by a therapeutic proton pencil scanning beam in a 300  ×  300  ×  600 mm3 water phantom was performed using a set of thermoluminescence detectors (TLDs): MTS-7 (7LiF:Mg,Ti), MTS-6 (6LiF:Mg,Ti), MTS-N (natLiF:Mg,Ti) and TLD-700 (7LiF:Mg,Ti), radiophotoluminescent (RPL) detectors GD-352M and GD-302M, and polyallyldiglycol carbonate (PADC)-based (C12H18O7) track-etched detectors. Neutron and gamma-ray doses, as well as linear energy transfer distributions, were experimentally determined at 200 points within the phantom. In parallel, the Geant4 Monte Carlo code was applied to calculate neutron and gamma radiation spectra at the position of each detector. For the cubic proton target volume of 100  ×  100  ×  100 mm3 (spread out Bragg peak with a modulation of 100 mm) the scattered photon doses along the main axis of the phantom perpendicular to the primary beam were approximately 0.5 mGy Gy‑1 at a distance of 100 mm and 0.02 mGy Gy‑1 at 300 mm from the center of the target. For the neutrons, the corresponding values of dose equivalent were found to be ~0.7 and ~0.06 mSv Gy‑1, respectively. The measured neutron doses were comparable with the out-of-field neutron doses from a similar experiment with 20 MV x-rays, whereas photon doses for the scanning proton beam were up to three orders of magnitude lower.

Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study

PubMed Central

Falchook, Gerald; Kurzrock, Razelle; Gouw, Launce; Hong, David; McGregor, Kimberly A.; Zhou, Xiaofei; Shi, Hongliang; Fingert, Howard; Sharma, Sunil

2014-01-01

Background This phase 1b study evaluated an enteric-coated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237). Methods Patients with advanced, non-hematologic malignancies received oral alisertib ECT for 7 days BID followed by 14 days treatment-free (21-day cycles; 3+3 dose escalation schema). Objectives were to assess safety, pharmacokinetics, and antitumor activity, and to define a recommended phase 2 dose (RP2D) of alisertib. Results 24 patients were treated. Median age was 57 years. Patients received a median of 2 cycles (range 1–12). The RP2D was determined as 50 mg BID for 7 days (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. The most common drug-related adverse event (AE) was neutropenia (50%). At doses ≥40 mg BID, 7 patients had drug-related AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. Following administration of alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h; systemic exposure increased with increasing dose over 10–60 mg BID. Mean t½ was ~21 h following multiple dosing. Renal clearance was negligible. Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored). Conclusions Alisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 days and is being evaluated in ongoing phase 2 studies. PMID:24879333

Dose distribution and mapping with 3D imaging presentation in intraoral and panoramic examinations

NASA Astrophysics Data System (ADS)

Chen, Hsiu-Ling; Huang, Yung-Hui; Wu, Tung-Hsin; Wang, Shih-Yuan; Lee, Jason J. S.

2011-10-01

In current medical imaging applications, high quality images not only provide more diagnostic value for anatomic delineation but also offer functional information for treatment direction. However, this approach would potentially subscribe higher radiation dose in dental radiographies, which has been putatively associated with low-birth-weight during pregnancy, which affects the hypothalamus-pituitary-thyroid axis or thereby directly affects the reproductive organs. The aim of this study was to apply the high resolution 3-D image mapping technique to evaluate radiation doses from the following aspects: (1) verifying operating parameters of dental X-ray units, (2) measuring the leakage radiations and (3) mapping dose with 3-D radiographic imaging to evaluate dose distribution in head and neck regions. From the study results, we found that (1) leakage radiation from X-ray units was about 21.31±15.24 mR/h (<100 mR/h), (2) error of actual tube voltage for 60 kVp setting was from 0.2% to 6.5%, with an average of 2.5% (<7%) and (3) the error of exposure time for a 0.5-1.5 s setting was within 0.7-8.5%, with an average of 7.3% (<10%) error as well. Our 3-D dose mapping demonstrated that dose values were relatively lower in soft tissues and higher in bone surfaces compared with other investigations. Multiple causes could contribute to these variations, including irradiation geometry, image equipment and type of technique applied, etc. From the results, we also observed that larger accumulated doses were presented in certain critical organs, such as salivary gland, thyroid gland and bone marrow. Potential biological affects associated with these findings warrant further investigation.

Experimental investigation of the 100 keV X-ray dose response of the high-temperature thermoluminescence in LiF:Mg,Ti (TLD-100): theoretical interpretation using the unified interaction model.

PubMed

Livingstone, J; Horowitz, Y S; Oster, L; Datz, H; Lerch, M; Rosenfeld, A; Horowitz, A

2010-03-01

The dose response of LiF:Mg,Ti (TLD-100) chips was measured from 1 to 50,000 Gy using 100 keV X rays at the European Synchroton Radiation Facility. Glow curves were deconvoluted into component glow peaks using a computerised glow curve deconvolution (CGCD) code based on first-order kinetics. The normalised dose response, f(D), of glow peaks 4 and 5 and 5b (the major components of composite peak 5), as well as peaks 7 and 8 (two of the major components of the high-temperature thermoluminescence (HTTL) at high levels of dose) was separately determined and theoretically interpreted using the unified interaction model (UNIM). The UNIM is a nine-parameter model encompassing both the irradiation/absorption stage and the thermally induced relaxation/recombination stage with an admixture of both localised and delocalised recombination mechanisms. The effects of radiation damage are included in the present modelling via the exponential removal of luminescent centres (LCs) at high dose levels. The main features of the experimentally measured dose response are: (i) increase in f(D)(max) with glow peak temperature, (ii) increase in D(max) (the dose level at which f(D)(max) occurs) with increasing glow peak temperature, and (iii) decreased effects of radiation damage with increasing glow peak temperature. The UNIM interpretation of this behaviour requires both strongly decreasing values of ks (the relative contribution of localised recombination) as a function of glow peak temperature and, as well, significantly different values of the dose-filling constants of the trapping centre (TC) and LC for peaks 7 and 8 than those used for peaks 4 and 5. This suggests that different TC/LC configurations are responsible for HTTL. The relative intensity of peak 5a (a low-temperature satellite of peak 5 arising from localised recombination) was found to significantly increase at higher dose levels due to preferential electron and hole population of the trapping/recombination complex giving rise to composite glow peak 5. It is also demonstrated that possible changes in the trapping cross section of the LC and the competitive centres due to increasing sample/glow peak temperature do not significantly influence these observations/conclusions.

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

TH-CD-202-10: Tumor Metabolic Control Probability & Dose Response Mapping for Adaptive Dose Painting by Number

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, S; Wilson, G; Krauss, D

Purpose: Adaptive dose-painting-by-number (DPbN) requires a dose-response-mapping (DRM) obtained early in the treatment course. To obtain DRM, voxel-by-voxel tumor dose response needs to be quantified. Our recent study has demonstrated that voxel-by-voxel radio-sensitivity of patient tumor can be determined using tumor-metabolic-ratio measured early during the treatment using FDG-PET images. In this study, the measurements were utilized to construct tumor metabolic control probability (TMCP) and DRM for DPbN. Methods: FDG-PET/CT images of 18 HN cancer patients obtained pre- and weekly during the treatment were used. Spatial parametric images of tumor-metabolic-ratio (dSUV) were constructed following voxel-by-voxel deformable image registration. Each voxel valuemore » in dSUV was a function of baseline SUV and delivered dose. Utilizing all values of dSUV in the controlled tumor group at the last treatment week, a cut-off function between the baseline SUV and dSUV was formed, and applied in early treatment days on dSUV of all tumors to model the TMCP. At the treatment week k, TMCP was constructed with respect to the tumor voxel dSUV appeared at the week using the maximum likelihood estimation for all dose levels, and used for DRM construction. Results: TMCPs estimated in the week 2 & 3 have D{sub 50}=11.1∼47.6Gy; γ{sub 50}=0.55∼0.92 respectively with respect to dSUV=0.3∼1.2. The corresponding DRM between tumor voxel dSUV and the expected treatment dose has sigmoid shape. The expected treatment dose are 26∼40Gy (for 95% TMCP) for high sensitive tumor voxels with dSUV=0.3∼0.5; and 65∼110Gy for low sensitive tumor voxels with the dSUV>1.0 depending on the time of the estimation. Conclusion: TMCP can be constructed voxel-by-voxel in human tumor using multiple FDG-PET imaging obtained in early treatment days. TMCP provides a potential quantitative objective of tumor DRM for DPbN to plan the best dose, escalate or de-escalate, in tumor adaptively based on its own radio-sensitivity.« less

SU-E-T-157: Evaluation and Comparison of Doses to Pelvic Lymph Nodes and to Point B with 3D Image Guided Treatment Planning for High Dose Brachytherapy for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, N.

2014-06-01

Purpose: To estimate and compare the doses received by the obturator, external and internal iliac lymph nodes and point Methods: CT-MR fused image sets of 15 patients obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicator, were used to generate treatment plans optimized to deliver a prescription dose to HRCTV-D90 and to minimize the doses to organs at risk (OARs). For each set of image, target volume (GTV, HRCTV) OARs (Bladder, Rectum, Sigmoid), and both left and right pelvic lymph nodes (obturator, external and internal iliac lymph nodes) were delineated. Dose-volume histograms (DVH) were generatedmore » for pelvic nodal groups (left and right obturator group, internal and external iliac chains) Per fraction DVH parameters used for dose comparison included dose to 100% volume (D100), and dose received by 2cc (D2cc), 1cc (D1cc) and 0.1 cc (D0.1cc) of nodal volume. Dose to point B was compared with each DVH parameter using 2 sided t-test. Pearson correlation were determined to examine relationship of point B dose with nodal DVH parameters. Results: FIGO clinical stage varied from 1B1 to IIIB. The median pretreatment tumor diameter measured on MRI was 4.5 cm (2.7– 6.4cm).The median dose to bilateral point B was 1.20 Gy ± 0.12 or 20% of the prescription dose. The correlation coefficients were all <0.60 for all nodal DVH parameters indicating low degree of correlation. Only 2 cc of obturator nodes was not significantly different from point B dose on t-test. Conclusion: Dose to point B does not adequately represent the dose to any specific pelvic nodal group. When using image guided 3D dose-volume optimized treatment nodal groups should be individually identified and delineated to obtain the doses received by pelvic nodes.« less

Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design.

PubMed

Tevaarwerk, Amye; Wilding, George; Eickhoff, Jens; Chappell, Rick; Sidor, Carolyn; Arnott, Jamie; Bailey, Howard; Schelman, William; Liu, Glenn

2012-06-01

MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK). Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks. Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites. Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

Fructo-oligosaccharide improved brain β-amyloid, β-secretase, cognitive function, and plasma antioxidant levels in D-galactose-treated Balb/cJ mice.

PubMed

Yen, Chi-Hua; Wang, Cheng-Hsin; Wu, Wen-Tzu; Chen, Hsiao-Ling

2017-05-01

Long-term d-galactose injection induces accelerated aging in experimental rodent models. The aim of this study was to determine the effects of dietary fructo-oligosaccharide (FO) on the brain β-amyloid (Aβ), amyloid-associated enzymes, cognitive function, and plasma antioxidant levels in d-galactose-treated Balb/c mice. The subcutaneous (s.c.) injection and the dietary treatment were conducted simultaneously for 49 days. Mice (12 weeks of age) were divided into five groups (n = 14/group): control (s.c. saline, control diet) serving as a young control, DG (s.c. 1.2 g d-galactose/kg body weight, control diet), DG + LFO (2.5% w/w FO, low-dose FO diet), DG + HFO (5% w/w FO, high-dose FO diet), and DG + E (α-tocopherol 0.2% w/w, vitamin E diet) as an antioxidant reference group. Another group of older mice (64 weeks of age) without any injection served as a natural aging (NA) group. The DG and NA groups had greater Aβ levels in the cortex, hippocampus, and the whole brain. High-dose FO, similar to α-tocopherol, attenuated the d-galactose-induced Aβ density in the cortex and hippocampus. In addition, FO attenuated the d-galactose-induced protein expression of Aβ and beta-site amyloid precursor cleaving enzyme of the whole brain in a dose-response manner. Either dose of FO supplementation, similar to α-tocopherol, attenuated the d-galactose-induced cognitive dysfunction. In addition, FO improved the plasma ascorbic acid level in a dose-response manner. Dietary FO (2.5-5% w/w diet) could attenuate the development of Alzheimer's disease, which was likely to be associated with its systematic antioxidant effects.

Analysis of neutron propagation from the skyshine port of a fusion neutron source facility

NASA Astrophysics Data System (ADS)

Wakisaka, M.; Kaneko, J.; Fujita, F.; Ochiai, K.; Nishitani, T.; Yoshida, S.; Sawamura, T.

2005-12-01

The process of neutron leaking from a 14 MeV neutron source facility was analyzed by calculations and experiments. The experiments were performed at the Fusion Neutron Source (FNS) facility of the Japan Atomic Energy Institute, Tokai-mura, Japan, which has a port on the roof for skyshine experiments, and a 3He counter surrounded with a polyethylene moderator of different thicknesses was used to estimate the energy spectra and dose distributions. The 3He counter with a 3-cm-thick moderator was also used for dose measurements, and the doses evaluated by the counter counts and the calculated count-to-dose conversion factor agreed with the calculations to within ˜30%. The dose distribution was found to fit a simple analytical expression, D(r)=Q{exp(-r/λD)}/{r} and the parameters Q and λD are discussed.

Vitamin D(3) is more potent than vitamin D(2) in humans.

PubMed

Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G

2011-03-01

Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

Direct vitamin D3 actions on rhesus macaque follicles in three-dimensional culture: assessment of follicle survival, growth, steroid, and antimüllerian hormone production.

PubMed

Xu, Jing; Hennebold, Jon D; Seifer, David B

2016-12-01

To investigate the direct actions of active 1,25-dihydroxy vitamin D3 (VD3) upon primate follicular development at specific stages of folliculogenesis. Secondary preantral follicles were isolated from rhesus monkeys ovaries, encapsulated in alginate, and cultured for 40 days. Follicles were randomly assigned to experimental groups of control, low-dose VD3 (LVD3; 25 pg/mL), and high-dose VD3 (HVD3; 100 pg/mL). National primate research center. Adult, female rhesus macaques (Macaca mulatta). None. Follicle survival and growth, as well as oocyte size, were assessed. Progesterone (P 4 ), androstenedione (A 4 ), E 2 , and antimüllerian hormone (AMH) concentrations in culture media were measured. Compared with the control group, LVD3 increased preantral follicle survival at week 2 by >66%, while HVD3 increased antral follicle diameters at week 5. Follicles with diameters ≥500 μm at week 5 were categorized as fast-growing follicles. Higher percentages of fast-growing follicles were obtained after HVD3 treatment. Although P 4 , A 4 , and E 2 production by antral follicles was not altered by VD3, AMH concentrations were 36% higher in the LVD3 group relative to controls at week 5. Oocytes with larger diameters were retrieved from antral follicles developed in both LVD3 and HVD3 groups compared with controls. The addition of LVD3 increased preantral follicle survival and maintained AMH production by antral follicles, while HVD3 improved antral follicle growth. VD3 supplement promoted oocyte growth in in vitro-developed follicles. Direct actions of VD3 on the primate follicle appear to be both dose and stage dependent. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Lee, J; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul

Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. Themore » gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.« less

Study of the impact of artificial articulations on the dose distribution under medical irradiation

NASA Astrophysics Data System (ADS)

Buffard, E.; Gschwind, R.; Makovicka, L.; Martin, E.; Meunier, C.; David, C.

2005-02-01

Perturbations due to the presence of high density heterogeneities in the body are not correctly taken into account in the Treatment Planning Systems currently available for external radiotherapy. For this reason, the accuracy of the dose distribution calculations has to be improved by using Monte Carlo simulations. In a previous study, we established a theoretical model by using the Monte Carlo code EGSnrc [I. Kawrakow, D.W.O. Rogers, The EGSnrc code system: MC simulation of electron and photon transport. Technical Report PIRS-701, NRCC, Ottawa, Canada, 2000] in order to obtain the dose distributions around simple heterogeneities. These simulations were then validated by experimental results obtained with thermoluminescent dosemeters and an ionisation chamber. The influence of samples composed of hip prostheses materials (titanium alloy and steel) and a substitute of bone were notably studied. A more complex model was then developed with the Monte Carlo code BEAMnrc [D.W.O. Rogers, C.M. MA, G.X. Ding, B. Walters, D. Sheikh-Bagheri, G.G. Zhang, BEAMnrc Users Manual. NRC Report PPIRS 509(a) rev F, 2001] in order to take into account the hip prosthesis geometry. The simulation results were compared to experimental measurements performed in a water phantom, in the case of a standard treatment of a pelvic cancer for one of the beams passing through the implant. These results have shown the great influence of the prostheses on the dose distribution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, R; Tian, L; Ge, H

Purpose: To evaluate the dosimetry of microscopic disease (MD) region of lung cancer in stereotactic body radiation therapy (SBRT). Methods: For simplicity, we assume organ moves along one dimension. The probability distribution function of tumor position was calculated according to the breathing cycle. The dose to the MD region was obtained through accumulating the treatment planning system calculated doses at different positions in a breathing cycle. A phantom experiment was then conducted to validate the calculated results using a motion phantom (The CIRS ‘Dynamic’ Thorax Phantom). The simulated breathing pattern used a cos4(x) curve with an amplitude of 10mm. Amore » 3-D conformal 7-field plan with 6X energy was created and the dose was calculated in the average intensity projection (AIP) simulation CT images. Both films (EBT2) and optically stimulated luminescence (OSL) detectors were inserted in the target of the phantom to measure the dose during radiation delivery (Varian Truebeam) and results were compared to planning dose parameters. Results: The Gamma analysis (3%/3mm) between measured dose using EBT2 film and calculated dose using AIP was 80.5%, indicating substantial dosimetric differences. While the Gamma analysis (3%/3mm) between measured dose using EBT2 and accumulated dose using 4D-CT was 98.9%, indicating the necessity of dose accumulation using 4D-CT. The measured doses using OSL and theoretically calculated doses using probability distribution function at the corresponding position were comparable. Conclusion: Use of static dose calculation in the treatment planning system could substantially underestimate the actually delivered dose in the MD region for a moving target. Funding Supported by NSFC, No.81372436.« less

Optical-CT 3D Dosimetry Using Fresnel Lenses with Minimal Refractive-Index Matching Fluid

PubMed Central

Bache, Steven; Malcolm, Javian; Adamovics, John; Oldham, Mark

2016-01-01

Telecentric optical computed tomography (optical-CT) is a state-of-the-art method for visualizing and quantifying 3-dimensional dose distributions in radiochromic dosimeters. In this work a prototype telecentric system (DFOS—Duke Fresnel Optical-CT Scanner) is evaluated which incorporates two substantial design changes: the use of Fresnel lenses (reducing lens costs from $10-30K t0 $1-3K) and the use of a ‘solid tank’ (which reduces noise, and the volume of refractively matched fluid from 1ltr to 10cc). The efficacy of DFOS was evaluated by direct comparison against commissioned scanners in our lab. Measured dose distributions from all systems were compared against the predicted dose distributions from a commissioned treatment planning system (TPS). Three treatment plans were investigated including a simple four-field box treatment, a multiple small field delivery, and a complex IMRT treatment. Dosimeters were imaged within 2h post irradiation, using consistent scanning techniques (360 projections acquired at 1 degree intervals, reconstruction at 2mm). DFOS efficacy was evaluated through inspection of dose line-profiles, and 2D and 3D dose and gamma maps. DFOS/TPS gamma pass rates with 3%/3mm dose difference/distance-to-agreement criteria ranged from 89.3% to 92.2%, compared to from 95.6% to 99.0% obtained with the commissioned system. The 3D gamma pass rate between the commissioned system and DFOS was 98.2%. The typical noise rates in DFOS reconstructions were up to 3%, compared to under 2% for the commissioned system. In conclusion, while the introduction of a solid tank proved advantageous with regards to cost and convenience, further work is required to improve the image quality and dose reconstruction accuracy of the new DFOS optical-CT system. PMID:27019460

Optical-CT 3D Dosimetry Using Fresnel Lenses with Minimal Refractive-Index Matching Fluid.

PubMed

Bache, Steven; Malcolm, Javian; Adamovics, John; Oldham, Mark

2016-01-01

Telecentric optical computed tomography (optical-CT) is a state-of-the-art method for visualizing and quantifying 3-dimensional dose distributions in radiochromic dosimeters. In this work a prototype telecentric system (DFOS-Duke Fresnel Optical-CT Scanner) is evaluated which incorporates two substantial design changes: the use of Fresnel lenses (reducing lens costs from $10-30K t0 $1-3K) and the use of a 'solid tank' (which reduces noise, and the volume of refractively matched fluid from 1 ltr to 10 cc). The efficacy of DFOS was evaluated by direct comparison against commissioned scanners in our lab. Measured dose distributions from all systems were compared against the predicted dose distributions from a commissioned treatment planning system (TPS). Three treatment plans were investigated including a simple four-field box treatment, a multiple small field delivery, and a complex IMRT treatment. Dosimeters were imaged within 2 h post irradiation, using consistent scanning techniques (360 projections acquired at 1 degree intervals, reconstruction at 2mm). DFOS efficacy was evaluated through inspection of dose line-profiles, and 2D and 3D dose and gamma maps. DFOS/TPS gamma pass rates with 3%/3mm dose difference/distance-to-agreement criteria ranged from 89.3% to 92.2%, compared to from 95.6% to 99.0% obtained with the commissioned system. The 3D gamma pass rate between the commissioned system and DFOS was 98.2%. The typical noise rates in DFOS reconstructions were up to 3%, compared to under 2% for the commissioned system. In conclusion, while the introduction of a solid tank proved advantageous with regards to cost and convenience, further work is required to improve the image quality and dose reconstruction accuracy of the new DFOS optical-CT system.

Effect of ketoconazole on cyclosporine dose in healthy dogs.

PubMed

Dahlinger, J; Gregory, C; Bea, J

1998-01-01

To determine the degree to which the dose of oral cyclosporine (CyA), in healthy dogs, can be decreased by concurrent oral administration of ketoconazole. Dogs in this study were observed for physical or biochemical side effects that might have been caused by the administration of CyA and ketoconazole. Prospective research study. Five healthy, intact female Beagle dogs. CyA was administered orally twice daily to achieve stable whole blood trough levels of 400 to 600 ng/mL. Ketoconazole was added at a low therapeutic dose (average dose: 13.6 mg/kg/d) then at a subtherapeutic dose (average dose: 4.7 mg/kg/d). CyA whole blood trough levels were monitored every 3 to 4 days and maintained at 400 to 600 ng/mL by adjusting CyA doses accordingly. Physical examination, CBC, biochemical profile, and urinalysis were performed at 2-week intervals throughout the study period. The initial mean dose of CyA required to achieve target blood levels was 14.5 mg/ kg/d. With concurrent ketoconazole (low therapeutic dose, average dose: 13.6 mg/kg/d) and CyA administration, the CyA dose declined to 3.4 mg/kg/day (range: 1.2 to 5.2 mg/kg/d), representing a 75% reduction in CyA dose and monetary savings of 57.8%. At a subtherapeutic dose of ketoconazole (average dose: 4.7 mg/kg/d), combination therapy resulted in a CyA dose of 10.1 mg/kg/day (4.9 to 10.6 mg/kg/d), representing a 38% reduction in CyA dose and monetary savings of 23.8%. Weight loss and transient hypoalbuminemia of unknown clinical significance were observed. Other physical and biochemical evaluations were unremarkable over the 12-week study period. The oral administration of ketoconazole can be used to reduce substantially the oral CyA dose needed to maintain selected blood levels in healthy dogs. The oral administration of ketoconazole can result in substantial cost savings to owners of dogs receiving CyA after renal allograft transplantation or for the treatment of autoimmune disease.

Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients With Type 2 Diabetes.

PubMed

Heise, Tim; Jordan, Jens; Wanner, Christoph; Heer, Martina; Macha, Sreeraj; Mattheus, Michaela; Lund, Søren S; Woerle, Hans J; Broedl, Uli C

2016-10-01

Our aim was to investigate the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on urinary and serum glucose and electrolytes, urinary volume, osmolality, and the renin-angiotensin system in patients with type 2 diabetes. In an open-label study, 22 patients receiving metformin (median age 56 years; range 40-65 years) received empagliflozin 25 mg once daily for 5 days. Food, fluid, and sodium intake were standardized for 3 days before and during treatment. Twenty patients completed treatment. After single and multiple doses of empagliflozin, mean (SE) changes from baseline in 24-hour urinary glucose excretion were 463.3 (57.3) mmol/d and 599.5 (60.0) mmol/d, respectively (83.5 [10.3] g/d and 108.0 [10.8] g/d, respectively) (both P < 0.001), and in fasting serum glucose concentration were -1.8 (0.4) mmol/L and -1.1 (0.3) mmol/L, respectively (both P < 0.001). After a single dose, mean (SE) change from baseline in urine sodium excretion was 45.3 (9.6) mmol/d (P < 0.001), and in urine volume was 341.0 (140.5) g/d (P = 0.025), but there were no changes compared with baseline in either parameter after multiple doses. There were no changes in plasma renin or serum aldosterone with single or multiple doses of empagliflozin. There was a nonsignificant reduction in weight after a single dose of empagliflozin and a mean (SE) change of -1.4 (0.5) kg after multiple doses (P = 0.020). Empagliflozin 25 mg increased urinary glucose excretion and decreased serum glucose and weight with transient natriuresis and increases in urine volume, without significant changes in the renin-angiotensin system. Clinicaltrials.gov Identifier: NCT01276288. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Intravitreal memantine retinal toxicity in rabbits.

PubMed

Moreno Páramo, D; Reyna Vielma, S; Rodríguez Reyes, A; Hernández Ayuso, I; Quiroz Mercado, H

2016-02-01

To histologically evaluate whether the intravitreal application of memantine produces retinal toxicity in rabbits. A cross-sectional design, experimental, descriptive study was performed on 16 eyes of 16 New Zealand rabbits of 3 kg, divided in 4 groups of 4 rabbits. A dose of 70 ng/ml of intravitreal memantine was administered in Group A, a dose of 150 ng/ml in Group B, a dose of 400 ng/ml in Group C, and Group D received 1 ml of balanced salt solution. The injected eye of half of each group was enucleated 15 days after the injection, and the rest within 30 days after injection. Following enucleation, each eye was placed in 10% formaldehyde. Histopathological analysis was performed on all enucleated eyes. The animals were treated according to the guidelines of the Association for Research on Vision and Ophthalmology (ARVO). Groups A, B and D did not show any histopathological changes after their enucleation at 15 and 30 days. Group C showed changes in the photoreceptor layer after enucleation at 15 and 30 days. In our study, it was observed that memantine concentrations at 70 ng/ml and 150 ng/ml are safe when administered intravitreally; however, doses of 400 ng/ml produced retinal structural changes. This research should continue to assess its clinical usefulness. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

SU-F-T-500: The Effectiveness of a Patient Specific Bolus Made by Using Three-Dimensional Printing Technique in Photon Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujimoto, K; Yuasa, Y; Shiinoki, T

Purpose: A commercially available bolus (commercial-bolus) would not completely contact with the irregular shape of a patient’s skin. The purposes of this study were to customize a patient specific three-dimensional (3D) bolus using a 3D printer (3D-bolus) and to evaluate its clinical feasibility for photon radiotherapy. Methods: The 3D-bolus was designed using a treatment planning system (TPS) in DICOM-RT format. To print the 3D bolus, the file was converted into stereolithography format. To evaluate its physical characteristics, plans were created for water equivalent phantoms without the bolus, with the 3D-bolus printed in a flat form, and with the virtual bolusmore » which supposed a commercial-bolus. These plans were compared with the percent depth dose (PDD) measured from the TPS. Furthermore, to evaluate its clinical feasibility, the treatment plans were created for RANDO phantoms without the bolus and with the 3D-bolus which was customized for contacting with the surface of the phantom. Both plans were compared with the dose volume histogram (DVH) of the target volume. Results: In the physical evaluation, dmax of the plan without the bolus, with the 3D-bolus, and with the virtual bolus were 2.2 cm, 1.6 cm, and 1.7 cm, respectively. In the evaluation of clinical feasibility, for the plan without the bolus, Dmax, Dmin, Dmean, D90%, and V90% of the target volume were 102.6 %, 1.6 %, 88.8 %, 57.2 %, and 69.3 %, respectively. By using the 3D-bolus, the prescription dose could be delivered to at least 90 % of the target volume, Dmax, Dmin, Dmean, D90%, and V90% of the target volume were 104.3 %, 91.6 %, 92.1 %, 91.7 %, and 98.0 %, respectively. The 3D-bolus has the potential to be useful for providing effective dose coverage in the buildup region. Conclusion: A 3D-bolus produced using 3D printing technique is comparable to a commercially available bolus.« less

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections.

PubMed

Zhang, You; Yin, Fang-Fang; Ren, Lei

2015-08-01

Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the "gold-standard" on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔDmin), maximum dose (ΔDmax), and mean dose (ΔDmean), and the absolute deviations of prescription dose coverage (ΔV100%) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔDmin, ΔDmax, ΔDmean, and ΔV100% (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔDmin, ΔDmax, ΔDmean, and ΔV100% of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

The synergistic effect of ω3 and Vit D3 on glycemia and TNF-α in islet transplantation.

PubMed

Gurol, A O; Okten-Kursun, A; Kasapoglu, P; Suzergoz, F; Kucuksezer, U C; Cevik, A; Tutuncu, Y; Yentur, S P; Gurol, S D; Kucuk, M; Yilmaz, M T

2016-01-27

The current treatment of type 1 diabetes consists of insulin administration. Transplantation of islets of Langerhans is considered very favorable because the full effect of insulin treatment cannot be obtained in severe cases. Although agents such as omega-3 (ω3) and vitamin D3 (Vit D3) are known to contribute to the success of islet allo-transplantation (ITX), in this study we aimed to experimentally determine their effects on glycemia and TNF-α production. Wistar albino rats, which were used as recipients, were given ω3, Vit D3, and islets by gavage, and intraperitoneal- and intraportal injections, respectively. Daclizumab (DAC) was used for immunosuppression. Glycemia levels decreased in rats treated with ω3 and vit D3. TNF-α increased in all groups due to application of STZ. After ITX (day +1), the weakest increase was observed in the ω3 + Vit D3 group. In the ITX+DAC group, compared with that of ITX only, DAC was shown to decrease levels of TNF- α following ITX, only in control group, however, similar levels of TNF-α were observed in other groups. The values in the treated groups were already lower than those of the controls in the ITX group and also remained almost equal in the ITX+DAC group. We suggest that the use of ω3 and Vit D3 together will improve the pro-inflammatory aspect encountered during and after ITXs, and contribute to the reduction of the dose of immunosuppressants in these procedures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, S; Mazur, T; Li, H

Purpose: The aim of this paper was to demonstrate the feasibility and creditability of computing and verifying 3D fluencies to assure IMRT and VMAT treatment deliveries, by correlating the passing rates of the 3D fluence-based QA (P(ά)) to the passing rates of 2D dose measurementbased QA (P(Dm)). Methods: 3D volumetric primary fluencies are calculated by forward-projecting the beam apertures and modulated by beam MU values at all gantry angles. We first introduce simulated machine parameter errors (MU, MLC positions, jaw, gantry and collimator) to the plan. Using passing rates of voxel intensity differences (P(Ir)) and 3D gamma analysis (P(γ)), calculatedmore » 3D fluencies, calculated 3D delivered dose, and measured 2D planar dose in phantom from the original plan are then compared with those from corresponding plans with errors, respectively. The correlations of these three groups of resultant passing rates, i.e. 3D fluence-based QA (P(ά,Ir) and P(ά,γ)), calculated 3D dose (P(Dc,Ir) and P(Dc,γ)), and 2D dose measurement-based QA (P(Dm,Ir) and P(Dm,γ)), will be investigated. Results: 20 treatment plans with 5 different types of errors were tested. Spearman’s correlations were found between P(ά,Ir) and P(Dc,Ir), and also between P(ά,γ) and P(Dc,γ), with averaged p-value 0.037, 0.065, and averaged correlation coefficient ρ-value 0.942, 0.871 respectively. Using Matrixx QA for IMRT plans, Spearman’s correlations were also obtained between P(ά,Ir) and P(Dm,Ir) and also between P(ά,γ) and P(Dm,γ), with p-value being 0.048, 0.071 and ρ-value being 0.897, 0.779 respectively. Conclusion: The demonstrated correlations improve the creditability of using 3D fluence-based QA for assuring treatment deliveries for IMRT/VMAT plans. Together with advantages of high detection sensitivity and better visualization of machine parameter errors, this study further demonstrates the accuracy and feasibility of 3D fluence based-QA in pre-treatment QA and daily QA. Research reported in this study is supported by the Agency for Healthcare Research and Quality (AHRQ) under award 1R01HS0222888. The senior author received research grants from ViewRay Inc. and Varian Medical System.« less

MO-B-BRB-00: Three Dimensional Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Full three-dimensional (3D) dosimetry using volumetric chemical dosimeters probed by 3D imaging systems has long been a promising technique for the radiation therapy clinic, since it provides a unique methodology for dose measurements in the volume irradiated using complex conformal delivery techniques such as IMRT and VMAT. To date true 3D dosimetry is still not widely practiced in the community; it has been confined to centres of specialized expertise especially for quality assurance or commissioning roles where other dosimetry techniques are difficult to implement. The potential for improved clinical applicability has been advanced considerably in the last decade by themore » development of improved 3D dosimeters (e.g., radiochromic plastics, radiochromic gel dosimeters and normoxic polymer gel systems) and by improved readout protocols using optical computed tomography or magnetic resonance imaging. In this session, established users of some current 3D chemical dosimeters will briefly review the current status of 3D dosimetry, describe several dosimeters and their appropriate imaging for dose readout, present workflow procedures required for good dosimetry, and analyze some limitations for applications in select settings. We will review the application of 3D dosimetry to various clinical situations describing how 3D approaches can complement other dose delivery validation approaches already available in the clinic. The applications presented will be selected to inform attendees of the unique features provided by full 3D techniques. Learning Objectives: L. John Schreiner: Background and Motivation Understand recent developments enabling clinically practical 3D dosimetry, Appreciate 3D dosimetry workflow and dosimetry procedures, and Observe select examples from the clinic. Sofie Ceberg: Application to dynamic radiotherapy Observe full dosimetry under dynamic radiotherapy during respiratory motion, and Understand how the measurement of high resolution dose data in an irradiated volume can help understand interplay effects during TomoTherapy or VMAT. Titania Juang: Special techniques in the clinic and research Understand the potential for 3D dosimetry in validating dose accumulation in deformable systems, and Observe the benefits of high resolution measurements for precision therapy in SRS and in MicroSBRT for small animal irradiators Geoffrey S. Ibbott: 3D Dosimetry in end-to-end dosimetry QA Understand the potential for 3D dosimetry for end-to-end radiation therapy process validation in the in-house and external credentialing setting. Canadian Institutes of Health Research; L. Schreiner, Modus QA, London, ON, Canada; T. Juang, NIH R01CA100835.« less

Design and characterization of a new high-dose-rate brachytherapy Valencia applicator for larger skin lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Candela-Juan, C., E-mail: ccanjuan@gmail.com; Niatsetski, Y.; Laarse, R. van der

Purpose: The aims of this study were (i) to design a new high-dose-rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a {sup 192}Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water. Methods: The PENELOPE2008 MC code was used to optimize dwell positions and dwell times.more » Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a {sup 192}Ir mHDR-v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber. Results: The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off-axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%. Conclusions: The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.« less

Skin dose in longitudinal and transverse linac-MRIs using Monte Carlo and realistic 3D MRI field models.

PubMed

Keyvanloo, A; Burke, B; Warkentin, B; Tadic, T; Rathee, S; Kirkby, C; Santos, D M; Fallone, B G

2012-10-01

The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient skin dose. To accurately quantify the magnitude of changes in skin dose, the authors use Monte Carlo calculations that incorporate realistic 3D magnetic field models of longitudinal and transverse linac-MR systems. Finite element method (FEM) is used to generate complete 3D magnetic field maps for 0.56 T longitudinal and transverse linac-MR magnet assemblies, as well as for representative 0.5 and 1.0 T Helmholtz MRI systems. EGSnrc simulations implementing these 3D magnetic fields are performed. The geometry for the BEAMnrc simulations incorporates the Varian 600C 6 MV linac, magnet poles, the yoke, and the magnetic shields of the linac-MRIs. Resulting phase-space files are used to calculate the central axis percent depth-doses in a water phantom and 2D skin dose distributions for 70 μm entrance and exit layers using DOSXYZnrc. For comparison, skin doses are also calculated in the absence of magnetic field, and using a 1D magnetic field with an unrealistically large fringe field. The effects of photon field size, air gap (longitudinal configuration), and angle of obliquity (transverse configuration) are also investigated. Realistic modeling of the 3D magnetic fields shows that fringe fields decay rapidly and have a very small magnitude at the linac head. As a result, longitudinal linac-MR systems mostly confine contaminant electrons that are generated in the air gap and have an insignificant effect on electrons produced further upstream. The increase in the skin dose for the longitudinal configuration compared to the zero B-field case varies from ∼1% to ∼14% for air gaps of 5-31 cm, respectively. (All dose changes are reported as a % of D(max).) The increase is also field-size dependent, ranging from ∼3% at 20 × 20 cm(2) to ∼11% at 5 × 5 cm(2). The small changes in skin dose are in contrast to significant increases that are calculated for the unrealistic 1D magnetic field. For the transverse configuration, the entrance skin dose is equal or smaller than that of the zero B-field case for perpendicular beams. For a 10 × 10 cm(2) oblique beam the transverse magnetic field decreases the entry skin dose for oblique angles less than ±20° and increases it by no more than 10% for larger angles up to ±45°. The exit skin dose is increased by 42% for a 10 × 10 cm(2) perpendicular beam, but appreciably drops and approaches the zero B-field case for large oblique angles of incidence. For longitudinal linac-MR systems only a small increase in the entrance skin dose is predicted, due to the rapid decay of the realistic magnetic fringe fields. For transverse linac-MR systems, changes to the entrance skin dose are small for most scenarios. For the same geometry, on the exit side a fairly large increase is observed for perpendicular beams, but significantly drops for large oblique angles of incidence. The observed effects on skin dose are not expected to limit the application of linac-MR systems in either the longitudinal or transverse configuration.

Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunliffe, Alexandra R.; Armato, Samuel G.; White, Bradley

2015-01-15

Purpose: To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Methods: Eighteen patients who received curative doses (≥60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4–75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps)more » using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm (“Fast” and “EMPIRE10”). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (d{sub E}) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of d{sub E}, dose (D), dose standard deviation (SD{sub dose}) in an eight-pixel neighborhood, and the registration algorithm used. Results: Over 1400 landmark point pairs were identified, with 58–93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9–10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average d{sub E} across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of d{sub E} (0.42 Gy/mm), D (0.05 Gy/Gy), SD{sub dose} (1.4 Gy/Gy), and the algorithm used (≤1 Gy). Conclusions: An average error of <4 Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration, with the majority of points yielding dose-mapping error <2 Gy (approximately 3% of the total prescribed dose). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, resulting in the smallest errors in mapped dose. Dose differences following registration increased significantly with increasing spatial registration errors, dose, and dose gradient (i.e., SD{sub dose}). This model provides a measurement of the uncertainty in the radiation dose when points are mapped between serial CT scans through deformable registration.« less

On-line estimations of delivered radiation doses in three-dimensional conformal radiotherapy treatments of carcinoma uterine cervix patients in linear accelerator.

PubMed

Putha, Suman Kumar; Saxena, P U; Banerjee, S; Srinivas, Challapalli; Vadhiraja, B M; Ravichandran, Ramamoorthy; Joan, Mary; Pai, K Dinesh

2016-01-01

Transmission of radiation fluence through patient's body has a correlation to the planned target dose. A method to estimate the delivered dose to target volumes was standardized using a beam level 0.6 cc ionization chamber (IC) positioned at electronic portal imaging device (EPID) plane from the measured transit signal (S t ) in patients with cancer of uterine cervix treated with three-dimensional conformal radiotherapy (3DCRT). The IC with buildup cap was mounted on linear accelerator EPID frame with fixed source to chamber distance of 146.3 cm, using a locally fabricated mount. S t s were obtained for different water phantom thicknesses and radiation field sizes which were then used to generate a calibration table against calculated midplane doses at isocenter (D iso,TPS ), derived from the treatment planning system. A code was developed using MATLAB software which was used to estimate the in vivo dose at isocenter (D iso,Transit ) from the measured S t s. A locally fabricated pelvic phantom validated the estimations of D iso,Transit before implementing this method on actual patients. On-line dose estimations were made (3 times during treatment for each patient) in 24 patients. The D iso,Transit agreement with D iso,TPS in phantom was within 1.7% and the mean percentage deviation with standard deviation is -1.37% ±2.03% ( n = 72) observed in patients. Estimated in vivo dose at isocenter with this method provides a good agreement with planned ones which can be implemented as part of quality assurance in pelvic sites treated with simple techniques, for example, 3DCRT where there is a need for documentation of planned dose delivery.

SU-E-T-482: In Vivo Dosimetry of An Anthropomorphic Phantom by Using the RADPOS System for Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohno, R; Motegi, K; Hotta, K

Purpose: Delivered doses in an anthropomorphic phantom were evaluated by using the RADPOS system for proton beam therapy. Methods: The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor with MOSFET dosimetry, allowing simultaneous online measurements of dose and spatial position. Through the RADPOS system, dose evaluation points can be determined. In vivo proton dosimetry was evaluated by using the RADPOS system and anthropomorphic head and neck phantom. MOSFET doses measured at 3D positions obtained with the RADPOS were compared to the treatment plan values that were calculated by a simplified Monte Carlo (SMC) method. Although the MOSFET responsemore » depends strongly on the linear energy transfer (LET) of proton beam, the MOSFET responses to proton beams were corrected with the SMC. Here, the SMC calculated only dose deposition determined by the experimental depth–dose distribution and lateral displacement of protons due to both multiple scattering effect in materials and incident angle. As a Result, the SMC could quickly calculate accurate doses in even heterogeneities. Results: In vivo dosimetry by using the RADPOS, as well as the MOSFET doses agreed in comparison with calculations by the SMC in the range of −3.0% to 8.3%. Most measurement errors occurred because of the uncertainties of dose calculations due to the position error of 1 mm. Conclusion: We evaluated the delivered doses in the anthropomorphic phantom by using the RADPOS system for proton beam therapy. The MOSFET doses agreed in comparison with calculations by the SMC within the measurement error. Therefore, we could successfully control the uncertainties of the measurement positions by using the RADPOS system within 1 mm in in vivo proton dosimetry. We aim for the clinical application of in vivo proton dosimetry with this RADPOS system.« less

Dynamic electronic collimation method for 3-D catheter tracking on a scanning-beam digital x-ray system

PubMed Central

Dunkerley, David A. P.; Slagowski, Jordan M.; Funk, Tobias; Speidel, Michael A.

2017-01-01

Abstract. Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy system capable of tomosynthesis-based 3-D catheter tracking. This work proposes a method of dose-reduced 3-D catheter tracking using dynamic electronic collimation (DEC) of the SBDX scanning x-ray tube. This is achieved through the selective deactivation of focal spot positions not needed for the catheter tracking task. The technique was retrospectively evaluated with SBDX detector data recorded during a phantom study. DEC imaging of a catheter tip at isocenter required 340 active focal spots per frame versus 4473 spots in full field-of-view (FOV) mode. The dose-area product (DAP) and peak skin dose (PSD) for DEC versus full FOV scanning were calculated using an SBDX Monte Carlo simulation code. The average DAP was reduced to 7.8% of the full FOV value, consistent with the relative number of active focal spots (7.6%). For image sequences with a moving catheter, PSD was 33.6% to 34.8% of the full FOV value. The root-mean-squared-deviation between DEC-based 3-D tracking coordinates and full FOV 3-D tracking coordinates was less than 0.1 mm. The 3-D distance between the tracked tip and the sheath centerline averaged 0.75 mm. DEC is a feasible method for dose reduction during SBDX 3-D catheter tracking. PMID:28439521

MO-H-19A-03: Patient Specific Bolus with 3D Printing Technology for Electron Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, W; Swann, B; Siderits, R

2014-06-15

Purpose: Bolus is widely used in electron radiotherapy to achieve desired dose distribution. 3D printing technologies provide clinicians with easy access to fabricate patient specific bolus accommodating patient body surface irregularities and tissue inhomogeneity. This study presents the design and the clinical workflow of 3D printed bolus for patient electron therapy in our clinic. Methods: Patient simulation CT images free of bolus were exported from treatment planning system (TPS) to an in-house developed software package. Bolus with known material properties was designed in the software package and then exported back to the TPS as a structure. Dose calculation was carriedmore » out to examine the coverage of the target. After satisfying dose distribution was achieved, the bolus structure was transferred in Standard Tessellation Language (STL) file format for the 3D printer to generate the machine codes for printing. Upon receiving printed bolus, a quick quality assurance was performed with patient resimulated with bolus in place to verify the bolus dosimetric property before treatment started. Results: A patient specific bolus for electron radiotherapy was designed and fabricated in Form 1 3D printer with methacrylate photopolymer resin. Satisfying dose distribution was achieved in patient with bolus setup. Treatment was successfully finished for one patient with the 3D printed bolus. Conclusion: The electron bolus fabrication with 3D printing technology was successfully implemented in clinic practice.« less

Methods, software and datasets to verify DVH calculations against analytical values: Twenty years late(r)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelms, Benjamin; Stambaugh, Cassandra; Hunt, Dylan

2015-08-15

Purpose: The authors designed data, methods, and metrics that can serve as a standard, independent of any software package, to evaluate dose-volume histogram (DVH) calculation accuracy and detect limitations. The authors use simple geometrical objects at different orientations combined with dose grids of varying spatial resolution with linear 1D dose gradients; when combined, ground truth DVH curves can be calculated analytically in closed form to serve as the absolute standards. Methods: DICOM RT structure sets containing a small sphere, cylinder, and cone were created programmatically with axial plane spacing varying from 0.2 to 3 mm. Cylinders and cones were modeledmore » in two different orientations with respect to the IEC 1217 Y axis. The contours were designed to stringently but methodically test voxelation methods required for DVH. Synthetic RT dose files were generated with 1D linear dose gradient and with grid resolution varying from 0.4 to 3 mm. Two commercial DVH algorithms—PINNACLE (Philips Radiation Oncology Systems) and PlanIQ (Sun Nuclear Corp.)—were tested against analytical values using custom, noncommercial analysis software. In Test 1, axial contour spacing was constant at 0.2 mm while dose grid resolution varied. In Tests 2 and 3, the dose grid resolution was matched to varying subsampled axial contours with spacing of 1, 2, and 3 mm, and difference analysis and metrics were employed: (1) histograms of the accuracy of various DVH parameters (total volume, D{sub max}, D{sub min}, and doses to % volume: D99, D95, D5, D1, D0.03 cm{sup 3}) and (2) volume errors extracted along the DVH curves were generated and summarized in tabular and graphical forms. Results: In Test 1, PINNACLE produced 52 deviations (15%) while PlanIQ produced 5 (1.5%). In Test 2, PINNACLE and PlanIQ differed from analytical by >3% in 93 (36%) and 18 (7%) times, respectively. Excluding D{sub min} and D{sub max} as least clinically relevant would result in 32 (15%) vs 5 (2%) scored deviations for PINNACLE vs PlanIQ in Test 1, while Test 2 would yield 53 (25%) vs 17 (8%). In Test 3, statistical analyses of volume errors extracted continuously along the curves show PINNACLE to have more errors and higher variability (relative to PlanIQ), primarily due to PINNACLE’s lack of sufficient 3D grid supersampling. Another major driver for PINNACLE errors is an inconsistency in implementation of the “end-capping”; the additional volume resulting from expanding superior and inferior contours halfway to the next slice is included in the total volume calculation, but dose voxels in this expanded volume are excluded from the DVH. PlanIQ had fewer deviations, and most were associated with a rotated cylinder modeled by rectangular axial contours; for coarser axial spacing, the limited number of cross-sectional rectangles hinders the ability to render the true structure volume. Conclusions: The method is applicable to any DVH-calculating software capable of importing DICOM RT structure set and dose objects (the authors’ examples are available for download). It includes a collection of tests that probe the design of the DVH algorithm, measure its accuracy, and identify failure modes. Merits and applicability of each test are discussed.« less

Constituent components of out-of-field scatter dose for 18-MV intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy: a comparison with 6-MV and implications for carcinogenesis.

PubMed

Ruben, Jeremy D; Smith, Ryan; Lancaster, Craig M; Haynes, Matthew; Jones, Phillip; Panettieri, Vanessa

2014-11-01

To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. In absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite reducing internal/patient scatter. Out-of-field carcinogenic risk is thus increased (but improved in-field dose conformity may offset this). Potentially increased carcinogenic risk should be weighed against any benefit 18-MV IMRT may provide. Copyright © 2014 Elsevier Inc. All rights reserved.

Constituent Components of Out-of-Field Scatter Dose for 18-MV Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy: A Comparison With 6-MV and Implications for Carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruben, Jeremy D., E-mail: jeremy.ruben@wbrc.org.au; Department of Surgery, Monash University, Melbourne; Smith, Ryan

Purpose: To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. Methods and Materials: Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. Results: Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. Inmore » absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. Conclusions: Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite reducing internal/patient scatter. Out-of-field carcinogenic risk is thus increased (but improved in-field dose conformity may offset this). Potentially increased carcinogenic risk should be weighed against any benefit 18-MV IMRT may provide.« less

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, Jeffrey V.; Keall, Paul J.; Wu Qiuwen

2005-10-01

Purpose: The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. Methods and Materials: Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errorsmore » of {sigma} = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with {sigma} = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for {sigma} = {sigma} = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D{sub 98}), clinical target volume (CTV) D{sub 90}, nodes D{sub 90}, cord D{sub 2}, and parotid D{sub 50} and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. Results: Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error {sigma} exceeded 3 mm. Simulated systematic setup errors with {sigma} = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a {sigma} = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with {sigma} = {sigma} = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the {sigma} = {sigma} = 3.0 mm simulations to 5.4% of the plans simulated. Conclusions: Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.« less

Results of daily oral dosing with up to 60,000 international units (iu) of vitamin D3 for 2 to 6 years in 3 adult males.

PubMed

McCullough, Patrick; Amend, Jeffrey

2017-10-01

In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computed 88% TCP dose for SBRT of NSCLC from tumour hypoxia modelling

NASA Astrophysics Data System (ADS)

Ruggieri, Ruggero; Stavreva, Nadejda; Naccarato, Stefania; Stavrev, Pavel

2013-07-01

In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20-22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677-82), actually close to (18-20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149-56). Here, we compare our computed iso-TCP = 88% dose per fraction (d88) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d-1), reoxygenation of chronic hypoxia (ch-), at rate a (d-1) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603-8), we here maintained (a(d-1), C, OERch, OERah/OERch, AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (No) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (αo/βo(Gy), λ(d-1)) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d88(n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d88(±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D88(n) = d88(n)*n, exhibited a relative minimum around n = 8. Computed d88(n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly radioresistant cell subpopulation is properly modelled. The computed minimum D88(n) around n = 8 suggests the adoption of 6 ≤ n ≤ 10 instead of n = 3 in SBRT of small NSCLC tumours.

Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Tucker, Susan L.; Martel, Mary K.

2012-11-15

Introduction: We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials: Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade {>=}3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results:more » Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade {>=}3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Conclusions: Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.« less

Predictors of high-grade esophagitis after definitive three-dimensional conformal therapy, intensity-modulated radiation therapy, or proton beam therapy for non-small cell lung cancer.

PubMed

Gomez, Daniel R; Tucker, Susan L; Martel, Mary K; Mohan, Radhe; Balter, Peter A; Lopez Guerra, Jose Luis; Liu, Hongmei; Komaki, Ritsuko; Cox, James D; Liao, Zhongxing

2012-11-15

We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade≥3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105). Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT. Copyright © 2012 Elsevier Inc. All rights reserved.

Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis

PubMed Central

2012-01-01

Background To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow. PMID:23176540

SU-F-J-126: Influence of Six Dimensional Motions in Frameless Stereotactic Dosimetry Incorporating Rotational Shifts as Equivalent Translational Shifts: A Feasibility Study for Elekta-BrainLAB Stereotactic System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarkar, B; GLA University, Mathura, UP; Manikandan, A

2016-06-15

Purpose: Six dimensional positional shifts (translational and rotational) determined by a volumetric imaging system were mathematically combined and incorporated as simple translational shifts and the resultant impact on dose characteristics was studied. Methods: Thirty patients who underwent either single fraction (12 Gy) or five fractions (5 Gy per fraction) stereotactic treatments were included in this study. They were immobilized using a double layered thermoplastic mask from BrainLAB. Isocenter matching was done using infrared marker of ExacTrac. An initial cone beam CT (CBCT) gave positional shifts in 6-dimensions that were applied through 6-D motion enabled couch. A verification CBCT was donemore » following corrections before treatment. These 6-D positional shifts determined at each imaging session from the first CBCT were mathematically combined to give three simple translational shifts. Doses were recalculated in the patient matrix with these positional errors present by moving the whole image dataset. Doses were also recalculated after second CBCT with only residual errors present. PTV dose statistics were compared. Results: For the approved plans V100%(PTV), V100%(GTV), D95%(PTV), D95%(GTV), D1%(PTV) and D1%(GTV) were 96.2±3.0%, 98.2±1.4%, 102%±1.7%, 103±1.2%, 107.9±8.9% and 109.3±7.5% of prescription dose respectively. With the positional errors present (after 1st CBCT) the corresponding values were 86.7±4.9%, 91.3±2.9%, 89.6±4.2%, 95.9±3.7%, 108.3±9.9% and 108.6±4.5%. Post-correction (after 2nd CBCT) with only residual errors present, values were 94.5±5.7%, 97.3±2.9%, 99.3%±3.2%, 102%±2.1%, 107.6±8.5% and 109.0±7.6% respectively. Significant and nominal OAR dose variation was observed between pre- and post-table corrections. Conclusion: Positional errors significantly affect PTV dose statistics. They need to be corrected before delivery of stereotactic treatments although the magnitude of dose changes can vary from patient-to-patient depending on the tumor location. As expected after the table corrections, residual errors result in insignificant dose deviations. For frameless stereotactic treatments having a six-dimensional motion enabled couch is highly recommended to reduce quantum of dose deviations.« less

Evaluation of six TPS algorithms in computing entrance and exit doses.

PubMed

Tan, Yun I; Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun; Elliott, Alex

2014-05-08

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%-3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison.

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

PubMed

Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

2017-06-06

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

[Effects of fructose on triglycerides in individuals with diabetes: a Meta-analysis of experimental trials].

PubMed

Xiang, Xuesong; Zhao, Jia; Zhu, Jing; Zhang, Peng; Wang, Zhu; Yang, Yuexin

2015-05-01

To assess the effects of fructose on the blood triglycerides, particularly examining treatment dose, duration, and control of food in individuals with diabetes. A systematic review and Meta-analysis of experimental clinical trials were conducted to investigate the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol. MedLine, EMBASE, The Cochrane Library, CMBdisc, CNKI (1970-2014), and some related journals were searched. Heterogeneity was assessed by 2 tests and quantified by I2. Meta-analysis was conducted by RevMan 5.3. 15 reports (21 trials) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides under specific conditions in individuals with type 2 diabetes. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the dose was ≥ 100 g fructose/d (WMD 0.17, 95% CI0.08 - 0.25, P < 0.0001). A triglyceride-raising effect with heterogeneity was seen in type 2 diabetes when the reference carbohydrate was starch (WMD 0.13, 95% CI 0.02 - 0.23 , P = 0.02). Effect of fructose on the level of TG in type 2 diabetes patients is more sensitive than that in type 1 diabetes. The effect on triglycerides is dose dependent and depends on what kinds of carbohydrate is being exchanged with fructose.

Determining the mechanical properties of a radiochromic silicone-based 3D dosimeter

NASA Astrophysics Data System (ADS)

Kaplan, L. P.; Høye, E. M.; Balling, P.; Muren, L. P.; Petersen, J. B. B.; Poulsen, P. R.; Yates, E. S.; Skyt, P. S.

2017-07-01

New treatment modalities in radiotherapy (RT) enable delivery of highly conformal dose distributions in patients. This creates a need for precise dose verification in three dimensions (3D). A radiochromic silicone-based 3D dosimetry system has recently been developed. Such a dosimeter can be used for dose verification in deformed geometries, which requires knowledge of the dosimeter’s mechanical properties. In this study we have characterized the dosimeter’s elastic behaviour under tensile and compressive stress. In addition, the dose response under strain was determined. It was found that the dosimeter behaved as an incompressible hyperelastic material with a non-linear stress/strain curve and with no observable hysteresis or plastic deformation even at high strains. The volume was found to be constant within a 2% margin at deformations up to 60%. Furthermore, it was observed that the dosimeter returned to its original geometry within a 2% margin when irradiated under stress, and that the change in optical density per centimeter was constant regardless of the strain during irradiation. In conclusion, we have shown that this radiochromic silicone-based dosimeter’s mechanical properties make it a viable candidate for dose verification in deformable 3D geometries.

Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy.

PubMed

McCullough, Patrick; Heaney, Robert

2017-10-01

Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to work effectively when intestinal absorption is impaired. The optimal dosing regimen still needs to be determined for the average Crohn's disease patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Q

Purpose: According to clinical and research requirement, we develop a function of automatic reading dose of interest from dose volume histogram(DVH), to replace the traditional method with a mouse one by one point, and it's also verified. Methods: The DVH automatic reading function will be developed in an in-house developed radiotherapy information management system(RTIMS), which is based on Apache+PHP+MySQL. A DVH ASCII file is exported from Varian Eclipse V8.6, which includes the following contents: 1. basic information of patient; 2. dose information of plan; 3. dose information of structures, including basic information and dose volume data of target volume andmore » organ at risk. And the default exported dose volume data also includes relative doses by 1% step and corresponding absolute doses and cumulative relative volumes, and the volumes are 4 decimal fraction. Clinically, we often need read the doses of some integer percent volumes, such as D50 and D30. So it couldn't be directly obtained from the above data, but we can use linear interpolation bye the near volumes and doses: Dx=D2−(V2−Vx)*(D2−D1)/(V2−V1), and program a function to search, read and calculate the corresponding data. And the doses of all preseted volume of interest of all structures can be automatically read one by one patient, and saved as a CSV file. To verify it, we select 24 IMRT plans for prostate cancer, and doses of interest are PTV D98/D95/D5/D2, bladder D30/D50, and rectum D25/D50. Two groups of data, using the automatic reading method(ARM) and pointed dose method(PDM), are analyzed with SPSS 16. The absolute difference=D-ARM-D-PDM, relative difference=absolute difference*100%/prescription dose(7600cGy). Results: The differences are as following: PTV D98/D95/D5/D2: −0.04%/− 0.04%/0.13%/0.19%, bladder D30/D50: −0.02%/0.01%, and rectum D25/D50: 0.03%/0.01%. Conclusion: Using this function, the error is very small, and can be neglected. It could greatly improve the efficiency of clinical work. Project supported by the National Natural Science Foundation of China (Grant No.81101694)« less

Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials.

PubMed

Del Gobbo, Liana C; Falk, Michael C; Feldman, Robin; Lewis, Kara; Mozaffarian, Dariush

2015-12-01

The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established. We examined the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides], lipoproteins [apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100], blood pressure, and inflammation (C-reactive protein) in adults aged ≥18 y without prevalent CVD. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta-regression. Publication bias was evaluated by using funnel plots and Egger's and Begg's tests. Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (-4.7 mg/dL; 95% CI: -5.3, -4.0 mg/dL), LDL cholesterol (-4.8 mg/dL; 95% CI: -5.5, -4.2 mg/dL), ApoB (-3.7 mg/dL; 95% CI: -5.2, -2.3 mg/dL), and triglycerides (-2.2 mg/dL; 95% CI: -3.8, -0.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity < 0.001 each); stronger effects were observed for ≥60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (-11.5 mg/dL; 95% CI: -16.2, -6.8 mg/dL) than in healthy populations (-2.5 mg/dL; 95% CI: -4.7, -0.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found. Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations. © 2015 American Society for Nutrition.

An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder

PubMed Central

Rele, Shilpa; Millet, Robert; Kim, Sungman; Paik, Jong-Woo; Kim, Seonghwan; Masand, Prakash S.

2015-01-01

Introduction: Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD. Method: This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions–Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis. Results: Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI-S (P = .83), CGI-I (P = .51), or HARS scores (P = .61). Dry mouth (n = 55), nausea (n = 10), and diarrhea (n = 5) were the most common side effects, with diarrhea reported in 5 subjects in the 40-mg/d initiation group. No serious adverse events were reported. Conclusions: The present study indicates the potential benefit of switching to vilazodone in patients with MDD who are inadequate responders to SSRIs or SNRIs. There were no meaningful differences in efficacy or tolerability between the 3 different dose-initiation strategies with vilazodone; however, diarrhea appeared to be more frequently reported with the 40-mg/d dose. Given the modest sample size, larger studies are required to confirm our findings. Trial Registration: ClinicalTrials.gov identifiers: NCT02015546 and NCT01473381 PMID:26693034

A Biomechanical Model for Lung Fibrosis in Proton Beam Therapy

NASA Astrophysics Data System (ADS)

King, David J. S.

The physics of protons makes them well-suited to conformal radiotherapy due to the well-known Bragg peak effect. From a proton's inherent stopping power, uncertainty effects can cause a small amount of dose to overflow to an organ at risk (OAR). Previous models for calculating normal tissue complication probabilities (NTCPs) relied on the equivalent uniform dose model (EUD), in which the organ was split into 1/3, 2/3 or whole organ irradiation. However, the problem of dealing with volumes <1/3 of the total volume renders this EUD based approach no longer applicable. In this work the case for an experimental data-based replacement at low volumes is investigated. Lung fibrosis is investigated as an NTCP effect typically arising from dose overflow from tumour irradiation at the spinal base. Considering a 3D geometrical model of the lungs, irradiations are modelled with variable parameters of dose overflow. To calculate NTCPs without the EUD model, experimental data is used from the quantitative analysis of normal tissue effects in the clinic (QUANTEC) data. Additional side projects are also investigated, introduced and explained at various points. A typical radiotherapy course for the patient of 30x2Gy per fraction is simulated. A range of geometry of the target volume and irradiation types is investigated. Investigations with X-rays found the majority of the data point ratios (ratio of EUD values found from calculation based and data based methods) at 20% within unity showing a relatively close agreement. The ratios have not systematically preferred one particular type of predictive method. No Vx metric was found to consistently outperform another. In certain cases there is a good agreement and not in other cases which can be found predicted in the literature. The overall results leads to conclusion that there is no reason to discount the use of the data based predictive method particularly, as a low volume replacement predictive method.

Systematic analysis of the scatter environment in clinical intra-operative high dose rate (IOHDR) brachytherapy

NASA Astrophysics Data System (ADS)

Oh, Moonseong

Most brachytherapy planning systems are based on a dose calculation algorithm that assumes an infinite scatter environment surrounding the target volume and applicator. In intra-operative high dose rate brachytherapy (IOHDR) where treatment catheters are typically laid either directly on a tumor bed or within applicators that may have little or no scatter material above them, the lack of scatter from one side of the applicator can result in serious underdosage during treatment. Therefore, full analyses of the physical processes such as the photoelectric effect, Rayleigh, and Compton scattering that contribute to dosimetric errors have to be investigated and documented to result in more accurate treatment delivery to patients undergoing IOHDR procedures. Monte Carlo simulation results showed the Compton scattering effect is about 40 times more probable than photoelectric effect for the treated areas of single source, 4 x 4, and 2 x 4 cm2. Also, the dose variations with and without photoelectric effect were 0.3 ˜ 0.7%, which are within the uncertainty in Monte Carlo simulations. Also, Monte Carlo simulation studies were done to verify the following experimental results for quantification of dosimetric errors in clinical IOHDR brachytherapy. The first experimental study was performed to quantify the inaccuracy in clinical dose delivery due to the incomplete scatter conditions inherent in IOHDR brachytherapy. Treatment plans were developed for 3 different treatment surface areas (4 x 4, 7 x 7, 12 x 12 cm2), each with prescription points located at 3 distances (0.5 cm, 1.0 cm, and 1.5 cm) from the source dwell positions. Measurements showed that the magnitude of the underdosage varies from about 8% to 13% of the prescription dose as the prescription depth is increased from 0.5 cm to 1.5 cm. This treatment error was found to be independent of the irradiated area and strongly dependent on the prescription distance. The study was extended to confirm the underdosage for various shape of treated area (especially, irregular shape), which can be applied in clinical cases. Treatment plans of 10 patients previously treated at Roswell Park Cancer Institute in Buffalo, which had irregular shapes of treated areas, were used. In IOHDR brachytherapy, a 2-dimensional (2-D) planar geometry is typically used without considering the curved shape of target surfaces. In clinical cases, this assumption of the planar geometry may cause the serious dose delivery errors to target volumes. The second study was performed to investigate the dose errors to curved surfaces. Seven rectangular shaped plans (five for 1.0 cm and two for 0.5 cm prescription depth) and archived irregular shaped plans of 2 patients were analyzed. Cylindrical phantoms with six radii (ranged 1.35 to 12.5 cm) were used to simulate the treatment planning geometries, which were calculated in 2-D plans. Actual doses delivered to prescription points were over-estimated up to 15% on the concave side of curved applicators for all cylindrical phantoms with 1.0 cm prescription depth. Also, delivered doses decreased by up to 10% on the convex side of curved applicators for small treated areas (≤ 5catheters), but interestingly, any dose dependence was not shown with large treated areas. Our measurements have shown inaccuracy in dose delivery when the original planar treatment plan was delivered in a curved applicator setting. Dose errors arising due to the tumor curvature may be significant in a clinical set up and merit attention during planning.

A Phase 2 Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2014-10-01

number/communicate to site coordinator N/A Task V.5 (mo 6-47): implement methods to educate/monitor participants on aspects of vit D3 and calcium...potential side effects of vit D3 supplementation CRFs for adverse event reporting have been developed and included in the protocols submitted for IRB...Task VI.3 (mo 6-47): document acceptance of storage sample in the CGRP database and vit D3 study database The process for storage of sample in the

A graphite calorimeter for absolute measurements of absorbed dose to water: application in medium-energy x-ray filtered beams.

PubMed

Pinto, M; Pimpinella, M; Quini, M; D'Arienzo, M; Astefanoaei, I; Loreti, S; Guerra, A S

2016-02-21

The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) has designed and built a graphite calorimeter that, in a water phantom, has allowed the determination of the absorbed dose to water in medium-energy x-rays with generating voltages from 180 to 250 kV. The new standard is a miniaturized three-bodies calorimeter, with a disc-shaped core of 21 mm diameter and 2 mm thickness weighing 1.134 g, sealed in a PMMA waterproof envelope with air-evacuated gaps. The measured absorbed dose to graphite is converted into absorbed dose to water by means of an energy-dependent conversion factor obtained from Monte Carlo simulations. Heat-transfer correction factors were determined by FEM calculations. At a source-to-detector distance of 100 cm, a depth in water of 2 g cm(-2), and at a dose rate of about 0.15 Gy min(-1), results of calorimetric measurements of absorbed dose to water, D(w), were compared to experimental determinations, D wK, obtained via an ionization chamber calibrated in terms of air kerma, according to established dosimetry protocols. The combined standard uncertainty of D(w) and D(wK) were estimated as 1.9% and 1.7%, respectively. The two absorbed dose to water determinations were in agreement within 1%, well below the stated measurement uncertainties. Advancements are in progress to extend the measurement capability of the new in-water-phantom graphite calorimeter to other filtered medium-energy x-ray qualities and to reduce the D(w) uncertainty to around 1%. The new calorimeter represents the first implementation of in-water-phantom graphite calorimetry in the kilovoltage range and, allowing independent determinations of D(w), it will contribute to establish a robust system of absorbed dose to water primary standards for medium-energy x-ray beams.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.