Normal tissue complication probability modelling of tissue fibrosis following breast radiotherapy

NASA Astrophysics Data System (ADS)

Alexander, M. A. R.; Brooks, W. A.; Blake, S. W.

2007-04-01

Cosmetic late effects of radiotherapy such as tissue fibrosis are increasingly regarded as being of importance. It is generally considered that the complication probability of a radiotherapy plan is dependent on the dose uniformity, and can be reduced by using better compensation to remove dose hotspots. This work aimed to model the effects of improved dose homogeneity on complication probability. The Lyman and relative seriality NTCP models were fitted to clinical fibrosis data for the breast collated from the literature. Breast outlines were obtained from a commercially available Rando phantom using the Osiris system. Multislice breast treatment plans were produced using a variety of compensation methods. Dose-volume histograms (DVHs) obtained for each treatment plan were reduced to simple numerical parameters using the equivalent uniform dose and effective volume DVH reduction methods. These parameters were input into the models to obtain complication probability predictions. The fitted model parameters were consistent with a parallel tissue architecture. Conventional clinical plans generally showed reducing complication probabilities with increasing compensation sophistication. Extremely homogenous plans representing idealized IMRT treatments showed increased complication probabilities compared to conventional planning methods, as a result of increased dose to areas receiving sub-prescription doses using conventional techniques.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

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

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.« less

Biological and dosimetric characterisation of spatially fractionated proton minibeams

NASA Astrophysics Data System (ADS)

Meyer, Juergen; Stewart, Robert D.; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-12-01

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

PubMed

Meyer, Juergen; Stewart, Robert D; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-11-21

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Dose uniformity of budesonide Easyhaler® under simulated real-life conditions and with low inspiration flow rates.

PubMed

Haikarainen, Jussi; Rytilä, Paula; Roos, Sirkku; Metsärinne, Sirpa; Happonen, Anita

2017-01-01

Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing. The influence of various IFRs (31, 43, and 54 L/min) on the DD was also investigated. Acceptable dose uniformity was declared when mean DD were within 80-120% of expected dose; all data reported descriptively. DD was constant (range: 93-109% of expected dose) at all in-use periods and after exposure to high temperature and humidity for a duration of up to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of expected dose). Similarly, DD was constant and within 10% of expected dose across all IFRs. Results indicate that budesonide Easyhaler® delivers consistently accurate doses in various real-life conditions. Budesonide Easyhaler® can be expected to consistently deliver a uniform dose and improve asthma control regardless of high temperature and humidity or varying IFR.

A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

NASA Astrophysics Data System (ADS)

Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

2004-08-01

Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

Adapting radiotherapy to hypoxic tumours

NASA Astrophysics Data System (ADS)

Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

2006-10-01

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO2-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.

Development of a facility for high-precision irradiation of cells with carbon ions.

PubMed

van Goethem, Marc-Jan; Niemantsverdriet, Maarten; Brandenburg, Sytze; Langendijk, Johannes A; Coppes, Robert P; van Luijk, Peter

2011-01-01

Compared to photons, using particle radiation in radiotherapy reduces the dose and irradiated volume of normal tissues, potentially reducing side effects. The biological effect of dose deposited by particles such as carbon ions, however, differs from that of dose deposited by photons. The inaccuracy in models to estimate the biological effects of particle radiation remains the most important source of uncertainties in particle therapy. Improving this requires high-precision studies on biological effects of particle radiation. Therefore, the authors aimed to develop a facility for reproducible and high-precision carbon-ion irradiation of cells in culture. The combined dose nonuniformity in the lateral and longitudinal direction should not exceed +/-1.5%. Dose to the cells from particles than other carbon ions should not exceed 5%. A uniform lateral dose distribution was realized using a single scatter foil and quadrupole magnets. A modulator wheel was used to create a uniform longitudinal dose distribution. The choice of beam energy and the optimal design of these components was determined using GEANT4 and SRIM Monte Carlo simulations. Verification of the uniformity of the dose distribution was performed using a scintillating screen (lateral) and a water phantom (longitudinal). The reproducibility of dose delivery between experiments was assessed by repeated measurements of the spatial dose distribution. Moreover, the reproducibility of dose-response measurements was tested by measuring the survival of irradiated HEK293 cells in three independent experiments. The relative contribution of dose from nuclear reaction fragments to the sample was found to be <5% when using 90 MeV/u carbon ions. This energy still allows accurate dosimetry conforming to the IAEA Report TRS-398, facilitating comparison to dose-effect data obtained with other radiation qualities. A 1.3 mm long spread-out Bragg peak with a diameter of 30 mm was created, allowing the irradiation of cell samples with the specified accuracy. Measurements of the transverse and longitudinal dose distribution showed that the dose variation over the sample volume was +/-0.8% and +/-0.7% in the lateral and longitudinal directions, respectively. The track-averaged LET of 132 +/- 10 keV/microm and dose-averaged LET of 189 +/- 15 keV/microm at the position of the sample were obtained from a GEANT4 simulation, which was validated experimentally. Three separately measured cell-survival curves yielded nearly identical results. With the new facility, high-precision carbon-ion irradiations of biological samples can be performed with highly reproducible results.

The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

NASA Astrophysics Data System (ADS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

2008-11-01

Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the convolution process. The assumption of an effective FSU size is consistent with most of the effects seen when different portions of the rat spinal cord are irradiated to different doses. The effective FSU length from these experiments is about 8.5 ± 0.5 mm. This length could be interpreted as an effective size of the functional subunits in a rat spinal cord, where multiple myelin sheaths are connected by a single oligodendrocyte and repair is limited by the range of oligodendrocyte progenitor cell diffusion. It was even possible to suggest a more likely than uniform effective FSU sensitivity distribution from the experimental data.

Impact energy and retained dose uniformity in enhanced glow discharge plasma immersion ion implantation

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

Lu, Q. Y.; Fu, Ricky K. Y.; Chu, Paul K.

2009-08-10

The implantation energy and retained dose uniformity in enhanced glow discharge plasma immersion ion implantation (EGD-PIII) is investigated numerically and experimentally. Depth profiles obtained from different samples processed by EGD-PIII and traditional PIII are compared. The retained doses under different pulse widths are calculated by integrating the area under the depth profiles. Our results indicate that the improvement in the impact energy and retained dose uniformity by this technique is remarkable.

Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity.

PubMed

Hausman, Debra S; Cambron, R Thomas; Sakr, Adel

2005-07-14

On-line Raman spectroscopy was used to evaluate the effect of blending time on low dose, 1%, blend uniformity of azimilide dihydrochloride. An 8 qt blender was used for the experiments and instrumented with a Raman probe through the I-bar port. The blender was slowed to 6.75 rpm to better illustrate the blending process (normal speed is 25 rpm). Uniformity was reached after 20 min of blending at 6.75 rpm (135 revolutions or 5.4 min at 25 rpm). On-line Raman analysis of blend uniformity provided more benefits than traditional thief sampling and off-line analysis. On-line Raman spectroscopy enabled generating data rich blend profiles, due to the ability to collect a large number of samples during the blending process (sampling every 20s). In addition, the Raman blend profile was rapidly generated, compared to the lengthy time to complete a blend profile with thief sampling and off-line analysis. The on-line Raman blend uniformity results were also significantly correlated (p-value < 0.05) to the HPLC uniformity results of thief samples.

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

Qiu, J; Zheng, X; Liu, H

Purpose: This study is to evaluate the feasibility of simultaneously integrated boost (SIB) to hypoxic subvolume (HTV) in nasopharyngeal carcinomas under the guidance of 18F-Fluoromisonidazole (FMISO) PET/CT using a novel non-uniform volumetric modulated arc therapy (VMAT)technique. Methods: Eight nasopharyngeal carcinoma patients treated with conventional uniform VMAT were retrospectively analyzed. For each treatment, actual conventional uniform VMAT plan with two or more arcs (2–2.5 arcs, totally rotating angle < 1000o) was designed with dose boost to hopxic subvolume (total dose, 84Gy) in the gross tumor volme (GTV) under the guidance of 18F- FMISO PET/CT. Based on the same dataset, experimental singlemore » arc non-uniform VAMT plans were generated with the same dose prescription using customized software tools. Dosimetric parameters, quality assurance and the efficiency of the treatment delivery were compared between the uniform and non-uniform VMAT plans. Results: To develop the non-uniform VMAT technique, a specific optimization model was successfully established. Both techniques generate high-quality plans with pass rate (>98%) with the 3mm, 3% criterion. HTV received dose of 84.1±0.75Gy and 84.1±1.2Gy from uniform and non-uniform VMAT plans, respectively. In terms of target coverage and dose homogeneity, there was no significant statistical difference between actual and experimental plans for each case. However, for critical organs at risk (OAR), including the parotids, oral cavity and larynx, dosimetric difference was significant with better dose sparing form experimental plans. Regarding plan implementation efficiency, the average machine time was 3.5 minutes for the actual VMAT plans and 3.7 minutes for the experimental nonuniform VMAT plans (p>0.050). Conclusion: Compared to conventional VMAT technique, the proposed non-uniform VMAT technique has the potential to produce efficient and safe treatment plans, especially in cases with complicated anatomical structures and demanding dose boost to subvolumes.« less

A comparison of intensity modulated x-ray therapy to intensity modulated proton therapy for the delivery of non-uniform dose distributions

NASA Astrophysics Data System (ADS)

Flynn, Ryan

2007-12-01

The distribution of biological characteristics such as clonogen density, proliferation, and hypoxia throughout tumors is generally non-uniform, therefore it follows that the optimal dose prescriptions should also be non-uniform and tumor-specific. Advances in intensity modulated x-ray therapy (IMXT) technology have made the delivery of custom-made non-uniform dose distributions possible in practice. Intensity modulated proton therapy (IMPT) has the potential to deliver non-uniform dose distributions as well, while significantly reducing normal tissue and organ at risk dose relative to IMXT. In this work, a specialized treatment planning system was developed for the purpose of optimizing and comparing biologically based IMXT and IMPT plans. The IMXT systems of step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) and the IMPT systems of intensity modulated spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT), were simulated. A thorough phantom study was conducted in which several subvolumes, which were contained within a base tumor region, were boosted or avoided with IMXT and IMPT. Different boosting situations were simulated by varying the size, proximity, and the doses prescribed to the subvolumes, and the size of the phantom. IMXT and IMPT were also compared for a whole brain radiation therapy (WBRT) case, in which a brain metastasis was simultaneously boosted and the hippocampus was avoided. Finally, IMXT and IMPT dose distributions were compared for the case of non-uniform dose prescription in a head and neck cancer patient that was based on PET imaging with the Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) hypoxia marker. The non-uniform dose distributions within the tumor region were comparable for IMXT and IMPT. IMPT, however, was capable of delivering the same non-uniform dose distributions within a tumor using a 180° arc as for a full 360° rotation, which resulted in the reduction of normal tissue integral dose by a factor of up to three relative to IMXT, and the complete sparing of organs at risk distal to the tumor region.

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

PubMed

Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

2010-09-01

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

Alterations in cell migration and cell viability of wounded human skin fibroblasts following visible red light exposure

NASA Astrophysics Data System (ADS)

Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

2014-02-01

The present study intended to examine the effect of visible red light on structural and cellular parameters on wounded skin fibroblast cells. To achieve the stated objective, uniform scratch was created on confluent monolayered human skin fibroblast cells, and were exposed to single dose of He-Ne laser (15 mm spot, 6.6808 mWcm-2) at 1, 2, 3, 4, 5, 6 and 7 Jcm-2 in the presence and absence of 10% fetal bovine serum (FBS). Beam profile measurements of the expanded laser beam were conducted to ensure the beam uniformity. The influence of laser dose on the change in temperature was recorded using sensitive temperature probe. Additionally, following laser exposure cell migration and cell survival were documented at different time intervals on wounded human skin fibroblast cells grown in vitro. Beam profile measurements indicated more or less uniform power distribution over the whole beam area. Temperature monitoring of sham irradiated control and laser treatment groups displayed negligible temperature change indicating the absence of thermal effect at the tested laser doses. In the absence of 10% FBS, single exposure of different laser doses failed to produce any significant effects on cell migration or cell survival. However, in the presence of serum single exposure of 5 J/cm2 on wounded skin fibroblasts significantly enhanced the cell migration (P<0.05) compared to the other tested doses (1, 2, 3, 4, 6 and 7 J/cm2) and sham irradiated controls. In conclusion, the LLLT acts by improving cell migration and cell proliferation to produce measurable changes in wounded fibroblast cells.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

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

Han, Eun Young, E-mail: eyhan@uams.edu; Kim, Dong-Wook; Zhang, Xin

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently,more » the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.« less

Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

PubMed

Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

2010-06-01

Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a significant contributor to the secondary neutron dose equivalent to a distant organ at risk. Improving conformity of the radiation field to the patient-specific collimator can significantly reduce secondary neutron dose equivalent to the patient. Therefore, it is important to increase the number of available generic field sizes in double scattering systems as well as in uniform scanning nozzles.

WE-EF-BRA-06: Feasibility of Spatially Modulated Proton Beams for Small Animal Research

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

Lee, E; Meyer, J

Purpose: To investigate the feasibility of proton minibeam radiotherapy (pMBRT) for small animal research. The motivation is to explore with protons the extraordinary normal tissue sparing effects to spatially modulated beams as observed on high flux synchrotron beam lines. We hypothesized that we can design a multi-slit collimator for our proton beam line to produce planar-parallel dose profiles with high modulation in the entrance region and homogenous dose coverage in the overlap of the Bragg peaks. Methods: The high dose rate 50 MeV research proton beamline at the University of Washington was modeled using the TOol for PArticle Simulation (TOPAS)more » Monte Carlo package. A brass collimator was implemented to generate proton minibeams. The collimator consists of an array of 2 cm long slits to cover an area of 2×2 cm{sup 2}. The slit widths (0.1–1 mm), center-to-center (ctc) distances (1–3 mm) and collimator thickness (1–7 cm) were varied to evaluate the effect on dose rate, the peak-to-valley dose ratios (PVDR) and the change of penumbra and peak width (FWHM) with depth. Results: The Bragg peak was at a depth of ∼21 mm. The penumbra and FWHM remained relatively constant to a depth of about 10–15 mm. The PVDR ranged from 1.6 to 26 and the dose rate dropped exponentially with collimator thickness. A uniform dose can be achieved at depth with slightly compromised PVDRs and dose rate. Conclusion: The technical realization of pMBRT is feasible. The simulations have shown that it is possible to obtain uniform dose at depth while modulation is maintained on the entrance side. While the simulated beam widths are larger than on synchrotron generated microbeams the dosimetric advantage could avoid having to interlace two microbeams to achieve uniform dose in the target. The next steps are to build a collimator and verify the simulations experimentally.« less

The effects of small field dosimetry on the biological models used in evaluating IMRT dose distributions

NASA Astrophysics Data System (ADS)

Cardarelli, Gene A.

The primary goal in radiation oncology is to deliver lethal radiation doses to tumors, while minimizing dose to normal tissue. IMRT has the capability to increase the dose to the targets and decrease the dose to normal tissue, increasing local control, decrease toxicity and allow for effective dose escalation. This advanced technology does present complex dose distributions that are not easily verified. Furthermore, the dose inhomogeneity caused by non-uniform dose distributions seen in IMRT treatments has caused the development of biological models attempting to characterize the dose-volume effect in the response of organized tissues to radiation. Dosimetry of small fields can be quite challenging when measuring dose distributions for high-energy X-ray beams used in IMRT. The proper modeling of these small field distributions is essential in reproducing accurate dose for IMRT. This evaluation was conducted to quantify the effects of small field dosimetry on IMRT plan dose distributions and the effects on four biological model parameters. The four biological models evaluated were: (1) the generalized Equivalent Uniform Dose (gEUD), (2) the Tumor Control Probability (TCP), (3) the Normal Tissue Complication Probability (NTCP) and (4) the Probability of uncomplicated Tumor Control (P+). These models are used to estimate local control, survival, complications and uncomplicated tumor control. This investigation compares three distinct small field dose algorithms. Dose algorithms were created using film, small ion chamber, and a combination of ion chamber measurements and small field fitting parameters. Due to the nature of uncertainties in small field dosimetry and the dependence of biological models on dose volume information, this examination quantifies the effects of small field dosimetry techniques on radiobiological models and recommends pathways to reduce the errors in using these models to evaluate IMRT dose distributions. This study demonstrates the importance of valid physical dose modeling prior to the use of biological modeling. The success of using biological function data, such as hypoxia, in clinical IMRT planning will greatly benefit from the results of this study.

Dose uniformity of scored and unscored tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony; Khan, Mansoor; Gupta, Abhay; Faustino, Patrick

2016-06-20

This FDA laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5-2.1 standard deviation (SD) of the % label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3-9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting "can affect how much drug is present in the split tablet and available for absorption" as stated in the guidance (1). Copyright © 2016, Parenteral Drug Association.

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

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

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

Measurements of neutron dose equivalent for a proton therapy center using uniform scanning proton beams

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

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

Purpose: Neutron exposure is of concern in proton therapy, and varies with beam delivery technique, nozzle design, and treatment conditions. Uniform scanning is an emerging treatment technique in proton therapy, but neutron exposure for this technique has not been fully studied. The purpose of this study is to investigate the neutron dose equivalent per therapeutic dose, H/D, under various treatment conditions for uniform scanning beams employed at our proton therapy center. Methods: Using a wide energy neutron dose equivalent detector (SWENDI-II, ThermoScientific, MA), the authors measured H/D at 50 cm lateral to the isocenter as a function of proton range,more » modulation width, beam scanning area, collimated field size, and snout position. They also studied the influence of other factors on neutron dose equivalent, such as aperture material, the presence of a compensator, and measurement locations. They measured H/D for various treatment sites using patient-specific treatment parameters. Finally, they compared H/D values for various beam delivery techniques at various facilities under similar conditions. Results: H/D increased rapidly with proton range and modulation width, varying from about 0.2 mSv/Gy for a 5 cm range and 2 cm modulation width beam to 2.7 mSv/Gy for a 30 cm range and 30 cm modulation width beam when 18 Multiplication-Sign 18 cm{sup 2} uniform scanning beams were used. H/D increased linearly with the beam scanning area, and decreased slowly with aperture size and snout retraction. The presence of a compensator reduced the H/D slightly compared with that without a compensator present. Aperture material and compensator material also have an influence on neutron dose equivalent, but the influence is relatively small. H/D varied from about 0.5 mSv/Gy for a brain tumor treatment to about 3.5 mSv/Gy for a pelvic case. Conclusions: This study presents H/D as a function of various treatment parameters for uniform scanning proton beams. For similar treatment conditions, the H/D value per uncollimated beam size for uniform scanning beams was slightly lower than that from a passive scattering beam and higher than that from a pencil beam scanning beam, within a factor of 2. Minimizing beam scanning area could effectively reduce neutron dose equivalent for uniform scanning beams, down to the level close to pencil beam scanning.« less

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

Optimization of equivalent uniform dose using the L-curve criterion.

PubMed

Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R

2007-10-07

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

PubMed

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

2015-10-01

Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA.

PubMed

Han, Eun Young; Kim, Dong-Wook; Zhang, Xin; Penagaricano, Jose; Liang, Xiaoying; Hardee, Matthew; Morrill, Steve; Ratanatharathorn, Vaneerat

2015-01-01

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently, the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Background radiation: natural and man-made.

PubMed

Thorne, M C

2003-03-01

A brief overview and comparison is given of dose rates arising from natural background radiation and the fallout from atmospheric testing of nuclear weapons. Although there are considerable spatial variations in exposure to natural background radiation, it is useful to give estimates of worldwide average overall exposures from the various components of that background. Cosmic-ray secondaries of low linear energy transfer (LET), mainly muons and photons, deliver about 280 microSv a(-1). Cosmic-ray neutrons deliver about another 100 microSv a(-1). These low- and high-LET exposures are relatively uniform to the whole body. The effective dose rate from cosmogenic radionuclides is dominated by the contribution of 12 microSv a(-1) from 14C. This is due to relatively uniform irradiation of all organs and tissues from low-energy beta particles. Primordial radionuclides and their progeny (principally the 238U and 232Th series, and 40K) contribute about 480 microSv a(-1) of effective dose by external irradiation. This is relatively uniform photon irradiation of the whole body. Internally incorporated 40K contributes a further 165 microSv a(-1) of effective dose in adults, mainly from beta particles, but with a significant gamma component. Equivalent doses from 40K are somewhat higher in muscle than other soft tissues, but the distinction is less than a factor of three. Uranium and thorium series radionuclides give rise to an average effective dose rate of around 120 microSv a(-1). This includes a major alpha particle component, and exposures of radiosensitive tissues in lung, liver, kidney and the skeleton are recognised as important contributors to effective dose. Overall, these various sources give a worldwide average effective dose rate of about 1160 microSv a(-1). Exposure to 222Rn, 220Rn and their short-lived progeny has to be considered separately. This is very variable both within and between countries. For 222Rn and its progeny, a worldwide average effective dose rate is about 1105 microSv a(-1). For 220Rn and its progeny, the corresponding value is 91 microSv a(-1). In both cases, the effective dose is mainly due to a particle irradiation of the bronchial tissues of the lungs. Overall, the worldwide average effective dose rate from natural background is about 2400 microSv a(-1) or 2.4 mSv a(-1). For comparison, worldwide average effective dose rates from weapons fallout peaked at 113 microSv a(-1) (about 5% of natural background) in 1963 and have since fallen to about 5.5 microSv a(-1) (about 0.2% of natural background). These values perhaps serve to emphasise that even gross insults to the natural environment from anthropogenic releases of radioactive materials are likely to be of limited significance when set in the context of the ambient radioactive environment within which all organisms, including humans, have developed.

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

PubMed

Flynn, Aiden A; Pedley, R Barbara; Green, Alan J; Dearling, Jason L; El-Emir, Ethaar; Boxer, Geoffrey M; Boden, Robert; Begent, Richard H J

2003-02-01

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

NASA Astrophysics Data System (ADS)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.

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

Brady, S; Shulkin, B

Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed withmore » the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co-localization of hybrid CT anatomy and PET radioisotope uptake.« less

Dosimetry for radiobiological studies of the human hematopoietic system

NASA Technical Reports Server (NTRS)

Beck, W. L.; Stokes, T. R.; Lushbaugh, C. C.

1972-01-01

A system for estimating individual bone marrow doses in therapeutic radiation exposures of leukemia patients was studied. These measurements are used to make dose response correlations and to study the effect of dose protraction on peripheral blood cell levels. Three irradiators designed to produce a uniform field of high energy gamma radiation for total body exposures of large animals and man are also used for radiobiological studies.

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

PubMed Central

Vranić, Edina; Uzunović, Alija

2007-01-01

Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

PubMed

Al-Jundi, J; Ulanovsky, A; Pröhl, G

2009-10-01

The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

High sensitivity charge amplifier for ion beam uniformity monitor

DOEpatents

Johnson, Gary W.

2001-01-01

An ion beam uniformity monitor for very low beam currents using a high-sensitivity charge amplifier with bias compensation. The ion beam monitor is used to assess the uniformity of a raster-scanned ion beam, such as used in an ion implanter, and utilizes four Faraday cups placed in the geometric corners of the target area. Current from each cup is integrated with respect to time, thus measuring accumulated dose, or charge, in Coulombs. By comparing the dose at each corner, a qualitative assessment of ion beam uniformity is made possible. With knowledge of the relative area of the Faraday cups, the ion flux and areal dose can also be obtained.

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans.

PubMed

Bai, Chuanyong; Conwell, Richard; Kindem, Joel; Babla, Hetal; Gurley, Mike; De Los Santos, Romer; Old, Rex; Weatherhead, Randy; Arram, Samia; Maddahi, Jamshid

2010-06-01

We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 muSv). We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. The reconstructed attenuation coefficient of water at 140 keV was .150 +/- .003/cm in the uniform region of the ACR phantom, .151 +/- .003/cm and .151 +/- .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 +/- 6.5 before and 87.9 +/- 3.3 after AC (average +/- standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC.

Dose Distribution in Cone-Beam Breast Computed Tomography: An Experimental Phantom Study

NASA Astrophysics Data System (ADS)

Russo, Paolo; Lauria, Adele; Mettivier, Giovanni; Montesi, Maria Cristina; Villani, Natalia

2010-02-01

We measured the spatial distribution of absorbed dose in a 14 cm diameter PMMA half-ellipsoid phantom simulating the uncompressed breast, using an X-ray cone-beam breast computed tomography apparatus, assembled for laboratory tests. Thermoluminescent dosimeters (TLD-100) were placed inside the phantom in six positions, both axially and at the phantom periphery. To study the dose distribution inside the PMMA phantom two experimental setups were adopted with effective energies in the range 28.7-44.4 keV. Different values of effective energies were obtained by combining different configurations of added Cu filtration (0.05 mm or 0.2 mm) and tube voltages (from 50 kVp to 80 kVp). Dose values obtained by TLDs in different positions inside the PMMA are reported. To evaluate the dose distribution in the breast shaped volume, the values measured were normalized to the one obtained in the inner position inside the phantom. Measurements with a low energy setup show a gradual increment of dose going from the "chest wall" to the "nipple" (63% more at the "nipple" compared to the central position). Likewise, a gradual increment is observed going from the breast axis toward the periphery (82% more at the "skin" compared to the central position). A more uniform distribution of dose inside the PMMA was obtained with a high energy setup (the maximum variation was 33% at 35.5 keV effective energy in the radial direction). The most uniform distribution is obtained at 44.4 keV. The results of this study show how the dose is distributed: it varies as a function of effective energy of the incident X-ray beam and as a function of the position inside the volume (axial or peripheral position).

SU-F-T-70: A High Dose Rate Total Skin Electron Irradiation Technique with A Specific Inter-Film Variation Correction Method for Very Large Electron Beam Fields

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

Yang, X; Rosenfield, J; Dong, X

2016-06-15

Purpose: Rotational total skin electron irradiation (RTSEI) is used in the treatment of cutaneous T-cell lymphoma. Due to inter-film uniformity variations the dosimetry measurement of a large electron beam of a very low energy is challenging. This work provides a method to improve the accuracy of flatness and symmetry for a very large treatment field of low electron energy used in dual beam RTSEI. Methods: RTSEI is delivered by dual angles field a gantry of ±20 degrees of 270 to cover the upper and the lower halves of the patient body with acceptable beam uniformity. The field size is inmore » the order of 230cm in vertical height and 120 cm in horizontal width and beam energy is a degraded 6 MeV (6 mm of PMMA spoiler). We utilized parallel plate chambers, Gafchromic films and OSLDs as a measuring devices for absolute dose, B-Factor, stationary and rotational percent depth dose and beam uniformity. To reduce inter-film dosimetric variation we introduced a new specific correction method to analyze beam uniformity. This correction method uses some image processing techniques combining film value before and after radiation dose to compensate the inter-variation dose response differences among films. Results: Stationary and rotational depth of dose demonstrated that the Rp is 2 cm for rotational and the maximum dose is shifted toward the surface (3mm). The dosimetry for the phantom showed that dose uniformity reduced to 3.01% for the vertical flatness and 2.35% for horizontal flatness after correction thus achieving better flatness and uniformity. The absolute dose readings of calibrated films after our correction matched with the readings from OSLD. Conclusion: The proposed correction method for Gafchromic films will be a useful tool to correct inter-film dosimetric variation for the future clinical film dosimetry verification in very large fields, allowing the optimizations of other parameters.« less

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way it is commonly done for the gEUD. © 2012 American Association of Physicists in Medicine.

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets. © PDA, Inc. 2016.

[A practical procedure to improve the accuracy of radiochromic film dosimetry: a integration with a correction method of uniformity correction and a red/blue correction method].

PubMed

Uehara, Ryuzo; Tachibana, Hidenobu; Ito, Yasushi; Yoshino, Shinichi; Matsubayashi, Fumiyasu; Sato, Tomoharu

2013-06-01

It has been reported that the light scattering could worsen the accuracy of dose distribution measurement using a radiochromic film. The purpose of this study was to investigate the accuracy of two different films, EDR2 and EBT2, as film dosimetry tools. The effectiveness of a correction method for the non-uniformity caused from EBT2 film and the light scattering was also evaluated. In addition the efficacy of this correction method integrated with the red/blue correction method was assessed. EDR2 and EBT2 films were read using a flatbed charge-coupled device scanner (EPSON 10000G). Dose differences on the axis perpendicular to the scanner lamp movement axis were within 1% with EDR2, but exceeded 3% (Maximum: +8%) with EBT2. The non-uniformity correction method, after a single film exposure, was applied to the readout of the films. A corrected dose distribution data was subsequently created. The correction method showed more than 10%-better pass ratios in dose difference evaluation than when the correction method was not applied. The red/blue correction method resulted in 5%-improvement compared with the standard procedure that employed red color only. The correction method with EBT2 proved to be able to rapidly correct non-uniformity, and has potential for routine clinical IMRT dose verification if the accuracy of EBT2 is required to be similar to that of EDR2. The use of red/blue correction method may improve the accuracy, but we recommend we should use the red/blue correction method carefully and understand the characteristics of EBT2 for red color only and the red/blue correction method.

Characterizing the marker-dye correction for Gafchromic(®) EBT2 film: a comparison of three analysis methods.

PubMed

McCaw, Travis J; Micka, John A; Dewerd, Larry A

2011-10-01

Gafchromic(®) EBT2 film has a yellow marker dye incorporated into the active layer of the film that can be used to correct the film response for small variations in thickness. This work characterizes the effect of the marker-dye correction on the uniformity and uncertainty of dose measurements with EBT2 film. The effect of variations in time postexposure on the uniformity of EBT2 is also investigated. EBT2 films were used to measure the flatness of a (60)Co field to provide a high-spatial resolution evaluation of the film uniformity. As a reference, the flatness of the (60)Co field was also measured with Kodak EDR2 films. The EBT2 films were digitized with a flatbed document scanner 24, 48, and 72 h postexposure, and the images were analyzed using three methods: (1) the manufacturer-recommended marker-dye correction, (2) an in-house marker-dye correction, and (3) a net optical density (OD) measurement in the red color channel. The field flatness was calculated from orthogonal profiles through the center of the field using each analysis method, and the results were compared with the EDR2 measurements. Uncertainty was propagated through a dose calculation for each analysis method. The change in the measured field flatness for increasing times postexposure was also determined. Both marker-dye correction methods improved the field flatness measured with EBT2 film relative to the net OD method, with a maximum improvement of 1% using the manufacturer-recommended correction. However, the manufacturer-recommended correction also resulted in a dose uncertainty an order of magnitude greater than the other two methods. The in-house marker-dye correction lowered the dose uncertainty relative to the net OD method. The measured field flatness did not exhibit any unidirectional change with increasing time postexposure and showed a maximum change of 0.3%. The marker dye in EBT2 can be used to improve the response uniformity of the film. Depending on the film analysis method used, however, application of a marker-dye correction can improve or degrade the dose uncertainty relative to the net OD method. The uniformity of EBT2 was found to be independent of the time postexposure.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer

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

Chen, Guang-Pei, E-mail: gpchen@mcw.edu; Liu, Feng; White, Julia

2015-04-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volumemore » parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered.« less

A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

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

Hadley, Austin; Ding, George X., E-mail: george.ding@vanderbilt.edu

2014-01-01

Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fieldsmore » and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans.« less

Predictive value of tracer studies for /sup 131/I treatment in hyperthyroid cats

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

Broome, M.R.; Turrel, J.M.; Hays, M.T.

In 76 cats with hyperthyroidism, peak thyroidal radioiodine (/sup 131/I) uptakes and effective half-lives were determined after administration of tracer and therapeutic activities of /sup 131/I. In 6 additional hyperthyroid cats, only peak thyroidal uptakes after administration of tracer and therapeutic activities of /sup 131/I were determined. Good correlation was found between peak thyroidal uptakes of tracer and therapeutic /sup 131/I; however, only fair correlation was observed between effective half-lives. In 79% of the cats, the effective half-life for therapeutic /sup 131/I was longer than that for tracer /sup 131/I. After administration of therapeutic activity of /sup 131/I, monoexponential andmore » biphasic decay curves were observed in 51 and 16 cats, respectively. Using therapeutic kinetic data, radiation doses to the thyroid gland were calculated retrospectively on the basis of 2 methods for determining the activity of /sup 131/I administered: (1) actual administration of tracer-compensated activity and (2) hypothetic administration of uniform activity (3 mCi). Because of the good predictive ability of tracer kinetic data for the therapeutic kinetic data, the tracer-compensated radiation doses came significantly (P = 0.008) closer to the therapeutic goal than did the uniform-activity doses. In addition, the use of tracer kinetic information reduced the extent of the tendency for consistently high uniform-activity doses. A manual method for acquiring tracer kinetic data was developed and was an acceptable alternative to computerized techniques. Adoption of this method gives individuals and institutions with limited finances the opportunity to characterize the iodine kinetics in cats before proceeding with administration of therapeutic activities of /sup 131/I.« less

Investigation of non-uniform radiation damage observed in the ZEUS Beam Pipe Calorimeter at HERA

NASA Astrophysics Data System (ADS)

Bohnet, I.; Fricke, U.; Surrow, B.; Wick, K.

1999-08-01

The ZEUS Beam Pipe Calorimeter (BPC) is a small tungsten/scintillator sampling calorimeter. It is positioned at a distance of approximately 4 cm from the HERA beams and approximately 3 m from the interaction point. The accumulated doses measured at the front side of the BPC during the HERA runs 1995, 1996 and 1997 were 12 kGy, 11 kGy and 2.5 kGy, respectively. The radiation dose influenced the optical components of the BPC. The degradation of some of the scintillators due to radiation damage has been examined using different monitoring systems. A simulation code was developed which describes quantitatively the effects of non-uniform radiation damage. The following report describes the radiation monitoring, the effects on the scintillator material and the impact on the energy linearity of the BPC.

SU-E-T-549: A Combinatorial Optimization Approach to Treatment Planning with Non-Uniform Fractions in Intensity Modulated Proton Therapy

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

Papp, D; Unkelbach, J

2014-06-01

Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that deliversmore » a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.« less

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions

PubMed Central

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René

2015-01-01

Abstract Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment. PMID:26352860

Study of Fricke-gel dosimeter calibration for attaining precise measurements of the absorbed dose

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

Liosi, Giulia Maria; Benedini, Sara; Giacobbo, Francesca

2015-07-01

A method has been studied for attaining, with good precision, absolute measurements of the spatial distribution of the absorbed dose by means of the Fricke gelatin Xylenol Orange dosimetric system. With this aim, the dose response to subsequent irradiations was analyzed. In fact, the proposed modality is based on a pre-irradiation of each single dosimeter in a uniform field with a known dose, in order to extrapolate a calibration image for a subsequent non-uniform irradiation with an un-known dose to be measured. (authors)

Effects of beam irregularity on uniform scanning

NASA Astrophysics Data System (ADS)

Kim, Chang Hyeuk; Jang, Sea duk; Yang, Tae-Keun

2016-09-01

An active scanning beam delivery method has many advantages in particle beam applications. For the beam is to be successfully delivered to the target volume by using the active scanning technique, the dose uniformity must be considered and should be at least 2.5% in the case of therapy application. During beam irradiation, many beam parameters affect the 2-dimensional uniformity at the target layer. A basic assumption in the beam irradiation planning stage is that the shape of the beam is symmetric and follows a Gaussian distribution. In this study, a pure Gaussian-shaped beam distribution was distorted by adding parasitic Gaussian distribution. An appropriate uniform scanning condition was deduced by using a quantitative analysis based on the gamma value of the distorted beam and 2-dimensional uniformities.

A Multi-institution, Retrospective Analysis of Cervix Intracavitary Brachytherapy Treatments. Part 1: Is EQD2 Good Enough for Reporting Radiobiological Effects?

PubMed

Fields, Emma C; Melvani, Rakhi; Hajdok, George; D'Souza, David; Jones, Bernard; Stuhr, Kelly; Diot, Quentin; Fisher, Christine M; Mukhopadhyay, Nitai; Todor, Dorin

2017-09-01

When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices-T&O and tandem and ring (T&R)-and different styles; and (3) the same site using T&O and T&R with the same style. EUBED and gBEUD were calculated for 260 fractions from 3 institutions using BED(α/β = 10 Gy). EUBED uses an extra parameter α with smaller values associated with radioresistant tumors. Similarly, gBEUD uses a, which places variable emphasis on hot/cold spots. Distributions were compared using the Kolmogorov-Smirnoff test at 5% significance. For the 2 sites using T&O, the distribution of EUBED-BED(D90) was not different for values of α = 0.5 to 0.3 Gy -1 but was statistically different for values of α = 0.15 to 0.05 Gy -1 (P=.01, .002). The mean percentage differences between EUBED and BED(D90) ranged from 20% to 100% for α = 0.5 Gy -1 to 0.05 Gy -1 . Using gBEUD-BED(D90), the P values indicate the distributions to be similar for a = -10 but to be significantly different for other values of a (-5, -1, 1). Between sites and at the same site using T&O versus T&R, the distributions were statistically different with EUBED/gBEUD irrespective of parameter values at which these quantities were computed. These differences indicate that EUBED/gBEUD capture differences between the techniques and applicators that are not detected by the BED(D90). BED(D90) is unable to distinguish between plans created by different devices or optimized differently. EUBED/gBEUD distinguish between dose distributions created by different devices and styles of implant and planning. This discrepancy is particularly important with the increased use of magnetic resonance imaging and hybrid devices, whereby one has the ability to create dose distributions that are significant departures from the classic pear. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study.

PubMed

Jackson, J Benjamin; Crimaldi, Anthony J; Peindl, Richard; Norton, H James; Anderson, William E; Patt, Joshua C

2017-01-01

Cadaveric model. To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. N/A.

SU-F-T-578: Characterization of Vidar DosimetryPro Advantage RED Scanner with Application to SBRT and SRS QA

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

Dumas, M; Wen, N

Purpose: To use Gafchromic EBT3 film to quantify key dosimetric characteristics of the Vidar DosimetryPro Advantage RED film scanner for use in SBRT/SRS QA, by analyzing scanner uniformity and dose sensitivity. Method: Gafchromic EBT3 film was used in this study. Films were irradiated using 6MV FFF and 10MV FFF beams from a Varian Edge linear accelerator, with setup of 100cm SAD at depth 5 cm. Nine doses were delivered per film, with calibration dose ranges of 1–10 Gy and 3–24 Gy for 6MV FFF, and 3–27 Gy for 10MV FFF. Films were scanned with the long side of the filmmore » parallel to the detector array. Dose calibration curves were fitted to a 3rd degree polynomial. The derivative of a calibration curve was taken to determine the scanner’s sensitivity per dose delivered (OD/Gy). Scanner non-uniformity was calculated in 2 dimensions by taking the mean of standard deviation in each row and column. Absolute dose SRS/SBRT Gamma analyses were performed with passing criteria of 3% and 1mm DTA. For comparison, Gamma analyses were also performed using an Epson Expression 10000 XL. Results: Uniformity for the Vidar scanner was 0.37% +/− 0.03% in the perpendicular to scan direction and 0.67% +/− 0.05% in the parallel to scan direction, with an overall uniformity of 0.52% +/− 0.03%. Epson red channel uniformity was 0.85% +/− 0.05% and 0.88% +/− 0.08% for the green channel. The Vidar average dose sensitivity from 1–10 Gy was 0.112 OD/Gy and 0.061 OD/Gy for 3–24 Gy. SBRT/SRS Gamma pass rates were 97.8 +/− 1.4 for Vidar and 97.5 +/− 1.4 for Epson. Conclusion: The Vidar scanner has 41% less non-uniformity compared to Epson XL10000 green channel. The dose sensitivity is 2–3 time greater for the Vidar scanner compared to the Epson in the SRS/SBRT dose range of 5–24 Gy.« less

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer.

PubMed

Chen, Guang-Pei; Liu, Feng; White, Julia; Vicini, Frank A; Freedman, Gary M; Arthur, Douglas W; Li, X Allen

2015-01-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Charge amplifier with bias compensation

DOEpatents

Johnson, Gary W.

2002-01-01

An ion beam uniformity monitor for very low beam currents using a high-sensitivity charge amplifier with bias compensation. The ion beam monitor is used to assess the uniformity of a raster-scanned ion beam, such as used in an ion implanter, and utilizes four Faraday cups placed in the geometric corners of the target area. Current from each cup is integrated with respect to time, thus measuring accumulated dose, or charge, in Coulombs. By comparing the dose at each corner, a qualitative assessment of ion beam uniformity is made possible. With knowledge of the relative area of the Faraday cups, the ion flux and areal dose can also be obtained.

SU-E-P-14: Dosimetric Effects of Magnetic Field in MRI-Guided Radiation Therapy Delivery for Breast Cancer

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

Chen, G; Currey, A; Li, X

2015-06-15

Purpose: MRI-guided radiation therapy (RT) delivery would be beneficial for breast irradiation. The electron return effect due to the presence of a transverse magnetic field (TMF) may cause dosimetric issues on dose on skin and at the lung-tissue interface. The purpose of this study is to investigate these issues. Methods: IMRT plans with tangential beams and VMAT plans with 200 degree arcs to cover ipsilateral breast were generated for 10 randomly selected breast cancer cases using a research planning system (Monaco, Elekta) utilizing Monte Carlo dose calculation with or without a TMF of 1.5 T. Plans were optimized to delivermore » uniform dose to the whole breast with an exclusion of 5 mm tissue under the skin (PTV-EVAL). All four plans for each patient were re-scaled to have the same PTV-EVAL volume to receive the same prescription dose. The skin is defined as the first 5 mm of ipsilateral-breast tissue, plus extensions in the surrounding region. Results: The presence of 1.5 T TMF resulted in (1)increased skin dose, with the mean and maximum skin dose increase of 5% and 9%, respectively; (2) similar dose homogeneity within the PTV-EVAL; (3) the slightly improved (3%) dose homogeneity in the whole breast; (4) Averages of 9 and 16% increases in V5 and V20, respectively, for ipsilateral lung; and (5) increased the mean heart dose by 34%. VMAT plans don’t improve whole breast dose uniformity as compared that to the tangential plans. Conclusion: The presence of transverse magnetic field in MRI-guided RT delivery for whole breast irradiation can Result in slightly improved dose homogeneity in the whole breast, increased dose to the ipsilateral lung, heart, and skin. Plan optimization with additional specific dose volume constraints may eliminate/reduce these dose increases. This work is partially supported by Elekta Inc.« less

On Voxel based Iso-Tumor Control Probabilty and Iso-Complication Maps for Selective Boosting and Selective Avoidance Intensity Modulated Radiotherapy.

PubMed

Kim, Yusung; Tomé, Wolfgang A

2008-01-01

Voxel based iso-Tumor Control Probability (TCP) maps and iso-Complication maps are proposed as a plan-review tool especially for functional image-guided intensity-modulated radiotherapy (IMRT) strategies such as selective boosting (dose painting) and conformal avoidance IMRT. The maps employ voxel-based phenomenological biological dose-response models for target volumes and normal organs. Two IMRT strategies for prostate cancer, namely conventional uniform IMRT delivering an EUD = 84 Gy (equivalent uniform dose) to the entire PTV and selective boosting delivering an EUD = 82 Gy to the entire PTV, are investigated, to illustrate the advantages of this approach over iso-dose maps. Conventional uniform IMRT did yield a more uniform isodose map to the entire PTV while selective boosting did result in a nonuniform isodose map. However, when employing voxel based iso-TCP maps selective boosting exhibited a more uniform tumor control probability map compared to what could be achieved using conventional uniform IMRT, which showed TCP cold spots in high-risk tumor subvolumes despite delivering a higher EUD to the entire PTV. Voxel based iso-Complication maps are presented for rectum and bladder, and their utilization for selective avoidance IMRT strategies are discussed. We believe as the need for functional image guided treatment planning grows, voxel based iso-TCP and iso-Complication maps will become an important tool to assess the integrity of such treatment plans.

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans

PubMed Central

Conwell, Richard; Kindem, Joel; Babla, Hetal; Gurley, Mike; De Los Santos, Romer; Old, Rex; Weatherhead, Randy; Arram, Samia; Maddahi, Jamshid

2010-01-01

Background We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 μSv). Methods We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. Results The reconstructed attenuation coefficient of water at 140 keV was .150 ± .003/cm in the uniform region of the ACR phantom, .151 ± .003/cm and .151 ± .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 ± 6.5 before and 87.9 ± 3.3 after AC (average ± standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. Conclusion The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC. PMID:20169476

Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium.

PubMed

Shah, Rakhi B; Collier, Jarrod S; Sayeed, Vilayat A; Bryant, Arthur; Habib, Muhammad J; Khan, Mansoor A

2010-09-01

Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue.

A small-scale anatomical dosimetry model of the liver

NASA Astrophysics Data System (ADS)

Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

2014-07-01

Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and 125I, 90Y, 211At, 99mTc, 111In, 177Lu, 131I and 18F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons (125I) or high-LET alpha particles (211At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

Mixing of low-dose cohesive drug and overcoming of pre-blending step using a new gentle-wing high-shear mixer granulator.

PubMed

Alsulays, Bader B; Fayed, Mohamed H; Alalaiwe, Ahmed; Alshahrani, Saad M; Alshetaili, Abdullah S; Alshehri, Sultan M; Alanazi, Fars K

2018-05-16

The objective of this study was to examine the influence of drug amount and mixing time on the homogeneity and content uniformity of a low-dose drug formulation during the dry mixing step using a new gentle-wing high-shear mixer. Moreover, the study investigated the influence of drug incorporation mode on the content uniformity of tablets manufactured by different methods. Albuterol sulfate was selected as a model drug and was blended with the other excipients at two different levels, 1% w/w and 5% w/w at impeller speed of 300 rpm and chopper speed of 3000 rpm for 30 min. Utilizing a 1 ml unit side-sampling thief probe, triplicate samples were taken from nine different positions in the mixer bowl at selected time points. Two methods were used for manufacturing of tablets, direct compression and wet granulation. The produced tablets were sampled at the beginning, middle, and end of the compression cycle. An analysis of variance analysis indicated the significant effect (p < .05) of drug amount on the content uniformity of the powder blend and the corresponding tablets. For 1% w/w and 5% w/w formulations, incorporation of the drug in the granulating fluid provided tablets with excellent content uniformity and very low relative standard deviation (∼0.61%) during the whole tableting cycle compared to direct compression and granulation method with dry incorporation mode of the drug. Overall, gentle-wing mixer is a good candidate for mixing of low-dose cohesive drug and provides tablets with acceptable content uniformity with no need for pre-blending step.

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive Substances: A Systematic Review.

PubMed

Eserian, Jaqueline K; Lombardo, Márcia; Chagas, Jair R; Galduróz, José C F

2018-02-08

To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting. © Copyright 2018 Physicians Postgraduate Press, Inc.

A step-up test procedure to find the minimum effective dose.

PubMed

Wang, Weizhen; Peng, Jianan

2015-01-01

It is of great interest to find the minimum effective dose (MED) in dose-response studies. A sequence of decreasing null hypotheses to find the MED is formulated under the assumption of nondecreasing dose response means. A step-up multiple test procedure that controls the familywise error rate (FWER) is constructed based on the maximum likelihood estimators for the monotone normal means. When the MED is equal to one, the proposed test is uniformly more powerful than Hsu and Berger's test (1999). Also, a simulation study shows a substantial power improvement for the proposed test over four competitors. Three R-codes are provided in Supplemental Materials for this article. Go to the publishers online edition of Journal of Biopharmaceutical Statistics to view the files.

4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

NASA Astrophysics Data System (ADS)

Zhao, Qingya

2011-12-01

Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery mechanism. These three steps provide an innovative integrated framework for accurate 4D proton dose calculation and treatment planning for a moving tumor, which extends the functionalities of existing 3D planning systems. In short, this dissertation work addresses a few important problems for effective proton radiotherapy to a moving target. The outcomes of the dissertation are very useful for motion compensation with advanced image guided proton treatment.

The photon fluence non-uniformity correction for air kerma near Cs-137 brachytherapy sources.

PubMed

Rodríguez, M L; deAlmeida, C E

2004-05-07

The use of brachytherapy sources in radiation oncology requires their proper calibration to guarantee the correctness of the dose delivered to the treatment volume of a patient. One of the elements to take into account in the dose calculation formalism is the non-uniformity of the photon fluence due to the beam divergence that causes a steep dose gradient near the source. The correction factors for this phenomenon have been usually evaluated by the two theories available, both of which were conceived only for point sources. This work presents the Monte Carlo assessment of the non-uniformity correction factors for a Cs-137 linear source and a Farmer-type ionization chamber. The results have clearly demonstrated that for linear sources there are some important differences among the values obtained from different calculation models, especially at short distances from the source. The use of experimental values for each specific source geometry is recommended in order to assess the non-uniformity factors for linear sources in clinical situations that require special dose calculations or when the correctness of treatment planning software is verified during the acceptance tests.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

PubMed

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-07

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study

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

Giantsoudi, D.; Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Boston, Massachusetts 02114; Baltas, D.

2013-04-15

Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the differentmore » dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D{sub 10} or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.« less

Bowtie filters for dedicated breast CT: Analysis of bowtie filter material selection.

PubMed

Kontson, Kimberly; Jennings, Robert J

2015-09-01

For a given bowtie filter design, both the selection of material and the physical design control the energy fluence, and consequently the dose distribution, in the object. Using three previously described bowtie filter designs, the goal of this work is to demonstrate the effect that different materials have on the bowtie filter performance measures. Three bowtie filter designs that compensate for one or more aspects of the beam-modifying effects due to the differences in path length in a projection have been designed. The nature of the designs allows for their realization using a variety of materials. The designs were based on a phantom, 14 cm in diameter, composed of 40% fibroglandular and 60% adipose tissue. Bowtie design #1 is based on single material spectral matching and produces nearly uniform spectral shape for radiation incident upon the detector. Bowtie design #2 uses the idea of basis-material decomposition to produce the same spectral shape and intensity at the detector, using two different materials. With bowtie design #3, it is possible to eliminate the beam hardening effect in the reconstructed image by adjusting the bowtie filter thickness so that the effective attenuation coefficient for every ray is the same. Seven different materials were chosen to represent a range of chemical compositions and densities. After calculation of construction parameters for each bowtie filter design, a bowtie filter was created using each of these materials (assuming reasonable construction parameters were obtained), resulting in a total of 26 bowtie filters modeled analytically and in the penelope Monte Carlo simulation environment. Using the analytical model of each bowtie filter, design profiles were obtained and energy fluence as a function of fan-angle was calculated. Projection images with and without each bowtie filter design were also generated using penelope and reconstructed using FBP. Parameters such as dose distribution, noise uniformity, and scatter were investigated. Analytical calculations with and without each bowtie filter show that some materials for a given design produce bowtie filters that are too large for implementation in breast CT scanners or too small to accurately manufacture. Results also demonstrate the ability to manipulate the energy fluence distribution (dynamic range) by using different materials, or different combinations of materials, for a given bowtie filter design. This feature is especially advantageous when using photon counting detector technology. Monte Carlo simulation results from penelope show that all studied material choices for bowtie design #2 achieve nearly uniform dose distribution, noise uniformity index less than 5%, and nearly uniform scatter-to-primary ratio. These same features can also be obtained using certain materials with bowtie designs #1 and #3. With the three bowtie filter designs used in this work, the selection of material is an important design consideration. An appropriate material choice can improve image quality, dose uniformity, and dynamic range.

Bowtie filters for dedicated breast CT: Analysis of bowtie filter material selection

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

Kontson, Kimberly, E-mail: Kimberly.Kontson@fda.hhs.gov; Jennings, Robert J.

Purpose: For a given bowtie filter design, both the selection of material and the physical design control the energy fluence, and consequently the dose distribution, in the object. Using three previously described bowtie filter designs, the goal of this work is to demonstrate the effect that different materials have on the bowtie filter performance measures. Methods: Three bowtie filter designs that compensate for one or more aspects of the beam-modifying effects due to the differences in path length in a projection have been designed. The nature of the designs allows for their realization using a variety of materials. The designsmore » were based on a phantom, 14 cm in diameter, composed of 40% fibroglandular and 60% adipose tissue. Bowtie design #1 is based on single material spectral matching and produces nearly uniform spectral shape for radiation incident upon the detector. Bowtie design #2 uses the idea of basis-material decomposition to produce the same spectral shape and intensity at the detector, using two different materials. With bowtie design #3, it is possible to eliminate the beam hardening effect in the reconstructed image by adjusting the bowtie filter thickness so that the effective attenuation coefficient for every ray is the same. Seven different materials were chosen to represent a range of chemical compositions and densities. After calculation of construction parameters for each bowtie filter design, a bowtie filter was created using each of these materials (assuming reasonable construction parameters were obtained), resulting in a total of 26 bowtie filters modeled analytically and in the PENELOPE Monte Carlo simulation environment. Using the analytical model of each bowtie filter, design profiles were obtained and energy fluence as a function of fan-angle was calculated. Projection images with and without each bowtie filter design were also generated using PENELOPE and reconstructed using FBP. Parameters such as dose distribution, noise uniformity, and scatter were investigated. Results: Analytical calculations with and without each bowtie filter show that some materials for a given design produce bowtie filters that are too large for implementation in breast CT scanners or too small to accurately manufacture. Results also demonstrate the ability to manipulate the energy fluence distribution (dynamic range) by using different materials, or different combinations of materials, for a given bowtie filter design. This feature is especially advantageous when using photon counting detector technology. Monte Carlo simulation results from PENELOPE show that all studied material choices for bowtie design #2 achieve nearly uniform dose distribution, noise uniformity index less than 5%, and nearly uniform scatter-to-primary ratio. These same features can also be obtained using certain materials with bowtie designs #1 and #3. Conclusions: With the three bowtie filter designs used in this work, the selection of material is an important design consideration. An appropriate material choice can improve image quality, dose uniformity, and dynamic range.« less

On Voxel based Iso-Tumor Control Probabilty and Iso-Complication Maps for Selective Boosting and Selective Avoidance Intensity Modulated Radiotherapy

PubMed Central

Kim, Yusung; Tomé, Wolfgang A.

2010-01-01

Summary Voxel based iso-Tumor Control Probability (TCP) maps and iso-Complication maps are proposed as a plan-review tool especially for functional image-guided intensity-modulated radiotherapy (IMRT) strategies such as selective boosting (dose painting) and conformal avoidance IMRT. The maps employ voxel-based phenomenological biological dose-response models for target volumes and normal organs. Two IMRT strategies for prostate cancer, namely conventional uniform IMRT delivering an EUD = 84 Gy (equivalent uniform dose) to the entire PTV and selective boosting delivering an EUD = 82 Gy to the entire PTV, are investigated, to illustrate the advantages of this approach over iso-dose maps. Conventional uniform IMRT did yield a more uniform isodose map to the entire PTV while selective boosting did result in a nonuniform isodose map. However, when employing voxel based iso-TCP maps selective boosting exhibited a more uniform tumor control probability map compared to what could be achieved using conventional uniform IMRT, which showed TCP cold spots in high-risk tumor subvolumes despite delivering a higher EUD to the entire PTV. Voxel based iso-Complication maps are presented for rectum and bladder, and their utilization for selective avoidance IMRT strategies are discussed. We believe as the need for functional image guided treatment planning grows, voxel based iso-TCP and iso-Complication maps will become an important tool to assess the integrity of such treatment plans. PMID:21151734

Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2017-03-01

Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

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

Yao Rui; Bernard, Damian; Turian, Julius

2012-04-15

Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lungmore » dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.« less

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

Shusharina, N; Khan, F; Sharp, G

Purpose: To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. Methods: We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDGmore » PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. Results: The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 – 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. Conclusion: Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.« less

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

PubMed

Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

2017-03-01

The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

Proton recoil scintillator neutron rem meter

DOEpatents

Olsher, Richard H.; Seagraves, David T.

2003-01-01

A neutron rem meter utilizing proton recoil and thermal neutron scintillators to provide neutron detection and dose measurement. In using both fast scintillators and a thermal neutron scintillator the meter provides a wide range of sensitivity, uniform directional response, and uniform dose response. The scintillators output light to a photomultiplier tube that produces an electrical signal to an external neutron counter.

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.

Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction

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

Brady, Samuel L., E-mail: samuel.brady@stjude.org; Shulkin, Barry L.

2015-02-15

Purpose: To develop ultralow dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultralow doses (10–35 mA s). CT quantitation: noise, low-contrast resolution, and CT numbers for 11 tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% volume computed tomography dose index (0.39/3.64; mGy) from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET imagesmore » were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUV{sub bw}) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative dose reduction and noise control. Results: CT numbers were constant to within 10% from the nondose reduced CTAC image for 90% dose reduction. No change in SUV{sub bw}, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols was found down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62% and 86% (3.2/8.3–0.9/6.2). Noise magnitude in dose-reduced patient images increased but was not statistically different from predose-reduced patient images. Conclusions: Using ASiR allowed for aggressive reduction in CT dose with no change in PET reconstructed images while maintaining sufficient image quality for colocalization of hybrid CT anatomy and PET radioisotope uptake.« less

Biological Effects of Nuclear Explosions (BENE) Domain Guide

DTIC Science & Technology

2012-09-01

DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From – To) Technical Report October 2004-April 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER...greatly increased in the nearby region because increasing amounts of contaminated earth and debris are sucked up into the radioactive cloud. In the case...or a denial scenario involving radioisotopes will be non-uniform exposure with various doses and dose rates producing very large variations in

SU-E-T-748: Theoretical Investigation On Using High Energy Proton Beam for Total-Body-Irradiation

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

Zhang, M; Zou, J; Chen, T

2015-06-15

Purpose: The broad-slow-rising entrance dose region proximal to the Bragg peak made by a mono-energetic proton beam could potentially be used for total body irradiation (TBI). Due to the quasi-uniform dose deposition, customized thickness compensation may not be required to deliver a uniform dose to patients with varied thickness. We investigated the possibility, efficacy, and hardware requirement to use such proton beam for TBI. Methods: A wedge shaped water phantom with thickness varying from 2 cm to 40 cm was designed to mimic a patient. Geant4 based Monte Carlo code was used to simulate broad mono-energetic proton beams with energymore » ranging from 250 MeV to 300 MeV radiating the phantom. A 6 MV photon with 1 cm water equivalent build-up used for conventional TBI was also calculated. A paired-opposing beam arrangement with no thickness compensation was used to generate TBI plans for all beam energies. Dose from all particles were scored on a grid size of 2 mm{sup 3}. Dose uniformity across the phantom was calculated to evaluate the plan. The field size limit and the dose uniformity of Mevion S250 proton system was examined by using radiochromic films placed at extended treatment distance with the open large applicator and 90° gantry angle. Results: To achieve a maximum ± 7.5% dose variation, the largest patient thickness variation allowed for 250 MeV, 275 MeV, and 300 MeV proton beams were 27.0 cm, 34.9 cm and 36.7 cm. The value for 6 MV photon beam was only 8.0 cm to achieve the same dose variation. With open gantry, Mevion S250 system allows 5 m source-to-surface distance producing an expected 70 cm{sup 2} field size. Conclusion: Energetic proton beam can potentially be used to deliver TBI. Treatment planning and delivery would be much simple since no thickness compensation is required to achieve a uniform dose distribution.« less

Hanford Technical Basis for Multiple Dosimetry Effective Dose Methodology

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

Hill, Robin L.; Rathbone, Bruce A.

2010-08-01

The current method at Hanford for dealing with the results from multiple dosimeters worn during non-uniform irradiation is to use a compartmentalization method to calculate the effective dose (E). The method, as documented in the current version of Section 6.9.3 in the 'Hanford External Dosimetry Technical Basis Manual, PNL-MA-842,' is based on the compartmentalization method presented in the 1997 ANSI/HPS N13.41 standard, 'Criteria for Performing Multiple Dosimetry.' With the adoption of the ICRP 60 methodology in the 2007 revision to 10 CFR 835 came changes that have a direct affect on the compartmentalization method described in the 1997 ANSI/HPS N13.41more » standard, and, thus, to the method used at Hanford. The ANSI/HPS N13.41 standard committee is in the process of updating the standard, but the changes to the standard have not yet been approved. And, the drafts of the revision of the standard tend to align more with ICRP 60 than with the changes specified in the 2007 revision to 10 CFR 835. Therefore, a revised method for calculating effective dose from non-uniform external irradiation using a compartmental method was developed using the tissue weighting factors and remainder organs specified in 10 CFR 835 (2007).« less

SU-E-T-510: Interplay Between Spots Sizes, Spot / Line Spacing and Motion in Spot Scanning Proton Therapy

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

Lee, TK

Purpose In proton beam configuration for spot scanning proton therapy (SSPT), one can define the spacing between spots and lines of scanning as a ratio of given spot size. If the spacing increases, the number of spots decreases which can potentially decrease scan time, and so can whole treatment time, and vice versa. However, if the spacing is too large, the uniformity of scanned field decreases. Also, the field uniformity can be affected by motion during SSPT beam delivery. In the present study, the interplay between spot/ line spacing and motion is investigated. Methods We used four Gaussian-shape spot sizesmore » with 0.5cm, 1.0cm, 1.5cm, and 2.0cm FWHM, three spot/line spacing that creates uniform field profile which are 1/3*FWHM, σ/3*FWHM and 2/3*FWHM, and three random motion amplitudes within, +/−0.3mm, +/−0.5mm, and +/−1.0mm. We planned with 2Gy uniform single layer of 10×10cm2 and 20×20cm2 fields. Then, mean dose within 80% area of given field size, contrubuting MU per each spot assuming 1cGy/MU calibration for all spot sizes, number of spots and uniformity were calculated. Results The plans with spot/line spacing equal to or smaller than 2/3*FWHM without motion create ∼100% uniformity. However, it was found that the uniformity decreases with increased spacing, and it is more pronounced with smaller spot sizes, but is not affected by scanned field sizes. Conclusion It was found that the motion during proton beam delivery can alter the dose uniformity and the amount of alteration changes with spot size which changes with energy and spot/line spacing. Currently, robust evaluation in TPS (e.g. Eclipse system) performs range uncertainty evaluation using isocenter shift and CT calibration error. Based on presented study, it is recommended to add interplay effect evaluation to robust evaluation process. For future study, the additional interplay between the energy layers and motion is expected to present volumetric effect.« less

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug

PubMed Central

Alyami, Hamad; Dahmash, Eman; Bowen, James

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation. PMID:28609454

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug.

PubMed

Alyami, Hamad; Dahmash, Eman; Bowen, James; Mohammed, Afzal R

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.

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

Zheng, Y; Rana, S; Larson, G

Purpose: To analyze the toxicity of uniform scanning proton therapy for lung cancer patients and its correlation with dose distribution. Methods: In this study, we analyzed the toxicity of 128 lung cancer patients, including 18 small cell lung cancer and 110 non small cell lung cancer patients. Each patient was treated with uniform scanning proton beams at our center using typically 2–4 fields. The prescription was typically 74 Cobalt gray equivalent (CGE) at 2 CGE per fraction. 4D Computerized Tomography (CT) scans were used to evaluate the target motion and contour the internal target volume, and repeated 3 times duringmore » the course of treatment to evaluate the need for plan adaptation. Toxicity data for these patients were obtained from the proton collaborative group (PCG) database. For cases of grade 3 toxicities or toxicities of interest such as esophagitis and radiation dermatitis, dose distributions were reviewed and analyzed in attempt to correlate the toxicity with radiation dose. Results: At a median follow up time of about 21 months, none of the patients had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (81%: 52%-Grade 1, 28%-Grade 2, and 1% Grade 3), followed by fatigue (48%), Cough (46%), and Esophagitis (45%), as shown in Figure 1. Severe toxicities, such as Grade 3 dermatitis or pain of skin, had a clear correlation with high radiation dose. Conclusion: Uniform scanning proton therapy is well tolerated by lung cancer patients. Preliminary analysis indicates there is correlation between severe toxicity and high radiation dose. Understanding of radiation resulted toxicities and careful choice of beam arrangement are critical in minimizing toxicity of skin and other organs.« less

MO-FG-CAMPUS-IeP1-04: Kerma Area Product Calculation for Non-Uniform X-Ray Fields Using a Skin Dose Tracking System

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

Vijayan, S; Xiong, Z; Rudin, S

Purpose: The functionality of the Dose-Tracking System (DTS) has been expanded to include the calculation of the Kerma-Area Product (KAP) for non-uniform x-ray fields such as result from the use of compensation filters during fluoroscopic procedures Methods: The DTS calculates skin dose during fluoroscopic interventions and provides a color-coded dose map on a patient-graphic model. The KAP is the integral of air kerma over the x-ray field and is usually measured with a transmission-ionization chamber that intercepts the entire x-ray beam. The DTS has been modified to determine KAP when there are beam non-uniformities that can be modeled. For example,more » the DTS includes models of the three compensation filters with tapered edges located in the collimator assembly of the Toshiba Infinix fluoroscopic C-Arm and can track their movement. To determine the air kerma after the filters, DTS includes transmission factors for the compensation filters as a function of kVp and beam filtration. A virtual KAP dosimeter is simulated in the DTS by an array of graphic vertices; the air kerma at each vertex is corrected by the field non-uniformity, which in this case is the attenuation factor for those rays which pass through the filter. The products of individual vertex air-kerma values for all vertices within the beam times the effective-area-per-vertex are summed for each x-ray pulse to yield the KAP per pulse and the cumulative KAP for the procedure is then calculated. Results: The KAP values estimated by DTS with the compensation filter inserted into the x-ray field agree within ± 6% with the values displayed on the fluoroscopy unit monitor, which are measured with a transmission chamber. Conclusion: The DTS can account for field non-uniformities such as result from the use of compensation filters in calculating KAP and can obviate the need for a KAP transmission ionization chamber. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

Calibration of EBT2 film by the PDD method with scanner non-uniformity correction.

PubMed

Chang, Liyun; Chui, Chen-Shou; Ding, Hueisch-Jy; Hwang, Ing-Ming; Ho, Sheng-Yow

2012-09-21

The EBT2 film together with a flatbed scanner is a convenient dosimetry QA tool for verification of clinical radiotherapy treatments. However, it suffers from a relatively high degree of uncertainty and a tedious film calibration process for every new lot of films, including cutting the films into several small pieces, exposing with different doses, restoring them back and selecting the proper region of interest (ROI) for each piece for curve fitting. In this work, we present a percentage depth dose (PDD) method that can accurately calibrate the EBT2 film together with the scanner non-uniformity correction and provide an easy way to perform film dosimetry. All films were scanned before and after the irradiation in one of the two homemade 2 mm thick acrylic frames (one portrait and the other landscape), which was located at a fixed position on the scan bed of an Epson 10 000XL scanner. After the pre-irradiated scan, the film was placed parallel to the beam central axis and sandwiched between six polystyrene plates (5 cm thick each), followed by irradiation of a 20 × 20 cm² 6 MV photon beam. Two different beams on times were used on two different films to deliver a dose to the film ranging from 32 to 320 cGy. After the post-irradiated scan, the net optical densities for a total of 235 points on the beam central axis on the films were auto-extracted and compared with the corresponding depth doses that were calculated through the measurement of a 0.6 cc farmer chamber and the related PDD table to perform the curve fitting. The portrait film location was selected for routine calibration, since the central beam axis on the film is parallel to the scanning direction, where non-uniformity correction is not needed (Ferreira et al 2009 Phys. Med. Biol. 54 1073-85). To perform the scanner non-uniformity calibration, the cross-beam profiles of the film were analysed by referencing the measured profiles from a Profiler™. Finally, to verify our method, the films were exposed to 60° physical wedge fields and the compositive fields, and their relative dose profiles were compared with those from the water phantom measurement. The fitting uncertainty was less than 0.5% due to the many calibration points, and the overall calibration uncertainty was within 3% for doses above 50 cGy, when the average of four films were used for the calibration. According to our study, the non-uniformity calibration factor was found to be independent of the given dose for the EBT2 film and the relative dose differences between the profiles measured by the film and the Profiler were within 1.5% after applying the non-uniformity correction. For the verification tests, the relative dose differences between the measurements by films and in the water phantom, when the average of three films were used, were generally within 3% for the 60° wedge fields and compositive fields, respectively. In conclusion, our method is convenient, time-saving and cost-effective, since no film cutting is needed and only two films with two exposures are needed.

Search for ionisation density effects in the radiation absorption stage in LiF:Mg,Ti.

PubMed

Nail, I; Horowitz, Y S; Oster, L; Brandan, M E; Rodríguez-Villafuerte, M; Buenfil, A E; Ruiz-Trejo, C; Gamboa-Debuen, I; Avila, O; Tovar, V M; Olko, P; Ipe, N

2006-01-01

Optical absorption (OA) dose-response of LiF:Mg,Ti (TLD-100) is studied as a function of electron energy (ionisation density) and irradiation dose. Contrary to the situation in thermoluminescence dose-response where the supralinearity is strongly energy-dependent, no dependence of the OA dose filling constants on energy is observed. This result is interpreted as indicating a lack of competitive process in the radiation absorption stage. The lack of an energy dependence of the dose filling constant also suggests that the charge carrier migration distances are sufficiently large to smear out the differences in the non-uniform distribution of ionisation events created by the impinging gamma/electron radiation of various energies.

EVALUATION OF EYE LENS DOSE TO WORKERS IN THE STEAM GENERATOR AT THE KOREAN OPTIMIZED POWER REACTOR 1000.

PubMed

Maeng, Sung Jun; Kim, Jinhwan; Cho, Gyuseong

2018-03-15

ICRP (2011) revised the dose limit to the eye lens to 20 mSv/y based on a recent epidemiological study of radiation-induced cataracts. Maintenance of steam generators at nuclear power plants is one of the highest radiation-associated tasks within a non-uniform radiation field. This study aims to evaluate eye lens doses in the steam generators of the Korean OPR1000 design. The source term was characterized based on the CRUD-specific activity, and both the eye lens dose and organ dose were simulated using MCNP6 combined with an ICRP voxel phantom and a mesh phantom, respectively. The eye lens dose was determined to be 5.39E-02-9.43E-02 Sv/h, with a negligible effect by beta particles. As the effective dose was found to be 0.81-1.21 times the lens equivalent dose depending on the phantom angles, the former can be used to estimate the lens dose in the SG of the OPR1000 for radiation monitoring purposes.

Dosimetric comparison of helical tomotherapy, RapidArc, and a novel IMRT & Arc technique for esophageal carcinoma.

PubMed

Martin, Spencer; Chen, Jeff Z; Rashid Dar, A; Yartsev, Slav

2011-12-01

To compare radiotherapy treatment plans for mid- and distal-esophageal cancer with primary involvement of the gastroesophageal (GE) junction using a novel IMRT & Arc technique (IMRT & Arc), helical tomotherapy (HT), and RapidArc (RA1 and RA2). Eight patients treated on HT for locally advanced esophageal cancer with radical intent were re-planned for RA and IMRT&Arc. RA plans employed single and double arcs (RA1 and RA2, respectively), while IMRT&Arc plans had four fixed-gantry IMRT fields and a conformal arc. Dose-volume histogram statistics, dose uniformity, and dose homogeneity were analyzed to compare treatment plans. RA2 plans showed significant improvement over RA1 plans in terms of OAR dose and PTV dose uniformity and homogeneity. HT plan provided best dose uniformity (p=0.001) and dose homogeneity (p=0.002) to planning target volume (PTV), while IMRT&Arc and RA2 plans gave lowest dose to lungs among four radiotherapy techniques with acceptable PTV dose coverage. Mean V(10) of the lungs was significantly reduced by the RA2 plans compared to IMRT&Arc (40.3%, p=0.001) and HT (66.2%, p<0.001) techniques. Mean V(15) of the lungs for the RA2 plans also showed significant improvement over the IMRT&Arc (25.2%, p=0.042) and HT (34.8%, p=0.027) techniques. These improvements came at the cost of higher doses to the heart volume compared to HT and IMRT&Arc techniques. Mean lung dose (MLD) for the IMRT&Arc technique (21.2 ± 5.0% of prescription dose) was significantly reduced compared to HT (26.3%, p=0.004), RA1 (23.3%, p=0.028), and RA2 (23.2%, p=0.017) techniques. The IMRT&Arc technique is a good option for treating esophageal cancer with thoracic involvement. It achieved optimal low dose to the lungs and heart with acceptable PTV coverage. HT is a good option for treating esophageal cancer with little thoracic involvement as it achieves superior dose conformality and uniformity. The RA2 technique provided for improved treatment plans using additional arcs with low doses to the lungs at the cost of increased heart dose. Plan quality could still be improved through the use of additional arcs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Beam’s-eye-view dosimetrics (BEVD) guided rotational station parameter optimized radiation therapy (SPORT) planning based on reweighted total-variation minimization

NASA Astrophysics Data System (ADS)

Kim, Hojin; Li, Ruijiang; Lee, Rena; Xing, Lei

2015-03-01

Conventional VMAT optimizes aperture shapes and weights at uniformly sampled stations, which is a generalization of the concept of a control point. Recently, rotational station parameter optimized radiation therapy (SPORT) has been proposed to improve the plan quality by inserting beams to the regions that demand additional intensity modulations, thus formulating non-uniform beam sampling. This work presents a new rotational SPORT planning strategy based on reweighted total-variation (TV) minimization (min.), using beam’s-eye-view dosimetrics (BEVD) guided beam selection. The convex programming based reweighted TV min. assures the simplified fluence-map, which facilitates single-aperture selection at each station for single-arc delivery. For the rotational arc treatment planning and non-uniform beam angle setting, the mathematical model needs to be modified by additional penalty term describing the fluence-map similarity and by determination of appropriate angular weighting factors. The proposed algorithm with additional penalty term is capable of achieving more efficient and deliverable plans adaptive to the conventional VMAT and SPORT planning schemes by reducing the dose delivery time about 5 to 10 s in three clinical cases (one prostate and two head-and-neck (HN) cases with a single and multiple targets). The BEVD guided beam selection provides effective and yet easy calculating methodology to select angles for denser, non-uniform angular sampling in SPORT planning. Our BEVD guided SPORT treatment schemes improve the dose sparing to femoral heads in the prostate and brainstem, parotid glands and oral cavity in the two HN cases, where the mean dose reduction of those organs ranges from 0.5 to 2.5 Gy. Also, it increases the conformation number assessing the dose conformity to the target from 0.84, 0.75 and 0.74 to 0.86, 0.79 and 0.80 in the prostate and two HN cases, while preserving the delivery efficiency, relative to conventional single-arc VMAT plans.

SU-C-213-06: Dosimetric Verification of 3D Printed Electron Bolus

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

Rasmussen, K; Corbett, M; Pelletier, C

2015-06-15

Purpose: To determine the dosimetric effect of 3D printed bolus in an anthropomorphic phantom. Methods: Conformable bolus material was generated for an anthropomorphic phantom from a DICOM volume. The bolus generated was a uniform expansion of 5mm applied to the nose region of the phantom, as this is a difficult area to uniformly apply bolus clinically. A Printrbot metal 3D Printer using PLA plastic generated the bolus. A 9MeV anterior beam with a 5cm cone was used to deliver dose to the nose of the phantom. TLD measurements were compared to predicted values at the phantom surface. Film planes weremore » analyzed for the printed bolus, a standard 5mm bolus sheet placed on the phantom, and the phantom with no bolus applied to determine depth and dose distributions. Results: TLDs measured within 2.5% of predicted value for the 3D bolus. Film demonstrated a more uniform dose distribution in the nostril region for the 3d printed bolus than the standard bolus. This difference is caused by the air gap created around the nostrils by the standard bolus, creating a secondary build-up region. Both demonstrated a 50% central axis dose shift of 5mm relative to the no bolus film. HU for the bolus calculated the PLA electron density to be ∼1.1g/cc. Physical density was measured to be 1.3g/cc overall. Conclusion: 3D printed PLA bolus demonstrates improved dosimetric performance to standard bolus for electron beams with complex phantom geometry.« less

The preparation of gold nanoparticles and evaluation of their immunological function effects on rats.

PubMed

Wang, Yong-Tang; Lu, Xiu-Min; Zhu, Feng; Zhao, Min

2014-01-01

As a new type of biomaterials, gold nanoparticles (GNPs), also known as colloidal gold (CG), have a wide biomedical application. In this study, GNPs with diameters of 10, 15, and 25 nm were prepared by sodium citrate reduction, and detected by common optical property, ultraviolet-visible (UV-vis) absorbance spectroscopy, and scanning electron microscope (SEM), separately for identification of the particle size and uniformity. In order to observe the effects of GNPs on immune function, adult Sprague Dawley (SD) rats were immunized with the above three GNPs, each having three doses of 0.2, 0.4, and 0.6 ml, and rats without immunization served as negative control. After immunization, proliferation activity of blood and spleen lymphocyte and the levels of interleukin-2 (IL-2) in serum and supernatant of spleen lymphocyte were detected by thiazoleblue (MTT) assay and enzyme linked immunosorbent assay (ELISA), respectively. The results indicated that different size of GNPs was prepared, and the uniformity increased with the decrease of the size of particles. Different diameters and doses of GNPs have different effects on proliferation of blood and spleen lymphocyte, as well as the levels of IL-2 in serum and supernatant of spleen lymphocyte. The 15 nm CG in 0.6 ml dose group could most significantly promote blood and spleen lymphocyte proliferation, and enhance IL-2 levels in serum and supernatant of spleen lymphocyte. Taken together, the findings revealed that application of CG prepared by sodium citrate reduction could enhance specific and nonspecific immune responses, and the 0.6 ml dose of 15 nm CG might be the best immunizing dose in rats. This fact may serve as a further evidence for using CG as a novel immunoadjuvant in the future.

Comparative study of two negative CAR resists: EN-024M and NEB 31

NASA Astrophysics Data System (ADS)

Baik, Ki-Ho; Dean, Robert; Lem, Homer Y.; Osborne, Stephen P.; Mueller, Mark A.; Cole, Damon M.

2004-08-01

In this paper, two negative-tone chemically amplified resists (CAR) are evaluated. The methodology and results are compared and discussed. The resists include EN-024M from TOK, and NEB 31 from Sumitomo. Both resists show high contrast, good dry etch selectivity, and high environmental stability. EN-024M showed good coating uniformity while NEB31 showed a coating uniformity problem. This was a round "dimple" approximately one centimeter in diameter of different thickness and density at the center of the plate. We addressed the "dimple" coating problem as described in the paper. Optimum PAB and PEB temperatures and nominal to maximum doses for isolated features were determined by running a matrix of PAB and PEB temperatures along with a dose series. We evaluated the process and compared the lithographic performance in terms of dose sensitivity, dose and bake latitude, resolution, resist profile, OPC (Optical Proximity Correction) pattern fidelity, CD uniformity, environmental stability, Line Edge Roughness (LER) and etching bias and resistance.

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying

2012-06-01

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

The development and investigation of a prototype three-dimensional compensator for whole brain radiation therapy

NASA Astrophysics Data System (ADS)

Keall, Paul; Arief, Isti; Shamas, Sofia; Weiss, Elisabeth; Castle, Steven

2008-05-01

Whole brain radiation therapy (WBRT) is the standard treatment for patients with brain metastases, and is often used in conjunction with stereotactic radiotherapy for patients with a limited number of brain metastases, as well as prophylactic cranial irradiation. The use of open fields (conventionally used for WBRT) leads to higher doses to the brain periphery if dose is prescribed to the brain center at the largest lateral radius. These dose variations potentially compromise treatment efficacy and translate to increased side effects. The goal of this research was to design and construct a 3D 'brain wedge' to compensate dose heterogeneities in WBRT. Radiation transport theory was invoked to calculate the desired shape of a wedge to achieve a uniform dose distribution at the sagittal plane for an ellipsoid irradiated medium. The calculations yielded a smooth 3D wedge design to account for the missing tissue at the peripheral areas of the brain. A wedge was machined based on the calculation results. Three ellipsoid phantoms, spanning the mean and ± two standard deviations from the mean cranial dimensions were constructed, representing 95% of the adult population. Film was placed at the sagittal plane for each of the three phantoms and irradiated with 6 MV photons, with the wedge in place. Sagittal plane isodose plots for the three phantoms demonstrated the feasibility of this wedge to create a homogeneous distribution with similar results observed for the three phantom sizes, indicating that a single wedge may be sufficient to cover 95% of the adult population. The sagittal dose is a reasonable estimate of the off-axis dose for whole brain radiation therapy. Comparing the dose with and without the wedge the average minimum dose was higher (90% versus 86%), the maximum dose was lower (107% versus 113%) and the dose variation was lower (one standard deviation 2.7% versus 4.6%). In summary, a simple and effective 3D wedge for whole brain radiotherapy has been developed. The wedge gives a more uniform dose distribution than commonly used techniques. Further development and shape optimization may be necessary prior to clinical implementation.

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H

2011-06-01

To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

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

Acar, Hilal; Chiu-Tsao, Sou-Tung; Oezbay, Ismail

Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eyemore » plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.« less

Incorporating partial shining effects in proton pencil-beam dose calculation

NASA Astrophysics Data System (ADS)

Li, Yupeng; Zhang, Xiaodong; Fwu Lii, Ming; Sahoo, Narayan; Zhu, Ron X.; Gillin, Michael; Mohan, Radhe

2008-02-01

A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

Characterization and control of EUV scanner dose uniformity and stability

NASA Astrophysics Data System (ADS)

Robinson, Chris; Corliss, Dan; Meli, Luciana; Johnson, Rick

2018-03-01

The EUV source is an impressive feat of engineering that provides 13.5 nm radiation by vaporizing tin droplets with a high power CO2 laser and focusing the photons produced in the resultant plasma into the scanner illumination system. Great strides have been made in addressing the many potential stability challenges, but there are still residual spatial and temporal dose non-uniformity signatures. Since even small dose errors can impact the yieldable process window for the advanced lithography products that are exposed on EUV scanners it is crucial to monitor and control the dose variability. Using on-board metrology, the EUV scanner outputs valuable metrics that provide real time insight into the dose performance. We have supplemented scanner data collection with a wafer based methodology that provides high throughput, high sensitivity, quantitative characterization of the EUV scanner dose delivery. The technique uses open frame EUV exposures, so it is exclusive of lithographic pattern imaging, exclusive of lithographic mask pattern and not limited by placement of metrology features. Processed wafers are inspected rapidly, providing 20,000 pixels of detail per exposure field in approximately one minute. Exposing the wafer on the scanner with a bit less than the resist E0 (open frame clearing dose) results in good sensitivity to small variations in the EUV dose delivered. The nominal exposure dose can be modulated by field to calibrate the inspection results and provide quantitative assessment of variations with < 1% sensitivity. This technique has been used for dose uniformity assessments. It is also being used for long term dose stability monitoring and has proven valuable for short term dose stability follow up investigations.

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

NASA Astrophysics Data System (ADS)

Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

2002-12-01

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

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

Verification of the grid size and angular increment effects in lung stereotactic body radiation therapy using the dynamic conformal arc technique

NASA Astrophysics Data System (ADS)

Park, Hae-Jin; Suh, Tae-Suk; Park, Ji-Yeon; Lee, Jeong-Woo; Kim, Mi-Hwa; Oh, Young-Taek; Chun, Mison; Noh, O. Kyu; Suh, Susie

2013-06-01

The dosimetric effects of variable grid size and angular increment were systematically evaluated in the measured dose distributions of dynamic conformal arc therapy (DCAT) for lung stereotactic body radiation therapy (SBRT). Dose variations with different grid sizes (2, 3, and 4 mm) and angular increments (2, 4, 6, and 10°) for spherical planning target volumes (PTVs) were verified in a thorax phantom by using EBT2 films. Although the doses for identical PTVs were predicted for the different grid sizes, the dose discrepancy was evaluated using one measured dose distribution with the gamma tool because the beam was delivered in the same set-up for DCAT. The dosimetric effect of the angular increment was verified by comparing the measured dose area histograms of organs at risk (OARs) at each angular increment. When the difference in the OAR doses is higher than the uncertainty of the film dosimetry, the error is regarded as the angular increment effect in discretely calculated doses. In the results, even when a 2-mm grid size was used with an elaborate dose calculation, 4-mm grid size led to a higher gamma pass ratio due to underdosage, a steep-dose descent gradient, and lower estimated PTV doses caused by the smoothing effect in the calculated dose distribution. An undulating dose distribution and a difference in the maximum contralateral lung dose of up to 14% were observed in dose calculation using a 10° angular increment. The DCAT can be effectively applied for an approximately spherical PTV in a relatively uniform geometry, which is less affected by inhomogeneous materials and differences in the beam path length.

Dosimetric verification of stereotactic radiosurgery/stereotactic radiotherapy dose distributions using Gafchromic EBT3.

PubMed

Cusumano, Davide; Fumagalli, Maria L; Marchetti, Marcello; Fariselli, Laura; De Martin, Elena

2015-01-01

Aim of this study is to examine the feasibility of using the new Gafchromic EBT3 film in a high-dose stereotactic radiosurgery and radiotherapy quality assurance procedure. Owing to the reduced dimensions of the involved lesions, the feasibility of scanning plan verification films on the scanner plate area with the best uniformity rather than using a correction mask was evaluated. For this purpose, signal values dispersion and reproducibility of film scans were investigated. Uniformity was then quantified in the selected area and was found to be within 1.5% for doses up to 8 Gy. A high-dose threshold level for analyses using this procedure was established evaluating the sensitivity of the irradiated films. Sensitivity was found to be of the order of centiGray for doses up to 6.2 Gy and decreasing for higher doses. The obtained results were used to implement a procedure comparing dose distributions delivered with a CyberKnife system to planned ones. The procedure was validated through single beam irradiation on a Gafchromic film. The agreement between dose distributions was then evaluated for 13 patients (brain lesions, 5 Gy/die prescription isodose ~80%) using gamma analysis. Results obtained using Gamma test criteria of 5%/1 mm show a pass rate of 94.3%. Gamma frequency parameters calculation for EBT3 films showed to strongly depend on subtraction of unexposed film pixel values from irradiated ones. In the framework of the described dosimetric procedure, EBT3 films proved to be effective in the verification of high doses delivered to lesions with complex shapes and adjacent to organs at risk. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dosimetric verification of stereotactic radiosurgery/stereotactic radiotherapy dose distributions using Gafchromic EBT3

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

Cusumano, Davide, E-mail: davide.cusumano@unimi.it; Fumagalli, Maria L.; Marchetti, Marcello

2015-10-01

Aim of this study is to examine the feasibility of using the new Gafchromic EBT3 film in a high-dose stereotactic radiosurgery and radiotherapy quality assurance procedure. Owing to the reduced dimensions of the involved lesions, the feasibility of scanning plan verification films on the scanner plate area with the best uniformity rather than using a correction mask was evaluated. For this purpose, signal values dispersion and reproducibility of film scans were investigated. Uniformity was then quantified in the selected area and was found to be within 1.5% for doses up to 8 Gy. A high-dose threshold level for analyses usingmore » this procedure was established evaluating the sensitivity of the irradiated films. Sensitivity was found to be of the order of centiGray for doses up to 6.2 Gy and decreasing for higher doses. The obtained results were used to implement a procedure comparing dose distributions delivered with a CyberKnife system to planned ones. The procedure was validated through single beam irradiation on a Gafchromic film. The agreement between dose distributions was then evaluated for 13 patients (brain lesions, 5 Gy/die prescription isodose ~80%) using gamma analysis. Results obtained using Gamma test criteria of 5%/1 mm show a pass rate of 94.3%. Gamma frequency parameters calculation for EBT3 films showed to strongly depend on subtraction of unexposed film pixel values from irradiated ones. In the framework of the described dosimetric procedure, EBT3 films proved to be effective in the verification of high doses delivered to lesions with complex shapes and adjacent to organs at risk.« less

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

PubMed

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

External exposure doses due to gamma emitting natural radionuclides in some Egyptian building materials.

PubMed

Moharram, B M; Suliman, M N; Zahran, N F; Shennawy, S E; El Sayed, A R

2012-01-01

Using of building materials containing naturally occurring radionuclides as (238)U, (232)Th and (40)K and their progeny results in an external exposures of the housing of such buildings. In the present study, indoor dose rates for typical Egyptian rooms are calculated using the analytical method and activity concentrations of natural radionuclides in some building materials. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling assumed. Different room models are assumed to discuss variation of indoor dose rates according to variation in room construction. Activity concentrations of (238)U, (232)Th and (40)K content in eight samples representative Clay soil and different building materials used in most recent Egyptian building were measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The specific activity for (238)U, (232)Th and (40)K, from the selected samples, were in the range 14.15-60.64, 2.75-84.66 and 7.35-554.4Bqkg(-1), respectively. The average indoor absorbed dose rates in air ranged from 0.005μGyh(-1) to 0.071μGyh(-1) and the corresponding population-weighted annual effective dose due to external gamma radiation varies from 0.025 to 0.345mSv. An outdoor dose rate for typical building samples in addition to some radiological hazards has been introduced for comparison. Copyright © 2011 Elsevier Ltd. All rights reserved.

Plasma Doping—Enabling Technology for High Dose Logic and Memory Applications

NASA Astrophysics Data System (ADS)

Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

2008-11-01

As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

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

Liu, G; Liu, J

Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vectormore » Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer hospital of Hunan province.« less

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.

Comparison of low-contrast detectability between two CT reconstruction algorithms using voxel-based 3D printed textured phantoms.

PubMed

Solomon, Justin; Ba, Alexandre; Bochud, François; Samei, Ehsan

2016-12-01

To use novel voxel-based 3D printed textured phantoms in order to compare low-contrast detectability between two reconstruction algorithms, FBP (filtered-backprojection) and SAFIRE (sinogram affirmed iterative reconstruction) and determine what impact background texture (i.e., anatomical noise) has on estimating the dose reduction potential of SAFIRE. Liver volumes were segmented from 23 abdominal CT cases. The volumes were characterized in terms of texture features from gray-level co-occurrence and run-length matrices. Using a 3D clustered lumpy background (CLB) model, a fitting technique based on a genetic optimization algorithm was used to find CLB textures that were reflective of the liver textures, accounting for CT system factors of spatial blurring and noise. With the modeled background texture as a guide, four cylindrical phantoms (Textures A-C and uniform, 165 mm in diameter, and 30 mm height) were designed, each containing 20 low-contrast spherical signals (6 mm diameter at nominal contrast levels of ∼3.2, 5.2, 7.2, 10, and 14 HU with four repeats per signal). The phantoms were voxelized and input into a commercial multimaterial 3D printer (Object Connex 350), with custom software for voxel-based printing (using principles of digital dithering). Images of the textured phantoms and a corresponding uniform phantom were acquired at six radiation dose levels (SOMATOM Flash, Siemens Healthcare) and observer model detection performance (detectability index of a multislice channelized Hotelling observer) was estimated for each condition (5 contrasts × 6 doses × 2 reconstructions × 4 backgrounds = 240 total conditions). A multivariate generalized regression analysis was performed (linear terms, no interactions, random error term, log link function) to assess whether dose, reconstruction algorithm, signal contrast, and background type have statistically significant effects on detectability. Also, fitted curves of detectability (averaged across contrast levels) as a function of dose were constructed for each reconstruction algorithm and background texture. FBP and SAFIRE were compared for each background type to determine the improvement in detectability at a given dose, and the reduced dose at which SAFIRE had equivalent performance compared to FBP at 100% dose. Detectability increased with increasing radiation dose (P = 2.7 × 10 -59 ) and contrast level (P = 2.2 × 10 -86 ) and was higher in the uniform phantom compared to the textured phantoms (P = 6.9 × 10 -51 ). Overall, SAFIRE had higher d' compared to FBP (P = 0.02). The estimated dose reduction potential of SAFIRE was found to be 8%, 10%, 27%, and 8% for Texture-A, Texture-B, Texture-C and uniform phantoms. In all background types, detectability was higher with SAFIRE compared to FBP. However, the relative improvement observed from SAFIRE was highly dependent on the complexity of the background texture. Iterative algorithms such as SAFIRE should be assessed in the most realistic context possible.

A Technique for Murine Irradiation in a Controlled Gas Environment

PubMed Central

Walb, M. C.; Moore, J. E.; Attia, A.; Wheeler, K. T.; Miller, M. S.; Munley, M. T.

2013-01-01

NASA’s extra-vehicular activities (EVAs) involve exposure to high energy photons while breathing 100% oxygen. Using previously verified mouse models, our laboratory is studying whether low dose irradiation under these hyperoxic conditions could lead to an increase in carcinogenic potential. To simulate the environment astronauts encounter during an EVA, enclosed chambers were constructed that allowed for mouse movement, controlled gas conditions, and uniform radiation dose delivery. Custom-built gas chambers with input/output gas valves and dividers that allowed for uniform gas flow were used to keep 6 unanesthetized mice separated while they were irradiated. The chambers were supplied with 100% oxygen or air using ball valves linked together with T-splitters. A calibrated ion chamber was used to verify the radiation dose distribution across an entire chamber. Mice were placed in the gas environments for 0.5 h, irradiated with a 10 or 18 MV photon beam from a medical linear accelerator, and left in their gas environment for 2 h post-irradiation. We irradiated 200 mice (5 different doses between 0–1000 mGy) under normoxic or 100% oxygen conditions. For the next step of this research, these mice will be euthanized 9 months post-irradiation, and lung tumors will be counted and sized to determine if hyperoxia increases the carcinogenic effect for this model. PMID:22846321

Forward treatment planning techniques to reduce the normalization effect in Gamma Knife radiosurgery.

PubMed

Cheng, Hao-Wen; Lo, Wei-Lun; Kuo, Chun-Yuan; Su, Yu-Kai; Tsai, Jo-Ting; Lin, Jia-Wei; Wang, Yu-Jen; Pan, David Hung-Chi

2017-11-01

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications. © 2017 Shuang Ho Hospital-Taipei Medical University. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

NASA Astrophysics Data System (ADS)

Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

2016-08-01

We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

The effect of anterior proton beams in the setting of a prostate-rectum spacer

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

Christodouleas, John P., E-mail: christojo@uphs.upenn.edu; Tang, Shikui; Susil, Robert C.

2013-10-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangementmore » anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.« less

The effect of anterior proton beams in the setting of a prostate-rectum spacer

PubMed Central

Christodouleas, John P.; Tang, Shikui; Susil, Robert C.; McNutt, Todd R.; Song, Danny Y.; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; DeWeese, Theodore L.; Lu, Hsiao-Ming; Both, Stefan

2014-01-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS. PMID:23578497

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.

Evaluation and optimization of the new EBT2 radiochromic film dosimetry system for patient dose verification in radiotherapy

NASA Astrophysics Data System (ADS)

Richley, L.; John, A. C.; Coomber, H.; Fletcher, S.

2010-05-01

A new radiochromic film, the yellow Gafchromic EBT2, has been marketed as a drop-in replacement for the discontinued blue EBT film. In order to verify the manufacturer's claims prior to clinical use, EBT2 was characterized in transmission, and the less commonly used, reflection modes with an Epson Expression 10000XL A3 flatbed scanner. The red channel was confirmed to provide the greatest sensitivity and was used for all measurements. The post-irradiation darkening of the film was investigated, and the relative response was found to be dose dependent with higher doses stabilizing earlier than lower doses. After 13 h all dose levels had stabilized to within 1% of their value at 24 h. Uniformity of irradiated EBT2 films was within 0.8% and 1.2% (2SD of signal), in reflection and transmission modes, respectively. The light scattering effect, arising from the structure and thickness of EBT2, was found to give rise to an apparent scanner non-uniformity of up to 5.5% in signal. In reflection mode, differences of up to 1.2% were found between the signal obtained from a small film fragment (5 × 5 cm2) and the signal obtained from the same fragment bordered by extra film. Further work is needed to determine the origin of this effect, as there will be implications for reflection dosimetry of intensity modulated fields; reflection mode cannot yet be regarded as a viable alternative to transmission mode. Our results suggest that EBT2 film is a valid alternative, rather than a direct replacement for EBT film.

A Science and Risk-Based Pragmatic Methodology for Blend and Content Uniformity Assessment.

PubMed

Sayeed-Desta, Naheed; Pazhayattil, Ajay Babu; Collins, Jordan; Doshi, Chetan

2018-04-01

This paper describes a pragmatic approach that can be applied in assessing powder blend and unit dosage uniformity of solid dose products at Process Design, Process Performance Qualification, and Continued/Ongoing Process Verification stages of the Process Validation lifecycle. The statistically based sampling, testing, and assessment plan was developed due to the withdrawal of the FDA draft guidance for industry "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment." This paper compares the proposed Grouped Area Variance Estimate (GAVE) method with an alternate approach outlining the practicality and statistical rationalization using traditional sampling and analytical methods. The approach is designed to fit solid dose processes assuring high statistical confidence in both powder blend uniformity and dosage unit uniformity during all three stages of the lifecycle complying with ASTM standards as recommended by the US FDA.

Optical CT imaging of solid radiochromic dosimeters in mismatched refractive index solutions using a scanning laser and large area detector.

PubMed

Dekker, Kurtis H; Battista, Jerry J; Jordan, Kevin J

2016-08-01

The practical use of the PRESAGE® solid plastic dosimeter is limited by the inconvenience of immersing it in high-viscosity oils to achieve refractive index matching for optical computed tomography (CT) scanning. The oils are slow to mix and difficult to clean from surfaces, and the dosimeter rotation can generate dynamic Schlieren inhomogeneity patterns in the reference liquid, limiting the rotational and overall scan speed. Therefore, it would be beneficial if lower-viscosity, water-based solutions with slightly unmatched refractive index could be used instead. The purpose of this work is to demonstrate the feasibility of allowing mismatched conditions when using a scanning laser system with a large acceptance angle detector. A fiducial-based ray path measurement technique is combined with an iterative CT reconstruction algorithm to reconstruct images. A water based surrounding liquid with a low viscosity was selected for imaging PRESAGE® solid dosimeters. Liquid selection was optimized to achieve as high a refractive index as possible while avoiding rotation-induced Schlieren effects. This led to a refractive index mismatch of 6% between liquid and dosimeters. Optical CT scans were performed with a fan-beam scanning-laser optical CT system with a large area detector to capture most of the refracted rays. A fiducial marker placed on the wall of a cylindrical sample occludes a given light ray twice. With knowledge of the rotation angle and the radius of the cylindrical object, the actual internal path of each ray through the dosimeter can be calculated. Scans were performed with 1024 projections of 512 data samples each, and rays were rebinned to form 512 parallel-beam projections. Reconstructions were performed on a 512 × 512 grid using 100 iterations of the SIRT iterative CT algorithm. Proof of concept was demonstrated with a uniformly attenuating solution phantom. PRESAGE® dosimeters (11 cm diameter) were irradiated with Cobalt-60 irradiator to achieve either a uniform dose or a 2-level "step-dose" pattern. With 6% refractive index mismatching, a circular field of view of 85% of the diameter of a cylindrical sample can be reconstructed accurately. Reconstructed images of the test solution phantom were uniform (within 3%) inside this radius. However, the dose responses of the PRESAGE® samples were not spatially uniform, with variations of at least 5% in sensitivity. The variation appears as a "cupping" artifact with less sensitivity in the middle than at the periphery of the PRESAGE® cylinder. Polarization effects were also detected for these samples. The fiducial-based ray path measurement scheme, coupled with an iterative reconstruction algorithm, enabled optical CT scanning of PRESAGE® dosimeters immersed in mismatched refractive index solutions. However, improvements to PRESAGE® dose response uniformity are required.

Preservative-free triamcinolone acetonide suspension developed for intravitreal injection.

PubMed

Bitter, Christoph; Suter, Katja; Figueiredo, Verena; Pruente, Christian; Hatz, Katja; Surber, Christian

2008-02-01

All commercially available triamcinolone acetonide (TACA) suspensions, used for intravitreal treatment, contain retinal toxic vehicles (e.g., benzyl alcohol, solubilizer). Our aim was to find a convenient and reproducible method to compound a completely preservative-free TACA suspension, adapted to the intraocular physiology, with consistent quality (i.e., proven sterility and stability, constant content and dose uniformity, defined particle size, and 1 year shelf life). We evaluated two published (Membrane-filter, Centrifugation) and a newly developed method (Direct Suspending) to compound TACA suspensions for intravitreal injection. Parameters as TACA content (HPLC), particle size (microscopy and laser spectrometry), sterility, and bacterial endotoxins were assessed. Stability testing (at room temperature and 40 degrees C) was performed: color and homogeneity (visually), particle size (microscopically), TACA content and dose uniformity (HPLC) were analyzed according to International Conference on Harmonisation guidelines. Contrary to the known methods, the direct suspending method is convenient, provides a TACA suspension, which fulfills all compendial requirements, and has a 2-year shelf life. We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA--not biased by varying doses and toxic compounds or their residues.

MRI-based IMRT planning for MR-linac: comparison between CT- and MRI-based plans for pancreatic and prostate cancers

NASA Astrophysics Data System (ADS)

Prior, Phil; Chen, Xinfeng; Botros, Maikel; Paulson, Eric S.; Lawton, Colleen; Erickson, Beth; Li, X. Allen

2016-05-01

The treatment planning in radiation therapy (RT) can be arranged to combine benefits of computed tomography (CT) and magnetic resonance imaging (MRI) together to maintain dose calculation accuracy and improved target delineation. Our aim is study the dosimetric impact of uniform relative electron density assignment on IMRT treatment planning with additional consideration given to the effect of a 1.5 T transverse magnetic field (TMF) in MR-Linac. A series of intensity modulated RT (IMRT) plans were generated for two representative tumor sites, pancreas and prostate, using CT and MRI datasets. Representative CT-based IMRT plans were generated to assess the impact of different electron density (ED) assignment on plan quality using CT without the presence of a 1.5 T TMF. The relative ED (rED) values used were taken from the ICRU report 46. Four types of rED assignment in the organs at risk (OARs), the planning target volumes (PTV) and in the non-specified tissue (NST) were considered. Dose was recalculated (no optimization) using a Monaco 5.09.07a research planning system employing Monte Carlo calculations with an option to include TMF. To investigate the dosimetric effect of different rED assignment, the dose-volume parameters (DVPs) obtained from these specific rED plans were compared to those obtained from the original plans based on CT. Overall, we found that uniform rED assignment results in differences in DVPs within 3% for the PTV and 5% for OAR. The presence of 1.5 T TMF on IMRT DVPs resulted in differences that were generally within 3% of the Gold St for both the pancreas and prostate. The combination of uniform rED assignment and TMF produced differences in DVPs that were within 4-5% of the Gold St. Larger differences in DVPs were observed for OARs on T2-based plans. The effects of using different rED assignments and the presence of 1.5 T TMF for pancreas and prostate IMRT plans are generally within 3% and 5% of PTV and OAR Gold St values. There are noticeable dosimetric differences between the CT- and MRI-based IMRT plans caused by a combination of anatomical changes between the two image acquisition times, uniform rED assignment and 1.5 T TMF. This work was present in part at the 2014 ASTRO annual meeting.

Ion recombination and polarity correction factors for a plane-parallel ionization chamber in a proton scanning beam.

PubMed

Liszka, Małgorzata; Stolarczyk, Liliana; Kłodowska, Magdalena; Kozera, Anna; Krzempek, Dawid; Mojżeszek, Natalia; Pędracka, Anna; Waligórski, Michael Patrick Russell; Olko, Paweł

2018-01-01

To evaluate the effect on charge collection in the ionization chamber (IC) in proton pencil beam scanning (PBS), where the local dose rate may exceed the dose rates encountered in conventional MV therapy by up to three orders of magnitude. We measured values of the ion recombination (k s ) and polarity (k pol ) correction factors in water, for a plane-parallel Markus TM23343 IC, using the cyclotron-based Proteus-235 therapy system with an active proton PBS of energies 30-230 MeV. Values of k s were determined from extrapolation of the saturation curve and the Two-Voltage Method (TVM), for planar fields. We compared our experimental results with those obtained from theoretical calculations. The PBS dose rates were estimated by combining direct IC measurements with results of simulations performed using the FLUKA MC code. Values of k s were also determined by the TVM for uniformly irradiated volumes over different ranges and modulation depths of the proton PBS, with or without range shifter. By measuring charge collection efficiency versus applied IC voltage, we confirmed that, with respect to ion recombination, our proton PBS represents a continuous beam. For a given chamber parameter, e.g., nominal voltage, the value of k s depends on the energy and the dose rate of the proton PBS, reaching c. 0.5% for the TVM, at the dose rate of 13.4 Gy/s. For uniformly irradiated regular volumes, the k s value was significantly smaller, within 0.2% or 0.3% for irradiations with or without range shifter, respectively. Within measurement uncertainty, the average value of k pol , for the Markus TM23343 IC, was close to unity over the whole investigated range of clinical proton beam energies. While no polarity effect was observed for the Markus TM23343 IC in our pencil scanning proton beam system, the effect of volume recombination cannot be ignored. © 2017 American Association of Physicists in Medicine.

Dosimetry procedures for an industrial irradiation plant

NASA Astrophysics Data System (ADS)

Grahn, Ch.

Accurate and reliable dosimetry procedures constitute a very important part of process control and quality assurance at a radiation processing plant. γ-Dose measurements were made on the GBS 84 irradiator for food and other products on pallets or in containers. Chemical dosimeters wre exposed in the facility under conditions of the typical plant operation. The choice of the dosimeter systems employed was based on the experience in chemical dosimetry gained over several years. Dose uniformity information was obtained in air, spices, bulbs, feeds, cosmetics, plastics and surgical goods. Most products currently irradiated require dose uniformity which can be efficiently provided by pallet or box irradiators like GBS 84. The radiation performance characteristics and some dosimetry procedures are discussed.

SU-E-T-540: Volumetric Modulated Total Body Irradiation Using a Rotational Lazy Susan-Like Immobilization System

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

Gu, X; Hrycushko, B; Lee, H

2014-06-01

Purpose: Traditional extended SSD total body irradiation (TBI) techniques can be problematic in terms of patient comfort and/or dose uniformity. This work aims to develop a comfortable TBI technique that achieves a uniform dose distribution to the total body while reducing the dose to organs at risk for complications. Methods: To maximize patient comfort, a lazy Susan-like couch top immobilization system which rotates about a pivot point was developed. During CT simulation, a patient is immobilized by a Vac-Lok bag within the body frame. The patient is scanned head-first and then feet-first following 180° rotation of the frame. The twomore » scans are imported into the Pinnacle treatment planning system and concatenated to give a full-body CT dataset. Treatment planning matches multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. VMAT fields of the torso are optimized to satisfy lung dose constraints while achieving a therapeutic dose to the torso. The multiple isocenter VMAT fields are delivered with an indexed couch, followed by body frame rotation about the pivot point to treat the lower body isocenters. The treatment workflow was simulated with a Rando phantom, and the plan was mapped to a solid water slab phantom for point- and film-dose measurements at multiple locations. Results: The treatment plan of 12Gy over 8 fractions achieved 80.2% coverage of the total body volume within ±10% of the prescription dose. The mean lung dose was 8.1 Gy. All ion chamber measurements were within ±1.7% compared to the calculated point doses. All relative film dosimetry showed at least a 98.0% gamma passing rate using a 3mm/3% passing criteria. Conclusion: The proposed patient comfort-oriented TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs.« less

Three-Dimensional Dose Calculation for Total Body Irradiation

NASA Astrophysics Data System (ADS)

Ito, Akira

Bone Marrow Transplant (BMT) therapy has been a big success in the treatment of leukemia and other haematopoietic diseases 1 . Prior to BMT, total body irradiation (TBI) is given to the patient for the purpose of (1) killing leukemia cells in bone marrow, as well as in the whole body, and (2) producing immuno-suppressive status in the patient so that the donor's marrow cells will be transplanted without rejection. TBI employs a very large field photon beam to irradiate the whole body of the patient. A uniform dose distribution over the entire body is the treatment goal. To prevent the occurrence of a serious side effect (interstitial pneumonia), the lung dose should not exceed a certain level. This novel technique poses various new radiological physics problems. The accurate assessment of dose and dose distribution in the patient is essential. Physical and dosimetric problems associated with TBI are reviewed elsewhere 2,3 .

An investigation of nonuniform dose deposition from an electron beam

NASA Astrophysics Data System (ADS)

Lilley, William; Luu, Kieu X.

1994-08-01

In a search for an explanation of nonuniform electron-beam dose deposition, the integrated tiger series (ITS) of coupled electron/photon Monte Carlo transport codes was used to calculate energy deposition in the package materials of an application-specific integrated circuit (ASIC) while the thicknesses of some of the materials were varied. The thicknesses of three materials that were in the path of an electron-beam pulse were varied independently so that analysis could determine how the radiation dose measurements using thermoluminescent dosimeters (TLD's) would be affected. The three materials were chosen because they could vary during insertion of the die into the package or during the process of taking dose measurements. The materials were aluminum, HIPEC (a plastic), and silver epoxy. The calculations showed that with very small variations in thickness, the silver epoxy had a large effect on the dose uniformity over the area of the die.

Development of a center for light ion therapy and accurate tumor diagnostics at karolinska institutet and hospital

NASA Astrophysics Data System (ADS)

Brahme, Anders; Lind, Bengt K.

2002-04-01

Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the "classical" approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose high-precision "boost" treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionization density dose to the normal tissue stroma inside the tumor and to ensure a microscopically uniform dose delivery. The principal idea of the center is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy center will therefore be combined with advanced tumor diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumor diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy where alterations in the delivered dose can be corrected by subsequent treatments

Poster — Thur Eve — 53: Novel Technique for the Measurement of Ultra-Superficial Doses Using Gafchromic Film

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

Marcos, M.; Devic, S.

2014-08-15

Purpose: Dose build-up and electron contamination are two closely related quantities with important implications in radiotherapy, yet they are quite difficult to measure with great certainty. We present a novel technique for measuring ultra-superficial doses. Method and Materials: We used Gafchromic EBT-3 film which have an effective point of measurement of roughly 153 micros (effective depth in water). By peeling off one of the polyester layers, the active layer becomes the top layer and we obtain a film with a effective point of measurement of 15 microns (effective depth in water). A film calibration was performed using a 180 kVpmore » orthovoltage beam. Since the active layer of the film may have been compressed or perturbed during the peeling of clear polyester we use a triple-channel film calibration technique to minimize the effects of non-uniformity in the active layer. We measured surface doses of orthovoltage beams with lead cutouts in place to introduce contaminant photoelectrons. Results: Our measurements show that the dose enhancement near the edges of the lead were about 125% relative to central axis for 6 cm diameter cutouts up to 170% for 2 cm diameter cutouts, which were within 5% of our EGSnrc based Monte Carlo simulations.« less

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

Yi, B; Chung, H; Mutaf, Y

Purpose: To test a novel total body irradiation (TBI) system using conformal partial arc with patient lying on the stationary couch which is biologically equivalent to a moving couch TBI. This improves the scanning field TBI, which is previously presented. Methods: The Uniform MU Modulated arc Segments TBI or UMMS-TBI scans the treatment plane with a constant machine dose rate and a constant gantry rotation speed. A dynamic MLC pattern which moves while gantry rotates has been designed so that the treatment field moves same distance at the treatment plane per each gantry angle, while maintaining same treatment field sizemore » (34cm) at the plane. Dose across the plane varies due to the geometric differences including the distance from the source to a point of interest and the different attenuation from the slanted depth which changes the effective depth. Beam intensity is modulated to correct the dose variation across the plane by assigning the number of gantry angles inversely proportional to the uncorrected dose. Results: Measured dose and calculated dose matched within 1 % for central axis and 3% for off axis for various patient scenarios. Dose from different distance does not follow the inverse square relation as it is predicted from calculation. Dose uniformity better than 5% across 180 cm at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 200 MU/min. Conclusion: This novel technique, yet accurate but easy to implement enables TBI treatment in a small treatment room with less program development preparation than other techniques. The VMAT function of treatment delivery is not required to modulate beams. One delivery pattern can be used for different patients by changing the monitor units.« less

SU-E-T-287: Patterns of Patient Specific Dosimetry in Total Body Irradiation.

PubMed

Akino, Y; McMullen, K; Das, I

2012-06-01

Total body irradiation (TBI) is commonly used for conditioning prior to transplant in hematologic and immunologic diseases. Due to variability in body thickness, achieving dose uniformity across body within ±10% of the prescribed dose is challenging. The dose uniformity is further complicated by, techniques and beam energy used, lung shielding and selection of detector. The translational table technique for TBI could compensate for estimated delivered dose to whole body by adjusting couch speed during treatment. However, it is difficult to accurately estimate the dose by calculation and hence in vivo dosimetry (IVD) is routinely performed for TBI. The patterns of patient specific dosimetry, IVD are presented in this study. Under IRB exempt status, 161 patients who received TBI treatment between 2006 and 2011 were retrospectively analyzed using the treatment records from Cobalt-60 teletherapy unit and translational treatment couch. During treatment, IVD detectors (TLD, diode, or MOSFET) were placed on patient surface; both entrance and exit dose were recorded at the patient's head, neck, mediastinum, umbilicus, and knee. When large differences between prescribed and measured dose were observed, the dose delivery was corrected for subsequent fractions by adjustment in couch speed and/or bolus placement. Across the entire cohort, the mean (range) percent variance between calculated and measured dose were -2.3% (-66.2 - 35.3), 1.1% (-62.2 - 40.3), -1.9% (-66.4 - 46.6), -1.1% (-35.2 - 42.9), and 3.4% (-47.9 - 108.5) for head, neck, mediastinum, umbilicus, and knee, respectively. When the dose differences for multiple fractions were averaged, the compliance (±10%) between prescription and measured dose was improved as at umbilicus from 83.9% to 98.5%. Actual dose measurement analysis of TBI patients reveals a potentially wide variance from calculated dose. Dose uniformity can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments. This work was supported by the JSPS Core-to-Core Program No. 23003. © 2012 American Association of Physicists in Medicine.

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

Radiochromic film dosimetry for UV-C treatments of apple fruit

USDA-ARS?s Scientific Manuscript database

Radiochromic films were evaluated for their suitability to estimate UV-C doses and dose uniformity on apple fruit surface. Parameters investigated included film type, color changes of the films in response to different UV-C doses, color stability of films, UV-C light intensity, and temperature. In...

Regulating exposure of the lens of the eye to ionising radiations.

PubMed

Thorne, M C

2012-06-01

The International Commission on Radiological Protection (ICRP) has reviewed recent epidemiological evidence suggesting that, for the lens of the eye, the threshold in absorbed dose for the induction of deleterious health effects is about 0.5 Gy. On this basis, the Commission recommends that for occupational exposure in planned exposure situations, the equivalent dose limit for the lens of the eye should be 20 mSv in a year, averaged over defined periods of 5 yr, with exposure not exceeding 50 mSv in any single year. This paper summarises the data that have been taken into account by the ICRP and critically examines whether the proposed downward revision of the dose limit is justified. Overall, it is concluded that the accumulating radiobiological and epidemiological evidence makes it more appropriate to treat cataract induction as a stochastic rather than a deterministic effect. Within this framework, it is illogical to have the same dose limit for the lens of the eye as for the whole body irradiated uniformly. This could be addressed either by removing the special dose limit for the lens of the eye, assigning it an appropriate tissue weighting factor and including it in the computation of the effective dose, or through a composite approach involving the use of a tissue weighting factor for effective dose computations together with a special limit on the equivalent dose to the lens of the eye to ensure that no individual was subject to an unacceptably high risk of induction of clinically significant cataracts.

Isoniazid, Pyrazinamide and Rifampicin Content Variation in Split Fixed-Dose Combination Tablets

PubMed Central

Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

2014-01-01

Setting In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. Objective To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Design Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. Results All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. Conclusion In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis. PMID:25004128

Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets.

PubMed

Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

2014-01-01

In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.

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

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

PubMed

Hancock, Bruno C; Garcia-Munoz, Salvador

2013-03-01

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

An evaluation of the Meditech M250 and a comparison with other CT scanners.

PubMed

Greensmith, R; Richardson, R B; Sargood, A J; Stevens, P H; Mackintosh, I P

1985-11-01

The Meditech M250 computerised tomography (CT) machine was evaluated during the first half of 1984. Measurements were made of noise, modulation transfer function, slice width, radiation dose profile, uniformity and linearity of CT number, effective photon energy and parameters relating to machine specification, such as pixel size and scan time. All breakdowns were logged to indicate machine reliability. A comparison with the established EMI CT1010 and CT5005 was made for noise, resolution and multislice radiation dose, as well as the dose efficiency or quality (Q) factor for both head and body modes of operation. The M250 was found to perform to its intended specification with an acceptable level of reliability.

Does partial titin degradation affect sarcomere length non-uniformities and force in active and passive myofibrils?

PubMed

Joumaa, Venus; Bertrand, Fanny; Liu, Shuyue; Poscente, Sophia; Herzog, Walter

2018-05-16

The aim of this study was to determine the role of titin in preventing the development of sarcomere length non-uniformities following activation and after active and passive stretch, by determining the effect of partial titin degradation on sarcomere length non-uniformities and force in passive and active myofibrils. Selective partial titin degradation was performed using a low dose of trypsin. Myofibrils were set at a sarcomere length of 2.4 µm and then passively stretched to sarcomere lengths of 3.4 µm and 4.4 µm. In the active condition, myofibrils were set at a sarcomere length of 2.8µm, activated and actively stretched by 1 µm/sarcomere. The extent of sarcomere length non-uniformities was calculated for each sarcomere as the absolute difference between sarcomere length and the mean sarcomere length of the myofibril. Our main finding is that partial titin degradation does not increase sarcomere length non-uniformities after passive stretch and activation compared to when titin is intact, but increases the extent of sarcomere length non-uniformities after active stretch. Furthermore, when titin was partially degraded, active and passive stresses were substantially reduced. These results suggest that titin plays a crucial role in actively stretched myofibrils and is likely involved in active and passive force production.

CD uniformity control for thick resist process

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Liu, Yu-Lin; Wang, Weihung; Yang, Mars; Yang, Elvis; Yang, T. H.; Chen, K. C.

2017-03-01

In order to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories, 3D stacked flash cell array has been proposed. In constructing 3D NAND flash memories, the higher bit number per area is achieved by increasing the number of stacked layers. Thus the so-called "staircase" patterning to form electrical connection between memory cells and word lines has become one of the primarily critical processes in 3D memory manufacture. To provide controllable critical dimension (CD) with good uniformity involving thick photo-resist has also been of particular concern for staircase patterning. The CD uniformity control has been widely investigated with relatively thinner resist associated with resolution limit dimension but thick resist coupling with wider dimension. This study explores CD uniformity control associated with thick photo-resist processing. Several critical parameters including exposure focus, exposure dose, baking condition, pattern size and development recipe, were found to strongly correlate with the thick photo-resist profile accordingly affecting the CD uniformity control. To minimize the within-wafer CD variation, the slightly tapered resist profile is proposed through well tailoring the exposure focus and dose together with optimal development recipe. Great improvements on DCD (ADI CD) and ECD (AEI CD) uniformity as well as line edge roughness were achieved through the optimization of photo resist profile.

Nanoscale dose deposition in cell structures under X-ray irradiation treatment assisted with nanoparticles: An analytical approach to the relative biological effectiveness.

PubMed

Melo-Bernal, W; Chernov, V; Chernov, G; Barboza-Flores, M

2018-08-01

In this study, an analytical model for the assessment of the modification of cell culture survival under ionizing radiation assisted with nanoparticles (NPs) is presented. The model starts from the radial dose deposition around a single NP, which is used to describe the dose deposition in a cell structure with embedded NPs and, in turn, to evaluate the number of lesions formed by ionizing radiation. The model is applied to the calculation of relative biological effectiveness values for cells exposed to 0.5mg/g of uniformly dispersed NPs with a radius of 10nm made of Fe, I, Gd, Hf, Pt and Au and irradiated with X-rays of energies 20keV higher than the element K-shell binding energy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Ju, N; Chen, C; Gans, S

Purpose: A fixed-beam room could be underutilized in a multi-room proton center. We investigated the use of proton pencil beam scanning (PBS) on a fixed-beam as an alternative for posterior fossa tumor bed (PF-TB) boost treatments which were usually treating on a gantry with uniform scanning. Methods: Five patients were treated with craniospinal irradiation (CSI, 23.4 or 36.0 Gy(RBE)) followed by a PF-TB boost to 54 Gy(RBE) with proton beams. Three PF-TB boost plans were generated for each patient: (1) a uniform scanning (US) gantry plan with 4–7 posterior fields shaped with apertures and compensators (2) a PBS plan usingmore » bi-lateral and vertex fields with a 3-mm planning organ-at-risk volume (PRV) expansion around the brainstem and (3) PBS fields using same beam arrangement but replacing the PRV with robust optimization considering a 3-mm setup uncertainty. Results: A concave 54-Gy(RBE) isodose line surrounding the brainstem could be achieved using all three techniques. The mean V95% of the PTV was 99.7% (range: 97.6% to 100%) while the V100% of the PTV ranged from 56.3% to 93.1% depending on the involvement of the brainstem with the PTV. The mean doses received by 0.05 cm{sup 3} of the brainstem were effectively identical: 54.0 Gy(RBE), 53.4 Gy(RBE) and 53.3 Gy(RBE) for US, PBS optimized with PRV, and PBS optimized with robustness plans respectively. The cochlea mean dose increased by 23% of the prescribed boost dose in average from the bi-lateral fields used in the PBS plan. Planning time for the PBS plan with PRV was 5–10 times less than the US plan and the robustly optimized PBS plan. Conclusion: We have demonstrated that a fixed-beam with PBS can deliver a dose distribution comparable to a gantry plan using uniform scanning. Planning time can be reduced substantially using a PRV around the brainstem instead of robust optimization.« less

A Biodosimeter for Multiparametric Determination of Radiation Dose, Radiation Quality, and Radiation Risk

NASA Technical Reports Server (NTRS)

Richmond, Robert; Cruz, Angela; Jansen, Heather; Bors, Karen

2003-01-01

Predicting risk of human cancer following exposure of an individual or a population to ionizing radiation is challenging. To an approximation, this is because uncertainties of uniform absorption of dose and the uniform processing of dose-related damage at the cellular level within a complex set of biological variables degrade the confidence of predicting the delayed expression of cancer as a relatively rare event. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the risk of developing cancer by the cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported. This is the demonstration of a dose responsive field effect of enhanced expression of keratin 18 (K18) in cultures of human mammary epithelial cells irradiated with cesium-1 37 gamma-rays. Dose response of enhanced K18 expression was experimentally extended over a range of 30 to 90 cGy for cells evaluated at mid-log phase. K18 has been reported to be a marker for tumor staging and for apoptosis, and thereby serves as an example of a potential marker for cancer risk, where the reality of such predictive value would require additional experimental development. Since observed radiogenic increase in expression of K18 is a field effect, ie., chronically present in all cells of the irradiated population, it may be hypothesized that K18 expression in specific cells absorbing particulate irradiation, such as the high-LET-producing atomic nuclei of space radiation, will report on both the single-cell distributions of those particles amongst cells within the exposed population, and that the relatively high dose per cell delivered by densely ionizing tracks of those intersecting particles will lead to cell-specific high-expression levels of K18, thereby providing analytical end points that may be used to resolve both the quantity and the quality of the radiation dose absorbed by individual cells. The principal value of this reported potential multiparametric cellular biodosimeter is suggested to be that it justifies a search for similar but more robust radiogenic assays. That is, K18 is only one radiation dose-sensitive expressed protein, whereas analytical techniques of genomics and proteomics can be used to simultaneously analyze multiple gene and protein expressions resulting from radiation-dose absorption. The potential usefulness of multiparametric cellular biodosimeters will be best realized from quantitatively profiling these multiple markers using these modern techniques.

Collimated proton pencil-beam scanning for superficial targets: impact of the order of range shifter and aperture

NASA Astrophysics Data System (ADS)

Bäumer, C.; Janson, M.; Timmermann, B.; Wulff, J.

2018-04-01

To assess if apertures shall be mounted upstream or downstream of a range shifting block if these field-shaping devices are combined with the pencil-beam scanning delivery technique (PBS). The lateral dose fall-off served as a benchmark parameter. Both options realizing PBS-with-apertures were compared to the uniform scanning mode. We also evaluated the difference regarding the out-of-field dose caused by interactions of protons in beam-shaping devices. The potential benefit of the downstream configuration over the upstream configuration was estimated analytically. Guided by this theoretical evaluation a mechanical adapter was developed which transforms the upstream configuration provided by the proton machine vendor to a downstream configuration. Transversal dose profiles were calculated with the Monte-Carlo based dose engine of the commercial treatment planning system RayStation 6. Two-dimensional dose planes were measured with an ionization chamber array and a scintillation detector at different depths and compared to the calculation. Additionally, a clinical example for the irradiation of the orbit was compared for both PBS options and a uniform scanning treatment plan. Assuming the same air gap the lateral dose fall-off at the field edge at a few centimeter depth is 20% smaller for the aperture-downstream configuration than for the upstream one. For both options of PBS-with-apertures the dose fall-off is larger than in uniform scanning delivery mode if the minimum accelerator energy is 100 MeV. The RayStation treatment planning system calculated the width of the lateral dose fall-off with an accuracy of typically 0.1 mm–0.3 mm. Although experiments and calculations indicate a ranking of the three delivery options regarding lateral dose fall-off, there seems to be a limited impact on a multi-field treatment plan.

Nanodosimetry-Based Plan Optimization for Particle Therapy

PubMed Central

Schulte, Reinhard W.

2015-01-01

Treatment planning for particle therapy is currently an active field of research due uncertainty in how to modify physical dose in order to create a uniform biological dose response in the target. A novel treatment plan optimization strategy based on measurable nanodosimetric quantities rather than biophysical models is proposed in this work. Simplified proton and carbon treatment plans were simulated in a water phantom to investigate the optimization feasibility. Track structures of the mixed radiation field produced at different depths in the target volume were simulated with Geant4-DNA and nanodosimetric descriptors were calculated. The fluences of the treatment field pencil beams were optimized in order to create a mixed field with equal nanodosimetric descriptors at each of the multiple positions in spread-out particle Bragg peaks. For both proton and carbon ion plans, a uniform spatial distribution of nanodosimetric descriptors could be obtained by optimizing opposing-field but not single-field plans. The results obtained indicate that uniform nanodosimetrically weighted plans, which may also be radiobiologically uniform, can be obtained with this approach. Future investigations need to demonstrate that this approach is also feasible for more complicated beam arrangements and that it leads to biologically uniform response in tumor cells and tissues. PMID:26167202

Sizes of particles formed during municipal wastewater treatment.

PubMed

Lech, Smoczynski; Marta, Kosobucka; Michal, Smoczynski; Harsha, Ratnaweera; Krystyna, Pieczulis-Smoczynska

2017-02-01

Volumetric diameters Dv and specific surface area SpS of sludge particles formed during chemical coagulation and electrocoagulation of sewage were determined. The obtained aggregate-flocs differed substantially in both Dv and SpS values. The differences in Dv and SpS values of the analyzed particles were interpreted based on theoretical models for expanding aggregates. The most uniform particles were formed under exposure to: (a) optimal and maximal doses of PIX, (b) optimal doses of PAX, (c) maximal doses of the Al electro-coagulant. The lowest PIX dose produced the least uniform particles. Sludge aggregates-particles produced under exposure to minimal doses of PIX and the Al electro-coagulant were characterized by the lowest SpS values. Sludge particles coagulated by PAX and the particles formed at higher doses of PIX and the Al electro-coagulant had higher SpS values. The particles formed at all doses of the applied coagulants and electro-coagulants were generally classified into two size ranges: the main range and the secondary range. Most particles belonged to the main size range. An increase in the percentage of colloidal hydroxide particles in sewage sludge increased SpS.

Multicentre dose audit for clinical trials of radiation therapy in Asia

PubMed Central

Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C.R. Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-01-01

Abstract A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. PMID:27864507

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

Yeslbagg, Y. Ue.; Kuecuekoemeroglu, A.; Kurnaz, A.

Indoor radon studies have been conducted in Artvin, Eastern alack sea region of Turkey using SSNTD type nuclear track detector (CR-39). Radon measurements were done for 4 seasons in 73 dwellings, selected as uniformly distributed as possible. The radon concentrations vary from 21 aq m{sup -3} to 321 aq m{sup -3} with the annual mean concentration of 132 aq m{sup -3} for Artvin. Seasonal variation indoor radon shows high in winter low values in summer. The resulting estimated annual effective dose-equivalent due to inhalation of radon for inhabitants is 3.32 mSv y{sup -1} and the total annual effective dose liesmore » in the range of the action level (3-10 mSv y{sup -1}) recommended by the ICRP.« less

Quantifying the interplay effect in prostate IMRT delivery using a convolution-based method.

PubMed

Li, Haisen S; Chetty, Indrin J; Solberg, Timothy D

2008-05-01

The authors present a segment-based convolution method to account for the interplay effect between intrafraction organ motion and the multileaf collimator position for each particular segment in intensity modulated radiation therapy (IMRT) delivered in a step-and-shoot manner. In this method, the static dose distribution attributed to each segment is convolved with the probability density function (PDF) of motion during delivery of the segment, whereas in the conventional convolution method ("average-based convolution"), the static dose distribution is convolved with the PDF averaged over an entire fraction, an entire treatment course, or even an entire patient population. In the case of IMRT delivered in a step-and-shoot manner, the average-based convolution method assumes that in each segment the target volume experiences the same motion pattern (PDF) as that of population. In the segment-based convolution method, the dose during each segment is calculated by convolving the static dose with the motion PDF specific to that segment, allowing both intrafraction motion and the interplay effect to be accounted for in the dose calculation. Intrafraction prostate motion data from a population of 35 patients tracked using the Calypso system (Calypso Medical Technologies, Inc., Seattle, WA) was used to generate motion PDFs. These were then convolved with dose distributions from clinical prostate IMRT plans. For a single segment with a small number of monitor units, the interplay effect introduced errors of up to 25.9% in the mean CTV dose compared against the planned dose evaluated by using the PDF of the entire fraction. In contrast, the interplay effect reduced the minimum CTV dose by 4.4%, and the CTV generalized equivalent uniform dose by 1.3%, in single fraction plans. For entire treatment courses delivered in either a hypofractionated (five fractions) or conventional (> 30 fractions) regimen, the discrepancy in total dose due to interplay effect was negligible.

Surface applicator of a miniature X-ray tube for superficial electronic brachytherapy of skin cancer.

PubMed

Kim, Hyun Nam; Lee, Ju Hyuk; Park, Han Beom; Kim, Hyun Jin; Cho, Sung Oh

2018-01-01

We designed and fabricated a surface applicator of a novel carbon nanotube (CNT)-based miniature X-ray tube for the use in superficial electronic brachytherapy of skin cancer. To investigate the effectiveness of the surface applicator, the performance of the applicator was numerically and experimentally analyzed. The surface applicator consists of a graphite flattening filter and an X-ray shield. A Monte Carlo radiation transport code, MCNP6, was used to optimize the geometries of both the flattening filter and the shield so that X-rays are generated uniformly over the desired region. The performance of the graphite filter was compared with that of conventional aluminum (Al) filters of different geometries using the numerical simulations. After fabricating a surface applicator, the X-ray spatial distribution was measured to evaluate the performance of the applicator. The graphite filter shows better spatial dose uniformity and less dose distortion than Al filters. Moreover, graphite allows easy fabrication of the flattening filter due to its low X-ray attenuation property, which is particularly important for low-energy electronic brachytherapy. The applicator also shows that no further X-ray shielding is required for the application because unwanted X-rays are completely protected. As a result, highly uniform X-ray dose distribution was achieved from the miniature X-ray tube mounted with the surface applicators. The measured values of both flatness and symmetry were less than 5% and the measured penumbra values were less than 1 mm. All these values satisfy the currently accepted tolerance criteria for radiation therapy. The surface applicator exhibits sufficient performance capability for their application in electronic brachytherapy of skin cancers. © 2017 American Association of Physicists in Medicine.

Luminescence imaging of water during uniform-field irradiation by spot scanning proton beams

NASA Astrophysics Data System (ADS)

Komori, Masataka; Sekihara, Eri; Yabe, Takuya; Horita, Ryo; Toshito, Toshiyuki; Yamamoto, Seiichi

2018-06-01

Luminescence was found during pencil-beam proton irradiation to water phantom and range could be estimated from the luminescence images. However, it is not yet clear whether the luminescence imaging is applied to the uniform fields made of spot-scanning proton-beam irradiations. For this purpose, imaging was conducted for the uniform fields having spread out Bragg peak (SOBP) made by spot scanning proton beams. We designed six types of the uniform fields with different ranges, SOBP widths and irradiation fields. One of the designed fields was irradiated to water phantom and a cooled charge coupled device camera was used to measure the luminescence image during irradiations. We estimated the ranges, field widths, and luminescence intensities from the luminescence images and compared those with the dose distribution calculated by a treatment planning system. For all types of uniform fields, we could obtain clear images of the luminescence showing the SOBPs. The ranges and field widths evaluated from the luminescence were consistent with those of the dose distribution calculated by a treatment planning system within the differences of  ‑4 mm and  ‑11 mm, respectively. Luminescence intensities were almost proportional to the SOBP widths perpendicular to the beam direction. The luminescence imaging could be applied to uniform fields made of spot scanning proton beam irradiations. Ranges and widths of the uniform fields with SOBP could be estimated from the images. The luminescence imaging is promising for the range and field width estimations in proton therapy.

Effects of body and organ size on absorbed dose: there is no standard patient. [Radiation dose distribution in patients following radionuclide administration

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

Poston, J.W.

1976-01-01

The problem of estimating the absorbed dose to organs and tissues of the human body due to the presence of a radiopharmaceutical in one or more organs is discussed. Complications are introduced by the fact that the body is not homogeneous and in many cases the organ shapes are not regular. Publications of the MIRD Committee have provided a direct means of estimating the absorbed dose (or absorbed fraction) for a number of radioisotopes. These estimates are based on Monte Carlo calculations for monoenergetic photons distributed uniformly in organs of an adult phantom. The medical physicist finds that his patientmore » does not resemble the adult phantom. In addition, the absorbed fractions for the adult are not reasonable values for the child. This paper examines how these absorbed fraction estimates apply to a nonstandard patient. (auth)« less

Use of electron cyclotron resonance x-ray source for nondestructive testing application

NASA Astrophysics Data System (ADS)

Baskaran, R.; Selvakumaran, T. S.

2006-03-01

Electron cyclotron resonance (ECR) technique is being used for generating x rays in the low-energy region (<150keV). Recently, the source is used for the calibration of thermoluminescent dosimetry (TLD) badges. In order to qualify the ECR x-ray source for imaging application, the source should give uniform flux over the area under study. Lead collimation arrangement is made to get uniform flux. The flux profile is measured using a teletector at different distance from the port and uniform field region of 10×10cm2 has been marked at 20cm from the x-ray exit port. A digital-to-analog converter (DAC) circuit pack is used for examining the source performance. The required dose for nondestructive testing examination has been estimated using a hospital x-ray machine and it is found to be 0.05mSv. Our source experimental parameters are tuned and the DAC circuit pack was exposed for nearly 7min to get the required dose value. The ECR x-ray source operating parameters are argon pressure: 10-5Torr, microwave power: 350W, and coil current: 0A. The effective energy of the x-ray spectrum is nearly 40keV. The x-ray images obtained from ECR x-ray source and hospital medical radiography machine are compared. It is found that the image obtained from ECR x-ray source is suitable for NDT application.

Dosimetry of a Small-Animal Irradiation Model using a 6 MV Linear Accelerator

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

Fitch, F. Moran; Martinez-Davalos, A.; Garcia-Garduno, O. A.

2010-12-07

A custom made rat-like phantom was used to measure dose distributions using a 6 MV linear accelerator. The phantom has air cavities that simulate the lungs and cylindrical inserts that simulate the backbone. The calculated dose distributions were obtained with the BrainScan v.5.31 TPS software. For the irradiation two cases were considered: (a) near the region where the phantom has two air cavities that simulate the lungs, and (b) with an entirely uniform phantom. The treatment plan consisted of two circular cone arcs that imparted a 500 cGy dose to a simulated lesion in the backbone. We measured dose distributionsmore » using EBT2 GafChromic film and an Epson Perfection V750 scanner working in transmission mode. Vertical and horizontal profiles, isodose curves from 50 to 450 cGy, dose and distance to agreement (DTA) histograms and Gamma index were obtained to compare the dose distributions using DoseLab v4.11. As a result, these calculations show very good agreement between calculated and measured dose distribution in both cases. With a 2% 2 mm criteria 100% of the points pass the Gamma test for the uniform case, while 98.9% of the points do it for the lungs case.« less

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants.

PubMed

Mavroidis, Panayiotis; Katsilieri, Zaira; Kefala, Vasiliki; Milickovic, Natasa; Papanikolaou, Nikos; Karabis, Andreas; Zamboglou, Nikolaos; Baltas, Dimos

2010-09-01

One of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices. The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P + and the biologically effective uniform dose ([Formula: see text]) were used for treatment plan evaluation and comparison. Our results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant ( p = 0.002). The HIPO with MR treatment plans produced a higher P + by 0.5%, which stemmed from a better sparing of the OARs by 1.0%. Both the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions.

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants

PubMed Central

Katsilieri, Zaira; Kefala, Vasiliki; Milickovic, Natasa; Papanikolaou, Nikos; Karabis, Andreas; Zamboglou, Nikolaos; Baltas, Dimos

2010-01-01

Purpose One of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices. Material and methods The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P+ and the biologically effective uniform dose (D¯¯) were used for treatment plan evaluation and comparison. Results Our results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant (p = 0.002). The HIPO with MR treatment plans produced a higher P+ by 0.5%, which stemmed from a better sparing of the OARs by 1.0%. Conclusions Both the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions. PMID:27853473

TU-D-209-02: A Backscatter Point Spread Function for Entrance Skin Dose Determination

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

Vijayan, S; Xiong, Z; Shankar, A

Purpose: To determine the distribution of backscattered radiation to the skin resulting from a non-uniform distribution of primary radiation through convolution with a backscatter point spread function (PSF). Methods: A backscatter PSF is determined using Monte Carlo simulation of a 1 mm primary beam incident on a 30 × 30 cm × 20 cm thick PMMA phantom using EGSnrc software. A primary profile is similarly obtained without the phantom and the difference from the total provides the backscatter profile. This scatter PSF characterizes the backscatter spread for a “point” primary interaction and can be convolved with the entrance primary dosemore » distribution to obtain the total entrance skin dose. The backscatter PSF was integrated into the skin dose tracking system (DTS), a graphical utility for displaying the color-coded skin dose distribution on a 3D graphic of the patient during interventional fluoroscopic procedures. The backscatter convolution method was validated for the non-uniform beam resulting from the use of an ROI attenuator. The ROI attenuator is a copper sheet with about 20% primary transmission (0.7 mm thick) containing a circular aperture; this attenuator is placed in the beam to reduce dose in the periphery while maintaining full dose in the region of interest. The DTS calculated primary plus backscatter distribution is compared to that measured with GafChromic film and that calculated using EGSnrc Monte-Carlo software. Results: The PSF convolution method used in the DTS software was able to account for the spread of backscatter from the ROI region to the region under the attenuator. The skin dose distribution determined using DTS with the ROI attenuator was in good agreement with the distributions measured with Gafchromic film and determined by Monte Carlo simulation Conclusion: The PSF convolution technique provides an accurate alternative for entrance skin dose determination with non-uniform primary x-ray beams. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

High-dose MVCT image guidance for stereotactic body radiation therapy

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

Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.

Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machinemore » by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.« less

High-dose MVCT image guidance for stereotactic body radiation therapy.

PubMed

Westerly, David C; Schefter, Tracey E; Kavanagh, Brian D; Chao, Edward; Lucas, Dan; Flynn, Ryan T; Miften, Moyed

2012-08-01

Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp∕mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.

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

Oborn, B; Ge, Y; Hardcastle, N

Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: 9 clinical lung plans were recalculated using Monte Carlo methods and external inline (parallel to the beam direction) magnetic fields of 0.5 T, 1.0 T and 3 T were included. Three plans were 6MV 3D-CRT and six were 6MV IMRT. The GTV’s ranged from 0.8 cc to 73 cc, while the PTV ranged from 1 cc to 180 cc. Results: The inline magnetic field has a moderatemore » impact in lung dose distributions by reducing the lateral scatter of secondary electrons and causing a small local dose increase. Superposition of multiple small beams acts to superimpose the small dose increases and can lead to significant dose enhancements, especially when the GTV is low density. Two plans with very small, low mean density GTV’s (<1 cc, ρ(mean)<0.35g/cc) showed uniform increases of 16% and 23% at 1 T throughout the PTV. Three plans with moderate mean density PTV’s (3–13 cc, ρ(mean)=0.58–0.67 g/cc) showed 6% mean dose enhancement at 1 T in the PTV, however not uniform throughout the GTV/PTV. Replanning would benefit these cases. The remaining 5 plans had large dense GTV’s (∼ 1 g/cc) and so only a minimal (<2%) enhancement was seen. In general the mean dose enhancement at 0.5 T was 60% less than 1 T, while 5–50% higher at 3 T. Conclusions: A paradigm shift in the efficacy of small lung tumor radiotherapy is predicted with future inline MRI-linac systems. This will be achieved by carefully taking advantage of the reduction of lateral electronic disequilibrium withing lung tissue that is induced naturally inside strong inline magnetic fields.« less

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

2000-05-01

We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

Margin estimation and disturbances of irradiation field in layer-stacking carbon-ion beams for respiratory moving targets.

PubMed

Tajiri, Shinya; Tashiro, Mutsumi; Mizukami, Tomohiro; Tsukishima, Chihiro; Torikoshi, Masami; Kanai, Tatsuaki

2017-11-01

Carbon-ion therapy by layer-stacking irradiation for static targets has been practised in clinical treatments. In order to apply this technique to a moving target, disturbances of carbon-ion dose distributions due to respiratory motion have been studied based on the measurement using a respiratory motion phantom, and the margin estimation given by the square root of the summation Internal margin2+Setup margin2 has been assessed. We assessed the volume in which the variation in the ratio of the dose for a target moving due to respiration relative to the dose for a static target was within 5%. The margins were insufficient for use with layer-stacking irradiation of a moving target, and an additional margin was required. The lateral movement of a target converts to the range variation, as the thickness of the range compensator changes with the movement of the target. Although the additional margin changes according to the shape of the ridge filter, dose uniformity of 5% can be achieved for a spherical target 93 mm in diameter when the upward range variation is limited to 5 mm and the additional margin of 2.5 mm is applied in case of our ridge filter. Dose uniformity in a clinical target largely depends on the shape of the mini-peak as well as on the bolus shape. We have shown the relationship between range variation and dose uniformity. In actual therapy, the upper limit of target movement should be considered by assessing the bolus shape. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

SU-E-T-193: FMEA Severity Scores - Do We Really Know?

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

Khan, A; Robertson, JD; Narra, V

2014-06-01

Purpose: Mycosis fungoides is a common form of cutaneous T-cell lymphoma which generally affects the skin. A typical course of treatment may include fractionated total skin electron beam therapy. Given the difficulties in uniformly irradiating some regions of the body and the need for frequent visits within the context of a fractionated protocol, this study investigated the feasibility of delivering the dose using form-fitting cloth which contained phosphorous-32 as a source for beta particle irradiation. Methods: A piece of fabric (0.97 g) consisting of a blend of spandex and flame retardant material impregnated with phosphorus-31 (2000 ppm) was bombarded withmore » neutrons to produce phosphorus-32. The cloth was then laid flat and a stack of radiochromic film placed on top. Sheets of film and tissue equivalent plastic were layered to form a stack measuring a total of 1 cm thickness and remained sandwiched for 77.3 hr. Results: The initial activity of the activated cloth was 44 μCi of P-32. The absorbed dose was uniform within planes parallel to the cloth and exponentially dependent on depth, delivering 560cGy at 0.3mm and falling to 20cGy at 3mm. Conclusion: The total dose prescribed for a typical course of TSET for mycosis fungoides is 36Gy delivered over 9 weeks and is expected to treat to at least 5mm depth. Therefore, the P-32 impregnated cloth may not be clinically indicated to treat this disease given the unfavorable depth-dose characteristics. However, a major advantage of using form-fitting cloth is the uniformity with which the dose could be delivered over the skin in areas which are not flat. Increasing the distance between cloth and skin could improve the depth-dose characteristics.« less

Clean focus, dose and CD metrology for CD uniformity improvement

NASA Astrophysics Data System (ADS)

Lee, Honggoo; Han, Sangjun; Hong, Minhyung; Kim, Seungyoung; Lee, Jieun; Lee, DongYoung; Oh, Eungryong; Choi, Ahlin; Kim, Nakyoon; Robinson, John C.; Mengel, Markus; Pablo, Rovira; Yoo, Sungchul; Getin, Raphael; Choi, Dongsub; Jeon, Sanghuck

2018-03-01

Lithography process control solutions require more exacting capabilities as the semiconductor industry goes forward to the 1x nm node DRAM device manufacturing. In order to continue scaling down the device feature sizes, critical dimension (CD) uniformity requires continuous improvement to meet the required CD error budget. In this study we investigate using optical measurement technology to improve over CD-SEM methods in focus, dose, and CD. One of the key challenges is measuring scanner focus of device patterns. There are focus measurement methods based on specially designed marks on scribe-line, however, one issue of this approach is that it will report focus of scribe line which is potentially different from that of the real device pattern. In addition, scribe-line marks require additional design and troubleshooting steps that add complexity. In this study, we investigated focus measurement directly on the device pattern. Dose control is typically based on using the linear correlation behavior between dose and CD. The noise of CD measurement, based on CD-SEM for example, will not only impact the accuracy, but also will make it difficult to monitor dose signature on product wafers. In this study we will report the direct dose metrology result using an optical metrology system which especially enhances the DUV spectral coverage to improve the signal to noise ratio. CD-SEM is often used to measure CD after the lithography step. This measurement approach has the advantage of easy recipe setup as well as the flexibility to measure critical feature dimensions, however, we observe that CD-SEM metrology has limitations. In this study, we demonstrate within-field CD uniformity improvement through the extraction of clean scanner slit and scan CD behavior by using optical metrology.

Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

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

Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.

2013-01-01

Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD wasmore » calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.« less

COMPARISON OF ORGAN DOSES IN HUMAN PHANTOMS: VARIATIONS DUE TO BODY SIZE AND POSTURE.

PubMed

Feng, Xu; Xiang-Hong, Jia; Qian, Liu; Xue-Jun, Yu; Zhan-Chun, Pan; Chun-Xin, Yang

2017-04-20

Organ dose calculations performed using human phantoms can provide estimates of astronauts' health risks due to cosmic radiation. However, the characteristics of such phantoms strongly affect the estimation precision. To investigate organ dose variations with body size and posture in human phantoms, a non-uniform rational B-spline boundary surfaces model was constructed based on cryosection images. This model was used to establish four phantoms with different body size and posture parameters, whose organs parameters were changed simultaneously and which were voxelised with 4 × 4 × 4 mm3 resolution. Then, using Monte Carlo transport code, the organ doses caused by ≤500 MeV isotropic incident protons were calculated. The dose variations due to body size differences within a certain range were negligible, and the doses received in crouching and standing-up postures were similar. Therefore, a standard Chinese phantom could be established, and posture changes cannot effectively protect astronauts during solar particle events. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multicentre dose audit for clinical trials of radiation therapy in Asia.

PubMed

Mizuno, Hideyuki; Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C R Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-05-01

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Treatment of cooling tower blowdown water containing silica, calcium and magnesium by electrocoagulation.

PubMed

Liao, Z; Gu, Z; Schulz, M C; Davis, J R; Baygents, J C; Farrell, J

2009-01-01

This research investigated the effectiveness of electrocoagulation using iron and aluminium electrodes for treating cooling tower blowdown (CTB) waters containing dissolved silica (Si(OH)(4)), Ca(2 + ) and Mg(2 + ). The removal of each target species was measured as a function of the coagulant dose in simulated CTB waters with initial pH values of 5, 7, and 9. Experiments were also performed to investigate the effect of antiscaling compounds and coagulation aids on hardness ion removal. Both iron and aluminum electrodes were effective at removing dissolved silica. For coagulant doses < or =3 mM, silica removal was a linear function of the coagulant dose, with 0.4 to 0.5 moles of silica removed per mole of iron or aluminium. Iron electrodes were only 30% as effective at removing Ca(2 + ) and Mg(2 + ) as compared to silica. There was no measurable removal of hardness ions by aluminium electrodes in the absence of organic additives. Phosphonate based antiscaling compounds were uniformly effective at increasing the removal of Ca(2 + ) and Mg(2 + ) by both iron and aluminium electrodes. Cationic and amphoteric polymers used as coagulation aids were also effective at increasing hardness ion removal.

Gaining Control over Radiolytic Synthesis of Uniform Sub-3-nanometer Palladium Nanoparticles: Use of Aromatic Liquids in the Electron Microscope

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

Abellan Baeza, Patricia; Parent, Lucas R.; Al Hasan, Naila M.

2016-01-07

Synthesizing nanomaterials of uniform shape and size is of critical importance to access and manipulate the novel structure-property relationships arising at the nanoscale. In this work we synthesize Pd nanoparticles with well-controlled size using in situ liquid-stage scanning transmission electron microscopy (STEM) and demonstrate a match between the reaction kinetics and products of the radiolytic and chemical syntheses of size-stabilized Pd nanoparticles. We quantify the effect of electron dose on the nucleation kinetics, and compare these results with in situ small angle X-ray scattering (SAXS) experiments investigating the effect of temperature during chemical synthesis. This work introduces methods for precisemore » control of nanoparticle synthesis in the STEM and provides a means to uncover the fundamental processes behind the size and shape stabilization of nanoparticles.« less

Bowtie filters for dedicated breast CT: Theory and computational implementation

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

Kontson, Kimberly, E-mail: Kimberly.Kontson@fda.hhs.gov; Jennings, Robert J.

Purpose: To design bowtie filters with improved properties for dedicated breast CT to improve image quality and reduce dose to the patient. Methods: The authors present three different bowtie filters designed for a cylindrical 14-cm diameter phantom with a uniform composition of 40/60 breast tissue, which vary in their design objectives and performance improvements. Bowtie design #1 is based on single material spectral matching and produces nearly uniform spectral shape for radiation incident upon the detector. Bowtie design #2 uses the idea of basis material decomposition to produce the same spectral shape and intensity at the detector, using two differentmore » materials. Bowtie design #3 eliminates the beam hardening effect in the reconstructed image by adjusting the bowtie filter thickness so that the effective attenuation coefficient for every ray is the same. All three designs are obtained using analytical computational methods and linear attenuation coefficients. Thus, the designs do not take into account the effects of scatter. The authors considered this to be a reasonable approach to the filter design problem since the use of Monte Carlo methods would have been computationally intensive. The filter profiles for a cone-angle of 0° were used for the entire length of each filter because the differences between those profiles and the correct cone-beam profiles for the cone angles in our system are very small, and the constant profiles allowed construction of the filters with the facilities available to us. For evaluation of the filters, we used Monte Carlo simulation techniques and the full cone-beam geometry. Images were generated with and without each bowtie filter to analyze the effect on dose distribution, noise uniformity, and contrast-to-noise ratio (CNR) homogeneity. Line profiles through the reconstructed images generated from the simulated projection images were also used as validation for the filter designs. Results: Examples of the three designs are presented. Initial verification of performance of the designs was done using analytical computations of HVL, intensity, and effective attenuation coefficient behind the phantom as a function of fan-angle with a cone-angle of 0°. The performance of the designs depends only weakly on incident spectrum and tissue composition. For all designs, the dynamic range requirement on the detector was reduced compared to the no-bowtie-filter case. Further verification of the filter designs was achieved through analysis of reconstructed images from simulations. Simulation data also showed that the use of our bowtie filters can reduce peripheral dose to the breast by 61% and provide uniform noise and CNR distributions. The bowtie filter design concepts validated in this work were then used to create a computational realization of a 3D anthropomorphic bowtie filter capable of achieving a constant effective attenuation coefficient behind the entire field-of-view of an anthropomorphic breast phantom. Conclusions: Three different bowtie filter designs that vary in performance improvements were described and evaluated using computational and simulation techniques. Results indicate that the designs are robust against variations in breast diameter, breast composition, and tube voltage, and that the use of these filters can reduce patient dose and improve image quality compared to the no-bowtie-filter case.« less

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

Non-uniform dose distributions in cranial radiation therapy

NASA Astrophysics Data System (ADS)

Bender, Edward T.

Radiation treatments are often delivered to patients with brain metastases. For those patients who receive radiation to the entire brain, there is a risk of long-term neuro-cognitive side effects, which may be due to damage to the hippocampus. In clinical MRI and CT scans it can be difficult to identify the hippocampus, but once identified it can be partially spared from radiation dose. Using deformable image registration we demonstrate a semi-automatic technique for obtaining an estimated location of this structure in a clinical MRI or CT scan. Deformable image registration is a useful tool in other areas such as adaptive radiotherapy, where the radiation oncology team monitors patients during the course of treatment and adjusts the radiation treatments if necessary when the patient anatomy changes. Deformable image registration is used in this setting, but there is a considerable level of uncertainty. This work represents one of many possible approaches at investigating the nature of these uncertainties utilizing consistency metrics. We will show that metrics such as the inverse consistency error correlate with actual registration uncertainties. Specifically relating to brain metastases, this work investigates where in the brain metastases are likely to form, and how the primary cancer site is related. We will show that the cerebellum is at high risk for metastases and that non-uniform dose distributions may be advantageous when delivering prophylactic cranial irradiation for patients with small cell lung cancer in complete remission.

Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP.

PubMed

Muselík, Jan; Franc, Aleš; Doležel, Petr; Goněc, Roman; Krondlová, Anna; Lukášová, Ivana

2014-09-01

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.

The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy

NASA Astrophysics Data System (ADS)

Gear, J. I.; Flux, G. D.; Charles-Edwards, E.; Partridge, M.; Cook, G.; Ott, R. J.

2006-07-01

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R2 was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5-35 s-1 with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally irradiated gels. Curve fits to the calibration data followed a single exponential function. The correlation coefficients for internally and externally irradiated gels were 0.991 and 0.985, respectively. With the ability to accurately calibrate internally dosed polymer gels, this technology shows promise as a means to evaluate dosimetry methods, particularly in cases of non-uniform uptake of a radionuclide.

Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

2016-09-01

The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

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

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Quality correction factors of composite IMRT beam deliveries: theoretical considerations.

PubMed

Bouchard, Hugo

2012-11-01

In the scope of intensity modulated radiation therapy (IMRT) dosimetry using ionization chambers, quality correction factors of plan-class-specific reference (PCSR) fields are theoretically investigated. The symmetry of the problem is studied to provide recommendable criteria for composite beam deliveries where correction factors are minimal and also to establish a theoretical limit for PCSR delivery k(Q) factors. The concept of virtual symmetric collapsed (VSC) beam, being associated to a given modulated composite delivery, is defined in the scope of this investigation. Under symmetrical measurement conditions, any composite delivery has the property of having a k(Q) factor identical to its associated VSC beam. Using this concept of VSC, a fundamental property of IMRT k(Q) factors is demonstrated in the form of a theorem. The sensitivity to the conditions required by the theorem is thoroughly examined. The theorem states that if a composite modulated beam delivery produces a uniform dose distribution in a volume V(cyl) which is symmetric with the cylindrical delivery and all beams fulfills two conditions in V(cyl): (1) the dose modulation function is unchanged along the beam axis, and (2) the dose gradient in the beam direction is constant for a given lateral position; then its associated VSC beam produces no lateral dose gradient in V(cyl), no matter what beam modulation or gantry angles are being used. The examination of the conditions required by the theorem lead to the following results. The effect of the depth-dose gradient not being perfectly constant with depth on the VSC beam lateral dose gradient is found negligible. The effect of the dose modulation function being degraded with depth on the VSC beam lateral dose gradient is found to be only related to scatter and beam hardening, as the theorem holds also for diverging beams. The use of the symmetry of the problem in the present paper leads to a valuable theorem showing that k(Q) factors of composite IMRT beam deliveries are close to unity under specific conditions. The theoretical limit k(Q(pcsr),Q(msr) ) (f(pcsr),f(msr) )=1 is determined based on the property of PCSR deliveries to provide a uniform dose in the target volume. The present approach explains recent experimental observations and proposes ideal conditions for IMRT reference dosimetry. The result of this study could potentially serve as a theoretical basis for reference dosimetry of composite IMRT beam deliveries or for routine IMRT quality assurance.

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution canmore » be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.« less

Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy.

PubMed

Nuyttens, Joost J; Moiseenko, Vitali; McLaughlin, Mark; Jain, Sheena; Herbert, Scott; Grimm, Jimm

2016-04-01

Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose-escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Helical Tomotherapy vs. Intensity-Modulated Proton Therapy for Whole Pelvis Irradiation in High-Risk Prostate Cancer Patients: Dosimetric, Normal Tissue Complication Probability, and Generalized Equivalent Uniform Dose Analysis

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

Widesott, Lamberto, E-mail: widesott@yahoo.it; Pierelli, Alessio; Fiorino, Claudio

2011-08-01

Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. Methods and Materials: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100{sup o}; 100{sup o}) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normalmore » tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. Results: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving {>=}95% of the prescribed dose (V{sub 95%}) was on average >97% in HT and >99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. Conclusions: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.« less

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time.

Patterns of patient specific dosimetry in total body irradiation

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

Akino, Yuichi; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871; McMullen, Kevin P.

2013-04-15

Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at ourmore » institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10%. However, some large differences greater than 35% were also found at several points. For one case, the knee received double the prescribed dose. When the dose differences for multiple fractions were averaged, compliance ({+-}10%) between the prescription and measured dose was improved compared to the dose difference of the first single fraction, for example, as at umbilicus, which improved from 83.9% to 98.5%. Conclusions: Actual dose measurement analysis of TBI patients revealed a potentially wide variance from the calculated dose. Based from their IVD method for TBI using Cobalt-60 irradiator and moving table, {+-}10% over entire body is hard to achieve. However, it can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments.« less

Gafchromic EBT3 film dosimetry in electron beams — energy dependence and improved film read‐out

PubMed Central

Ojala, Jarkko; Kaijaluoto, Sampsa; Jokelainen, Ilkka; Kosunen, Antti

2016-01-01

For megavoltage photon radiation, the fundamental dosimetry characteristics of Gafchromic EBT3 film were determined in  60Co gamma ray beam with addition of experimental and Monte Carlo (MC)‐simulated energy dependence of the film for 6 MV photon beam and 6 MeV, 9 MeV, 12 MeV, and 16 MeV electron beams in water phantom. For the film read‐out, two phase correction of scanner sensitivity was applied: a matrix correction for scanning area and dose‐dependent correction by iterative procedure. With these corrections, the uniformity of response can be improved to be within ±50 pixel values (PVs). To improve the read‐out accuracy, a procedure with flipped film orientations was established. With the method, scanner uniformity can be improved further and dust particles, scratches and/or dirt on scanner glass can be detected and eliminated. Responses from red and green channels were averaged for read‐out, which decreased the effect of noise present in values from separate channels. Since the signal level with the blue channel is considerably lower than with other channels, the signal variation due to different perturbation effects increases the noise level so that the blue channel is not recommended to be used for dose determination. However, the blue channel can be used for the detection of emulsion thickness variations for film quality evaluations with unexposed films. With electron beams ranging from 6 MeV to 16 MeV and at reference measurement conditions in water, the energy dependence of the EBT3 film is uniform within 0.5%, with uncertainties close to 1.6% (k=2). Including 6 MV photon beam and the electron beams mentioned, the energy dependence is within 1.1%. No notable differences were found between the experimental and MC‐simulated responses, indicating negligible change in intrinsic energy dependence of the EBT3 film for 6 MV photon beam and 6 MeV–16 MeV electron beams. Based on the dosimetric characteristics of the EBT3 film, the read‐out procedure established, the nearly uniform energy dependence found and the estimated uncertainties, the EBT3 film was concluded to be a suitable 2D dosimeter for measuring electron or mixed photon/electron dose distributions in water phantom. Uncertainties of 3.7% (k=2) for absolute and 2.3% (k=2) for relative dose were estimated. PACS numbers: 87.53.Bn, 87.55.K‐, 87.55.Qr PMID:26894368

Impact of grid size on uniform scanning and IMPT plans in XiO treatment planning system for brain cancer

PubMed Central

Zheng, Yuanshui

2015-01-01

The main purposes of this study are to: 1) evaluate the accuracy of XiO treatment planning system (TPS) for different dose calculation grid size based on head phantom measurements in uniform scanning proton therapy (USPT); and 2) compare the dosimetric results for various dose calculation grid sizes based on real computed tomography (CT) dataset of pediatric brain cancer treatment plans generated by USPT and intensity‐modulated proton therapy (IMPT) techniques. For phantom study, we have utilized the anthropomorphic head proton phantom provided by Imaging and Radiation Oncology Core (IROC). The imaging, treatment planning, and beam delivery were carried out following the guidelines provided by the IROC. The USPT proton plan was generated in the XiO TPS, and dose calculations were performed for grid size ranged from 1 to 3 mm. The phantom containing thermoluminescent dosimeter (TLDs) and films was irradiated using uniform scanning proton beam. The irradiated TLDs were read by the IROC. The calculated doses from the XiO for different grid sizes were compared to the measured TLD doses provided by the IROC. Gamma evaluation was done by comparing calculated planar dose distribution of 3 mm grid size with measured planar dose distribution. Additionally, IMPT plan was generated based on the same CT dataset of the IROC phantom, and IMPT dose calculations were performed for grid size ranged from 1 to 3 mm. For comparative purpose, additional gamma analysis was done by comparing the planar dose distributions of standard grid size (3 mm) with that of other grid sizes (1, 1.5, 2, and 2.5 mm) for both the USPT and IMPT plans. For patient study, USPT plans of three pediatric brain cancer cases were selected. IMPT plans were generated for each of three pediatric cases. All patient treatment plans (USPT and IMPT) were generated in the XiO TPS for a total dose of 54 Gy (relative biological effectiveness [RBE]). Treatment plans (USPT and IMPT) of each case was recalculated for grid sizes of 1, 1.5, 2, and 2.5 mm; these dosimetric results were then compared with that of 3 mm grid size. Phantom study results: There was no distinct trend exhibiting the dependence of grid size on dose calculation accuracy when calculated point dose of different grid sizes were compared to the measured point (TLD) doses. On average, the calculated point dose was higher than the measured dose by 1.49% and 2.63% for the right and left TLDs, respectively. The gamma analysis showed very minimal differences among planar dose distributions of various grid sizes, with percentage of points meeting gamma index criteria 1% and 1 mm to be from 97.92% to 99.97%. The gamma evaluation using 2% and 2 mm criteria showed both the IMPT and USPT plans have 100% points meeting the criteria. Patient study results: In USPT, there was no very distinct relationship between the absolute difference in mean planning target volume (PTV) dose and grid size, whereas in IMPT, it was found that the decrease in grid size slightly increased the PTV maximum dose and decreased the PTV mean dose and PTV D50%. For the PTV doses, the average differences were up to 0.35 Gy (RBE) and 1.47 Gy (RBE) in the USPT and IMPT plans, respectively. Dependency on grid size was not very clear for the organs at risk (OARs), with average difference ranged from −0.61 Gy (RBE) to 0.53 Gy (RBE) in the USPT plans and from −0.83 Gy (RBE) to 1.39 Gy (RBE) in the IMPT plans. In conclusion, the difference in the calculated point dose between the smallest grid size (1 mm) and the largest grid size (3 mm) in phantom for USPT was typically less than 0.1%. Patient study results showed that the decrease in grid size slightly increased the PTV maximum dose in both the USPT and IMPT plans. However, no distinct trend was obtained between the absolute difference in dosimetric parameter and dose calculation grid size for the OARs. Grid size has a large effect on dose calculation efficiency, and use of 2 mm or less grid size can increase the dose calculation time significantly. It is recommended to use grid size either 2.5 or 3 mm for dose calculations of pediatric brain cancer plans generated by USPT and IMPT techniques in XiO TPS. PACS numbers: 87.55.D‐, 87.55.ne, 87.55.dk PMID:26699310

Dosimetric evaluation of integrated IMRT treatment of the chest wall and supraclavicular region for breast cancer after modified radical mastectomy

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

Yang, Bo; Wei, Xian-ding; Zhao, Yu-tian

2014-07-01

To investigate the dosimetric characteristics of irradiation of the chest wall and supraclavicular region as an integrated volume with intensity-modulated radiation therapy (IMRT) after modified radical mastectomy. This study included 246 patients who received modified radical mastectomy. The patients were scanned with computed tomography, and the chest wall (with or without the internal mammary lymph nodes) and supraclavicular region were delineated. For 143 patients, the chest wall and supraclavicular region were combined as an integrated planning volume and treated with IMRT. For 103 patients, conventional treatments were employed with 2 tangential fields for the chest wall, abutting a mixed fieldmore » of 6-MV x-rays (16 Gy) and 9-MeV electrons (34 Gy) for the upper supraclavicular region. The common prescription dose was 50 Gy/25 Fx/5 W to 90% of the target volume. The dosimetric characteristics of the chest wall, the supraclavicular region, and normal organs were compared. For the chest wall target, compared with conventional treatments, the integrated IMRT plans lowered the maximum dose, increased the minimum dose, and resulted in better conformity and uniformity of the target volume. There was an increase in minimum, average, and 95% prescription dose for the integrated IMRT plans in the supraclavicular region, and conformity and uniformity were improved. The V{sub 30} of the ipsilateral lung and V{sub 10}, V{sub 30}, and mean dose of the heart on the integrated IMRT plans were lower than those of the conventional plans. The V{sub 5} and V{sub 10} of the ipsilateral lung and V{sub 5} of the heart were higher on the integrated IMRT plans (p < 0.05) than on conventional plans. Without an increase in the radiation dose to organs at risk, the integrated IMRT treatment plans improved the dose distribution of the supraclavicular region and showed better dose conformity and uniformity of the integrated target volume of the chest wall and supraclavicular region.« less

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Angular dependence of the MOSFET dosimeter and its impact on in vivo surface dose measurement in breast cancer treatment.

PubMed

Qin, S; Chen, T; Wang, L; Tu, Y; Yue, N; Zhou, J

2014-08-01

The focus of this study is the angular dependence of two types of Metal Oxide Semiconductor Field Effect Transistor (MOSFET) dosimeters (MOSFET20 and OneDose/OneDosePlus) when used for surface dose measurements. External beam radiationat different gantry angles were delivered to a cubic solid water phantom with a MOSFET placed on the top surface at CAX. The long axis of the MOSFET was oriented along the gantry axis of rotation, with the dosimeter (bubble side) facing the radiation source. MOSFET-measured surface doses were compared against calibrated radiochromic film readings. It was found that both types of MOSFET dosimeters exhibited larger than previously reported angular dependence when measuring surface dose in beams at large oblique angles. For the MOSFET20 dosimeter the measured surface dose deviation against film readings was as high as 17% when the incident angle was 72 degrees to the norm of the phantom surface. It is concluded that some MOSFET dosimeters may have a strong angular dependence when placed on the surface of water-equivalent material, even though they may have an isotropic angular response when surrounded by uniform medium. Extra on-surface calibration maybe necessary before using MOSFET dosimeters for skin dose measurement in tangential fields.

Radiation exposure to foetus and breasts from dental X-ray examinations: effect of lead shields.

PubMed

Kelaranta, Anna; Ekholm, Marja; Toroi, Paula; Kortesniemi, Mika

2016-01-01

Dental radiography may involve situations where the patient is known to be pregnant or the pregnancy is noticed after the X-ray procedure. In such cases, the radiation dose to the foetus, though low, needs to be estimated. Uniform and widely used guidance on dental X-ray procedures during pregnancy are presently lacking, the usefulness of lead shields is unclear and practices vary. Upper estimates of radiation doses to the foetus and breasts of the pregnant patient were estimated with an anthropomorphic female phantom in intraoral, panoramic, cephalometric and CBCT dental modalities with and without lead shields. The upper estimates of foetal doses varied from 0.009 to 6.9 μGy, and doses at the breast level varied from 0.602 to 75.4 μGy. With lead shields, the foetal doses varied from 0.005 to 2.1 μGy, and breast doses varied from 0.002 to 10.4 μGy. The foetal dose levels without lead shielding were <1% of the annual dose limit of 1 mSv for a member of the public. Albeit the relative shielding effect, the exposure-induced increase in the risk of breast cancer death for the pregnant patient (based on the breast dose only) and the exposure-induced increase in the risk of childhood cancer death for the unborn child are minimal, and therefore, need for foetal and breast lead shielding was considered irrelevant. Most important is that pregnancy is never a reason to avoid or to postpone a clinically justified dental radiographic examination.

Experiences using IAEA Code of practice for radiation sterilization of tissue allografts: Validation and routine control

NASA Astrophysics Data System (ADS)

Hilmy, N.; Febrida, A.; Basril, A.

2007-11-01

Problems of tissue allografts in using International Standard (ISO) 11137 for validation of radiation sterilization dose (RSD) are limited and low numbers of uniform samples per production batch, those are products obtained from one donor. Allograft is a graft transplanted between two different individuals of the same species. The minimum number of uniform samples needed for verification dose (VD) experiment at the selected sterility assurance level (SAL) per production batch according to the IAEA Code is 20, i.e., 10 for bio-burden determination and the remaining 10 for sterilization test. Three methods of the IAEA Code have been used for validation of RSD, i.e., method A1 that is a modification of method 1 of ISO 11137:1995, method B (ISO 13409:1996), and method C (AAMI TIR 27:2001). This paper describes VD experiments using uniform products obtained from one cadaver donor, i.e., cancellous bones, demineralized bone powders and amnion grafts from one life donor. Results of the verification dose experiments show that RSD is 15.4 kGy for cancellous and demineralized bone grafts and 19.2 kGy for amnion grafts according to method A1 and 25 kGy according to methods B and C.

Study of quality and stability of ursodeoxycholic acid formulations for oral pediatric administration.

PubMed

Santoveña, A; Sánchez-Negrín, E; Charola, L; Llabrés, M; Fariña, J B

2014-12-30

This paper describes a rational method of characterizing the biopharmaceutical stability of two oral suspensions of ursodeoxycholic acid (UDCA) used in pediatrics. Because there is no commercial presentation of UDCA that can administer appropriate doses for infants and children, an active pharmaceutical ingredient (API) formulation is required. Due to its very low solubility and low dose in the formula (1.5%), two different suspensions with minimal use of excipients were studied, avoiding the use of complex additives and those not recommended by the European Medicines Agency (EMA). Adherence to Standard Operating Procedure (SOP) allows the preparation of formulations with appropriately sized and stable particles, and suitable rheological behavior in withdrawing the dose after stirring. Dose uniformity, expressed as mass and content variability, was determined using the criteria of the European and the United States Pharmacopoeia. Additionally, dose content variation of every mass determined was studied. A rational method was developed for determining the dose uniformity of UDCA in suspensions, whether freshly prepared or after storage under different conditions for 30 and 60 days. This method permits detection of differences between doses taken at different heights in the vessel at various times and storage conditions. UDCA was stable under all conditions studied, requiring the presence of glycerol in the formulation to obtain the declared API value after stirring. Storage of UDCA suspensions in a refrigerator increased variability between doses. Copyright © 2014 Elsevier B.V. All rights reserved.

A reproducible radiation delivery method for unanesthetized rodents during periods of hind limb unloading

NASA Astrophysics Data System (ADS)

Walb, M. C.; Black, P. J.; Payne, V. S.; Munley, M. T.; Willey, J. S.

2015-07-01

Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their dosimetry properties, this method may find great utility in the implementation of future ground-based studies that examine the combined spaceflight challenges of reduced loading and radiation while using the HLU rodent model.

A geometric model of mortality and crop protection for insects feeding on discrete toxicant deposits.

PubMed

Ebert, Timothy; Derksen, Richard

2004-04-01

Current theory governing the biological effectiveness of toxicants stresses the dose-response relationship and focuses on uniform toxicant distributions in the insect's environment. However, toxicants are seldom uniformly dispersed under field conditions. Toxicant distribution affects bioavailability, but the mechanics of such interactions is not well documented. We present a geometric model of the interactions between insects and heterogeneously distributed toxicants. From the model, we conclude the following: 1) There is an optimal droplet size, and droplets both smaller and larger than this optimum will decrease efficacy. 2) There is an ideal droplet distribution. Droplets should be spaced based on two criteria: calculate the allowable damage, double this quantity, and one lethal deposit should be placed in this area; and define the quantity of leaf the larva could eat before the toxicant decays below the lethal level and place one lethal deposit within this area. 3) Distributions of toxicant where deposits are sublethal will often be ineffective, but the application is wasteful if deposits contain more than a lethal dose. 4) Insect behavior both as individuals and collectively influences the level of crop production provided by an application. This conclusion has implications for both crop protection and natural plant-insect interactions. The effective utilization of new more environmentally sensitive toxicants may depend on how well we understand how heterogeneous toxicant distributions interact with insect behavior to determine the biological outcome.

Determining optimum wavelength of ultraviolet rays to pre-exposure of non-uniformity error correction in Gafchromic EBT2 films

NASA Astrophysics Data System (ADS)

Katsuda, Toshizo; Gotanda, Rumi; Gotanda, Tatsuhiro; Akagawa, Takuya; Tanki, Nobuyoshi; Kuwano, Tadao; Noguchi, Atsushi; Yabunaka, Kouichi

2018-03-01

Gafchromic films have been used to measure X-ray doses in diagnostic radiology such as computed tomography. The double-exposure technique is used to correct non-uniformity error of Gafchromic EBT2 films. Because of the heel effect of diagnostic x-rays, ultraviolet A (UV-A) is intended to be used as a substitute for x-rays. When using a UV-A light-emitting diode (LED), it is necessary to determine the effective optimal UV wavelength for the active layer of Gafchromic EBT2 films. This study evaluated the relation between the increase in color density of Gafchromic EBT2 films and the UV wavelengths. First, to correct non-uniformity, a Gafchromic EBT2 film was pre-irradiated using uniform UV-A radiation for 60 min from a 72-cm distance. Second, the film was irradiated using a UV-LED with a wavelength of 353-410 nm for 60 min from a 5.3-cm distance. The maximum, minimum, and mean ± standard deviation (SD) of pixel values of the subtraction images were evaluated using 0.5 inches of a circular region of interest (ROI). The highest mean ± SD (8915.25 ± 608.86) of the pixel value was obtained at a wavelength of 375 nm. The results indicated that 375 nm is the most effective and sensitive wavelength of UV-A for Gafchromic EBT2 films and that UV-A can be used as a substitute for x-rays in the double-exposure technique.

Total skin electron therapy in the lying‐on‐the‐floor position using a customized flattening filter to accommodate frail patients

PubMed Central

Antolak, John A.

2013-01-01

A total skin electron (TSE) floor technique is presented for treating patients who are unable to safely stand for extended durations. A customized flattening filter is used to eliminate the need for field junctioning, improve field uniformity, and reduce setup time. The flattening filter is constructed from copper and polycarbonate, fits into the linac's accessory slot, and is optimized to extend the useful height and width of the beam such that no field junctions are needed during treatment. A TSE floor with flattening filter (TSE FF) treatment course consisted of six patient positions: three supine and three prone. For all treatment fields, electron beam energy was 6 MeV; collimator settings were an x of 30 cm, y of 40 cm, and θcoll of 0°; and a 0.4 cm thick polycarbonate spoiler was positioned in front of the patient. Percent depth dose (PDD) and photon contamination for the TSE FF technique were compared with our standard technique, which is similar to the Stanford technique. Beam profiles were measured using radiochromic film, and dose uniformity was verified using an anthropomorphic radiological phantom. The TSE FF technique met field uniformity requirements specified by the American Association of Physicists in Medicine Task Group 30. TSE FF R80 ranges from 4 to 4.8 mm. TSE FF photon contamination was ~ 3%. Anthropomorphic radiological phantom verification demonstrated that dose to the entire skin surface was expected to be within about ±15% of the prescription dose, except for the perineum, scalp vertex, top of shoulder, and soles of the feet. The TSE floor technique presented herein eliminates field junctioning, is suitable for patients who cannot safely stand during treatment, and provides comparable quality and uniformity to the Stanford technique. PACS number: 87 PMID:24036864

Orthovoltage radiation therapy treatment planning using Monte Carlo simulation: treatment of neuroendocrine carcinoma of the maxillary sinus

NASA Astrophysics Data System (ADS)

Gao, Wanbao; Raeside, David E.

1997-12-01

Dose distributions that result from treating a patient with orthovoltage beams are best determined with a treatment planning system that uses the Monte Carlo method, and such systems are not readily available. In the present work, the Monte Carlo method was used to develop a computer code for determining absorbed dose distributions in orthovoltage radiation therapy. The code was used in planning treatment of a patient with a neuroendocrine carcinoma of the maxillary sinus. Two lateral high-energy photon beams supplemented by an anterior orthovoltage photon beam were utilized in the treatment plan. For the clinical case and radiation beams considered, a reasonably uniform dose distribution is achieved within the target volume, while the dose to the lens of each eye is 4 - 8% of the prescribed dose. Therefore, an orthovoltage photon beam, when properly filtered and optimally combined with megavoltage beams, can be effective in the treatment of cancers below the skin, providing that accurate treatment planning is carried out to establish with accuracy and precision the doses to critical structures.

Leukemia and other cancers following radiation treatment of pelvic disease

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

Smith, P.G.

1977-04-01

Follow-up studies of patients treated for cancer of the cervix with radiotherapy have shown such women to be at little or no increased risk of leukemia subsequent to the radiation exposure. However, women exposed to lower doses of radiation in the pelvic area, in the induction of an artificial menopause, appear to show increased risks of both leukemia and cancers of those sites directly in the radiation field. The studies of these two types of radiation exposure are reviewed. The findings may possibly be reconciled with each other on the basis of the distribution of radiation dose to the bonemore » marrow. Irradiation for cancer of the cervix delivers radiation doses to a small portion of the marrow which are probably lethal for most marrow cells. The mean dose to cells distant from the cervix may be too small to produce a detectable increase in leukemia incidence. The lower and more uniformly distributed radiation dose used to induce an artificial menopause will be less lethal for marrow cells and may consequently deliver a higher ''effective'' marrow dose to surviving cells, resulting in an increased leukemia risk.« less

SU-E-T-191: Commissioning and Dosimetric Characteristics of Elekta Agility for Total Skin Electron Beam (TSEB) Therapy

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

Sayler, E; Charpentier, P; Micaily, B

2015-06-15

Purpose The purpose of this work is to publish beam data from Elekta Synergy(R) linear accelerators with Agility(TM) MLC for total skin electron beam (TSEB) therapy using the HDRE1 (High Dose Rate Electron 6MeV) energy. Method & Materials The optimal gantry angles for TSEB were determined using ion chamber measurements along a vertical profile at 450cm SSD. After gantry angles were chosen, field uniformity was measured over the entire treatment area. Uniformity was measured with and without the patient support device, allowing the dosimetric effect of the support device to be determined. Beam output and PDD were measured at themore » calibration point (450cm SSD) for a dual beam using a parallel plate chamber in solid water. These measurements were repeated with the chamber and phantom rotated about the patient isocenter at various angles, in order to measure the contribution from oblique beams. This technique provides a precise measurement of the treatment skin dose (TSD). Lastly, ion chamber measurements were verified by film and diodes. Results The optimal gantry angle for 450 cm SSD was determined to be 90±16°. This achieved uniformity better than 96% on the vertical axis, and 92% along the horizontal axis. HDRE1 was calibrated to deliver 10 cGy/MU at standard geometry (100 cm SSD, 1.2 cm depth). Thus at TSEB geometry (450 cm SSD, 0.1 cm depth) the output of the AP dual field was measured to be 0.35 cGy/MU. The TSD of a 20 cm radius cylinder for six (equally, 60° spaced) dual fields was measured to be 1.19 cGy/MU. Percent Depth Dose data for the AP dual field and TSD are shown in Figure 2. Conclusion This paper provides a modern procedure for commissioning TSEB therapy on a linear accelerator, and clinical beam data for the Elekta Synergy(R) with Agility(TM) MLC.« less

Alloy nanoparticle synthesis using ionizing radiation

DOEpatents

Nenoff, Tina M [Sandia Park, NM; Powers, Dana A [Albuquerque, NM; Zhang, Zhenyuan [Durham, NC

2011-08-16

A method of forming stable nanoparticles comprising substantially uniform alloys of metals. A high dose of ionizing radiation is used to generate high concentrations of solvated electrons and optionally radical reducing species that rapidly reduce a mixture of metal ion source species to form alloy nanoparticles. The method can make uniform alloy nanoparticles from normally immiscible metals by overcoming the thermodynamic limitations that would preferentially produce core-shell nanoparticles.

SU-F-T-671: Effects of Collimator Material On Proton Minibeams

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

Lee, E; Sandison, G; Cao, N

2016-06-15

Purpose: To investigate the dosimetric effects of collimator material on spatially modulated proton minibeams (pMBRT). Methods: pMBRT holds promise to exhibit shallow depth normal-tissue sparing effects similar to synchrotron based microbeams while also retaining potential for uniform dose distributions for tumor targets. TOPAS Monte Carlo simulations were performed for a 5cm thick multislit collimator with 0.3mm slits and 1mm center-to-center spacing for a 50.5MeV proton minibeam while varying collimator material between brass, tungsten, and iron. The collimator was placed both “flush” at the water phantom surface and at 5cm distance to investigate the effects on surface dose, peak-to-valley-dose-ratio (PVDR) andmore » neutron contribution. Results: For flush placement, the neutron dose at the phantom surface for the tungsten collimator was approximately 20% higher than for brass and iron. This was not reflected in the overall surface dose, which was comparable for all materials due to the relatively low neutron contribution of <0.1%. When the collimator was retracted, the overall neutron contribution was essentially identical for all three collimators. Surface dose dropped by ∼40% for all collimator materials with air gap compared to being flush with the phantom surface. This surface dose reduction was at the cost of increase in valley dose for all collimator materials due to increased angular divergence of the mini-beams at the surface and their consequent geometric penumbra at depth. When the collimator was placed at distance from the phantom surface the PVDR decreased. The peak-to-entrance-dose ratio was highest for the iron collimator with 5cm air gap. Conclusion: The dosimetric difference between the collimator materials is minimal despite the relatively higher neutron contribution at the phantom surface for the tungsten collimator when placed flush. The air gap between the collimator and phantom surface strongly influences all dosimetry parameters due to the influence of scatter on the narrow spatial modulation.« less

SU-E-T-404: Simple Field-In-Field Technique for Total Body Irradiation in Large Patients

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

Chi, P; Pinnix, C; Dabaja, B

2014-06-01

Purpose: A simple Field-in-Field technique for Total Body Irradiation (TBI) was developed for traditional AP/PA TBI treatments to improve dosimetric uniformity in patients with large separation. Methods: TBI at our institution currently utilizes an AP/PA technique at an extended source-to-surface distance (SSD) of 380cm with patients in left decubitus position during the AP beam and in right decubitus during the PA beam. Patients who have differences in thickness (separation) between the abdomen and head greater than 10cm undergo CT simulation in both left and right decubitus treatment positions. One plan for each CT is generated to evaluate dose to patientmore » midline with both AP and PA fields, but only corresponding AP fields will be exported for treatment for patient left decubitus position and PA fields for patient right decubitus position. Subfields are added by collimating with the x-ray jaws according to separation changes at 5–7% steps to minimize hot regions to less than 10%. Finally, the monitor units (MUs) for the plans are verified with hand calculation and water phantom measurements. Results: Dose uniformity (+/−10%) is achieved with field-in-field using only asymmetric jaws. It is dosimetrically robust with respect to minor setup/patient variations inevitable due to patient conditions. MUs calculated with Pinnacle were verified in 3 clinical cases and only a 2% difference was found compared to homogeneous calculation. In-vivo dosimeters were also used to verify doses received by each patient with and confirmed dose variations less than 10%. Conclusion: We encountered several cases with separation differences that raised uniformity concerns — based on a 1% dose difference per cm separation difference assumption. This could Resultin an unintended hot spot, often in the head/neck, up to 25%. This method allows dose modulation without adding treatment complexity nor introducing radiobiological variations, providing a reasonable solution for this unique TBI situation.« less

Introduction of a deformable x-ray CT polymer gel dosimetry system

NASA Astrophysics Data System (ADS)

Maynard, E.; Heath, E.; Hilts, M.; Jirasek, A.

2018-04-01

This study introduces the first 3D deformable dosimetry system based on x-ray computed tomography (CT) polymer gel dosimetry and establishes the setup reproducibility, deformation characteristics and dose response of the system. A N-isopropylacrylamide (NIPAM)-based gel formulation optimized for x-ray CT gel dosimetry was used, with a latex balloon serving as the deformable container and low-density polyethylene and polyvinyl alcohol providing additional oxygen barrier. Deformable gels were irradiated with a 6 MV calibration pattern to determine dosimetric response and a dosimetrically uniform plan to determine the spatial uniformity of the response. Wax beads were added to each gel as fiducial markers to track the deformation and setup of the gel dosimeters. From positions of the beads on CT images the setup reproducibility and the limits and reproducibility of gel deformation were determined. Comparison of gel measurements with Monte Carlo dose calculations found excellent dosimetric accuracy, comparable to that of an established non-deformable dosimetry system, with a mean dose discrepancy of 1.5% in the low-dose gradient region and a gamma pass rate of 97.9% using a 3%/3 mm criterion. The deformable dosimeter also showed good overall spatial dose uniformity throughout the dosimeter with some discrepancies within 20 mm of the edge of the container. Tracking of the beads within the dosimeter found that sub-millimetre setup accuracy is achievable with this system. The dosimeter was able to deform and relax when externally compressed by up to 30 mm without sustaining any permanent damage. Internal deformations in 3D produced average marker movements of up to 12 mm along the direction of compression. These deformations were also shown to be reproducible over 100 consecutive deformations. This work has established several important characteristics of a new deformable dosimetry system which shows promise for future clinical applications, including the validation of deformable dose accumulation algorithms.

Image quality and absorbed dose comparison of single- and dual-source cone-beam computed tomography.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Okazue, Toshiya; Kawakubo, Atsushi; Yamada, Kiyoshi; Nagata, Yasushi

2018-05-01

Dual-source cone-beam computed tomography (DCBCT) is currently available in the Vero4DRT image-guided radiotherapy system. We evaluated the image quality and absorbed dose for DCBCT and compared the values with those for single-source CBCT (SCBCT). Image uniformity, Hounsfield unit (HU) linearity, image contrast, and spatial resolution were evaluated using a Catphan phantom. The rotation angle for acquiring SCBCT and DCBCT images is 215° and 115°, respectively. The image uniformity was calculated using measurements obtained at the center and four peripheral positions. The HUs of seven materials inserted into the phantom were measured to evaluate HU linearity and image contrast. The Catphan phantom was scanned with a conventional CT scanner to measure the reference HU for each material. The spatial resolution was calculated using high-resolution pattern modules. Image quality was analyzed using ImageJ software ver. 1.49. The absorbed dose was measured using a 0.6-cm 3 ionization chamber with a 16-cm-diameter cylindrical phantom, at the center and four peripheral positions of the phantom, and calculated using weighted cone-beam CT dose index (CBCTDI w ). Compared with that of SCBCT, the image uniformity of DCBCT was slightly reduced. A strong linear correlation existed between the measured HU for DCBCT and the reference HU, although the linear regression slope was different from that of the reference HU. DCBCT had poorer image contrast than did SCBCT, particularly with a high-contrast material. There was no significant difference between the spatial resolutions of SCBCT and DCBCT. The absorbed dose for DCBCT was higher than that for SCBCT, because in DCBCT, the two x-ray projections overlap between 45° and 70°. We found that the image quality was poorer and the absorbed dose was higher for DCBCT than for SCBCT in the Vero4DRT. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

PubMed

Kainz, Kristofer; Firat, Selim; Wilson, J Frank; Schultz, Christopher; Siker, Malika; Wang, Andrew; Olson, Dan; Li, X Allen

2015-03-21

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

Investigation on using high-energy proton beam for total body irradiation (TBI).

PubMed

Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

2016-09-08

This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. © 2016 The Authors.

SU-E-T-457: Impact of Interfractional Variations On Anterior Vs. Lateral-Field Proton Therapy of Prostate Cancer

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

Moteabbed, M; Trofimov, A; Sharp, G C

2015-06-15

Purpose: To investigate the effects of interfractional anatomy and setup variations on plans with anterior-oblique vs. lateral beams for prostate cancer pencil beam scanning (PBS) and passive scattered (PS) proton therapy. Methods: Six patients with low/intermediate risk prostate cancer treated with PS proton therapy at our institution were selected. All patients underwent weekly verification CT scans. Implanted fiducials were used for localization, and endorectal balloons for prostate immobilization. New PBS plans with lateral beams, as well as PBS and PS plans with anterior-oblique beams (±35 deg) were created. PBS plans used two different spot sizes: ∼10mm (large) and ∼5mm (medium)more » sigma at 25cm range and optimized as single-field-uniform-dose with ∼8% non-uniformity. No range uncertainty margins were applied in PBS plans to maximize rectal sparing. Field-specific apertures were used when planning with large spots to sharpen the penumbrae. The planned dose was recomputed on each weekly CT with fiducials aligned to the simulation CT, scaled and accumulated via deformable image registration. Results: The dose volume analysis showed that although difference between planned and accumulated dose remains negligible for plans with conventional lateral beams using both PS and PBS, this is not the case for plans with anterior beams. The target coverage in anterior plans was largely degraded due to the variations in the beam path length and the absence of range margins. The average prostate D95 was reduced by 7.5/15.9% (using PS/PBS) after accumulation for anterior plans, compared with 0/0.4% for lateral plans. The average mean dose in organs-at-risk decreased by 1% for lateral and 2% for anterior plans, similarly for PS and PBS. Spot size did not affect the dose changes. Conclusion: Prostate plans using anterior beams may undergo clinically relevant interfractional dose degradation. Corrective strategies guided by in-vivo range measurements should be studied before clinical application of this technique.« less

On the interplay effects with proton scanning beams in stage III lung cancer.

PubMed

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-02-01

To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

SU-E-T-541: Bolus Effect of Thermoplastic Masks in IMRT and VMAT Head and Neck Treatments

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

Zhen, H; Nedzi, L; Chen, S

2014-06-01

Purpose: To quantitatively evaluate the bolus effect of thermoplalstic mask on patient skin dose during multi-field IMRT and VMAT treatment. Methods: The clinically approved target contours for five head and neck patients were deformably registered to an anthropomorphic Rando phantom. Two plans: Multifield IMRT plan with 7-9 beams and VMAT plan with 2-4 arcs were created for each patient following same dose constraints. 3mm skin was excluded from PTVs but not constrained during optimization. The prescription dose was 200-220 cGy/fraction. A thermoplastic head and shoulder mask was customized for the Rando phantom. Each plan was delivered to the phantom twicemore » with and without mask. During each delivery, two rectangular strips of EBT3 films (1cm x 6.8cm) were placed across the anterior upper and lower neck near PTVs to measure the surface dose. For consistency films were positioned at same locations for same patient. A total of 8 film strips were obtained for each patient. Film dose was calibrated in the range of 0-400cGy on the day of plan delivery. For dose comparison 3 regions of interests (ROIs) of 1×1 cm{sup 2} were selected at left, right and middle part of each film, resulting in 6 point doses at each plan delivery. Results: The films without mask show relatively uniform dose distribution while those with mask clearly show mesh pattern of mask, usually indicating an increase in skin dose. On average the increase in skin dose over all ROIs with mask was 31.9%(±14.8%) with a range of 11.4%- 58.4%. There is no statistically significant difference (p=0.44) between skin dose increase in VMAT (30.8%±15.3%) and IMRT delivery (33.0%±14.9%). Conclusion: Thermoplastic immobilization masks increase surface dose for HN patient by around 30%. The magnitude is comparable between multi-field IMRT and VMAT. Radiochromic EBT3 film serves as an effective tool to quantify bolus effect.« less

TH-AB-207A-06: The Use of Realistic Phantoms to Predict CT Dose to Pediatric Patients

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

Carver, D; Kost, S; Fraser, N

Purpose: To predict pediatric patient dose from diagnostic CT scans using Monte Carlo simulation of realistic reference phantoms of various ages, weights, and heights. Methods: A series of deformable pediatric reference phantoms using Non-Uniform Rational B-Splines (NURBS) was developed for a large range of ages, percentiles, and reference anatomy. Individual bones were modeled using age-dependent factors, and red marrow was modeled as functions of age and spatial distribution based on Cristy1. Organ and effective doses for the phantom series were calculated using Monte Carlo simulation of chest, abdominopelvic, and chest-abdomen-pelvis CT exams. Non-linear regression was performed to determine the relationshipmore » between dose-length-product (DLP)-normalized organ and effective doses and phantom diameter. Patient-specific voxel computational phantoms were also created by manual segmentation of previously acquired CT images for 40 pediatric patients (0.7 to 17 years). Organ and effective doses were determined by Monte Carlo simulation of these patient-specific phantoms. Each patient was matched to the closest pediatric reference phantom based primarily on age and diameter for all major organs within the torso. Results: A total of 80 NURBS phantoms were created ranging from newborn to 15 years with height/weight percentiles from 10 to 90%. Organ and effective dose normalized by DLP correlated strongly with exponentially decreasing average phantom diameter (R{sup 2} > 0.95 for most organs). A similar relationship was determined for the patient-specific voxel phantoms. Differences between patient-phantom matched organ-dose values ranged from 0.37 to 2.39 mGy (2.87% to 22.1%). Conclusion: Dose estimation using NURBS-based pediatric reference phantoms offers the ability to predict patient dose before and after CT examinations, and physicians and scientists can use this information in their analysis of dose prescriptions for particular subjects and study types. This may lead to practices that minimize radiation dose while still achieving high quality images and, ultimately, improved patient care. NIH/NCI 1 R01 CA155400-01A1.« less

FW-CADIS Method for Global and Semi-Global Variance Reduction of Monte Carlo Radiation Transport Calculations

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

Wagner, John C; Peplow, Douglas E.; Mosher, Scott W

2014-01-01

This paper presents a new hybrid (Monte Carlo/deterministic) method for increasing the efficiency of Monte Carlo calculations of distributions, such as flux or dose rate distributions (e.g., mesh tallies), as well as responses at multiple localized detectors and spectra. This method, referred to as Forward-Weighted CADIS (FW-CADIS), is an extension of the Consistent Adjoint Driven Importance Sampling (CADIS) method, which has been used for more than a decade to very effectively improve the efficiency of Monte Carlo calculations of localized quantities, e.g., flux, dose, or reaction rate at a specific location. The basis of this method is the development ofmore » an importance function that represents the importance of particles to the objective of uniform Monte Carlo particle density in the desired tally regions. Implementation of this method utilizes the results from a forward deterministic calculation to develop a forward-weighted source for a deterministic adjoint calculation. The resulting adjoint function is then used to generate consistent space- and energy-dependent source biasing parameters and weight windows that are used in a forward Monte Carlo calculation to obtain more uniform statistical uncertainties in the desired tally regions. The FW-CADIS method has been implemented and demonstrated within the MAVRIC sequence of SCALE and the ADVANTG/MCNP framework. Application of the method to representative, real-world problems, including calculation of dose rate and energy dependent flux throughout the problem space, dose rates in specific areas, and energy spectra at multiple detectors, is presented and discussed. Results of the FW-CADIS method and other recently developed global variance reduction approaches are also compared, and the FW-CADIS method outperformed the other methods in all cases considered.« less

High dose microCT does not contribute towards improved microPET/CT image quantitative accuracy and can limit longitudinal scanning of small animals

NASA Astrophysics Data System (ADS)

McDougald, Wendy A.; Collins, Richard; Green, Mark; Tavares, Adriana A. S.

2017-10-01

Obtaining accurate quantitative measurements in preclinical Positron Emission Tomography/Computed Tomography (PET/CT) imaging is of paramount importance in biomedical research and helps supporting efficient translation of preclinical results to the clinic. The purpose of this study was two-fold: (1) to investigate the effects of different CT acquisition protocols on PET/CT image quality and data quantification; and (2) to evaluate the absorbed dose associated with varying CT parameters. Methods: An air/water quality control CT phantom, tissue equivalent material phantom, an in-house 3D printed phantom and an image quality PET/CT phantom were imaged using a Mediso nanoPET/CT scanner. Collected data was analyzed using PMOD software, VivoQuant software and National Electric Manufactures Association (NEMA) software implemented by Mediso. Measured Hounsfield Unit (HU) in collected CT images were compared to the known HU values and image noise was quantified. PET recovery coefficients (RC), uniformity and quantitative bias were also measured. Results: Only less than 2% and 1% of CT acquisition protocols yielded water HU values < -80 and air HU values < -840, respectively. Four out of eleven CT protocols resulted in more than 100 mGy absorbed dose. Different CT protocols did not impact PET uniformity and RC, and resulted in <4% overall bias relative to expected radioactive concentration. Conclusion: Preclinical CT protocols with increased exposure times can result in high absorbed doses to the small animals. These should be avoided, as they do not contributed towards improved microPET/CT image quantitative accuracy and could limit longitudinal scanning of small animals.

Performance of optically stimulated luminescence Al₂O₃ dosimeter for low doses of diagnostic energy X-rays.

PubMed

Lim, Chang Seon; Lee, Sang Bock; Jin, Gye Hwan

2011-10-01

Personal dosimeters measure the radiation dose from exposure to hazardous sources outside the body. The present manuscript evaluates the performance of a commercially available optically stimulated luminescence (OSL) Al₂O₃ dosimeter using diagnostic energy X-rays. The OSL system satisfies the ANSI N13.11-2001 performance criteria for low dose diagnostic energy X-rays. Non-uniformity of sensitivity, dose linearity, X-ray energy response, and angular performance are all within the criteria of IEC-62387-1(2007). Copyright © 2011 Elsevier Ltd. All rights reserved.

Optical CT imaging of solid radiochromic dosimeters in mismatched refractive index solutions using a scanning laser and large area detector

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

Dekker, Kurtis H., E-mail: kdekker2@uwo.ca

Purpose: The practical use of the PRESAGE® solid plastic dosimeter is limited by the inconvenience of immersing it in high-viscosity oils to achieve refractive index matching for optical computed tomography (CT) scanning. The oils are slow to mix and difficult to clean from surfaces, and the dosimeter rotation can generate dynamic Schlieren inhomogeneity patterns in the reference liquid, limiting the rotational and overall scan speed. Therefore, it would be beneficial if lower-viscosity, water-based solutions with slightly unmatched refractive index could be used instead. The purpose of this work is to demonstrate the feasibility of allowing mismatched conditions when using amore » scanning laser system with a large acceptance angle detector. A fiducial-based ray path measurement technique is combined with an iterative CT reconstruction algorithm to reconstruct images. Methods: A water based surrounding liquid with a low viscosity was selected for imaging PRESAGE® solid dosimeters. Liquid selection was optimized to achieve as high a refractive index as possible while avoiding rotation-induced Schlieren effects. This led to a refractive index mismatch of 6% between liquid and dosimeters. Optical CT scans were performed with a fan-beam scanning-laser optical CT system with a large area detector to capture most of the refracted rays. A fiducial marker placed on the wall of a cylindrical sample occludes a given light ray twice. With knowledge of the rotation angle and the radius of the cylindrical object, the actual internal path of each ray through the dosimeter can be calculated. Scans were performed with 1024 projections of 512 data samples each, and rays were rebinned to form 512 parallel-beam projections. Reconstructions were performed on a 512 × 512 grid using 100 iterations of the SIRT iterative CT algorithm. Proof of concept was demonstrated with a uniformly attenuating solution phantom. PRESAGE® dosimeters (11 cm diameter) were irradiated with Cobalt-60 irradiator to achieve either a uniform dose or a 2-level “step-dose” pattern. Results: With 6% refractive index mismatching, a circular field of view of 85% of the diameter of a cylindrical sample can be reconstructed accurately. Reconstructed images of the test solution phantom were uniform (within 3%) inside this radius. However, the dose responses of the PRESAGE® samples were not spatially uniform, with variations of at least 5% in sensitivity. The variation appears as a “cupping” artifact with less sensitivity in the middle than at the periphery of the PRESAGE® cylinder. Polarization effects were also detected for these samples. Conclusions: The fiducial-based ray path measurement scheme, coupled with an iterative reconstruction algorithm, enabled optical CT scanning of PRESAGE® dosimeters immersed in mismatched refractive index solutions. However, improvements to PRESAGE® dose response uniformity are required.« less

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

Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and curcumin in vivo.

PubMed

Chen, Long; Liu, Tianjun; Wang, Qiangsong; Liu, Juan

2017-04-27

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD 50 was measured based on the acute oral toxicity (AOT) standard method. The best formulation was the three components combined at the same mass proportion revealed by the Uniform Design methodology. This combination could significantly reduce the paw swelling in acute paw swelling mouse model, could reduce paw swelling and alleviate the damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat model. The dose relationship was clear in both cases. Immunohistochemical staining of ankle tissue revealed that TRC combination was able to inhibit the expression of NF-κB p65 and TNF-α which were closely related to the inflammatory process. Analysis of serum mediators revealed TRC combination could inhibit the production of TNF-α, IL-1β, and IL-6 in the serum. Toxic study revealed this formulation was low toxic, LD 50 was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the TRC combination and the blank group, no mortality occurred at the administered doses of 5 g/kg. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Calculation of dose distribution above contaminated soil

NASA Astrophysics Data System (ADS)

Kuroda, Junya; Tenzou, Hideki; Manabe, Seiya; Iwakura, Yukiko

2017-07-01

The purpose of this study was to assess the relationship between altitude and the distribution of the ambient dose rate in the air over soil decontamination area by using PHITS simulation code. The geometry configuration was 1000 m ×1000 m area and 1m in soil depth and 100m in altitude from the ground to simulate the area of residences or a school grounds. The contaminated region is supposed to be uniformly contaminated by Cs-137 γ radiation sources. The air dose distribution and space resolution was evaluated for flux of the gamma rays at each altitude, 1, 5, 10, and 20m. The effect of decontamination was calculated by defining sharpness S. S was the ratio of an average flux and a flux at the center of denomination area in each altitude. The suitable flight altitude of the drone is found to be less than 15m above a residence and 31m above a school grounds to confirm the decontamination effect. The calculation results can be a help to determine a flight planning of a drone to minimize the clash risk.

Online compensation for target motion with scanned particle beams: simulation environment.

PubMed

Li, Qiang; Groezinger, Sven Oliver; Haberer, Thomas; Rietzel, Eike; Kraft, Gerhard

2004-07-21

Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy.

PubMed

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-07

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

NASA Astrophysics Data System (ADS)

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A New Approach to Integrate GPU-based Monte Carlo Simulation into Inverse Treatment Plan Optimization for Proton Therapy

PubMed Central

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2016-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6±15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size. PMID:27991456

SU-E-T-232: Custom High-Dose-Rate Brachytherapy Surface Mold Applicators: The Importance Source to Skin Distance

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

Park, S; Demanes, J; Kamrava, M

2015-06-15

Purpose: Surface mold applicators can be customized to fit irregular skin surfaces that are difficult to treat with other radiation therapy techniques. Optimal design of customized HDR skin brachytherapy is not well-established. We evaluated the impact of applicator thickness (source to skin distance) on target dosimetry. Methods: 27 patients had 34 treated sites: scalp 4, face 13, extremity 13, and torso 4. Custom applicators were constructed from 5–15 mm thick thermoplastic bolus molded over the skin lesion. A planar array of plastic brachytherapy catheters spaced 5–10 mm apart was affixed to the bolus. CT simulation was used to contour themore » target volume and to determine the prescription depth. Inverse planning simulated annealing followed by graphical optimization was used to plan and deliver 40–56 Gy in 8–16 fractions. Target coverage parameters (D90, Dmean, and V100) and dose uniformity (V110–200, D0.1cc, D1cc, and D2cc) were studied according to target depth (<5mm vs. ≥5mm) and applicator thickness (5–10mm vs. ≥10mm). Results: The average prescription depth was 4.2±1.5mm. The average bolus thickness was 9.2±2.4mm. The median CTV volume was 10.0 cc (0.2–212.4 cc). Similar target coverage was achieved with prescription depths of <5mm and ≥5mm (Dmean = 113.8% vs. 112.4% and D90 = 100.2% vs. 98.3%). The <5mm prescription depth plans were more uniform (D0.1cc = 131.8% vs. 151.8%). Bolus thickness <10mm vs. ≥10mm plans also had similar target coverage (Dmean = 118.2% vs. 110.7% and D90 = 100.1% vs. 99.0%). Applicators ≥10mm thick, however, provide more uniform target dosimetry (D0.1cc = 146.9% vs. 139.5%). Conclusion: Prescription depth is based upon the thickness of the lesion and upon the clinical needs of the patient. Applicators ≥10mm thick provide more dose uniformity than 5–10mm thick applicators. Applicator thickness is an important variable that should be considered during treatment planning to achieve optimal dose uniformity.« less

Dose-Related Effects of Alcohol on Cognitive Functioning

PubMed Central

Dry, Matthew J.; Burns, Nicholas R.; Nettelbeck, Ted; Farquharson, Aaron L.; White, Jason M.

2012-01-01

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties. PMID:23209840

Quality correction factors of composite IMRT beam deliveries: Theoretical considerations

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

Bouchard, Hugo

2012-11-15

Purpose: In the scope of intensity modulated radiation therapy (IMRT) dosimetry using ionization chambers, quality correction factors of plan-class-specific reference (PCSR) fields are theoretically investigated. The symmetry of the problem is studied to provide recommendable criteria for composite beam deliveries where correction factors are minimal and also to establish a theoretical limit for PCSR delivery k{sub Q} factors. Methods: The concept of virtual symmetric collapsed (VSC) beam, being associated to a given modulated composite delivery, is defined in the scope of this investigation. Under symmetrical measurement conditions, any composite delivery has the property of having a k{sub Q} factor identicalmore » to its associated VSC beam. Using this concept of VSC, a fundamental property of IMRT k{sub Q} factors is demonstrated in the form of a theorem. The sensitivity to the conditions required by the theorem is thoroughly examined. Results: The theorem states that if a composite modulated beam delivery produces a uniform dose distribution in a volume V{sub cyl} which is symmetric with the cylindrical delivery and all beams fulfills two conditions in V{sub cyl}: (1) the dose modulation function is unchanged along the beam axis, and (2) the dose gradient in the beam direction is constant for a given lateral position; then its associated VSC beam produces no lateral dose gradient in V{sub cyl}, no matter what beam modulation or gantry angles are being used. The examination of the conditions required by the theorem lead to the following results. The effect of the depth-dose gradient not being perfectly constant with depth on the VSC beam lateral dose gradient is found negligible. The effect of the dose modulation function being degraded with depth on the VSC beam lateral dose gradient is found to be only related to scatter and beam hardening, as the theorem holds also for diverging beams. Conclusions: The use of the symmetry of the problem in the present paper leads to a valuable theorem showing that k{sub Q} factors of composite IMRT beam deliveries are close to unity under specific conditions. The theoretical limit k{sub Q{sub p{sub c{sub s{sub r,Q{sub m{sub s{sub r}{sup f{sub p}{sub c}{sub s}{sub r},f{sub m}{sub s}{sub r}}}}}}}}}=1 is determined based on the property of PCSR deliveries to provide a uniform dose in the target volume. The present approach explains recent experimental observations and proposes ideal conditions for IMRT reference dosimetry. The result of this study could potentially serve as a theoretical basis for reference dosimetry of composite IMRT beam deliveries or for routine IMRT quality assurance.« less

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

PubMed

Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen.

PubMed

Smith, S D; Bolwell, B J; Rybicki, L A; Brown, S; Dean, R; Kalaycio, M; Sobecks, R; Andresen, S; Hsi, E D; Pohlman, B; Sweetenham, J W

2007-08-01

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease

PubMed Central

Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.; Huggins, John W.; Shamblin, Joshua; Robinson, Camenzind G.; Hensley, Lisa E.

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID:26147658

TLD measurements of in vivo mammographic exposures and the calculated mean glandular dose across the United States.

PubMed

Gentry, J R; DeWerd, L A

1996-06-01

An analysis is presented of the exposures received by TLDs placed on the breasts of 4400 women obtaining mammograms at 170 institutions across the United States. Mean glandular dose and exposure were examined as a function of compressed breast thickness. The exposure and mean glandular dose were found to increase linearly with breast thickness. The mean glandular dose typically delivered by the institutions was well below the limit of 3.0 mGy for the 4.5-cm breast. However, some institutions tend to uniformly give higher doses. In such institutions approximately 25% of 4.5-cm-thick breasts received a mean glandular dose exceeding 3.0 mGy.

Radiation exposure to foetus and breasts from dental X-ray examinations: effect of lead shields

PubMed Central

Ekholm, Marja; Toroi, Paula; Kortesniemi, Mika

2016-01-01

Objectives: Dental radiography may involve situations where the patient is known to be pregnant or the pregnancy is noticed after the X-ray procedure. In such cases, the radiation dose to the foetus, though low, needs to be estimated. Uniform and widely used guidance on dental X-ray procedures during pregnancy are presently lacking, the usefulness of lead shields is unclear and practices vary. Methods: Upper estimates of radiation doses to the foetus and breasts of the pregnant patient were estimated with an anthropomorphic female phantom in intraoral, panoramic, cephalometric and CBCT dental modalities with and without lead shields. Results: The upper estimates of foetal doses varied from 0.009 to 6.9 μGy, and doses at the breast level varied from 0.602 to 75.4 μGy. With lead shields, the foetal doses varied from 0.005 to 2.1 μGy, and breast doses varied from 0.002 to 10.4 μGy. Conclusions: The foetal dose levels without lead shielding were <1% of the annual dose limit of 1 mSv for a member of the public. Albeit the relative shielding effect, the exposure-induced increase in the risk of breast cancer death for the pregnant patient (based on the breast dose only) and the exposure-induced increase in the risk of childhood cancer death for the unborn child are minimal, and therefore, need for foetal and breast lead shielding was considered irrelevant. Most important is that pregnancy is never a reason to avoid or to postpone a clinically justified dental radiographic examination. PMID:26313308

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

Xu, Z; Baker, J; Hsia, A

Purpose: The commercially available Leipzig-style Cone for High Dose Rate (HDR) Brachytherapy has a steep depth dose curve and a non-uniform dose distribution. This work shows the performance of a Ring Surface Applicator created using a 3D printer that can generate a better dose distribution. Calculated doses were verified with film measurement. Methods: The water equivalent red-ABS plastic was used to print the Ring Surface Applicator which hosts three catheters: a center piece with a straight catheter and two concentric rings with diameters of 3.5 and 5.5 cm. Gafchromic EBT2 film, Epson Expression 10000 flatbed scanner, and the online softwaremore » at radiochromic.com were used to analyze the measured data. 10cm×10cm piece of film was sandwiched between two 15×10×5cm3 polystyrene phantoms. The applicator was positioned directly on top of the phantom. Measurement was done using dwell time and positions calculated by Eclipse BrachyVision treatment planning system (RTP). Results: Depth dose curve was generated from the plan and measurement. The results show that the measured and calculated depth dose were in agreement (<3%) from surface to 4mm depth. A discrepancy of 6% was observed at 5 mm depth, where the dose is typically prescribed to. For depths deeper than 5 mm, the measured doses were lower than those calculated by Eclipse BrachyVision. This can be attributed to a combination of simple calculation algorithm using TG-43 and the lack of inhomogeneity correction. Dose profiles at 5 mm depth were also generated from TPS calculation and measured with film. The measured and calculated profiles are similar. Consistent with the depth dose curve, the measured dose is lower than the calculated. Conclusion: Our results showed that the Ring Surface Applicator, printed using 3D printer, can generate more uniform dose distribution within the target volume and can be safely used in the clinic.« less

Three-dimensional radiotherapy of head and neck and esophageal carcinomas: a monoisocentric treatment technique to achieve improved dose distributions.

PubMed

Ahmad, M; Nath, R

2001-02-20

The specific aim of three-dimensional conformal radiotherapy is to deliver adequate therapeutic radiation dose to the target volume while concomitantly keeping the dose to surrounding and intervening normal tissues to a minimum. The objective of this study is to examine dose distributions produced by various radiotherapy techniques used in managing head and neck tumors when the upper part of the esophagus is also involved. Treatment planning was performed with a three-dimensional (3-D) treatment planning system. Computerized tomographic (CT) scans used by this system to generate isodose distributions and dose-volume histograms were obtained directly from the CT scanner, which is connected via ethernet cabling to the 3-D planning system. These are useful clinical tools for evaluating the dose distribution to the treatment volume, clinical target volume, gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams, different configurations of standard treatment techniques for head and neck and esophageal carcinoma were studied and the resulting dose distributions were analyzed. Film validation dosimetry in solid-water phantom was performed to assess the magnitude of dose inhomogeneity at the field junction. Real-time dose measurements on patients using diode dosimetry were made and compared with computed dose values. With regard to minimizing radiation dose to surrounding structures (i.e., lung, spinal cord, etc.), the monoisocentric technique gave the best isodose distributions in terms of dose uniformity. The mini-mantle anterior-posterior/posterior-anterior (AP/PA) technique produced grossly non-uniform dose distribution with excessive hot spots. The dose measured on the patient during the treatment agrees to within +/- 5 % with the computed dose. The protocols presented in this work for simulation, immobilization and treatment planning of patients with head and neck and esophageal tumors provide the optimum dose distributions in the target volume with reduced irradiation of surrounding non-target tissues, and can be routinely implemented in a radiation oncology department. The presence of a real-time dose-measuring system plays an important role in verifying the actual delivery of radiation dose.

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.

A trichrome beam model for biological dose calculation in scanned carbon-ion radiotherapy treatment planning.

PubMed

Inaniwa, T; Kanematsu, N

2015-01-07

In scanned carbon-ion (C-ion) radiotherapy, some primary C-ions undergo nuclear reactions before reaching the target and the resulting particles deliver doses to regions at a significant distance from the central axis of the beam. The effects of these particles on physical dose distribution are accounted for in treatment planning by representing the transverse profile of the scanned C-ion beam as the superposition of three Gaussian distributions. In the calculation of biological dose distribution, however, the radiation quality of the scanned C-ion beam has been assumed to be uniform over its cross-section, taking the average value over the plane at a given depth (monochrome model). Since these particles, which have relatively low radiation quality, spread widely compared to the primary C-ions, the radiation quality of the beam should vary with radial distance from the central beam axis. To represent its transverse distribution, we propose a trichrome beam model in which primary C-ions, heavy fragments with atomic number Z ≥ 3, and light fragments with Z ≤ 2 are assigned to the first, second, and third Gaussian components, respectively. Assuming a realistic beam-delivery system, we performed computer simulations using Geant4 Monte Carlo code for analytical beam modeling of the monochrome and trichrome models. The analytical beam models were integrated into a treatment planning system for scanned C-ion radiotherapy. A target volume of 20  ×  20  ×  40 mm(3) was defined within a water phantom. A uniform biological dose of 2.65 Gy (RBE) was planned for the target with the two beam models based on the microdosimetric kinetic model (MKM). The plans were recalculated with Geant4, and the recalculated biological dose distributions were compared with the planned distributions. The mean target dose of the recalculated distribution with the monochrome model was 2.72 Gy (RBE), while the dose with the trichrome model was 2.64 Gy (RBE). The monochrome model underestimated the RBE within the target due to the assumption of no radial variations in radiation quality. Conversely, the trichrome model accurately predicted the RBE even in a small target. Our results verify the applicability of the trichrome model for clinical use in C-ion radiotherapy treatment planning.

A trichrome beam model for biological dose calculation in scanned carbon-ion radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Inaniwa, T.; Kanematsu, N.

2015-01-01

In scanned carbon-ion (C-ion) radiotherapy, some primary C-ions undergo nuclear reactions before reaching the target and the resulting particles deliver doses to regions at a significant distance from the central axis of the beam. The effects of these particles on physical dose distribution are accounted for in treatment planning by representing the transverse profile of the scanned C-ion beam as the superposition of three Gaussian distributions. In the calculation of biological dose distribution, however, the radiation quality of the scanned C-ion beam has been assumed to be uniform over its cross-section, taking the average value over the plane at a given depth (monochrome model). Since these particles, which have relatively low radiation quality, spread widely compared to the primary C-ions, the radiation quality of the beam should vary with radial distance from the central beam axis. To represent its transverse distribution, we propose a trichrome beam model in which primary C-ions, heavy fragments with atomic number Z ≥ 3, and light fragments with Z ≤ 2 are assigned to the first, second, and third Gaussian components, respectively. Assuming a realistic beam-delivery system, we performed computer simulations using Geant4 Monte Carlo code for analytical beam modeling of the monochrome and trichrome models. The analytical beam models were integrated into a treatment planning system for scanned C-ion radiotherapy. A target volume of 20  ×  20  ×  40 mm3 was defined within a water phantom. A uniform biological dose of 2.65 Gy (RBE) was planned for the target with the two beam models based on the microdosimetric kinetic model (MKM). The plans were recalculated with Geant4, and the recalculated biological dose distributions were compared with the planned distributions. The mean target dose of the recalculated distribution with the monochrome model was 2.72 Gy (RBE), while the dose with the trichrome model was 2.64 Gy (RBE). The monochrome model underestimated the RBE within the target due to the assumption of no radial variations in radiation quality. Conversely, the trichrome model accurately predicted the RBE even in a small target. Our results verify the applicability of the trichrome model for clinical use in C-ion radiotherapy treatment planning.

Tabulated dose uniformity ratio and minimum dose data: rectangular 60Co source plaques

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

Galanter, L.

1971-01-01

The data tabulated herein extend to rectangular cobalt-60 plaques the information presented for square plaques in BNL 50145 (Revised). The user is referred to BNL 50145 (Revised) and to the other reports listed for a complete discussion of the parameters involved in data generation and for instructions on the use of these data in gamma irradiator design.

Simulation of angular and energy distributions of the PTB beta secondary standard.

PubMed

Faw, R E; Simons, G G; Gianakon, T A; Bayouth, J E

1990-09-01

Calculations and measurements have been performed to assess radiation doses delivered by the PTB Secondary Standard that employs 147Pm, 204Tl, and 90Sr:90Y sources in prescribed geometries, and features "beam-flattening" filters to assure uniformity of delivered doses within a 5-cm radius of the axis from source to detector plane. Three-dimensional, coupled, electron-photon Monte Carlo calculations, accounting for transmission through the source encapsulation and backscattering from the source mounting, led to energy spectra and angular distributions of electrons penetrating the source encapsulation that were used in the representation of pseudo sources of electrons for subsequent transport through the atmosphere, filters, and detectors. Calculations were supplemented by measurements made using bare LiF TLD chips on a thick polymethyl methacrylate phantom. Measurements using the 204Tl and 90Sr:90Y sources revealed that, even in the absence of the beam-flattening filters, delivered dose rates were very uniform radially. Dosimeter response functions (TLD:skin dose ratios) were calculated and confirmed experimentally for all three beta-particle sources and for bare LiF TLDs ranging in mass thickness from 10 to 235 mg cm-2.

Cumulative trauma and posttraumatic stress disorder among children exposed to the 9/11 World Trade Center attack.

PubMed

Mullett-Hume, Elizabeth; Anshel, Daphne; Guevara, Vivianne; Cloitre, Marylene

2008-01-01

Two and one-half years after the September 11, 2001 World Trade Center attack, 204 middle school students in an immigrant community located near Ground Zero were assessed for posttraumatic stress disorder (PTSD) symptoms as influenced by "dose" of exposure to the attack and accumulated lifetime traumas. Ninety percent of students reported at least one traumatic event other than 9/11 (e.g., community violence) with an average of 4 lifetime events reported. An interaction was obtained such that the dose-response effect depended on presence of other traumas. Among students with the lowest number of additional traumas, the usual dose-response pattern of increasing PTSD symptoms with increasing 9/11 exposure was observed; among those with medium to high cumulative life trauma, PTSD symptoms were substantially higher and uniformly so regardless of 9/11 exposure dose. Results suggest that traumas that precede or follow mass violence often have as much as if not greater impact on long-term symptom severity than high-dose exposure to the event. Implications regarding the presence of continuing or previous trauma exposure for postdisaster and early intervention policies are discussed. (c) 2008 APA, all rights reserved

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.

PubMed

Horn, Simon; Barnard, Stephen; Rothkamm, Kai

2011-01-01

Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.

Assessment of an organ-based tube current modulation in thoracic computed tomography.

PubMed

Matsubara, Kosuke; Sugai, Mai; Toyoda, Asami; Koshida, Haruka; Sakuta, Keita; Takata, Tadanori; Koshida, Kichiro; Iida, Hiroji; Matsui, Osamu

2012-03-08

Recently, specific computed tomography (CT) scanners have been equipped with organ-based tube current modulation (TCM) technology. It is possible that organ-based TCM will replace the conventional dose-reduction technique of reducing the effective milliampere-second. The aim of this study was to determine if organ-based TCM could reduce radiation exposure to the breasts without compromising the image uniformity and beam hardening effect in thoracic CT examinations. Breast and skin radiation doses and the absorbed radiation dose distribution within a single section were measured with an anthropomorphic phantom and radiophotoluminescent glass dosimeters using four approaches to thoracic CT (reference, organ-based TCM, copper shielding, and the combination of the above two techniques, hereafter referred to as the combination technique). The CT value and noise level were measured using the same calibration phantom. Organ-based TCM and copper shielding reduced radiation doses to the breast by 23.7% and 21.8%, respectively. However, the CT value increased, especially in the anterior region, using copper shielding. In contrast, the CT value and noise level barely increased using organ-based TCM. The combination technique reduced the radiation dose to the breast by 38.2%, but greatly increased the absorbed radiation dose from the central to the posterior regions. Moreover, the CT value increased in the anterior region and the noise level increased by more than 10% in the entire region. Therefore, organ-based TCM can reduce radiation doses to breasts with only small increases in noise levels, making it preferable for specific groups of patients, such as children and young women.

Therapeutic analysis of high-dose-rate {sup 192}Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

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

Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B.

Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model wasmore » used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to (13.4){sup 4} for the radiosensitive normal tissue depending on the cylinder size, treatment lengths, prescription depth, and dose as well. However, for a uniform cancer cell distribution, the EUDs were between 6.3 Gy × 4 and 7.1 Gy × 4, and the TRs were found to be between (1.4){sup 4} and (1.7){sup 4}. For the uniformly interspersed cancer and radio-resistant normal cells, the TRs were less than 1. The two VCBT prescription regimens were found to be equivalent in terms of EUDs and TRs. Conclusions: HDR VCBT strongly favors cylindrical target volume with the cancer cell distribution following its dosimetric trend. Assuming a half-Gaussian distribution of cancer cells, the HDR VCBT provides a considerable radiobiological advantage over the external beam radiotherapy (EBRT) in terms of sparing more normal tissues while maintaining the same level of cancer cell killing. But for the uniform cancer cell distribution and radio-resistant normal tissue, the radiobiology outcome of the HDR VCBT does not show an advantage over the EBRT. This study strongly suggests that radiation therapy design should consider the cancer cell distribution inside the target volume in addition to the shape of target.« less

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

2012-01-01

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy

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

Polsdofer, E; Crilly, R

Purpose: This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a “standard eye.” Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to themore » treatment planning process. Methods: Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant. Results: The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point. Conclusion: The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose.« less

Experimental verification of gain drop due to general ion recombination for a carbon-ion pencil beam

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

Tansho, Ryohei, E-mail: r-tansho@nirs.go.jp; Furukawa, Takuji; Hara, Yousuke

Purpose: Accurate dose measurement in radiotherapy is critically dependent on correction for gain drop, which is the difference of the measured current from the ideal saturation current due to general ion recombination. Although a correction method based on the Boag theory has been employed, the theory assumes that ionized charge density in an ionization chamber (IC) is spatially uniform throughout the irradiation volume. For particle pencil beam scanning, however, the charge density is not uniform, because the fluence distribution of a pencil beam is not uniform. The aim of this study was to verify the effect of the nonuniformity ofmore » ionized charge density on the gain drop due to general ion recombination. Methods: The authors measured the saturation curve, namely, the applied voltage versus measured current, using a large plane-parallel IC and 24-channel parallel-plate IC with concentric electrodes. To verify the effect of the nonuniform ionized charge density on the measured saturation curve, the authors calculated the saturation curve using a method which takes into account the nonuniform ionized charge density and compared it with the measured saturation curves. Results: Measurement values of the different saturation curves in the different channels of the concentric electrodes differed and were consistent with the calculated values. The saturation curves measured by the large plane-parallel IC were also consistent with the calculation results, including the estimation error of beam size and of setup misalignment. Although the impact of the nonuniform ionized charge density on the gain drop was clinically negligible with the conventional beam intensity, it was expected that the impact would increase with higher ionized charge density. Conclusions: For pencil beam scanning, the assumption of the conventional Boag theory is not valid. Furthermore, the nonuniform ionized charge density affects the prediction accuracy of gain drop when the ionized charge density is increased by a higher dose rate and/or lower beam size.« less

A two‐point scheme for optimal breast IMRT treatment planning

PubMed Central

2013-01-01

We propose an approach to determining optimal beam weights in breast/chest wall IMRT treatment plans. The goal is to decrease breathing effect and to maximize skin dose if the skin is included in the target or, otherwise, to minimize the skin dose. Two points in the target are utilized to calculate the optimal weights. The optimal plan (i.e., the plan with optimal beam weights) consists of high energy unblocked beams, low energy unblocked beams, and IMRT beams. Six breast and five chest wall cases were retrospectively planned with this scheme in Eclipse, including one breast case where CTV was contoured by the physician. Compared with 3D CRT plans composed of unblocked and field‐in‐field beams, the optimal plans demonstrated comparable or better dose uniformity, homogeneity, and conformity to the target, especially at beam junction when supraclavicular nodes are involved. Compared with nonoptimal plans (i.e., plans with nonoptimized weights), the optimal plans had better dose distributions at shallow depths close to the skin, especially in cases where breathing effect was taken into account. This was verified with experiments using a MapCHECK device attached to a motion simulation table (to mimic motion caused by breathing). PACS number: 87.55 de PMID:24257291

Heavy-ion conformal irradiation in the shallow-seated tumor therapy terminal at HIRFL.

PubMed

Li, Qiang; Dai, Zhongying; Yan, Zheng; Jin, Xiaodong; Liu, Xinguo; Xiao, Guoqing

2007-11-01

Basic research related to heavy-ion cancer therapy has been done at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Now a plan of clinical trial with heavy ions has been launched at IMP. First, superficially placed tumor treatment with heavy ions is expected in the therapy terminal at the Heavy Ion Research Facility in Lanzhou (HIRFL), where carbon ion beams with energy up to 100 MeV/u can be supplied. The shallow-seated tumor therapy terminal at HIRFL is equipped with a passive beam delivery system including two orthogonal dipole magnets, which continuously scan pencil beams laterally and generate a broad and uniform irradiation field, a motor-driven energy degrader and a multi-leaf collimator. Two different types of range modulator, ripple filter and ridge filter with which Guassian-shaped physical dose and uniform biological effective dose Bragg peaks can be shaped for therapeutic ion beams respectively, have been designed and manufactured. Therefore, two-dimensional and three-dimensional conformal irradiations to tumors can be performed with the passive beam delivery system at the earlier therapy terminal. Both the conformal irradiation methods have been verified experimentally and carbon-ion conformal irradiations to patients with superficially placed tumors have been carried out at HIRFL since November 2006.

Spatiotemporal radiotherapy planning using a global optimization approach

NASA Astrophysics Data System (ADS)

Adibi, Ali; Salari, Ehsan

2018-02-01

This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.

Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies.

PubMed

Balásházy, Imre; Farkas, Arpád; Madas, Balázs Gergely; Hofmann, Werner

2009-06-01

Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. The results obtained suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high, even at low average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10-100 mGy.

A study on comparison of Gafchromic EBT2 film response under single and cumulative exposure conditions

PubMed Central

Ganapathy, K.; Kurup, P.G.G.; Murali, V.; Muthukumaran, M.; Velmurugan, J.

2013-01-01

Gafchromic films are used as dosimeter for in vivo and in phantom dose measurements. The dose response of Gafchromic EBT2 film under single and repeated exposure conditions is compared in this study to analyze the usability of Gafchromic EBT2 films in cumulative dose measurements. The post-irradiation change in response of the film is studied for up to 4 days after irradiation. The effect of repeated exposure to scanner light on the response of the film is also studied. To check usability of Gafchromic EBT2 films in cumulative dose measurements, three EBT2 films were exposed to a daily fraction dose of 100 cGy, 150 cGy and 200 cGy, respectively, for 4 days. The dose response of the films exposed to cumulative irradiation was compared with the dose measured from films exposed to the same dose but in a single exposure. It is observed that the post-irradiation darkening of the film does not saturate and continue to take place even 4 days after irradiation. The dose measured from the EBT2 films after 4 days from irradiation was around 2% higher than the dose measured from the same films at 24 hours post-irradiation. It was also observed that the repeated exposure to scanner light does not produce any significant change in the film response. The dose response of films exposed to cumulative irradiation agrees with the dose response of films exposed to the same dose in a single irradiation with less than 3% difference. Gafchromic EBT2 films can be used to measure the cumulative dose delivered over multiple fractions, when the delivered dose is uniform across the film. PMID:24672151

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

PubMed Central

Mifflin, Steve W.

2017-01-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. PMID:28202437

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

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

Arentsen, L; Lopater, Z; Dusenbery, K

Purpose: Duputren’s contracture (DC) is a benign disease characterized by abnormal thickening of the fascial surfaces of the hands or feet causing curling of the surface, functional impairment, weakness, and pain. The purpose of the investigation is to describe the radiation treatment approaches, compare these techniques, and discuss the potential side effects and complications of these techniques. Methods: Early stage DC has been treated with 120 kVp X rays but also with high-energy electrons or photons. High-energy electrons have been the radiation of choice but severe contracture of the hand makes it difficult to produce a plan with acceptable dosemore » uniformity. High-energy photons can overcome this difficulty either by directing a beam onto the palmer or back of the surface of the hand, including bolus to maximize the surface dose. We calculated the dose to the bone for the 120 kVp treatment using published %DD data and mass energy absorption coefficients for bone and muscle. Results: The dose to underlying bone from megavoltage photons and electrons is essentially the same, but dose to the bone for using 120 kVp can be 4–5 times greater due to the photoelectric effect. For the 30 Gy dose deliver using this technique, the dose to the bone could be 84–105 Gy after taking the penetration of the beam into account. After radiotherapy, there is often decreased osteoblastic activity and vascular fibrosis that leads to osteitis, atrophy, and decreased metabolic bone activity. Incidence of fractures occurs routinely above 60 Gy with higher doses potentially leading to higher incidences of bone complications. Conclusion: Radiation therapy for DC using low-energy X rays can deliver a prohibitively high dose to the underlying bone potentially leading to severe bone complications.« less

Health Impacts from Acute Radiation Exposure

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

Strom, Daniel J.

2003-09-30

Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above thismore » is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.« less

A depth-sensing technique on 3D-printed compensator for total body irradiation patient measurement and treatment planning

PubMed Central

Lee, Min-Young; Han, Bin; Jenkins, Cesare; Xing, Lei; Suh, Tae-Suk

2016-01-01

Purpose: The purpose of total body irradiation (TBI) techniques is to deliver a uniform radiation dose to the entire volume of a patient’s body. Due to variations in the thickness of the patient, it is difficult to produce such a uniform dose distribution throughout the body. In many techniques, a compensator is used to adjust the dose delivered to various sections of the patient. The current study aims to develop and validate an innovative method of using depth-sensing cameras and 3D printing techniques for TBI treatment planning and compensator fabrication. Methods: A tablet with an integrated depth-sensing camera and motion tracking sensors was used to scan a RANDO™ phantom positioned in a TBI treatment booth to detect and store the 3D surface in a point cloud format. The accuracy of the detected surface was evaluated by comparing extracted body thickness measurements with corresponding measurements from computed tomography (CT) scan images. The thickness, source to surface distance, and off-axis distance of the phantom at different body section were measured for TBI treatment planning. A detailed compensator design was calculated to achieve a uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding, and a mixture of wax and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors. Results: The scan of the phantom took approximately 30 s. The mean error for thickness measurements at each section of phantom relative to CT was 0.48 ± 0.27 cm. The average fabrication error for the 3D-printed compensator was 0.16 ± 0.15 mm. In vivo measurements for an end-to-end test showed that overall dose differences were within 5%. Conclusions: A technique for planning and fabricating a compensator for TBI treatment using a depth camera equipped tablet and a 3D printer was demonstrated to be sufficiently accurate to be considered for further investigation. PMID:27806603

Accuracy and efficiency of published film dosimetry techniques using a flat-bed scanner and EBT3 film.

PubMed

Spelleken, E; Crowe, S B; Sutherland, B; Challens, C; Kairn, T

2018-03-01

Gafchromic EBT3 film is widely used for patient specific quality assurance of complex treatment plans. Film dosimetry techniques commonly involve the use of transmission scanning to produce TIFF files, which are analysed using a non-linear calibration relationship between the dose and red channel net optical density (netOD). Numerous film calibration techniques featured in the literature have not been independently verified or evaluated. A range of previously published film dosimetry techniques were re-evaluated, to identify whether these methods produce better results than the commonly-used non-linear, netOD method. EBT3 film was irradiated at calibration doses between 0 and 4000 cGy and 25 pieces of film were irradiated at 200 cGy to evaluate uniformity. The film was scanned using two different scanners: The Epson Perfection V800 and the Epson Expression 10000XL. Calibration curves, uncertainty in the fit of the curve, overall uncertainty and uniformity were calculated following the methods described by the different calibration techniques. It was found that protocols based on a conventional film dosimetry technique produced results that were accurate and uniform to within 1%, while some of the unconventional techniques produced much higher uncertainties (> 25% for some techniques). Some of the uncommon methods produced reliable results when irradiated to the standard treatment doses (< 400 cGy), however none could be recommended as an efficient or accurate replacement for a common film analysis technique which uses transmission scanning, red colour channel analysis, netOD and a non-linear calibration curve for measuring doses up to 4000 cGy when using EBT3 film.

Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation

PubMed Central

Sun, Wenjuan; JIA, Xianghong; XIE, Tianwu; XU, Feng; LIU, Qian

2013-01-01

With the rapid development of China's space industry, the importance of radiation protection is increasingly prominent. To provide relevant dose data, we first developed the Visible Chinese Human adult Female (VCH-F) phantom, and performed further modifications to generate the VCH-F Astronaut (VCH-FA) phantom, incorporating statistical body characteristics data from the first batch of Chinese female astronauts as well as reference organ mass data from the International Commission on Radiological Protection (ICRP; both within 1% relative error). Based on cryosection images, the original phantom was constructed via Non-Uniform Rational B-Spline (NURBS) boundary surfaces to strengthen the deformability for fitting the body parameters of Chinese female astronauts. The VCH-FA phantom was voxelized at a resolution of 2 × 2 × 4 mm3for radioactive particle transport simulations from isotropic protons with energies of 5000–10 000 MeV in Monte Carlo N-Particle eXtended (MCNPX) code. To investigate discrepancies caused by anatomical variations and other factors, the obtained doses were compared with corresponding values from other phantoms and sex-averaged doses. Dose differences were observed among phantom calculation results, especially for effective dose with low-energy protons. Local skin thickness shifts the breast dose curve toward high energy, but has little impact on inner organs. Under a shielding layer, organ dose reduction is greater for skin than for other organs. The calculated skin dose per day closely approximates measurement data obtained in low-Earth orbit (LEO). PMID:23135158

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

PubMed

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

SU-D-201-02: Prediction of Delivered Dose Based On a Joint Histogram of CT and FDG PET Images

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

Park, M; Choi, Y; Cho, A

2015-06-15

Purpose: To investigate whether pre-treatment images can be used in predicting microsphere distribution in tumors. When intra-arterial radioembolization using Y90 microspheres was performed, the microspheres were often delivered non-uniformly within the tumor, which could lead to an inefficient therapy. Therefore, it is important to estimate the distribution of microspheres. Methods: Early arterial phase CT and FDG PET images were acquired for patients with primary liver cancer prior to radioembolization (RE) using Y90 microspheres. Tumor volume was delineated on CT images and fused with FDG PET images. From each voxel (3.9×3.9×3.3 mm3) in the tumor, the Hounsfield unit (HU) from themore » CT and SUV values from the FDG PET were harvested. We binned both HU and SUV into 11 bins and then calculated a normalized joint-histogram in an 11×11 array.Patients also underwent a post-treatment Y90 PET imaging. Radiation dose for the tumor was estimated using convolution of the Y90 distribution with a dose-point kernel. We also calculated a fraction of the tumor volume that received a radiation dose great than 100Gy. Results: Averaged over 40 patients, 55% of tumor volume received a dose greater than 100Gy (range : 1.1 – 100%). The width of the joint histogram was narrower for patients with a high dose. For patients with a low dose, the width was wider and a larger fraction of tumor volume had low HU. Conclusion: We have shown the pattern of joint histogram of the HU and SUV depends on delivered dose. The patterns can predict the efficacy of uniform intra-arterial delivery of Y90 microspheres.« less

The influence of physical wedges on penumbra and in-field dose uniformity in ocular proton beams.

PubMed

Baker, Colin; Kacperek, Andrzej

2016-04-01

A physical wedge may be partially introduced into a proton beam when treating ocular tumours in order to improve dose conformity to the distal border of the tumour and spare the optic nerve. Two unwanted effects of this are observed: a predictable broadening of the beam penumbra on the wedged side of the field and, less predictably, an increase in dose within the field along a relatively narrow volume beneath the edge (toe) of the wedge, as a result of small-angle proton scatter. Monte Carlo simulations using MCNPX and direct measurements with radiochromic (GAFCHROMIC(®) EBT2) film were performed to quantify these effects for aluminium wedges in a 60 MeV proton beam as a function of wedge angle and position of the wedge relative to the patient. For extreme wedge angles (60° in eye tissue) and large wedge-to-patient distances (70 mm in this context), the 90-10% beam penumbra increased from 1.9 mm to 9.1 mm. In-field dose increases from small-angle proton scatter were found to contribute up to 21% additional dose, persisting along almost the full depth of the spread-out-Bragg peak. Profile broadening and in-field dose enhancement are both minimised by placing the wedge as close as possible to the patient. Use of lower atomic number wedge materials such as PMMA reduce the magnitude of both effects as a result of a reduced mean scattering angle per unit energy loss; however, their larger physical size and greater variation in density are undesirable. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparison of the extent of hippocampal sparing according to the tilt of a patient's head during WBRT using linear accelerator-based IMRT and VMAT.

PubMed

Moon, Sun Young; Yoon, Myonggeun; Chung, Mijoo; Chung, Weon Kuu; Kim, Dong Wook

2016-05-01

In this paper, we report the results of our investigation into whole brain radiotherapy (WBRT) using linear accelerator-based intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in lung cancer patients with a high risk of metastasis to the brain. Specifically, we assessed the absorbed dose and the rate of adverse effects for several organs at risk (OAR), including the hippocampus, according to the tilt of a patient's head. We arbitrarily selected five cases where measurements were made with the patients' heads tilted forward and five cases without such tilt. We set the entire brain as the planning target volume (PTV), and the hippocampi, the lenses, the eyes, and the cochleae as the main OAR, and formulated new plans for IMRT (coplanar, non-coplanar) and VMAT (coplanar, non-coplanar). Using the dose-volume histogram (DVH), we calculated and compared the effective uniform dose (EUD), normal tissue complication probability (NTCP) of the OAR and the mean and the maximum doses of hippocampus. As a result, if the patient tilted the head forward when receiving the Linac-based treatment, for the same treatment effect in the PTV, we confirmed that a lower dose entered the OAR, such as the hippocampus, eye, lens, and cochlea. Moreover, the damage to the hippocampus was expected to be the least when receiving coplanar VMAT with the head tilted forward. Accordingly, if patients tilt their heads forward when undergoing Linac-based WBRT, we anticipate that a smaller dose would be transmitted to the OAR, resulting in better quality of life following treatment. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

Some Radiation Techniques Used in the GU-3 Gamma Irradiator

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

Dodbiba, Andon; Ylli, Ariana; Stamo, Iliriana

2007-04-23

Different radiation techniques, measurement of dose and its distibution throughout the irradiated materials are the main problems treated in this paper. The oscillometry method combined with the ionization chamber, as an absolute dosimeter, is used for calibration of routine ECB dosimeters. The dose uniformity, for the used radiation techniques in our GU-3 Gamma Irradiator with Cs-137, is from 93% up to 99%.

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

NASA Astrophysics Data System (ADS)

Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.

2008-03-01

We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

Contrast-enhanced radiotherapy: feasibility and characteristics of the physical absorbed dose distribution for deep-seated tumors

NASA Astrophysics Data System (ADS)

Garnica-Garza, H. M.

2009-09-01

Radiotherapy using kilovoltage x-rays in conjunction with contrast agents incorporated into the tumor, gold nanoparticles in particular, could represent a potential alternative to current techniques based on high-energy linear accelerators. In this paper, using the voxelized Zubal phantom in conjunction with the Monte Carlo code PENELOPE to model a prostate cancer treatment, it is shown that in combination with a 360° arc delivery technique, tumoricidal doses of radiation can be delivered to deep-seated tumors while still providing acceptable doses to the skin and other organs at risk for gold concentrations in the tumor within the range of 7-10 mg-Au per gram of tissue. Under these conditions and using a x-ray beam with 90% of the fluence within the range of 80-200 keV, a 72 Gy physical absorbed dose to the prostate can be delivered, while keeping the rectal wall, bladder, skin and femoral heads below 65 Gy, 55 Gy, 40 Gy and 30 Gy, respectively. However, it is also shown that non-uniformities in the contrast agent concentration lead to a severe degradation of the dose distribution and that, therefore, techniques to locally quantify the presence of the contrast agent would be necessary in order to determine the incident x-ray fluence that best reproduces the dosimetry obtained under conditions of uniform contrast agent distribution.

Patient size and x-ray technique factors in head computed tomography examinations. I. Radiation doses.

PubMed

Huda, Walter; Lieberman, Kristin A; Chang, Jack; Roskopf, Marsha L

2004-03-01

We investigated how patient age, size and composition, together with the choice of x-ray technique factors, affect radiation doses in head computed tomography (CT) examinations. Head size dimensions, cross-sectional areas, and mean Hounsfield unit (HU) values were obtained from head CT images of 127 patients. For radiation dosimetry purposes patients were modeled as uniform cylinders of water. Dose computations were performed for 18 x 7 mm sections, scanned at a constant 340 mAs, for x-ray tube voltages ranging from 80 to 140 kV. Values of mean section dose, energy imparted, and effective dose were computed for patients ranging from the newborn to adults. There was a rapid growth of head size over the first two years, followed by a more modest increase of head size until the age of 18 or so. Newborns have a mean HU value of about 50 that monotonically increases with age over the first two decades of life. Average adult A-P and lateral dimensions were 186+/-8 mm and 147+/-8 mm, respectively, with an average HU value of 209+/-40. An infant head was found to be equivalent to a water cylinder with a radius of approximately 60 mm, whereas an adult head had an equivalent radius 50% greater. Adult males head dimensions are about 5% larger than for females, and their average x-ray attenuation is approximately 20 HU greater. For adult examinations performed at 120 kV, typical values were 32 mGy for the mean section dose, 105 mJ for the total energy imparted, and 0.64 mSv for the effective dose. Increasing the x-ray tube voltage from 80 to 140 kV increases patient doses by about a factor of 5. For the same technique factors, mean section doses in infants are 35% higher than in adults. Energy imparted for adults is 50% higher than for infants, but infant effective doses are four times higher than for adults. CT doses need to take into account patient age, head size, and composition as well as the selected x-ray technique factors.

An approach to assessing stochastic radiogenic risk in medical imaging

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

Wolbarst, Anthony B.; Hendee, William R.; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55901

2011-12-15

Purpose: This letter suggests a formalism, the medical effective dose (MED), that is suitable for assessing stochastic radiogenic risks in diagnostic medical procedures. Methods: The MED is derived from radiobiological and probabilistic first principals, including: (1) The independence of radiation-induced biological effects in neighboring voxels at low doses; (2) the linear no-threshold assumption for stochastic radiation injury (although other dose-response relationships could be incorporated, instead); (3) the best human radiation dose-response data currently available; and (4) the built-in possibility that the carcinogenic risk to an irradiated organ may depend on its volume. The MED involves a dose-risk summation over irradiatedmore » voxels at high spatial resolution; it reduces to the traditional effective dose when every organ is irradiated uniformly and when the dependence of risk on organ volumes is ignored. Standard relative-risk tissue weighting factors can be used with the MED approach until more refined data become available. Results: The MED is intended for clinical and phantom dosimetry, and it provides an estimate of overall relative radiogenic stochastic risk for any given dose distribution. A result of the MED derivation is that the stochastic risk may increase with the volume of tissue (i.e., the number of cells) irradiated, a feature that can be activated when forthcoming radiobiological research warrants it. In this regard, the MED resembles neither the standard effective dose (E) nor the CT dose index (CTDI), but it is somewhat like the CT dose-length product (DLP). Conclusions: The MED is a novel, probabilistically and biologically based means of estimating stochastic-risk-weighted doses associated with medical imaging. Built in, ab initio, is the ability to link radiogenic risk to organ volume and other clinical factors. It is straightforward to implement when medical dose distributions are available, provided that one is content, for the time being, to accept the relative tissue weighting factors published by the International Commission of Radiological Protection (ICRP). It requires no new radiobiological data and avoids major problems encountered by the E, CTDI, and CT-E formalisms. It makes possible relative inter-patient dosimetry, and also realistic intercomparisons of stochastic risks from different protocols that yield images of comparable quality.« less

On the interplay effects with proton scanning beams in stage III lung cancer

PubMed Central

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y.; Liao, Li; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.; Lim, Gino; Zhang, Xiaodong

2014-01-01

Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery. PMID:24506612

SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration

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

Zhu, J; Liang, J; Chen, S

Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition wasmore » used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ. Without including this effect in DIR, treatment dose in normal organ could be underestimated affecting treatment evaluation and planning modification. Acknowledgement: Partially Supported by Elekta Research Grant.« less

Comparison of different fractionation schedules toward a single fraction in high-dose-rate brachytherapy as monotherapy for low-risk prostate cancer using 3-dimensional radiobiological models.

PubMed

Mavroidis, Panayiotis; Milickovic, Natasa; Cruz, Wilbert F; Tselis, Nikolaos; Karabis, Andreas; Stathakis, Sotirios; Papanikolaou, Nikos; Zamboglou, Nikolaos; Baltas, Dimos

2014-01-01

The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P+), the biologically effective uniform dose, and the generalized equivalent uniform dose index. For the different fractionation schemes, the tumor control probabilities were 98.5% in 1×20 Gy, 98.6% in 2×14 Gy, 97.5% in 3×11 Gy, and 97.8% in 4×9.5 Gy. The corresponding P+ values were 88.8% in 1×20 Gy, 83.9% in 2×14 Gy, 86.0% in 3×11 Gy, and 82.3% in 4×9.5 Gy. With use of the fractionation scheme 4×9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1×19.68 Gy, 2×13.75 Gy, and 3×11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1×19.16 Gy with a P+ of 91.8%, 2×13.2 Gy with a P+ of 89.6%, 3×10.6 Gy with a P+ of 88.4%, and 4×9.02 Gy with a P+ of 86.9%. Among the fractionation schemes 1×20 Gy, 2×14 Gy, 3×11 Gy, and 4×9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4×9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models

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

Mavroidis, Panayiotis, E-mail: mavroidis@uthscsa.edu; Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm; Milickovic, Natasa

2014-01-01

Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimatedmore » through the complication-free tumor control probability (P{sub +}), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 × 20 Gy, 98.6% in 2 × 14 Gy, 97.5% in 3 × 11 Gy, and 97.8% in 4 × 9.5 Gy. The corresponding P{sub +} values were 88.8% in 1 × 20 Gy, 83.9% in 2 × 14 Gy, 86.0% in 3 × 11 Gy, and 82.3% in 4 × 9.5 Gy. With use of the fractionation scheme 4 × 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 × 19.68 Gy, 2 × 13.75 Gy, and 3 × 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 × 19.16 Gy with a P{sub +} of 91.8%, 2 × 13.2 Gy with a P{sub +} of 89.6%, 3 × 10.6 Gy with a P{sub +} of 88.4%, and 4 × 9.02 Gy with a P{sub +} of 86.9%. Conclusions: Among the fractionation schemes 1 × 20 Gy, 2 × 14 Gy, 3 × 11 Gy, and 4 × 9.5 Gy, the first scheme was more effective in terms of P{sub +}. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 × 9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.« less

A reusable OSL-film for 2D radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-11-01

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film’s reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after ‘beam on’ or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min-1) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film’s measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

A reusable OSL-film for 2D radiotherapy dosimetry.

PubMed

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-10-19

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff ). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film's reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after 'beam on' or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min -1 ) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film's measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

Effects of shape and size of agar gels on heating uniformity during pulsed microwave treatment.

PubMed

Soto-Reyes, Nohemí; Temis-Pérez, Ana L; López-Malo, Aurelio; Rojas-Laguna, Roberto; Sosa-Morales, María Elena

2015-05-01

Model gel systems with different shape (sphere, cylinder, and slab) and size (180 and 290 g) were prepared with agar (5%) and sucrose (5%). Dielectric constant (ε'), loss factor (ε"), thermophysical properties, and temperature distribution of the model system were measured. Each agar model system was immersed and suspended in water, and then, heated in a microwave oven with intermittent heating until the core temperature reached 50 °C. The ε' and ε" of agar gels decreased when frequency increased. The density and thermal conductivity values of the agar gels were 1033 kg/m(3) and 0.55 W/m °C, respectively. The temperature distribution of sphere, cylinder, and slab was different when similar power doses were applied. The slab reached 50 °C in less time (10 min) and showed a more uniform heating than spheres and cylinders in both sizes. Agar model systems of 180 g heated faster than those of 290 g. The coldest point was the center of the model systems in all studied cases. Shape and size are critical food factors that affect the heating uniformity during microwave heating processes. © 2015 Institute of Food Technologists®

Dose mapping using MCNP code and experiment for SVST-Co-60/B irradiator in Vietnam.

PubMed

Tran, Van Hung; Tran, Khac An

2010-06-01

By using MCNP code and ethanol-chlorobenzene (ECB) dosimeters the simulations and measurements of absorbed dose distribution in a tote-box of the Cobalt-60 irradiator, SVST-Co60/B at VINAGAMMA have been done. Based on the results Dose Uniformity Ratios (DUR), positions and values of minimum and maximum dose extremes in a tote-box, and efficiency of the irradiator for the different dummy densities have been gained. There is a good agreement between simulation and experimental results in comparison and they have valuable meanings for operation of the irradiator. Copyright 2010 Elsevier Ltd. All rights reserved.

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%).

PubMed

Marlowe, Zora T; Davio, Stephen R

2014-01-01

Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators. Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing - consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity. Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours. LE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.

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.

Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

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

Lobb, Eric, E-mail: eclobb2@gmail.com

2014-04-01

The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

2D dosimetry in a proton beam with a scintillating GEM detector

NASA Astrophysics Data System (ADS)

Seravalli, E.; de Boer, M. R.; Geurink, F.; Huizenga, J.; Kreuger, R.; Schippers, J. M.; van Eijk, C. W. E.

2009-06-01

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for pre-treatment verification of dose distributions in particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF4 scintillating gas mixture, inside which two gas electron multiplier (GEM) structures are mounted (Seravalli et al 2008b Med. Phys. Biol. 53 4651-65). Photons emitted by the excited Ar/CF4 gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD camera system. The intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the characterization of the scintillating GEM detector in terms of those properties that are of particular importance in relative dose measurements, e.g. response reproducibility, dose dependence, dose rate dependence, spatial and time response, field size dependence, response uniformity. The experiments were performed in a 150 MeV proton beam. We found that the detector response is very stable for measurements performed in succession (σ = 0.6%) and its response reproducibility over 2 days is about 5%. The detector response was found to be linear with the dose in the range 0.05-19 Gy. No dose rate effects were observed between 1 and 16 Gy min-1 at the shallow depth of a water phantom and 2 and 38 Gy min-1 at the Bragg peak depth. No field size effects were observed in the range 120-3850 mm2. A signal rise and fall time of 2 µs was recorded and a spatial response of <=1 mm was measured.

Effect of diet on the shedding of Escherichia coli O157:H7 in a sheep model.

PubMed Central

Kudva, I T; Hatfield, P G; Hovde, C J

1995-01-01

The purpose of this study was to develop a sheep model to investigate reproduction, transmission, and shedding of Escherichia coli O157:H7 in ruminants. In addition, we investigated the effect of diet change on these parameters. Six groups of twin lambs given oral inoculations of 10(5) or 10(9) CFU of E. coli O157:H7 and their nondosed mothers were monitored for colonization by culture of fecal samples. A modified selective-enrichment protocol that detected E. coli O157:H7 at levels as low as 0.06 CFU per g of ovine feces was developed. Horizontal transmission of infection occurred between the lambs and most of the nondosed mothers. When animals were kept in confinement and given alfalfa pellet feed, lambs receiving the higher dose shed the bacteria sooner and longer than all other animals. However, when the animals were released onto a sagebrush-bunchgrass range, every animal, regardless of its previous status (dosed at one of the inoculum levels tested or nondosed) shed E. coli O157:H7 uniformly. Shedding persisted for 15 days, after which all animals tested negative. E. coli O157:H7 reproduction and transmission and the combined effect of diet change and feed withholding were also investigated in a pilot study with experimentally inoculated rams. Withholding feed induced animals to shed the bacteria either by triggering growth of E. coli O157:H7 present in the intestines or by increasing susceptibility to infection. Introduction of a dietary change with brief starvation caused uniform shedding and clearance of E. coli O157:H7, and all animals then tested negative for the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7747956

Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

NASA Technical Reports Server (NTRS)

Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

2016-01-01

Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

A study on the reproducibility and spatial uniformity of N-isopropylacrylamide polymer gel dosimetry using a commercial 10X fast optical-computed tomography scanner

NASA Astrophysics Data System (ADS)

Chang, Y. J.; Lin, J. Q.; Hsieh, B. T.; Chen, C. H.

2013-06-01

This study investigated the reproducibility and spatial uniformity of N-isopropylacrylamide (NIPAM) polymer gel as well as the reproducibility of a NIPAM polymer gel dosimeter. A commercial 10X fast optical computed tomography scanner (OCTOPUS-10X, MGS Research, Inc., Madison, CT, USA) was used as the readout tool of the NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom measuring 10 cm (diameter) by 10 cm (height) by 3 mm (thickness) was irradiated by the four-field box treatment with a field size of 3 cm × 3 cm. The dose profiles were found to be consistent at the depths of 2.0 cm to 5.0 cm for two independent gel phantom batches, and the average uncertainty was less than 2%. The gamma pass rates were calculated to be between 94% and 95% at depths of 40 mm for two independent gel phantom batches using 4% dose difference and 4 mm distance-to-agreement criterion. The NIPAM polymer gel dosimeter was highly reproducible and spatially uniform. The results highlighted the potential of the NIPAM polymer gel dosimeter in radiotherapy.

Dosage variability of topical ocular hypotensive products: a densitometric assessment.

PubMed

Gaynes, Bruce I; Singa, Ramesh M; Cao, Ying

2009-02-01

To ascertain consequence of variability in drop volume obtained from multiuse topical ocular hypotensive products in terms of uniformity of product dosage. Densitometric assessment of drop volume dispensed from 2 alternative bottle positions. All except one product demonstrated a statistically significant difference in drop volume when administered at either a 45-degree or 90-degree bottle angle (Student t test, P<0.001). Product-specific drop volume ranged from a nadir of 22.36 microL to a high of 53.54 microL depending on bottle angle of administration. Deviation in drop dose was directly proportional to variability in drop volume. Variability in per drop dosage was conspicuous among products with a coefficient of variation from 1.49% to 15.91%. In accordance with drop volume, all products demonstrated a statistically significant difference in drop dose at 45-degree versus 90-degree administration angles. Drop volume was found unrelated to drop uniformity (Spearman r=0.01987 and P=0.9463). Variability and lack of uniformity in drop dosage is clearly evident among select ocular hypotensive products and is related to angle of drop administration. Erratic dosage of topical ocular hypotensive therapy may contribute in part to therapeutic failure and/or toxicity.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

NASA Astrophysics Data System (ADS)

Ghita, Mihaela; Coffey, Caroline B.; Butterworth, Karl T.; McMahon, Stephen J.; Schettino, Giuseppe; Prise, Kevin M.

2016-01-01

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

The use of radiochromic EBT2 film for the quality assurance and dosimetric verification of 3D conformal radiotherapy using Microtek ScanMaker 9800XL flatbed scanner

PubMed Central

Sim, GS; Ng, KH

2013-01-01

Radiochromic and radiographic films are widely used for radiation dosimetry due to the advantage of high spatial resolution and two‐dimensional dose measurement. Different types of scanners, including various models of flatbed scanners, have been used as part of the dosimetry readout procedure. This paper focuses on the characterization of the EBT2 film response in combination with a Microtek ScanMaker 9800XL scanner and the subsequent use in the dosimetric verification of a 3D conformal radiotherapy treatment. The film reproducibility and scanner uniformity of the Microtek ScanMaker 9800XL was studied. A three‐field 3D conformal radiotherapy treatment was planned on an anthropomorphic phantom and EBT2 film measurements were carried out to verify the treatment. The interfilm reproducibility was found to be 0.25%. Over a period of three months, the films darkened by 1%. The scanner reproducibility was ± 2% and a nonuniformity was ±1.9% along the direction perpendicular to the scan direction. EBT2 measurements showed an underdose of 6.2% at high‐dose region compared to TPS predicted dose. This may be due to the inability of the treatment planning system to predict the correct dose distribution in the presence of tissue inhomogeneities and the uncertainty of the scanner reproducibility and uniformity. The use of EBT2 film in conjunction with the axial CT image of the anthropomorphic phantom allows the evaluation of the anatomical location of dose discrepancies between the EBT2 measured dose distribution and TPS predicted dose distribution. PACS number: 87.55.Qr PMID:23835383

TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

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

Yi, B; Xu, H; Mutaf, Y

2015-06-15

Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speedmore » of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.« less

Alternative stitching method for massively parallel e-beam lithography

NASA Astrophysics Data System (ADS)

Brandt, Pieter; Tranquillin, Céline; Wieland, Marco; Bayle, Sébastien; Milléquant, Matthieu; Renault, Guillaume

2015-03-01

In this study a novel stitching method other than Soft Edge (SE) and Smart Boundary (SB) is introduced and benchmarked against SE. The method is based on locally enhanced Exposure Latitude without cost of throughput, making use of the fact that the two beams that pass through the stitching region can deposit up to 2x the nominal dose. The method requires a complex Proximity Effect Correction that takes a preset stitching dose profile into account. On a Metal clip at minimum half-pitch of 32 nm for MAPPER FLX 1200 tool specifications, the novel stitching method effectively mitigates Beam to Beam (B2B) position errors such that they do not induce increase in CD Uniformity (CDU). In other words, the same CDU can be realized inside the stitching region as outside the stitching region. For the SE method, the CDU inside is 0.3 nm higher than outside the stitching region. 5 nm direct overlay impact from B2B position errors cannot be reduced by a stitching strategy.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

PubMed

Szőke, István; Farkas, Arpád; Balásházy, Imre; Hofmann, Werner; Madas, Balázs G; Szőke, Réka

2012-06-01

The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

SU-E-T-76: Comparing Homogeneity Between Gafchromic Film EBT2 and EBT3

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

Mizuno, H; Sumida, I; Ogawa, K

2014-06-01

Purpose: We found out that homogeneity of EBT2 was different among lot numbers in previous study. Variation in local homogeneity of EBT3 among several lot numbers has not been reported. In this study, we investigated film homogeneity of Gafcrhomic EBT3 films compared with EBT2 films. Methods: All sheets from five lots were cut into 12 pieces to investigate film homogeneity, and were irradiated at 0.5, 2, and 3 Gy. To investigate intra- and inter-sheet uniformity, five sheets from five lots were exposed to 2 Gy: intra-sheet uniformity was evaluated by the coefficient of variation of homogeneity for all pieces ofmore » a single sheet, and inter-sheet uniformity was evaluated by the coefficient of variation of homogeneity among the same piece numbers in the five sheets. To investigate the difference of ADC value in various doses, a single sheet from each of five lots was irradiated at 0.5 Gy and 3 Gy in addition to 2 Gy. A scan resolution of 72 dots per inch (dpi) and color depth of 48-bit RGB were used. Films were analyzed by the inhouse software; Average of ADC value in center ROI and profile X and Y axis were measured. Results and Conclusion: Intra-sheet uniformity of non-irradiated EBT2 films were ranged from 0.1% to 0.4%, however that of irradiated EBT2 films were ranged from 0.2% to 1.5%. On the other hand, intra-sheet uniformity of irradiated and non-irradiated EBT3 films were from 0.2% to 0.6%. Inter-sheet uniformity of all films were less than 0.5%. It was interesting point that homogeneity of EBT3 between no-irradiated and irradiated films were similar value, whereas EBT2 had dose dependence of homogeneity in ADC value evaluation. These results suggested that EBT3 homogeneity was corrected by this feature.« less

Pancreatic enzymes prepared in bicarbonate solution for administration through enteral feeding tubes.

PubMed

Boullata, Angela M; Boullata, Joseph I

2015-07-15

The dissolution and physicochemical effects of preparing delayed-release pancrelipase in a sodium bicarbonate solution before administration via an enteral feeding tube were studied. Several doses of four delayed-release pancrelipase products (Creon, Pancreaze, Ultresa, Zenpep) were studied. The intact contents of pancrelipase capsules was added to 20 mL of 8.4% sodium bicarbonate solution to dissolve the enteric coating and liberate the enzymes into solution. In addition to visual observation, the pH, relative particle count, and osmolality of each admixture were assessed immediately and 5, 10, 20, and 30 minutes after admixture preparation. The only dose of Creon that was completely dissolved at 30 minutes was the 24,000 lipase unit dose. None of the doses of Pancreaze and only the lowest dose (23,000 lipase units) of Ultresa were completely dissolved at 30 minutes. However, Zenpep doses of 20,000 and 40,000 lipase units were completely dissolved 30 minutes after preparation. Higher doses of each pancrelipase product did not completely dissolve. The baseline pH of the solvent decreased slightly at the first few time points after pancrelipase was added. The relative particle count increased over time and with increasing doses. The osmolality of the mixtures varied by pancrelipase product. The dissolution of enteric coated granules in sodium bicarbonate varied with the pancrelipase product and dose. Zenpep 40,000 lipase units was found to most efficiently dissolve in sodium bicarbonate, possibly due to the consistent size of the product's granules and visibly thinner and uniform enteric coating. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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

Koger, B; Kirkby, C; Dept. of Oncology, Dept. Of Medical Physics, Jack Ady Cancer Centre, Lethbridge, Alberta

Introduction: The use of gold nanoparticles (GNPs) in radiotherapy has shown promise for therapeutic enhancement. In this study, we explore the feasibility of enhancing radiotherapy with GNPs in an arc-therapy context. We use Monte Carlo simulations to quantify the macroscopic dose-enhancement ratio (DER) and tumour to normal tissue ratio (TNTR) as functions of photon energy over various tumour and body geometries. Methods: GNP-enhanced arc radiotherapy (GEART) was simulated using the PENELOPE Monte Carlo code and penEasy main program. We simulated 360° arc-therapy with monoenergetic photon energies 50 – 1000 keV and several clinical spectra used to treat a spherical tumourmore » containing uniformly distributed GNPs in a cylindrical tissue phantom. Various geometries were used to simulate different tumour sizes and depths. Voxel dose was used to calculate DERs and TNTRs. Inhomogeneity effects were examined through skull dose in brain tumour treatment simulations. Results: Below 100 keV, DERs greater than 2.0 were observed. Compared to 6 MV, tumour dose at low energies was more conformai, with lower normal tissue dose and higher TNTRs. Both the DER and TNTR increased with increasing cylinder radius and decreasing tumour radius. The inclusion of bone showed excellent tumour conformality at low energies, though with an increase in skull dose (40% of tumour dose with 100 keV compared to 25% with 6 MV). Conclusions: Even in the presence of inhomogeneities, our results show promise for the treatment of deep-seated tumours with low-energy GEART, with greater tumour dose conformality and lower normal tissue dose than 6 MV.« less

Evidence for dose-dependent positively and negatively reinforcing effects of the substance P C-terminal analog DIME-C7.

PubMed

Hasenöhrl, R U; Gerhardt, P; Huston, J P

1990-12-01

Possible positive reinforcing and aversive effects of intraperitoneally (ip) administered substance P (SP) and its C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]-SP5-11 (DIME-C7) were investigated in rats. The 'conditioned corral preference and avoidance procedure' was used for assessing positive and negative reinforcement. Behavioural testing was conducted in a circular open field consisting of four uniform quadrants equally preferred by the rats prior to drug treatment. On 3 consecutive days, rats received an ip injection of either SP (37 nmol/kg), DIME-C7 (3.7, 7.4, 37, 185 nmol/kg) or vehicle (0.01 M acetic acid in saline) and were placed immediately into their assigned treatment corral. During the test for conditioned corral preference and avoidance, when provided a choice between the four quadrants, rats treated with SP and with the equimolar dose of DIME-C7 (37 nmol/kg) spent significant more time in the drug-paired corral, indicative of positive reinforcing effects. The doses of 3.7 and 7.4 nmol/kg DIME-C7 did not influence the preference behaviour. The high dose of 185 nmol/kg DIME-C7 led to a significant decrease in time spent in the previously drug-paired corral, suggestive of aversive effects of the treatment. Gross locomotor activity was not influenced by either treatment. These results are discussed in the framework of a structure/activity relationship for the reinforcing properties of peripheraly applied SP.

A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

PubMed

Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

2015-12-01

Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

An assessment of the doses received by members of the public in Japan following the nuclear accident at Fukushima Daiichi nuclear power plant.

PubMed

Bedwell, P; Mortimer, K; Wellings, J; Sherwood, J; Leadbetter, S J; Haywood, S M; Charnock, T; Jones, A R; Hort, M C

2015-12-01

The earthquake and tsunami on 11 March 2011, centred off the east coast of Japan, caused considerable destruction and substantial loss of life along large swathes of the Japanese coastline. The tsunami damaged the Fukushima Daiichi nuclear power plant (NPP), resulting in prolonged releases of radioactive material into the environment. This paper assesses the doses received by members of the public in Japan. The assessment is based on an estimated source term and atmospheric dispersion modelling rather than monitoring data. It is evident from this assessment that across the majority of Japan the estimates of dose are very low, for example they are estimated to be less than the annual average dose from natural background radiation in Japan. Even in the regions local to Fukushima Daiichi NPP (and not affected by any form of evacuation) the maximum lifetime effective dose is estimated to be well below the cumulative natural background dose over the same period. The impact of the urgent countermeasures on the estimates of dose was considered. And the relative contribution to dose from the range of exposure pathways and radionuclides were evaluated. Analysis of estimated doses focused on the geographic irregularity and the impact of the meteorological conditions. For example the dose to an infant's thyroid received over the first year was estimated to be greater in Hirono than in the non-evacuated region of Naraha, despite Hirono being further from the release location. A number of factors were identified and thought to contribute towards this outcome, including the local wind pattern which resulted in the recirculation of part of the release. The non-uniform nature of dose estimates strengthens the case for evaluations based on dispersion modelling.

SU-E-T-357: Electronic Compensation Technique to Deliver Total Body Dose

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

Lakeman, T; Wang, I; Podgorsak, M

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient’s immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has conventionally been used to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Methods: Treatment plans utilizing electronic compensation to deliver a total body dose were created retrospectively for patients for whom CTmore » data had been previously acquired. Each treatment plan includes two, specifically weighted, pair of opposed fields. One pair of open, large fields (collimator=45°), to encompass the patient’s entire anatomy, and one pair of smaller fields (collimator=0°) focused only on the thicker midsection of the patient. The optimal fluence for each one of the smaller fields was calculated at a patient specific penetration depth. Irregular surface compensators provide a more uniform dose distribution within the smaller opposed fields. Results: Dose-volume histograms (DVH) were calculated for the evaluating the electronic compensation technique. In one case, the maximum body doses calculated from the DVH were reduced from the non-compensated 195.8% to 165.3% in the electronically compensated plans, indicating a more uniform dose with the region of electronic compensation. The mean body doses calculated from the DVH were also reduced from the non-compensated 120.6% to 112.7% in the electronically compensated plans, indicating a more accurate delivery of the prescription dose. All calculated monitor units were well within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not substantially increase the beam on time while it can significantly reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.« less

Electronic compensation technique to deliver a total body dose

NASA Astrophysics Data System (ADS)

Lakeman, Tara E.

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been conventionally used to compensate for the varying thickness throughout the body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the electronic compensation to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Each treatment plan includes two pair of parallel opposed fields. One pair of large fields is used to encompass the majority of the patient's anatomy. The other pair are very small open fields focused only on the thin bottom portion of the patient's anatomy, which requires much less radiation than the rest of the body to reach 100% of the prescribed dose. A desirable fluence pattern was manually painted within each of the larger fields for each patient to provide a more uniform distribution. Results: Dose-volume histograms (DVH) were calculated for evaluating the electronic compensation technique. In the electronically compensated plans, the maximum body doses calculated from the DVH were reduced from the conventionally-compensated plans by an average of 15%, indicating a more uniform dose. The mean body doses calculated from the electronically compensated DVH remained comparable to that of the conventionally-compensated plans, indicating an accurate delivery of the prescription dose using electronic compensation. All calculated monitor units were within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not increase the beam on time beyond clinically acceptable limits while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.

SU-E-T-368: Evaluating Dosimetric Outcome of Modulated Photon Radiotherapy (XMRT) Optimization for Head and Neck Patients

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

McGeachy, P; Villarreal-Barajas, JE; Khan, R

2015-06-15

Purpose: The dosimetric outcome of optimized treatment plans obtained by modulating the photon beamlet energy and fluence on a small cohort of four Head and Neck (H and N) patients was investigated. This novel optimization technique is denoted XMRT for modulated photon radiotherapy. The dosimetric plans from XMRT for H and N treatment were compared to conventional, 6 MV intensity modulated radiotherapy (IMRT) optimization plans. Methods: An arrangement of two non-coplanar and five coplanar beams was used for all four H and N patients. Both XMRT and IMRT were subject to the same optimization algorithm, with XMRT optimization allowing bothmore » 6 and 18 MV beamlets while IMRT was restricted to 6 MV only. The optimization algorithm was based on a linear programming approach with partial-volume constraints implemented via the conditional value-at-risk method. H and N constraints were based off of those mentioned in the Radiation Therapy Oncology Group 1016 protocol. XMRT and IMRT solutions were assessed using metrics suggested by International Commission on Radiation Units and Measurements report 83. The Gurobi solver was used in conjunction with the CVX package to solve each optimization problem. Dose calculations and analysis were done in CERR using Monte Carlo dose calculation with VMC{sub ++}. Results: Both XMRT and IMRT solutions met all clinical criteria. Trade-offs were observed between improved dose uniformity to the primary target volume (PTV1) and increased dose to some of the surrounding healthy organs for XMRT compared to IMRT. On average, IMRT improved dose to the contralateral parotid gland and spinal cord while XMRT improved dose to the brainstem and mandible. Conclusion: Bi-energy XMRT optimization for H and N patients provides benefits in terms of improved dose uniformity to the primary target and reduced dose to some healthy structures, at the expense of increased dose to other healthy structures when compared with IMRT.« less

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

2017-11-15

To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative dosimetric and radiobiological assessment among a nonstandard RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecologic cancer

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

Pedicini, Piernicola, E-mail: ppiern@libero.it; Caivano, Rocchina; Fiorentino, Alba

2012-01-01

To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard (without vaginal applicator) RapidArc plans for 27 women with GC were developed to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were performed by means of dose-volume histogram and equivalent uniform dose (EUD) for planning target volume (PTV) and organs at risk (OARs). In addition, the integral dose and the overall treatment times were evaluated. RA, as well as IMRT, results in a high uniform dose onmore » PTV compared with HDR-BRT. However, the average of EUD for HDR-BRT was significantly higher than those with RA and IMRT. With respect to the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT. Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and better than HDR-BRT for the rectum because of a significant reduction of d{sub 2cc}, d{sub 1cc}, and d{sub max} (p < 0.01). Integral doses were always higher than HDR-BRT, although the values were very low. Delivery times were about the same and more than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion, the boost of dose on vaginal vault in patients affected by GC delivered by a nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT because of a reduction of delivery time and rectal dose at substantial comparable doses for the bladder and sigmoid. However HDR-BRT provides better performance in terms of PTV coverage as evidenced by a greater EUD.« less

Radiological assessment. A textbook on environmental dose analysis

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

Till, J.E.; Meyer, H.R.

1983-09-01

Radiological assessment is the quantitative process of estimating the consequences to humans resulting from the release of radionuclides to the biosphere. It is a multidisciplinary subject requiring the expertise of a number of individuals in order to predict source terms, describe environmental transport, calculate internal and external dose, and extrapolate dose to health effects. Up to this time there has been available no comprehensive book describing, on a uniform and comprehensive level, the techniques and models used in radiological assessment. Radiological Assessment is based on material presented at the 1980 Health Physics Society Summer School held in Seattle, Washington. Themore » material has been expanded and edited to make it comprehensive in scope and useful as a text. Topics covered include (1) source terms for nuclear facilities and Medical and Industrial sites; (2) transport of radionuclides in the atmosphere; (3) transport of radionuclides in surface waters; (4) transport of radionuclides in groundwater; (5) terrestrial and aquatic food chain pathways; (6) reference man; a system for internal dose calculations; (7) internal dosimetry; (8) external dosimetry; (9) models for special-case radionuclides; (10) calculation of health effects in irradiated populations; (11) evaluation of uncertainties in environmental radiological assessment models; (12) regulatory standards for environmental releases of radionuclides; (13) development of computer codes for radiological assessment; and (14) assessment of accidental releases of radionuclides.« less

Combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on CMOS APS image sensors

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; Sheng, Jiangkun

The combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on complementary metal-oxide semiconductor (CMOS) active pixel sensors (APS) have been discussed and some new experimental phenomena are presented. The samples are manufactured in the standard 0.35-μm CMOS technology. Two samples were first exposed to {sup 60}Co γ-rays up to the total ionizing dose (TID) level of 200 krad(Si) at the dose rates of 50.0 and 0.2 rad(Si)/s, and then exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence). One sample was first exposed to neutron fluence up to 1 × 10{supmore » 11} n/cm{sup 2} (1-MeV equivalent neutron fluence), and then exposed to {sup 60}Co γ-rays up to the TID level of 200 krad(Si) at the dose rate of 0.2 rad(Si)/s. The mean dark signal (K{sub D}), the dark signal non-uniformity (DSNU), and the noise (V{sub N}) versus the total dose and neutron fluence has been investigated. The degradation mechanisms of CMOS APS image sensors have been analyzed, especially for the interaction induced by neutron displacement damage and TID damage.« less

Pellicle transmission uniformity requirements

NASA Astrophysics Data System (ADS)

Brown, Thomas L.; Ito, Kunihiro

1998-12-01

Controlling critical dimensions of devices is a constant battle for the photolithography engineer. Current DUV lithographic process exposure latitude is typically 12 to 15% of the total dose. A third of this exposure latitude budget may be used up by a variable related to masking that has not previously received much attention. The emphasis on pellicle transmission has been focused on increasing the average transmission. Much less, attention has been paid to transmission uniformity. This paper explores the total demand on the photospeed latitude budget, the causes of pellicle transmission nonuniformity and examines reasonable expectations for pellicle performance. Modeling is used to examine how the two primary errors in pellicle manufacturing contribute to nonuniformity in transmission. World-class pellicle transmission uniformity standards are discussed and a comparison made between specifications of other components in the photolithographic process. Specifications for other materials or parameters are used as benchmarks to develop a proposed industry standard for pellicle transmission uniformity.

Commercial scale irradiation for insect disinfestation preserves peach quality

NASA Astrophysics Data System (ADS)

McDonald, Heather; McCulloch, Mary; Caporaso, Fred; Winborne, Ian; Oubichon, Michon; Rakovski, Cyril; Prakash, Anuradha

2012-06-01

Irradiation is approved as a generic quarantine treatment by the US Department of Agriculture, Animal and Plant Health Inspection Service. Due to the effectiveness of irradiation in controlling insects on commodities, there is a growing need to understand the effects of low dose irradiation on fruit quality. The goal of this study was to determine the sensitivity of peaches (Prunus persica) to irradiation, and secondly, to determine the effect of commercial scale treatment on shelf-life, overall quality and consumer liking. Six varieties of peaches were irradiated in small batches at 0.29, 0.49, 0.69 and 0.90 kGy to observe the sensitivity of peaches at different dose levels. Changes in quality were evaluated by 8 trained panelists using descriptive analysis. Sensory characteristics (color, smoothness, aroma, touch firmness, mouth firmness, graininess, overall flavor and off-flavor) were evaluated at 2-4 day intervals and untreated samples served as control. To simulate commercial treatment, peaches were irradiated in pallet quantities at a target dose level of 0.4 kGy. The average absorbed dose was 0.66 kGy with an average dose uniformity ratio of 1.57. Commercially treated peaches were evaluated by 40-80 untrained consumers for acceptability routinely throughout the shelf life. Titratable acidity, Brix, texture and weight loss were also monitored for both commercial and small scale irradiated peaches. There was no dose effect on TA, Brix and weight loss due to irradiation. Peaches irradiated at 0.69 and 0.90 kGy were darker in flesh color, more juicy and less firm as determined by the trained panel and analytical pressure tests. Commercial scale irradiation did not adversely affect shelf life but was seen to enhance ripening. This, however, was perceived as a positive change by consumers. Overall, consumers rated the acceptability of irradiated peaches higher than untreated peaches. Statistical analysis was performed using linear mixed models to find determinates of irradiation on peaches.

Optimization of GATE and PHITS Monte Carlo code parameters for spot scanning proton beam based on simulation with FLUKA general-purpose code

NASA Astrophysics Data System (ADS)

Kurosu, Keita; Das, Indra J.; Moskvin, Vadim P.

2016-01-01

Spot scanning, owing to its superior dose-shaping capability, provides unsurpassed dose conformity, in particular for complex targets. However, the robustness of the delivered dose distribution and prescription has to be verified. Monte Carlo (MC) simulation has the potential to generate significant advantages for high-precise particle therapy, especially for medium containing inhomogeneities. However, the inherent choice of computational parameters in MC simulation codes of GATE, PHITS and FLUKA that is observed for uniform scanning proton beam needs to be evaluated. This means that the relationship between the effect of input parameters and the calculation results should be carefully scrutinized. The objective of this study was, therefore, to determine the optimal parameters for the spot scanning proton beam for both GATE and PHITS codes by using data from FLUKA simulation as a reference. The proton beam scanning system of the Indiana University Health Proton Therapy Center was modeled in FLUKA, and the geometry was subsequently and identically transferred to GATE and PHITS. Although the beam transport is managed by spot scanning system, the spot location is always set at the center of a water phantom of 600 × 600 × 300 mm3, which is placed after the treatment nozzle. The percentage depth dose (PDD) is computed along the central axis using 0.5 × 0.5 × 0.5 mm3 voxels in the water phantom. The PDDs and the proton ranges obtained with several computational parameters are then compared to those of FLUKA, and optimal parameters are determined from the accuracy of the proton range, suppressed dose deviation, and computational time minimization. Our results indicate that the optimized parameters are different from those for uniform scanning, suggesting that the gold standard for setting computational parameters for any proton therapy application cannot be determined consistently since the impact of setting parameters depends on the proton irradiation technique. We therefore conclude that customization parameters must be set with reference to the optimized parameters of the corresponding irradiation technique in order to render them useful for achieving artifact-free MC simulation for use in computational experiments and clinical treatments.

Quantitative investigation of the effects of the scanning parameters in the digitization of EBT and EBT2 Gafchromic film dosimetry with flatbed scanners.

PubMed

Hu, Yida; Ahmad, Salahuddin; Ali, Imad

2012-01-01

With increasing popularity and complexity of intensity-modulated radiation therapy (IMRT) delivery modalities including regular and arc therapies, there is a growing challenge for validating the accuracy of dose distributions. Gafchromic films have superior characteristics for dose verification over other conventional dosimeters. In order to optimize the use of Gafchromic films in clinical IMRT quality assurance procedures, the scanning parameters of EBT and EBT2 films with a flatbed scanner were investigated. The effects of several parameters including scanning position, orientation, uniformity, film sensitivity and optical density (OD) growth after irradiation were quantified. The profiles of the EBT and EBT2 films had a noise level of 0.6% and 0.7%, respectively. Considerable orientation dependence was observed and the scanner value difference between landscape and portrait modes were about 12% and 10% for EBT and EBT2 films, respectively. The highest response sensitivity was observed using digitized red color images of the EBT2 film scanned with landscape mode. The total system non-uniformity composed of contributions from the film and the scanner was less than 1.7%. OD variations showed that EBT gray scale grew slower, however, reached higher growth values of 15% when compared with EBT2 gray scale which grew 12% after a long time (480 hours) post-irradiation. The EBT film using the red color channel showed the minimal growth where OD increased up to 3% within 3 days after irradiation, and took one week to stabilize.

Within-wafer CD variation induced by wafer shape

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Yang, Mars; Yang, Elvis; Yang, T. H.; Chen, K. C.

2016-03-01

In order to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories, 3D stacked vertical flash cell array has been proposed. In constructing 3D NAND flash memories, the bit number per unit area is increased as increasing the number of stacked layers. However, the increased number of stacked layers has made the film stress control extremely important for maintaining good process quality. The residual film stress alters the wafer shape accordingly several process impacts have been readily observed across wafer, such as film deposition non-uniformity, etch rate non-uniformity, wafer chucking error on scanner, materials coating/baking defects, overlay degradation and critical dimension (CD) non-uniformity. The residual tensile and compressive stresses on wafers will result in concave and convex wafer shapes, respectively. This study investigates within-wafer CD uniformity (CDU) associated with wafer shape change induced by the 3D NAND flash memory processes. Within-wafer CDU was correlated with several critical parameters including different wafer bow heights of concave and convex wafer shapes, photo resists with different post exposure baking (PEB) temperature sensitivities, and DoseMapper compensation. The results indicated the trend of within-wafer CDU maintains flat for convex wafer shapes with bow height up to +230um and concave wafer shapes with bow height ranging from 0 ~ -70um, while the within-wafer CDU trends up from -70um to -246um wafer bow heights. To minimize the within-wafer CD distribution induced by wafer warpage, carefully tailoring the film stack and thermal budget in the process flow for maintaining the wafer shape at CDU friendly range is indispensable and using photo-resist materials with lower PEB temperature sensitivity is also suggested. In addition, DoseMapper compensation is also an alternative to greatly suppress the within-wafer CD non-uniformity but the photo-resist profile variation induced by across-wafer PEB temperature non-uniformity attributed to wafer warpage is uncorrectable, and the photo-resist profile variation is believed to affect across-wafer etch bias uniformity to some degree.

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

Kauweloa, K; Gutierrez, A; Bergamo, A

Purpose: There is growing interest about biological effective dose (BED) and its application in treatment plan evaluation due to its stronger correlation with treatment outcome. An approximate biological effective dose (BEDA) equation was introduced to simplify BED calculations by treatment planning systems in multi-phase treatments. The purpose of this work is to reveal its mathematical properties relative to the true, multi-phase BED (BEDT) equation. Methods: The BEDT equation was derived and used to reveal the mathematical properties of BEDA. MATLAB (MathWorks, Natick, MA) was used to simulate and analyze common and extreme clinical multi-phase cases. In those cases, percent errormore » (Perror) and Bland-Altman analysis were used to study the significance of the inaccuracies of BEDA for different combinations of total doses, numbers of fractions, doses per fractions and α over β values. All the calculations were performed on a voxel-basis in order to study how dose distributions would affect the accuracy of BEDA. Results: When the voxel dose-per-fractions (DPF) delivered by both phases are equal, BEDA and BEDT are equal. In heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the imprecision of BEDA is greater. It was shown that as the α over β ratio increased the accuracy of BEDA would improve. Examining twenty-four cases, it was shown that the range of DPF ratios for a 3 Perror varied from 0.32 to 7.50Gy, whereas for Perror of 1 the range varied from 0.50 to 2.96Gy. Conclusion: The DPF between the different phases should be equal in order to render BEDA accurate. OARs typically receive heterogeneous dose distributions hence the probability of equal DPFs is low. Consequently, the BEDA equation should only be used for targets or OARs that receive uniform or very similar dose distributions by the different treatment phases.« less

Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer.

PubMed

Rasmussen, Jacob H; Håkansson, Katrin; Vogelius, Ivan R; Aznar, Marianne C; Fischer, Barbara M; Friborg, Jeppe; Loft, Annika; Kristensen, Claus A; Bentzen, Søren M; Specht, Lena

2016-07-01

The CONTRAST (CONventional vs.Tumor Recurrence Adapted Specification of Target dose) phase I trial tested the safety of FDG PET guided dose redistribution in patients receiving accelerated chemo-radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC). CONTRAST was designed with two pre-defined dose-escalation steps to the FDG PET-avid volume (GTVPET). The primary end point was any early grade 4+ toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). The dose to GTVPET was escalated to a uniform prescription of 82Gy EQD2 in the first step. All patients received accelerated radiotherapy (6 fractions a week) delivering 34 fractions of 2.34Gy to the GTVPET as well as concomitant weekly cisplatin. Inclusion criteria were (1) primary SCC of oral cavity, oro- or hypo-pharynx, or laynx, (2) candidates for concomitant chemo-radiotherapy and (3) p16 negative tumors or p16 positive tumors in patients with smoking history of >10 pack years. GTVPET was defined by a specialist in nuclear medicine and a radiologist, while the anatomic GTV was defined in collaboration between an oncologist and a radiologist. Median follow up time from the end of treatment was 18months (range 7-21months). All 15 patients completed treatment without interruptions and no incidents of early grade 4+ toxicity were observed. Four patients had ulceration at the evaluation two months after treatment, two have subsequently healed, but two remain, raising concerns regarding late effects. With all 15 cases having completed four month follow up and no incidence of early grade 4+ toxicity FDG PET based dose escalation to 82Gy passed the protocol-defined criterion for dose escalation. However, two cases of concern regarding late outcome led us to refrain from further dose escalation and proceed with the current dose level in a larger comparative effectiveness trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

PubMed

Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

1988-02-01

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

Geant4 simulation for a study of a possible use of carbon ions pencil beam for the treatment of ocular melanomas with the active scanning system at CNAO Centre

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

Farina, E.; Piersimoni, P.; Riccardi, C.

The aim of this work is to validate the Geant4 application reproducing the CNAO (National Centre for Oncological Hadrontherapy) beamline and to study of a possible use of carbon ion pencil beams for the treatment of ocular melanomas at the CNAO Centre. The promising aspect of carbon ions radiotherapy for the treatment of this disease lies in its superior relative radiobiological effectiveness (RBE). The Monte Carlo Geant4 toolkit is used to simulate the complete CNAO extraction beamline, with the active and passive components along it. A human eye modeled detector, including a realistic target tumor volume, is used as target.more » Cross check with previous studies at CNAO using protons allows comparisons on possible benefits on using such a technique with respect to proton beams. Before the eye-detector irradiation a validation of the Geant4 simulation with CNAO experimental data is carried out with both carbon ions and protons. Important beam parameters such as the transverse FWHM and scanned radiation field 's uniformity are tested within the simulation and compared with experimental measurements at CNAO Centre. The physical processes involved in secondary particles generation by carbon ions and protons in the eye-detector are reproduced to take into account the additional dose to the primary beam given to irradiated eye's tissues. A study of beam shaping is carried out to produce a uniform 3D dose distribution (shaped on the tumor) by the use of a spread out Bragg peak. The eye-detector is then irradiated through a two dimensional transverse beam scan at different depths. In the use case the eye-detector is rotated of an angle of 40 deg. in the vertical direction, in order to mis-align the tumor from healthy tissues in front of it. The treatment uniformity on the tumor in the eye-detector is tested. For a more quantitative description of the deposited dose in the eye-detector and for the evaluation of the ratio between the dose deposited in the tumor and the other eye components, proton and carbon DVHs (Dose Volume Histograms) are compared. A high statistics simulated sample is used to minimize statistical errors. In the simulation a new particle generation method is developed in order to reproduce the experimental treatment plan by importing the DICOM RT-PLAN file, which contains all the information on the irradiation geometries and sequences (treatment plan parameters). Conclusions Even further validations must be done, the good results so far obtained by this work point out and confirm the possibility of using carbon ions delivered with active scanning beams to treat the ocular melanoma.« less

Reload of an industrial cylindrical cobalt source rack

NASA Astrophysics Data System (ADS)

Gharbi, F.; Kadri, O.; Trabelsi, A.

2006-10-01

This work presents a Monte Carlo study of the cylindrical cobalt source rack geometry of the Tunisian gamma irradiation facility, using the GEANT code developed at CERN. The study investigates the question of the reload of the source rack. The studied configurations consist in housing four new cobalt pencils, two in the upper and two in the lower cylinder of the source rack. Global dose rate uniformity inside a "dummy" product for the case of routine and nonroutine irradiation, and as function of the product bulk density, was calculated for eight hypothetical configurations. The same calculation was also performed for both of the original and the ideal (but not practical) configurations. It was shown that hypothetical cases produced dose uniformity variations, according to product density, that were statistically no different than the original and the ideal configurations and that the reload procedure cannot improve the irradiation quality inside the facilities using cylindrical cobalt source racks.

A quality control method for intensity-modulated radiation therapy planning based on generalized equivalent uniform dose.

PubMed

Pang, Haowen; Sun, Xiaoyang; Yang, Bo; Wu, Jingbo

2018-05-01

To ensure good quality intensity-modulated radiation therapy (IMRT) planning, we proposed the use of a quality control method based on generalized equivalent uniform dose (gEUD) that predicts absorbed radiation doses in organs at risk (OAR). We conducted a retrospective analysis of patients who underwent IMRT for the treatment of cervical carcinoma, nasopharyngeal carcinoma (NPC), or non-small cell lung cancer (NSCLC). IMRT plans were randomly divided into data acquisition and data verification groups. OAR in the data acquisition group for cervical carcinoma and NPC were further classified as sub-organs at risk (sOAR). The normalized volume of sOAR and normalized gEUD (a = 1) were analyzed using multiple linear regression to establish a fitting formula. For NSCLC, the normalized intersection volume of the planning target volume (PTV) and lung, the maximum diameter of the PTV (left-right, anterior-posterior, and superior-inferior), and the normalized gEUD (a = 1) were analyzed using multiple linear regression to establish a fitting formula for the lung gEUD (a = 1). The r-squared and P values indicated that the fitting formula was a good fit. In the data verification group, IMRT plans verified the accuracy of the fitting formula, and compared the gEUD (a = 1) for each OAR between the subjective method and the gEUD-based method. In conclusion, the gEUD-based method can be used effectively for quality control and can reduce the influence of subjective factors on IMRT planning optimization. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Improved dosimetry techniques for intravascular brachytherapy

NASA Astrophysics Data System (ADS)

Sehgal, Varun

Coronary artery disease leads to the accumulation of atheromatous plaque leading to coronary stenosis. Coronary intervention techniques such as balloon angioplasty and atherectomy are used to address coronary stenosis and establish a stable lumen thus enhancing blood flow to the myocardium. Restenosis or re-blockage of the arteries is a major limitation of the above mentioned interventional techniques. Neointimal hyperplasia or proliferation of cells in response to the vascular injury as a result of coronary intervention is considered to be one of the major causes of restenosis. Recent studies indicated that irradiation of the coronary lesion site, with radiation doses ranging from 15 to 30 Gy, leads to diminishing neointimal hyperplasia with subsequent reduction in restenosis. The radiation dose is given by catheter-based radiation delivery systems using beta-emitters 90Sr/90Y, 32P and gamma-emitting 192Ir among others. However the dose schema used for dose prescription for these sources are relatively simplistic, and are based on calculations using uniform homogenous water or tissue media and simple cylinder geometry. Stenotic coronary vessels are invariably lined with atheromatous plaque of heterogeneous composition, the radiation dose distribution obtained from such dosimetry data can cause significant variations in the actual dose received by a given patient. Such discrepancies in dose calculation can introduce relatively large uncertainties in the limits of dose window for effective and safe application of intravascular brachytherapy, and consequently in the clinical evaluation of the efficacy of this modality. In this research study we investigated the effect of different geometrical and material heterogeneities, including residual plaque, catheter non-centering, lesion eccentricity and cardiac motion on the radiation dose delivered at the lesion site. Correction factors including dose perturbation factors and dose variation factors have been calculated using Monte Carlo-based radiation transport code MCNP and tabulated for a range of different coronary geometries and different radionuclides. A new technique using imaging techniques such as intravascular ultrasound and angiography to assess dosimetry for realistic coronary arteries is also introduced. The results indicate the need for accurate assessment of post-intervention clinical measurements such as minimal lumen diameter and residual plaque burden and incorporating them into dose calculations.

[Prophylaxis of alcoholic disease of the liver].

PubMed

Beliakin, S A

2009-08-01

Military doctors should have a uniform position to the use of alcohol. Now alcohol is the basic pathogenic factor in development of a lethal cirrhosis of a liver. The most known sayings justifying the use of alcohol, are insolvent. Useful doses of alcohol does not exist. The quantity of used alcohol has the great value. Only at achievement of age 21 year it is possible to use safe doses of alcohol. A safe dose of pure alcohol (ethanol) less than 30,0 in day. In a basis of prophylaxis of a cirrhosis of a liver there is a medical educational activity.

Gamma irradiation to improve plant vigour, grain development, and yield attributes of wheat

NASA Astrophysics Data System (ADS)

Singh, Bhupinder; Datta, P. S.

2010-02-01

Utilizing low dose gamma radiation holds promise for physiological crop improvement. Seed treatment of low dose gamma radiation 0.01-0.10 kGy reduced plant height, improved plant vigour, flag leaf area, total and number of EBT. Gamma irradiation increased grain yield due to an increase in number of EBT and grain number while 1000 grain weight was negatively affected. Further uniformity in low dose radiation response in wheat in the field suggests that the affect is essentially at physiological than at genetic level and that role of growth hormones could be crucial.

Phase holograms in PMMA with proximity effect correction

NASA Technical Reports Server (NTRS)

Maker, Paul D.; Muller, R. E.

1993-01-01

Complex computer generated phase holograms (CGPH's) have been fabricated in PMMA by partial e-beam exposure and subsequent partial development. The CGPH was encoded as a sequence of phase delay pixels and written by the JEOL JBX-5D2 E-beam lithography system, a different dose being assigned to each value of phase delay. Following carefully controlled partial development, the pattern appeared rendered in relief in the PMMA, which then acts as the phase-delay medium. The exposure dose was in the range 20-200 micro-C/sq cm, and very aggressive development in pure acetone led to low contrast. This enabled etch depth control to better than plus or minus lambda(sub vis)/60. That result was obtained by exposing isolated 50 micron square patches and measuring resist removal over the central area where the proximity effect dose was uniform and related only to the local exposure. For complex CGPH's with pixel size of the order of the e-beam proximity effect radius, the patterns must be corrected for the extra exposure caused by electrons scattered back up out of the substrate. This has been accomplished by deconvolving the two-dimensional dose deposition function with the desired dose pattern. The deposition function, which plays much the same role as an instrument response function, was carefully measured under the exact conditions used to expose the samples. The devices fabricated were designed with 16 equal phase steps per retardation cycle, were up to 1 cm square, and consisted of up to 100 million 0.3-2.0 micron square pixels. Data files were up to 500 MB long and exposure times ranged to tens of hours. A Fresnel phase lens was fabricated that had diffraction limited optical performance with better than 85 percent efficiency.

Evaluation of a novel triple-channel radiochromic film analysis procedure using EBT2.

PubMed

van Hoof, Stefan J; Granton, Patrick V; Landry, Guillaume; Podesta, Mark; Verhaegen, Frank

2012-07-07

A novel approach to read out radiochromic film was introduced recently by the manufacturer of GafChromic film. In this study, the performance of this triple-channel film dosimetry method was compared against the conventional single-red-channel film dosimetry procedure, with and without inclusion of a pre-irradiation (pre-IR) film scan, using EBT2 film and kilo- and megavoltage photon beams up to 10 Gy. When considering regions of interest averaged doses, the triple-channel method and both single-channel methods produced equivalent results. Absolute dose discrepancies between the triple-channel method, both single-channel methods and the treatment planning system calculated dose values, were no larger than 5 cGy for dose levels up to 2.2 Gy. Signal to noise in triple-channel dose images was found to be similar to signal to noise in single-channel dose images. The accuracy of resulting dose images from the triple- and single-channel methods with inclusion of pre-IR film scan was found to be similar. Results of a comparison of EBT2 data from a kilovoltage depth dose experiment to corresponding Monte Carlo depth dose data produced dose discrepancies of 9.5 ± 12 cGy and 7.6 ± 6 cGy for the single-channel method with inclusion of a pre-IR film scan and the triple-channel method, respectively. EBT2 showed to be energy sensitive at low kilovoltage energies with response differences of 11.9% and 15.6% in the red channel at 2 Gy between 50-225 kVp and 80-225 kVp photon spectra, respectively. We observed that the triple-channel method resulted in non-uniformity corrections of ±1% and consistency values of 0-3 cGy for the batches and dose levels studied. Results of this study indicate that the triple-channel radiochromic film read-out method performs at least as well as the single-channel method with inclusion of a pre-IR film scan, reduces film non-uniformity and saves time with elimination of a pre-IR film scan.

Variations in corticosteroid/anesthetic injections for painful shoulder conditions: comparisons among orthopaedic surgeons, rheumatologists, and physical medicine and primary-care physicians.

PubMed

Skedros, John G; Hunt, Kenneth J; Pitts, Todd C

2007-07-06

Variations in corticosteroid/anesthetic doses for injecting shoulder conditions were examined among orthopaedic surgeons, rheumatologists, and primary-care sports medicine (PCSMs) and physical medicine and rehabilitation (PMRs) physicians to provide data needed for documenting inter-group differences for establishing uniform injection guidelines. 264 surveys, sent to these physicians in our tri-state area of the western United States, addressed corticosteroid/anesthetic doses and types used for subacromial impingement, degenerative glenohumeral and acromioclavicular arthritis, biceps tendinitis, and peri-scapular trigger points. They were asked about preferences regarding: 1) fluorinated vs. non-fluorinated corticosteroids, 2) acetate vs. phosphate types, 3) patient age, and 4) adjustments for special considerations including young athletes and diabetics. 169 (64% response rate, RR) surveys were returned: 105/163 orthopaedic surgeons (64%RR), 44/77 PCSMs/PMRs (57%RR), 20/24 rheumatologists (83%RR). Although corticosteroid doses do not differ significantly between specialties (p > 0.3), anesthetic volumes show broad variations, with surgeons using larger volumes. Although 29% of PCSMs/PMRs, 44% rheumatologists, and 41% surgeons exceed "recommended" doses for the acromioclavicular joint, >98% were within recommendations for the subacromial bursa and glenohumeral joint. Depo-Medrol(R) (methylprednisolone acetate) and Kenalog(R) (triamcinolone acetonide) are most commonly used. More rheumatologists (80%) were aware that there are acetate and phosphate types of corticosteroids as compared to PCSMs/PMRs (76%) and orthopaedists (60%). However, relatively fewer rheumatologists (25%) than PCSMs/PMRs (32%) or orthopaedists (32%) knew that phosphate types are more soluble. Fluorinated corticosteroids, which can be deleterious to soft tissues, were used with these frequencies for the biceps sheath: 17% rheumatologists, 8% PCSMs/PMRs, 37% orthopaedists. Nearly 85% use the same non-fluorinated corticosteroid for all injections; <10% make adjustments for diabetic patients. Variations between specialists in anesthetic doses suggest that surgeons (who use significantly larger volumes) emphasize determining the percentage of pain attributable to the injected region. Alternatively, this might reflect a more profound knowledge that non-surgeons specialists have of the potentially adverse cardiovascular effects of these agents. Variations between these specialists in corticosteroid/anesthetic doses and/or types, and their use in some special situations (e.g., diabetics), bespeak the need for additional investigations aimed at establishing uniform injection guidelines, and for identifying knowledge deficiencies that warrant advanced education.

SU-F-J-162: Is Bulky Electron Density Assignment Appropriatefor MRI-Only Based Treatment Planning for Lung Cancer?

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

Prior, P; Chen, X; Johnstone, C

Purpose: To assess the appropriateness of bulky electron density assisment for MRI-only treatment planning for lung cancer via comparing dosimetric difference between MRI- and CT-based plans. Methods: Planning 4DCTs acquired for six representative lung cancer patients were used to generate CT-based IMRT plans. To avoid the effect of anatomic difference between CT and MRI, MRI-based plans were generated using CTs by forcing the relative electron density (rED) of organ specific values from ICRU report 46 and using the mean rED value of the internal target volume (ITV) of the patient for the ITV. Both CT and “MRI” plans were generatedmore » using a research planning system (Monaco, Elekta) employing Monte Carlo dose calculation the following dose-volume-parameters (DVPs): D99 – dose delivered to 99% of the ITV/PTV volume; D95; D5; D1; Vpd –volume receiving the prescription dose; V5 – volume of normal lung irradiated > 5 Gy; and V20. The percent point difference and dose difference was used for comparison for Vpd-V5-V20 and D99-D1, respectively. Four additional plans per patient were calculated with rEDITV = 0.6 and 1.0 and rEDlung = 0.1 and 0.5. Results: Noticeable differences in the ITV and PTV point doses and DVPs were observed. Variations in Vpd ranged from 0.0–6.4% and 0.32–18.3% for the ITV and PTV, respectively. The ITV and PTV variations in D99, D95, D5 and D1 were 0.15–3.2 Gy. The normal lung V5 & V20 variations were no larger than 1.9%. In some instances, varying the rEDITV between rEDmean, 0.6 and 1.0 resulted in D95 increases ranging from 3.9–6.3%. Uniform rED assignment on normal lung affected DVPs of ITV and PTV by 4.0–9.8% and 0.3–19.6%, respectively. Conclusion: The commonly-used uniform rED assignment in MRI-only based planning may not be appropriate for lung-cancer. A voxel based method, e.g. synthetic CT generated from MRI data, is required. This work was partially funded by Elekta, Inc.« less

Variations in corticosteroid/anesthetic injections for painful shoulder conditions: comparisons among orthopaedic surgeons, rheumatologists, and physical medicine and primary-care physicians

PubMed Central

Skedros, John G; Hunt, Kenneth J; Pitts, Todd C

2007-01-01

Background Variations in corticosteroid/anesthetic doses for injecting shoulder conditions were examined among orthopaedic surgeons, rheumatologists, and primary-care sports medicine (PCSMs) and physical medicine and rehabilitation (PMRs) physicians to provide data needed for documenting inter-group differences for establishing uniform injection guidelines. Methods 264 surveys, sent to these physicians in our tri-state area of the western United States, addressed corticosteroid/anesthetic doses and types used for subacromial impingement, degenerative glenohumeral and acromioclavicular arthritis, biceps tendinitis, and peri-scapular trigger points. They were asked about preferences regarding: 1) fluorinated vs. non-fluorinated corticosteroids, 2) acetate vs. phosphate types, 3) patient age, and 4) adjustments for special considerations including young athletes and diabetics. Results 169 (64% response rate, RR) surveys were returned: 105/163 orthopaedic surgeons (64%RR), 44/77 PCSMs/PMRs (57%RR), 20/24 rheumatologists (83%RR). Although corticosteroid doses do not differ significantly between specialties (p > 0.3), anesthetic volumes show broad variations, with surgeons using larger volumes. Although 29% of PCSMs/PMRs, 44% rheumatologists, and 41% surgeons exceed "recommended" doses for the acromioclavicular joint, >98% were within recommendations for the subacromial bursa and glenohumeral joint. Depo-Medrol® (methylprednisolone acetate) and Kenalog® (triamcinolone acetonide) are most commonly used. More rheumatologists (80%) were aware that there are acetate and phosphate types of corticosteroids as compared to PCSMs/PMRs (76%) and orthopaedists (60%). However, relatively fewer rheumatologists (25%) than PCSMs/PMRs (32%) or orthopaedists (32%) knew that phosphate types are more soluble. Fluorinated corticosteroids, which can be deleterious to soft tissues, were used with these frequencies for the biceps sheath: 17% rheumatologists, 8% PCSMs/PMRs, 37% orthopaedists. Nearly 85% use the same non-fluorinated corticosteroid for all injections; <10% make adjustments for diabetic patients. Conclusion Variations between specialists in anesthetic doses suggest that surgeons (who use significantly larger volumes) emphasize determining the percentage of pain attributable to the injected region. Alternatively, this might reflect a more profound knowledge that non-surgeons specialists have of the potentially adverse cardiovascular effects of these agents. Variations between these specialists in corticosteroid/anesthetic doses and/or types, and their use in some special situations (e.g., diabetics), bespeak the need for additional investigations aimed at establishing uniform injection guidelines, and for identifying knowledge deficiencies that warrant advanced education. PMID:17617900

An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Wen, Ning; Kumarasiri, Akila; Nurushev, Teamour; Burmeister, Jay; Xing, Lei; Liu, Dezhi; Glide-Hurst, Carri; Kim, Jinkoo; Zhong, Hualiang; Movsas, Benjamin; Chetty, Indrin J.

2013-11-01

The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7-9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIM-CT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation based on biological models, might yield higher quality treatments.

Design, fabrication, and implementation of voxel-based 3D printed textured phantoms for task-based image quality assessment in CT

NASA Astrophysics Data System (ADS)

Solomon, Justin; Ba, Alexandre; Diao, Andrew; Lo, Joseph; Bier, Elianna; Bochud, François; Gehm, Michael; Samei, Ehsan

2016-03-01

In x-ray computed tomography (CT), task-based image quality studies are typically performed using uniform background phantoms with low-contrast signals. Such studies may have limited clinical relevancy for modern non-linear CT systems due to possible influence of background texture on image quality. The purpose of this study was to design and implement anatomically informed textured phantoms for task-based assessment of low-contrast detection. Liver volumes were segmented from 23 abdominal CT cases. The volumes were characterized in terms of texture features from gray-level co-occurrence and run-length matrices. Using a 3D clustered lumpy background (CLB) model, a fitting technique based on a genetic optimization algorithm was used to find the CLB parameters that were most reflective of the liver textures, accounting for CT system factors of spatial blurring and noise. With the modeled background texture as a guide, a cylinder phantom (165 mm in diameter and 30 mm height) was designed, containing 20 low-contrast spherical signals (6 mm in diameter at targeted contrast levels of ~3.2, 5.2, 7.2, 10, and 14 HU, 4 repeats per signal). The phantom was voxelized and input into a commercial multi-material 3D printer (Object Connex 350), with custom software for voxel-based printing. Using principles of digital half-toning and dithering, the 3D printer was programmed to distribute two base materials (VeroWhite and TangoPlus, nominal voxel size of 42x84x30 microns) to achieve the targeted spatial distribution of x-ray attenuation properties. The phantom was used for task-based image quality assessment of a clinically available iterative reconstruction algorithm (Sinogram Affirmed Iterative Reconstruction, SAFIRE) using a channelized Hotelling observer paradigm. Images of the textured phantom and a corresponding uniform phantom were acquired at six dose levels and observer model performance was estimated for each condition (5 contrasts x 6 doses x 2 reconstructions x 2 backgrounds = 120 total conditions). Based on the observer model results, the dose reduction potential of SAFIRE was computed and compared between the uniform and textured phantom. The dose reduction potential of SAFIRE was found to be 23% based on the uniform phantom and 17% based on the textured phantom. This discrepancy demonstrates the need to consider background texture when assessing non-linear reconstruction algorithms.

Predictive parameters for selection of electronic tissue compensation radiotherapy in early-stage breast cancer patients after breast-conserving surgery.

PubMed

Song, Yanbo; Zhang, Miao; Gan, Lu; Chen, Xiaopin; Zhang, Tao; Yue, Ning J; Goyal, Sharad; Haffty, Bruce; Ren, Guosheng

2016-05-31

Electronic tissue compensation (eComp) is an external beam planning technique allowing user to manually generate dynamic beam fluence to produce more uniform or modulated dose distribution. In this study, we compared the effectiveness between conventional three-dimensional conformal radiotherapy (3DCRT) and eComp for whole breast irradiation. 3DCRT and eComp planning techniques were used to generate treatment plans for 60 whole breast patients, respectively. The planning goal was to cover 95% of the planning target volume (PTV) with 95% of the prescription dose while minimizing doses to lung, heart, and skin. Comparing to 3DCRT plans, on the average, eComp treatment planning process was about 7 minutes longer, but resulted in lower lung V20Gy, lower mean skin dose, with similar heart dose. The benefits were more pronounced for larger breast patients. Statistical analyses were performed between critical organ doses and patient anatomic features, i.e., central lung distance (CLD), maximal heart distance (MHD), maximal heart length (MHL) and breast separation (BS) to explore any correlations and planning method selection. It was found that to keep the lung V20Gy lower than 20% and mean skin dose lower than 85% of the prescription dose, eComp was the preferred method for patients with more than 2.3 cm CLD or larger than 22.5 cm BS. The study results may be useful in providing a handy criterion in clinical practice allowing us to easily choose between different planning techniques to satisfy the planning goal with minimal increase in complexity and cost.

Assessment of an organ‐based tube current modulation in thoracic computed tomography

PubMed Central

Sugai, Mai; Toyoda, Asami; Koshida, Haruka; Sakuta, Keita; Takata, Tadanori; Koshida, Kichiro; Iida, Hiroji; Matsui, Osamu

2012-01-01

Recently, specific computed tomography (CT) scanners have been equipped with organ‐based tube current modulation (TCM) technology. It is possible that organ‐based TCM will replace the conventional dose‐reduction technique of reducing the effective milliampere‐second. The aim of this study was to determine if organ‐based TCM could reduce radiation exposure to the breasts without compromising the image uniformity and beam hardening effect in thoracic CT examinations. Breast and skin radiation doses and the absorbed radiation dose distribution within a single section were measured with an anthropomorphic phantom and radiophotoluminescent glass dosimeters using four approaches to thoracic CT (reference, organ‐based TCM, copper shielding, and the combination of the above two techniques, hereafter referred to as the combination technique). The CT value and noise level were measured using the same calibration phantom. Organ‐based TCM and copper shielding reduced radiation doses to the breast by 23.7% and 21.8%, respectively. However, the CT value increased, especially in the anterior region, using copper shielding. In contrast, the CT value and noise level barely increased using organ‐based TCM. The combination technique reduced the radiation dose to the breast by 38.2%, but greatly increased the absorbed radiation dose from the central to the posterior regions. Moreover, the CT value increased in the anterior region and the noise level increased by more than 10% in the entire region. Therefore, organ‐based TCM can reduce radiation doses to breasts with only small increases in noise levels, making it preferable for specific groups of patients, such as children and young women. PACS numbers: 87.53.Bn; 87.57.Q‐; 87.57.qp PMID:22402390

Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

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

Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI; Department of Radiation Oncology, Rigshospitalet

2011-07-01

Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeledmore » as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.« less

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

Cardiovascular effects of the essential oil of Alpinia zerumbet leaves and its main constituent, Terpinen-4-ol, in rats: role of the autonomic nervous system.

PubMed

Lahlou, Saad; Galindo, Charles Antonio Barros; Leal-Cardoso, José Henrique; Fonteles, Manassés Claudino; Duarte, Gloria Pinto

2002-12-01

Cardiovascular effects of intravenous ( i. v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) were investigated in rats. Additionally this study examined (I) whether the autonomic nervous system is involved in the mediation of EOAZ-induced changes in mean aortic pressure (MAP) and heart rate (HR), and (II) whether these changes could be, at least in part, attributed to the actions of terpinen-4-ol (Trp-4-ol), the major constituent of EOAZ. In both pentobarbitone-anaesthetised and conscious rats, i. v. bolus injections of EOAZ (1 to 20 mg/kg) elicited immediate and dose-dependent decreases in MAP. In anaesthetised rats, EOAZ decreased HR only at higher doses (10 and 20 mg/kg), while changes of this parameter were not uniform in conscious rats. Hypotensive responses to EOAZ were of the same order of magnitude or duration, irrespective of whether the animal was under general anaesthesia. Pretreatment of anaesthetised rats with bilateral vagotomy did not modify significantly the hypotensive and bradycardic responses to EOAZ. In conscious rats, i. v. injections of bolus doses (1 to 10 mg/kg) of Trp-4-ol also elicited immediate and dose-dependent decreases in MAP. However, these hypotensive effects were significantly greater than those evoked by the same doses of EOAZ (1 to 10 mg/kg). Intravenous pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) had no significant effects on the EOAZ-induced hypotension. These data show that i. v. treatment with the EOAZ in either anaesthetised or conscious rats induced an immediate and significant hypotension, an effect that could be partially attributed to the actions of Trp-4-ol. The hypotension appears independent of the presence of an operational sympathetic nervous system, suggesting that the EOAZ may be a direct vasorelaxant agent.

TU-H-BRC-08: Use and Validation of Flexible 3D Printed Tissue Compensators for Post-Mastectomy Radiation Therapy

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

Craft, D; Kry, S; Salehpour, M

Purpose: Patient-specific tissue equivalent compensators can be used for post-mastectomy radiation therapy (PMRT) to achieve homogenous dose distributions with single-field treatments. However, current fabrication methods are time consuming and expensive. 3D-printing technology could overcome these limitations. The purposes of this study were to [1] evaluate materials for 3D-printed compensators [2] design and print a compensator to achieve a uniform thickness to a clinical target volume (CTV), and [3] demonstrate that a single-field electron compensator plan is a clinically feasible treatment option for PMRT. Methods: Blocks were printed with three materials; print accuracy, density, Hounsfield units (HU), and percent depth dosesmore » (PDD) were evaluated. For a CT scan of an anthropomorphic phantom, we used a ray-tracing method to design a compensator that achieved uniform thickness from compensator surface to CTV. The compensator was printed with flexible tissue equivalent material whose physical and radiological properties were most similar to soft tissue. A single-field electron compensator plan was designed and compared with two standard-of-care techniques. The compensator plan was validated with thermoluminescent dosimeter (TLD) measurements. Results: We identified an appropriate material for 3D-printed compensators that had high print accuracy (99.6%) and was similar to soft tissue; density was 1.04, HU was - 45 ± 43, and PDD curves agreed with clinical curves within 3 mm. We designed and printed a compensator that conformed well to the phantom surface and created a uniform thickness to the CTV. In-house fabrication was simple and inexpensive (<$75). Compared with the two standard plans, the compensator plan resulted in overall more homogeneous dose distributions and performed similarly in terms of lung/heart doses and 90% isodose coverage of the CTV. TLD measurements agreed well with planned doses (within 5 %). Conclusions: We have demonstrated that 3D-printed compensators make single-field electron therapy a clinically feasible treatment option for PMRT.« less

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

Cheng, C; Liu, H; Indiana University Bloomington, Bloomington, IN

Purpose: A rapid cycling proton beam has several distinct characteristics superior to a slow extraction synchrotron: The beam energy and energy spread, beam intensity and spot size can be varied spot by spot. The feasibility of using a spot scanning beam from a rapidc-ycling-medical-synchrotron (RCMS) at 10 Hz repetition frequency is investigated in this study for its application in proton therapy. Methods: The versatility of the beam is illustrated by two examples in water phantoms: (1) a cylindrical PTV irradiated by a single field and (2) a spherical PTV irradiated by two parallel opposed fields. A uniform dose distribution ismore » to be delivered to the volumes. Geant4 Monte Carlo code is used to validate the dose distributions in each example. Results: Transverse algorithms are developed to produce uniform distributions in each transverseplane in the two examples with a cylindrical and a spherical PTV respectively. Longitudinally, different proton energies are used in successive transverse planes toproduce the SOBP required to cover the PTVs. In general, uniformity of dosedistribution within 3% is obtained for the cylinder and 3.5% for the sphere. The transversealgorithms requires only few hundred beam spots for each plane The algorithms may beapplied to larger volumes by increasing the intensity spot by spot for the same deliverytime of the same dose. The treatment time can be shorter than 1 minute for any fieldconfiguration and tumor shape. Conclusion: The unique beam characteristics of a spot scanning beam from a RCMS at 10 Hz repetitionfrequency are used to design transverse and longitudinal algorithms to produce uniformdistribution for any arbitrary shape and size of targets. The proposed spot scanning beam ismore versatile than existing spot scanning beams in proton therapy with better beamcontrol and lower neutron dose. This work is supported in part by grants from the US Department of Energy under contract; DE-FG02-12ER41800 and the National Science Foundation NSF PHY-1205431.« less

EUV local CDU healing performance and modeling capability towards 5nm node

NASA Astrophysics Data System (ADS)

Jee, Tae Kwon; Timoshkov, Vadim; Choi, Peter; Rio, David; Tsai, Yu-Cheng; Yaegashi, Hidetami; Koike, Kyohei; Fonseca, Carlos; Schoofs, Stijn

2017-10-01

Both local variability and optical proximity correction (OPC) errors are big contributors to the edge placement error (EPE) budget which is closely related to the device yield. The post-litho contact hole healing will be demonstrated to meet after-etch local variability specifications using a low dose, 30mJ/cm2 dose-to-size, positive tone developed (PTD) resist with relevant throughput in high volume manufacturing (HVM). The total local variability of the node 5nm (N5) contact holes will be characterized in terms of local CD uniformity (LCDU), local placement error (LPE), and contact edge roughness (CER) using a statistical methodology. The CD healing process has complex etch proximity effects, so the OPC prediction accuracy is challenging to meet EPE requirements for the N5. Thus, the prediction accuracy of an after-etch model will be investigated and discussed using ASML Tachyon OPC model.

Retrospective assessment of solvent exposure in paint manufacturing.

PubMed Central

Glass, D C; Spurgeon, A; Calvert, I A; Clark, J L; Harrington, J M

1994-01-01

This paper describes how exposure to solvents at two large paint making sites was assessed in a study carried out to investigate the possibility of neuropsychological effects resulting from long term exposure to organic solvents. A job exposure matrix was constructed by buildings and year. A detailed plant history was taken and this was used to identify uniform exposure periods during which workers' exposure to solvents was not thought to have changed significantly. Exposure monitoring data, collected by the company before the study, was then used to characterise exposure within each uniform exposure period. Estimates were made for periods during which no air monitoring was available. Individual detailed job histories were collected for subjects and controls. The job histories were used to estimate exposure on an individual basis with the job exposure matrix. Exposure was expressed as duration, cumulative dose, and intensity of exposure. Classification of exposure by duration alone was found to result in misclassification of subjects. PMID:7951794

Impact of neutron irradiation on the structural and optical properties of PVP/gelatin blends doped with dysprosium (III) chloride

NASA Astrophysics Data System (ADS)

Basha, Ahmad Fouad; Basha, Mohammad Ahmad-Fouad

2017-12-01

Polymer composites of a system of Polyvinylpyrrolidone (PVP)/gelatin/DyCl3.6H2O were prepared in three groups that have different concentrations of PVP/gelatin contents to study the effect of neutron irradiation on their structural and optical properties. Results showed that the interaction of neutrons led to various complex phenomena, mainly bond breaking, main chain scission and intermolecular cross-linking. These processes introduced defects inside the material that were responsible for the changes in their optical and structural properties. All the calculated parameters were found to be dependent on the irradiation fluence in a uniform manner that makes these materials excellent candidates in the applications of dosimetry and radiology. Moreover, the sensitivity of the three groups of composites to the irradiation doses was found to be different. The variation in the structure of the composite group that contains the least PVP content was found to be less significant; hence, these materials were more stable against high doses that make them suitable for high radiation dose applications.

Method for simulating dose reduction in digital mammography using the Anscombe transformation.

PubMed

Borges, Lucas R; Oliveira, Helder C R de; Nunes, Polyana F; Bakic, Predrag R; Maidment, Andrew D A; Vieira, Marcelo A C

2016-06-01

This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

Dynamic scan control in STEM: Spiral scans

DOE PAGES

Lupini, Andrew R.; Borisevich, Albina Y.; Kalinin, Sergei V.; ...

2016-06-13

Here, scanning transmission electron microscopy (STEM) has emerged as one of the foremost techniques to analyze materials at atomic resolution. However, two practical difficulties inherent to STEM imaging are: radiation damage imparted by the electron beam, which can potentially damage or otherwise modify the specimen and slow-scan image acquisition, which limits the ability to capture dynamic changes at high temporal resolution. Furthermore, due in part to scan flyback corrections, typical raster scan methods result in an uneven distribution of dose across the scanned area. A method to allow extremely fast scanning with a uniform residence time would enable imaging atmore » low electron doses, ameliorating radiation damage and at the same time permitting image acquisition at higher frame-rates while maintaining atomic resolution. The practical complication is that rastering the STEM probe at higher speeds causes significant image distortions. Non-square scan patterns provide a solution to this dilemma and can be tailored for low dose imaging conditions. Here, we develop a method for imaging with alternative scan patterns and investigate their performance at very high scan speeds. A general analysis for spiral scanning is presented here for the following spiral scan functions: Archimedean, Fermat, and constant linear velocity spirals, which were tested for STEM imaging. The quality of spiral scan STEM images is generally comparable with STEM images from conventional raster scans, and the dose uniformity can be improved.« less

Dynamics of magnetized plasma sheaths around a trench

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

Hatami, M. M., E-mail: m-hatami@kntu.ac.ir

2016-08-15

Considering a magnetized plasma sheath, the temporal evolution of the ion properties (the incident ion flux, the ion impact angle, and the incident ion dose) around a rectangular trench is studied numerically. Our results show that the ion flux along the bottom surface greatly reduces in the presence of magnetic field and its uniformity improves, but the magnetic field does not considerably affect the ion flux along the sidewall. In addition, the thickness of the plasma sheath increases by increasing the magnetic field while its conformality to the target surface reduces faster. Moreover, it is shown that any increase inmore » the magnitude (inclination angle) of the magnetic field causes a decrease (an increase) in the angle of incidence of ions on the bottom and sidewall surfaces. Furthermore, in the presence of magnetic field, the ions strike nearly normal to the surface of the bottom while they become less oblique along the sidewall surface. In addition, contrary to the corners of the trench, it is found that the magnetic field greatly affects the incident ion dose at the center of the trench surfaces. Also, it is shown that the incident ion dose along the sidewall is the highest near the center of the sidewall in both magnetized and magnetic-free cases. However, uniformity of the incident ion dose along the sidewall is better than that along the bottom in both magnetized and unmagnetized plasma sheath.« less

Dynamic scan control in STEM: Spiral scans

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

Lupini, Andrew R.; Borisevich, Albina Y.; Kalinin, Sergei V.

Here, scanning transmission electron microscopy (STEM) has emerged as one of the foremost techniques to analyze materials at atomic resolution. However, two practical difficulties inherent to STEM imaging are: radiation damage imparted by the electron beam, which can potentially damage or otherwise modify the specimen and slow-scan image acquisition, which limits the ability to capture dynamic changes at high temporal resolution. Furthermore, due in part to scan flyback corrections, typical raster scan methods result in an uneven distribution of dose across the scanned area. A method to allow extremely fast scanning with a uniform residence time would enable imaging atmore » low electron doses, ameliorating radiation damage and at the same time permitting image acquisition at higher frame-rates while maintaining atomic resolution. The practical complication is that rastering the STEM probe at higher speeds causes significant image distortions. Non-square scan patterns provide a solution to this dilemma and can be tailored for low dose imaging conditions. Here, we develop a method for imaging with alternative scan patterns and investigate their performance at very high scan speeds. A general analysis for spiral scanning is presented here for the following spiral scan functions: Archimedean, Fermat, and constant linear velocity spirals, which were tested for STEM imaging. The quality of spiral scan STEM images is generally comparable with STEM images from conventional raster scans, and the dose uniformity can be improved.« less

Performance test and image correction of CMOS image sensor in radiation environment

NASA Astrophysics Data System (ADS)

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2016-09-01

CMOS image sensors rival CCDs in domains that include strong radiation resistance as well as simple drive signals, so it is widely applied in the high-energy radiation environment, such as space optical imaging application and video monitoring of nuclear power equipment. However, the silicon material of CMOS image sensors has the ionizing dose effect in the high-energy rays, and then the indicators of image sensors, such as signal noise ratio (SNR), non-uniformity (NU) and bad point (BP) are degraded because of the radiation. The radiation environment of test experiments was generated by the 60Co γ-rays source. The camera module based on image sensor CMV2000 from CMOSIS Inc. was chosen as the research object. The ray dose used for the experiments was with a dose rate of 20krad/h. In the test experiences, the output signals of the pixels of image sensor were measured on the different total dose. The results of data analysis showed that with the accumulation of irradiation dose, SNR of image sensors decreased, NU of sensors was enhanced, and the number of BP increased. The indicators correction of image sensors was necessary, as it was the main factors to image quality. The image processing arithmetic was adopt to the data from the experiences in the work, which combined local threshold method with NU correction based on non-local means (NLM) method. The results from image processing showed that image correction can effectively inhibit the BP, improve the SNR, and reduce the NU.

Application of a color scanner for 60Co high dose rate brachytherapy dosimetry with EBT radiochromic film

PubMed Central

Ghorbani, Mahdi; Toossi, Mohammad Taghi Bahreyni; Mowlavi, Ali Asghar; Roodi, Shahram Bayani; Meigooni, Ali Soleimani

2012-01-01

Background. The aim of this study is to evaluate the performance of a color scanner as a radiochromic film reader in two dimensional dosimetry around a high dose rate brachytherapy source. Materials and methods A Microtek ScanMaker 1000XL film scanner was utilized for the measurement of dose distribution around a high dose rate GZP6 60Co brachytherapy source with GafChromic® EBT radiochromic films. In these investigations, the non-uniformity of the film and scanner response, combined, as well as the films sensitivity to scanner’s light source was evaluated using multiple samples of films, prior to the source dosimetry. The results of these measurements were compared with the Monte Carlo simulated data using MCNPX code. In addition, isodose curves acquired by radiochromic films and Monte Carlo simulation were compared with those provided by the GZP6 treatment planning system. Results Scanning of samples of uniformly irradiated films demonstrated approximately 2.85% and 4.97% nonuniformity of the response, respectively in the longitudinal and transverse directions of the film. Our findings have also indicated that the film response is not affected by the exposure to the scanner’s light source, particularly in multiple scanning of film. The results of radiochromic film measurements are in good agreement with the Monte Carlo calculations (4%) and the corresponding dose values presented by the GZP6 treatment planning system (5%). Conclusions The results of these investigations indicate that the Microtek ScanMaker 1000XL color scanner in conjunction with GafChromic EBT film is a reliable system for dosimetric evaluation of a high dose rate brachytherapy source. PMID:23411947

Poster — Thur Eve — 58: Dosimetric validation of electronic compensation for radiotherapy treatment planning

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

Gräfe, James; Khan, Rao; Meyer, Tyler

2014-08-15

In this study we investigate the deliverability of dosimetric plans generated by the irregular surface compensator (ISCOMP) algorithm for 6 MV photon beams in Eclipse (Varian Medical System, CA). In contrast to physical tissue compensation, the electronic ISCOMP uses MLCs to dynamically modulate the fluence of a photon beam in order to deliver a uniform dose at a user defined plane in tissue. This method can be used to shield critical organs that are located within the treatment portal or improve dose uniformity by tissue compensation in inhomogeneous regions. Three site specific plans and a set of test fields weremore » evaluated using the γ-metric of 3%/ 3 mm on Varian EPID, MapCHECK, and Gafchromic EBT3 film with a clinical tolerance of >95% passing rates. Point dose measurements with an NRCC calibrated ionization chamber were also performed to verify the absolute dose delivered. In all cases the MapCHECK measured plans met the gamma criteria. The mean passing rate for the six EBT3 film field measurements was 96.2%, with only two fields at 93.4 and 94.0% passing rates. The EPID plans passed for fields encompassing the central ∼10 × 10 cm{sup 2} region of the detector; however for larger fields and greater off-axis distances discrepancies were observed and attributed to the profile corrections and modeling of backscatter in the portal dose calculation. The magnitude of the average percentage difference for 21 ion chamber point dose measurements and 17 different fields was 1.4 ± 0.9%, and the maximum percentage difference was −3.3%. These measurements qualify the algorithm for routine clinical use subject to the same pre-treatment patient specific QA as IMRT.« less

IMRT: Improvement in treatment planning efficiency using NTCP calculation independent of the dose-volume-histogram

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

Grigorov, Grigor N.; Chow, James C.L.; Grigorov, Lenko

2006-05-15

The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the dose-volume-histogram (DVH) which is generated by the treatment planning system after calculation of the 3D dose distribution. Including the NTCP in the objective function for intensity modulated radiation therapy (IMRT) plan optimization would make the planning more effective in reducing the postradiation effects. However, doing so would lengthen the total planning time. The purpose of this work is to establish a method for NTCP determination, independent of a DVH calculation, as a quality assurancemore » check and also as a mean of improving the treatment planning efficiency. In the study, the CTs of ten randomly selected prostate patients were used. IMRT optimization was performed with a PINNACLE3 V 6.2b planning system, using planning target volume (PTV) with margins in the range of 2 to 10 mm. The DVH control points of the PTV and OAR were adapted from the prescriptions of Radiation Therapy Oncology Group protocol P-0126 for an escalated prescribed dose of 82 Gy. This paper presents a new model for the determination of the rectal NTCP ({sub R}NTCP). The method uses a special function, named GVN (from Gy, Volume, NTCP), which describes the {sub R}NTCP if 1 cm{sup 3} of the volume of intersection of the PTV and rectum (R{sub int}) is irradiated uniformly by a dose of 1 Gy. The function was 'geometrically' normalized using a prostate-prostate ratio (PPR) of the patients' prostates. A correction of the {sub R}NTCP for different prescribed doses, ranging from 70 to 82 Gy, was employed in our model. The argument of the normalized function is the R{sub int}, and parameters are the prescribed dose, prostate volume, PTV margin, and PPR. The {sub R}NTCPs of another group of patients were calculated by the new method and the resulting difference was <{+-}5% in comparison to the NTCP calculated by the PINNACLE3 software where Kutcher's dose-response model for NTCP calculation is adopted.« less

Evaluation of the radiobiological gamma index with motion interplay in tangential IMRT breast treatment

PubMed Central

Sumida, Iori; Yamaguchi, Hajime; Das, Indra J.; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Kiesuke; Suzuki, Osamu; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

2016-01-01

The purpose of this study was to evaluate the impact of the motion interplay effect in early-stage left-sided breast cancer intensity-modulated radiation therapy (IMRT), incorporating the radiobiological gamma index (RGI). The IMRT dosimetry for various breathing amplitudes and cycles was investigated in 10 patients. The predicted dose was calculated using the convolution of segmented measured doses. The physical gamma index (PGI) of the planning target volume (PTV) and the organs at risk (OAR) was calculated by comparing the original with the predicted dose distributions. The RGI was calculated from the PGI using the tumor control probability (TCP) and the normal tissue complication probability (NTCP). The predicted mean dose and the generalized equivalent uniform dose (gEUD) to the target with various breathing amplitudes were lower than the original dose (P < 0.01). The predicted mean dose and gEUD to the OARs with motion were higher than for the original dose to the OARs (P < 0.01). However, the predicted data did not differ significantly between the various breathing cycles for either the PTV or the OARs. The mean RGI gamma passing rate for the PTV was higher than that for the PGI (P < 0.01), and for OARs, the RGI values were higher than those for the PGI (P < 0.01). The gamma passing rates of the RGI for the target and the OARs other than the contralateral lung differed significantly from those of the PGI under organ motion. Provided an NTCP value <0.05 is considered acceptable, it may be possible, by taking breathing motion into consideration, to escalate the dose to achieve the PTV coverage without compromising the TCP. PMID:27534793

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

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

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Monte Carlo study and design of system for implementation of Rotational Total Skin Electron Irradiation technique

NASA Astrophysics Data System (ADS)

Ansari, M.; Abbasi Davani, F.; Lamehi Rashti, M.; Monadi, Sh.; Emami, H.

2018-05-01

Total skin electron irradiation technique is used in treatment of the mycosis fungoid. The implementation of this technique requires non-standard measurements and complex dosimetry methods. Depending on the linear accelerator (Linac) type, bunker size, room dimensions and dosimetry equipment, the design of instruments for appropriate set up and implementation of TSEI in different radiation therapy centers varies. The studies which have been done in this article provide an introduction to the implementing of this method for the first time in Iran and its results can be used for the centers with similar specifications in the world. This article determined the electron beam characteristic of TSEI for the only electron accelerator, located at the radiation center of the Seyed Alshohada Hospital of Isfahan (NEPTUN 10PC), by performing Monte Carlo simulations and using EGSnrc-based codes (BEAMnrc and DOSXYZnrc). For the best uniformity of the vertical profile, the optimal angle of gantry was defined at SSD=350 cm. The effect of the degrader plane that is located at a distance of 20 cm from the patient surface, was evaluated on the amount of energy reduction of the beam, the opening of the electron beam field and the homogeneity of the dose distribution. The transversal dose distribution from the whole treatment with Stanford technique (six dual fields) and Rotational technique was simulated in a CT-based anthropomorphic phantom. Also, the percentage depth dose in the head, neck, thorax, abdomen and legs was obtained for both methods. The simulation results show that the 20o angle between the horizontal and the beam central axis is optimal in order to provide the best vertical dose uniformity. The mean energy decreases from 6.1 MeV (the exit window) to 3 MeV (the treatment surface) by placing a degrader with 0.8 cm thickness in front of the treatment plane. FWHM of the angular distribution of the electron beam increased from 15o at SSD=100 cm to more than 30o on the treatment surface by traversing the PMMA degrader. The MC calculated percentage depth dose curves in different organs of anthropomorphic phantom for RTSEI indicates that the depth of maximum dose is on the surface of the phantom and Isodose curve of 80% is formed at a depth less than 4 mm. the results also show, with the degrader plane in front of the patient, the degree of homogeneity of the dose distribution for both Stanford and rotational techniques is the same.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

NASA Astrophysics Data System (ADS)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ±1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

A higher radiotherapy dose is associated with more durable palliation and longer survival in patients with metastatic melanoma.

PubMed

Olivier, Kenneth R; Schild, Steven E; Morris, Christopher G; Brown, Paul D; Markovic, Svetomir N

2007-10-15

Oncologists are often reluctant to recommend radiotherapy (RT) to palliate metastatic melanoma due to a perception that this tumor is "radioresistant." The Mayo Clinic experience was analyzed to determine the efficacy of palliative RT. Eighty-four consecutive patients with 114 lesions that were not metastatic to the central nervous system (CNS) were evaluated for the response of the presenting symptom, the duration of response, and survival after RT. The median dose delivered was 30 grays (Gy) and the median biologic effective dose (BED) was 39.0 Gy(10). Performance status was not uniformly available for all patients. Complete resolution of the presenting symptom occurred in 10 lesions (9%). Of the lesions treated, there was partial improvement in 86 (75%), no change in 12 (11%), and worsening in 6 (5%) lesions. The median survival was 3.8 months and freedom from disease progression (FFP) for individual lesions was 6 months. Patients treated with >30 Gy had significantly longer FFP compared with patients given 30 Gy had a significantly longer survival than those given a lesser dose (median of 2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy(10) also were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months; P < .0001) compared with those receiving a BED 30 Gy and a BED >39.0 Gy(10) were found to be associated with longer palliation.

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PubMed

Todor, Dorin A; Barani, Igor J; Lin, Peck-Sun; Anscher, Mitchell S

2011-09-01

To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Moving Toward Focal Therapy in Prostate Cancer: Dual-Isotope Permanent Seed Implants as a Possible Solution

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

Todor, Dorin A., E-mail: dtodor@mcvh-vcu.edu; Barani, Igor J.; Lin, Peck-Sun

2011-09-01

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and Materials: Nine plans, using {sup 125}I, {sup 103}Pd, and {sup 131}Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTV{sub i}) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants,more » prescribed to conventional doses, were generated to achieve good PTV coverage. The PTV{sub i} were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. Results: The EUBED of PTV{sub i} in the setting of primary {sup 125}I implant increased 20-66% when {sup 103}Pd and {sup 131}Cs were used compared with {sup 125}I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTV{sub i} (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.« less

Correlation between model observers in uniform background and human observers in patient liver background for a low-contrast detection task in CT

NASA Astrophysics Data System (ADS)

Gong, Hao; Yu, Lifeng; Leng, Shuai; Dilger, Samantha; Zhou, Wei; Ren, Liqiang; McCollough, Cynthia H.

2018-03-01

Channelized Hotelling observer (CHO) has demonstrated strong correlation with human observer (HO) in both single-slice viewing mode and multi-slice viewing mode in low-contrast detection tasks with uniform background. However, it remains unknown if the simplest single-slice CHO in uniform background can be used to predict human observer performance in more realistic tasks that involve patient anatomical background and multi-slice viewing mode. In this study, we aim to investigate the correlation between CHO in a uniform water background and human observer performance at a multi-slice viewing mode on patient liver background for a low-contrast lesion detection task. The human observer study was performed on CT images from 7 abdominal CT exams. A noise insertion tool was employed to synthesize CT scans at two additional dose levels. A validated lesion insertion tool was used to numerically insert metastatic liver lesions of various sizes and contrasts into both phantom and patient images. We selected 12 conditions out of 72 possible experimental conditions to evaluate the correlation at various radiation doses, lesion sizes, lesion contrasts and reconstruction algorithms. CHO with both single and multi-slice viewing modes were strongly correlated with HO. The corresponding Pearson's correlation coefficient was 0.982 (with 95% confidence interval (CI) [0.936, 0.995]) and 0.989 (with 95% CI of [0.960, 0.997]) in multi-slice and single-slice viewing modes, respectively. Therefore, this study demonstrated the potential to use the simplest single-slice CHO to assess image quality for more realistic clinically relevant CT detection tasks.

Permethrin exposure from fabric-treated military uniforms under different wear-time scenarios.

PubMed

Proctor, Susan P; Maule, Alexis L; Heaton, Kristin J; Adam, Gina E

2014-11-01

The objective of the project was to ascertain whether urinary biomarkers of permethrin exposure are detected after wearing post-tailored, fabric-treated military uniforms under two different wear-time exposure scenarios. Study A occurred over 3.5 days and involved six participants wearing treated uniforms continuously for 30-32 h. Urine collection occurred at scheduled time points before, during, and after wearing the uniform. Study B, conducted over 19 days, included 11 participants wearing treated uniforms for 3 consecutive days, 8 h each day (with urine collection before, during, and after wear). Urinary biomarkers of permethrin (3-phenoxybenzoic acid (3PBA), cis- 2,2-(dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cDCCA), trans- 2,2-(dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (tDCCA)) were detected during and after wear. Biomarker detection generally occurred over the 10- to 12-h period after putting on the uniform and subsided 24 h following uniform removal (in both Study A and B scenarios). Those wearing permethrin-treated uniforms under the longer wear-time scenario (Study A) excreted significantly higher cumulative mean levels compared with those in Study B (3.29 times higher for 3PBA and 2.23 times higher for the sum of c/tDCCA (P≤0.001)). Findings suggest that wearing permethrin-treated clothing does increase absorbed, internal dose levels of permethrin above population levels and is significantly related to wear-time duration.

Evaluation of the dosimetric properties of a diode detector for small field proton radiosurgery.

PubMed

McAuley, Grant A; Teran, Anthony V; Slater, Jerry D; Slater, James M; Wroe, Andrew J

2015-11-08

The small fields and sharp gradients typically encountered in proton radiosurgery require high spatial resolution dosimetric measurements, especially below 1-2 cm diameters. Radiochromic film provides high resolution, but requires postprocessing and special handling. Promising alternatives are diode detectors with small sensitive volumes (SV) that are capable of high resolution and real-time dose acquisition. In this study we evaluated the PTW PR60020 proton dosimetry diode using radiation fields and beam energies relevant to radiosurgery applications. Energies of 127 and 157 MeV (9.7 to 15 cm range) and initial diameters of 8, 10, 12, and 20mm were delivered using single-stage scattering and four modulations (0, 15, 30, and 60mm) to a water tank in our treatment room. Depth dose and beam profile data were compared with PTW Markus N23343 ionization chamber, EBT2 Gafchromic film, and Monte Carlo simulations. Transverse dose profiles were measured using the diode in "edge-on" orientation or EBT2 film. Diode response was linear with respect to dose, uniform with dose rate, and showed an orientation-dependent (i.e., beam parallel to, or perpendicular to, detector axis) response of less than 1%. Diodevs. Markus depth-dose profiles, as well as Markus relative dose ratio vs. simulated dose-weighted average lineal energy plots, suggest that any LET-dependent diode response is negligible from particle entrance up to the very distal portion of the SOBP for the energies tested. Finally, while not possible with the ionization chamber due to partial volume effects, accurate diode depth-dose measurements of 8, 10, and 12 mm diameter beams were obtained compared to Monte Carlo simulations. Because of the small SV that allows measurements without partial volume effects and the capability of submillimeter resolution (in edge-on orientation) that is crucial for small fields and high-dose gradients (e.g., penumbra, distal edge), as well as negligible LET dependence over nearly the full the SOBP, the PTW proton diode proved to be a useful high-resolution, real-time metrology device for small proton field radiation measurements such as would be encountered in radiosurgery applications.

Organ dose calculations by Monte Carlo modeling of the updated VCH adult male phantom against idealized external proton exposure

NASA Astrophysics Data System (ADS)

Zhang, Guozhi; Liu, Qian; Zeng, Shaoqun; Luo, Qingming

2008-07-01

The voxel-based visible Chinese human (VCH) adult male phantom has offered a high-quality test bed for realistic Monte Carlo modeling in radiological dosimetry simulations. The phantom has been updated in recent effort by adding newly segmented organs, revising walled and smaller structures as well as recalibrating skeletal marrow distributions. The organ absorbed dose against external proton exposure was calculated at a voxel resolution of 2 × 2 × 2 mm3 using the MCNPX code for incident energies from 20 MeV to 10 GeV and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO), respectively. The effective dose on the VCH phantom was derived in compliance with the evaluation scheme for the reference male proposed in the 2007 recommendations of the International Commission on Radiological Protection (ICRP). Algorithm transitions from the revised radiation and tissue weighting factors are accountable for approximately 90% and 10% of effective dose discrepancies in proton dosimetry, respectively. Results are tabulated in terms of fluence-to-dose conversion coefficients for practical use and are compared with data from other models available in the literature. Anatomical variations between various computational phantoms lead to dose discrepancies ranging from a negligible level to 100% or more at proton energies below 200 MeV, corresponding to the spatial geometric locations of individual organs within the body. Doses show better agreement at higher energies and the deviations are mostly within 20%, to which the organ volume and mass differences should be of primary responsibility. The impact of body size on dose distributions was assessed by dosimetry of a scaled-up VCH phantom that was resized in accordance with the height and total mass of the ICRP reference man. The organ dose decreases with the directionally uniform enlargement of voxels. Potential pathways to improve the VCH phantom have also been briefly addressed. This work pertains to VCH-based systematic multi-particle dose investigations and will contribute to comparative dosimetry studies of ICRP standardized voxel phantoms in the near future.

Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Foster, Ryan D.; Kogel, Albert J. van der

2011-01-01

Purpose: To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. Methods and Materials: A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eightmore » dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 {+-} 0.1, 18.9 {+-} 0.1, 21.0 {+-} 0.1, 23.0 {+-} 0.2, and 25.3 {+-} 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 43% {+-} 3%, 48% {+-} 4%, 51% {+-} 2%, 57% {+-} 2%, and 59% {+-} 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. Results: A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. Conclusions: Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.« less

Dosimetric effects of patient rotational setup errors on prostate IMRT treatments

NASA Astrophysics Data System (ADS)

Fu, Weihua; Yang, Yong; Li, Xiang; Heron, Dwight E.; Saiful Huq, M.; Yue, Ning J.

2006-10-01

The purpose of this work is to determine dose delivery errors that could result from systematic rotational setup errors (ΔΦ) for prostate cancer patients treated with three-phase sequential boost IMRT. In order to implement this, different rotational setup errors around three Cartesian axes were simulated for five prostate patients and dosimetric indices, such as dose-volume histogram (DVH), tumour control probability (TCP), normal tissue complication probability (NTCP) and equivalent uniform dose (EUD), were employed to evaluate the corresponding dosimetric influences. Rotational setup errors were simulated by adjusting the gantry, collimator and horizontal couch angles of treatment beams and the dosimetric effects were evaluated by recomputing the dose distributions in the treatment planning system. Our results indicated that, for prostate cancer treatment with the three-phase sequential boost IMRT technique, the rotational setup errors do not have significant dosimetric impacts on the cumulative plan. Even in the worst-case scenario with ΔΦ = 3°, the prostate EUD varied within 1.5% and TCP decreased about 1%. For seminal vesicle, slightly larger influences were observed. However, EUD and TCP changes were still within 2%. The influence on sensitive structures, such as rectum and bladder, is also negligible. This study demonstrates that the rotational setup error degrades the dosimetric coverage of target volume in prostate cancer treatment to a certain degree. However, the degradation was not significant for the three-phase sequential boost prostate IMRT technique and for the margin sizes used in our institution.

Total skin electron irradiation: evaluation of dose uniformity throughout the skin surface.

PubMed

Anacak, Yavuz; Arican, Zumre; Bar-Deroma, Raquel; Tamir, Ada; Kuten, Abraham

2003-01-01

In this study, in vivo dosimetic data of 67 total skin electron irradiation (TSEI) treatments were analyzed. Thermoluminescent dosimetry (TLD) measurements were made at 10 different body points for every patient. The results demonstrated that the dose inhomogeneity throughout the skin surface is around 15%. The homogeneity was better at the trunk than at the extratrunk points, and was worse when a degrader was used. There was minimal improvement of homogeneity in subsequent days of treatment.

SU-E-T-09: A Dosimetric Analysis of Various Clinically Used Bolus Materials

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

Stowe, M; Yeager, C; Zhou, F

Purpose: To evaluate the dosimetric effect of various clinically used bolus materials. Methods: Materials investigated include solid water, superflab, wet gauze, wet sheets, Play-Doh{sup ™}, and gauze embedded with petroleum jelly. Each bolusing material was scanned in a Philips CT to determine the Hounsfield unit (HU) and to verify uniformity throughout the material. Using the corresponding HU, boluses of 0.5 cm and 1.0 cm thicknesses were created in the Eclipse treatment planning system (TPS) on a solid water phantom. Dose was calculated at various depths for beam energies 6 MV, 6 MeV, 9 MeV, and 12 MeV to determine themore » effects of each material on deposition of dose. In addition, linac-based measurements at these energies were made using a farmer chamber in solid water. Wet sheets and wet gauze were measured with various water content to quantify the effects on dose. Results: Preliminary CT scans find a range in HU of bolus materials from −120 to almost 300. There is a trend in the dose at depth based on the HU of the material; however inconsistencies are found when the bolus materials have a negative HU value. The measured data indicates that there is a linear relationship between the mass of water in a material and the dose reading, the slope of which is material dependent. Conclusion: Due to the variation in HU of the bolus materials studied, it is recommended that any new bolus be evaluated before clinical use to determine physical and dosimetric properties. If possible, patients should have bolus included in their CT scans; or if the bolus is created in the TPS, the HU should correspond to the material used. For water-soaked materials, once the bolus material is selected (gauze or sheet), the bolusing effect is only dependent on the amount of water applied to the material.« less

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

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

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

TH-EF-BRB-11: Volumetric Modulated Arc Therapy for Total Body Irradiation

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

Ouyang, L; Folkerts, M; Hrycushko, B

Purpose: To develop a modern, patient-comfortable total body irradiation (TBI) technique suitable for standard-sized linac vaults. Methods: An indexed rotatable immobilization system (IRIS) was developed to make possible total-body CT imaging and radiation delivery on conventional couches. Treatment consists of multi-isocentric volumetric modulated arc therapy (VMAT) to the upper body and parallel-opposed fields to the lower body. Each isocenter is indexed to the couch and includes a 180° IRIS rotation between the upper and lower body fields. VMAT fields are optimized to satisfy lung dose objectives while achieving a uniform therapeutic dose to the torso. End-to-end tests with a randomore » phantom were used to verify dosimetric characteristics. Treatment plan robustness regarding setup uncertainty was assessed by simulating global and regional isocenter setup shifts on patient data sets. Dosimetric comparisons were made with conventional extended distance, standing TBI (cTBI) plans using a Monte Carlo-based calculation. Treatment efficiency was assessed for eight courses of patient treatment. Results: The IRIS system is level and orthogonal to the scanned CT image plane, with lateral shifts <2mm following rotation. End-to-end tests showed surface doses within ±10% of the prescription dose, field junction doses within ±15% of prescription dose. Plan robustness tests showed <15% changes in dose with global setup errors up to 5mm in each direction. Local 5mm relative setup errors in the chest resulted in < 5% dose changes. Local 5mm shift errors in the pelvic and upper leg junction resulted in <10% dose changes while a 10mm shift error causes dose changes up to 25%. Dosimetric comparison with cTBI showed VMAT-TBI has advantages in preserving chest wall dose with flexibility in leveraging the PTV-body and PTV-lung dose. Conclusion: VMAT-TBI with the IRIS system was shown clinically feasible as a cost-effective approach to TBI for standard-sized linac vaults.« less

Multi-axis dose accumulation of noninvasive image-guided breast brachytherapy through biomechanical modeling of tissue deformation using the finite element method

PubMed Central

Ghadyani, Hamid R.; Bastien, Adam D.; Lutz, Nicholas N.; Hepel, Jaroslaw T.

2015-01-01

Purpose Noninvasive image-guided breast brachytherapy delivers conformal HDR 192Ir brachytherapy treatments with the breast compressed, and treated in the cranial-caudal and medial-lateral directions. This technique subjects breast tissue to extreme deformations not observed for other disease sites. Given that, commercially-available software for deformable image registration cannot accurately co-register image sets obtained in these two states, a finite element analysis based on a biomechanical model was developed to deform dose distributions for each compression circumstance for dose summation. Material and methods The model assumed the breast was under planar stress with values of 30 kPa for Young's modulus and 0.3 for Poisson's ratio. Dose distributions from round and skin-dose optimized applicators in cranial-caudal and medial-lateral compressions were deformed using 0.1 cm planar resolution. Dose distributions, skin doses, and dose-volume histograms were generated. Results were examined as a function of breast thickness, applicator size, target size, and offset distance from the center. Results Over the range of examined thicknesses, target size increased several millimeters as compression thickness decreased. This trend increased with increasing offset distances. Applicator size minimally affected target coverage, until applicator size was less than the compressed target size. In all cases, with an applicator larger or equal to the compressed target size, > 90% of the target covered by > 90% of the prescription dose. In all cases, dose coverage became less uniform as offset distance increased and average dose increased. This effect was more pronounced for smaller target–applicator combinations. Conclusions The model exhibited skin dose trends that matched MC-generated benchmarking results within 2% and clinical observations over a similar range of breast thicknesses and target sizes. The model provided quantitative insight on dosimetric treatment variables over a range of clinical circumstances. These findings highlight the need for careful target localization and accurate identification of compression thickness and target offset. PMID:25829938

SU-E-T-577: Obliquity Factor and Surface Dose in Proton Beam Therapy

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

Das, I; Andersen, A; Coutinho, L

2015-06-15

Purpose: The advantage of lower skin dose in proton beam may be diminished creating radiation related sequalae usually seen with photon and electron beams. This study evaluates the surface dose as a complex function of beam parameters but more importantly the effect of beam angle. Methods: Surface dose in proton beam depends on the beam energy, source to surface distance, the air gap between snout and surface, field size, material thickness in front of surface, atomic number of the medium, beam angle and type of nozzle (ie double scattering, (DS), uniform scanning (US) or pencil beam scanning (PBS). Obliquity factormore » (OF) is defined as ratio of surface dose in 0° to beam angle Θ. Measurements were made in water phantom at various beam angles using very small microdiamond that has shown favorable beam characteristics for high, medium and low proton energy. Depth dose measurements were performed in the central axis of the beam in each respective gantry angle. Results: It is observed that surface dose is energy dependent but more predominantly on the SOBP. It is found that as SSD increases, surface dose decreases. In general, SSD, and air gap has limited impact in clinical proton range. High energy has higher surface dose and so the beam angle. The OF rises with beam angle. Compared to OF of 1.0 at 0° beam angle, the value is 1.5, 1.6, 1,7 for small, medium and large range respectively for 60 degree angle. Conclusion: It is advised that just like range and SOBP, surface dose should be clearly understood and a method to reduce the surface dose should be employed. Obliquity factor is a critical parameter that should be accounted in proton beam therapy and a perpendicular beam should be used to reduce surface dose.« less

SU-G-JeP3-10: Update On a Real-Time Treatment Guidance System Using An IR Navigation System for Pleural PDT

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

Kim, M; Penjweini, R; Zhu, T

Purpose: Photodynamic therapy (PDT) is used in conjunction with surgical debulking of tumorous tissue during treatment for pleural mesothelioma. One of the key components of effective PDT is uniform light distribution. Currently, light is monitored with 8 isotropic light detectors that are placed at specific locations inside the pleural cavity. A tracking system with real-time feedback software can be utilized to improve the uniformity of light in addition to the existing detectors. Methods: An infrared (IR) tracking camera is used to monitor the movement of the light source. The same system determines the pleural geometry of the treatment area. Softwaremore » upgrades allow visualization of the pleural cavity as a two-dimensional volume. The treatment delivery wand was upgraded for ease of light delivery while incorporating the IR system. Isotropic detector locations are also displayed. Data from the tracking system is used to calculate the light fluence rate delivered. This data is also compared with in vivo data collected via the isotropic detectors. Furthermore, treatment volume information will be used to form light dose volume histograms of the pleural cavity. Results: In a phantom study, the light distribution was improved by using real-time guidance compared to the distribution when using detectors without guidance. With the tracking system, 2D data can be collected regarding light fluence rather than just the 8 discrete locations inside the pleural cavity. Light fluence distribution on the entire cavity can be calculated at every time in the treatment. Conclusion: The IR camera has been used successfully during pleural PDT patient treatment to track the motion of the light source and provide real-time display of 2D light fluence. It is possible to use the feedback system to deliver a more uniform dose of light throughout the pleural cavity.« less

WE-E-18A-01: Large Area Avalanche Amorphous Selenium Sensors for Low Dose X-Ray Imaging

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

Scheuermann, J; Goldan, A; Zhao, W

2014-06-15

Purpose: A large area indirect flat panel imager (FPI) with avalanche gain is being developed to achieve x-ray quantum noise limited low dose imaging. It uses a thin optical sensing layer of amorphous selenium (a-Se), known as High-Gain Avalanche Rushing Photoconductor (HARP), to detect optical photons generated from a high resolution x-ray scintillator. We will report initial results in the fabrication of a solid-state HARP structure suitable for a large area FPI. Our objective is to establish the blocking layer structures and defect suppression mechanisms that provide stable and uniform avalanche gain. Methods: Samples were fabricated as follows: (1) ITOmore » signal electrode. (2) Electron blocking layer. (3) A 15 micron layer of intrinsic a-Se. (4) Transparent hole blocking layer. (5) Multiple semitransparent bias electrodes to investigate avalanche gain uniformity over a large area. The sample was exposed to 50ps optical excitation pulses through the bias electrode. Transient time of flight (TOF) and integrated charge was measured. A charge transport simulation was developed to investigate the effects of varying blocking layer charge carrier mobility on defect suppression, avalanche gain and temporal performance. Results: Avalanche gain of ∼200 was achieved experimentally with our multi-layer HARP samples. Simulations using the experimental sensor structure produced the same magnitude of gain as a function of electric field. The simulation predicted that the high dark current at a point defect can be reduced by two orders of magnitude by blocking layer optimization which can prevent irreversible damage while normal operation remained unaffected. Conclusion: We presented the first solid state HARP structure directly scalable to a large area FPI. We have shown reproducible and uniform avalanche gain of 200. By reducing mobility of the blocking layers we can suppress defects and maintain stable avalanche. Future work will optimize the blocking layers to prevent lag and ghosting.« less

Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect on Plasma Drug Concentrations.

PubMed

Nidanapu, Ravi Prasad; Rajan, Sundaram; Mahadevan, Subramanian; Gitanjali, Batmanabane

2016-12-01

Tablet splitting is the process of dividing a tablet into portions to obtain a prescribed dose of medication. Very few studies have investigated whether split parts of a tablet deliver the expected amount of drug to patients. Our objectives were to evaluate the split parts of adult-dose tablet formulations for percentage of weight deviation, weight uniformity, weight loss, drug content, and the content uniformity of four antiepileptic drugs (AEDs) prescribed to pediatric patients. We also measured AED plasma concentrations in the children. We chose to study first-line AEDs (phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely prescribed in India. We asked caregivers to perform the same splitting process they follow in their homes on three whole tablets during their routine visit to the outpatient department. After caregivers split the tablets, we studied the weight and content of the split parts. We also used high-performance liquid chromatography to study plasma drug concentrations in children who had received split AEDs for at least 4 months. A total of 168 caregivers participated in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0 %) split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP) acceptable percentage weight deviation (PHE 169 [48.8 %], SVA 187 [51.9 %], carbamazepine 56 [41.1 %], phenobarbitone 127 [49.6 %]); 456 (41.5 %) split parts were outside the proxy IP specification for drug content (PHE 135 [39.0 %], SVA 140 [38.8 %], carbamazepine 51 [37.5 %], phenobarbitone 130 [50.7 %]), and 253 split parts were outside the acceptable content uniformity range of <85 % and >115 % (PHE 85 [24.5 %], SVA 98 [27.2 %], carbamazepine 14 [10.2 %], phenobarbitone 56 [21.8 %]). In total, 130 (72.2 %) patients had plasma drug concentrations outside the therapeutic range (PHE 36 [72.0 %], SVA 39 [78.0 %], carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]). Splitting adult-dosage formulations of AEDs results in patients not receiving the optimal dose. Plasma drug concentrations are also not optimal. Pediatric dosage formulations should be preferred to splitting adult-dosage formulations in pediatric epilepsy.

Lack of Osteoradionecrosis of the Mandible After Intensity-Modulated Radiotherapy for Head and Neck Cancer: Likely Contributions of Both Dental Care and Improved Dose Distributions

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

Ben-David, Merav A.; Diamante, Maximiliano; Radawski, Jeffrey D.

Purpose: To assess the prevalence and dosimetric and clinical predictors of mandibular osteoradionecrosis (ORN) in patients with head and neck cancer who underwent a pretherapy dental evaluation and prophylactic treatment according to a uniform policy and were treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Between 1996 and 2005, all patients with head-and-neck cancer treated with parotid gland-sparing IMRT in prospective studies underwent a dental examination and prophylactic treatment according to a uniform policy that included extractions of high-risk, periodontally involved, and nonrestorable teeth in parts of the mandible expected to receive high radiation doses, fluoride supplements, and the placementmore » of guards aiming to reduce electron backscatter off metal teeth restorations. The IMRT plans included dose constraints for the maximal mandibular doses and reduced mean parotid gland and noninvolved oral cavity doses. A retrospective analysis of Grade 2 or worse (clinical) ORN was performed. Results: A total of 176 patients had a minimal follow-up of 6 months. Of these, 31 (17%) had undergone teeth extractions before RT and 13 (7%) after RT. Of the 176 patients, 75% and 50% had received {>=}65 Gy and {>=}70 Gy to {>=}1% of the mandibular volume, respectively. Falloff across the mandible characterized the dose distributions: the average gradient (in the axial plane containing the maximal mandibular dose) was 11 Gy (range, 1-27 Gy; median, 8 Gy). At a median follow-up of 34 months, no cases of ORN had developed (95% confidence interval, 0-2%). Conclusion: The use of a strict prophylactic dental care policy and IMRT resulted in no case of clinical ORN. In addition to the dosimetric advantages offered by IMRT, meticulous dental prophylactic care is likely an essential factor in reducing ORN risk.« less

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

PubMed Central

Lee, T-F; Ting, H-M; Chao, P-J; Wang, H-Y; Shieh, C-S; Horng, M-F; Wu, J-M; Yeh, S-A; Cho, M-Y; Huang, E-Y; Huang, Y-J; Chen, H-C; Fang, F-M

2012-01-01

Objective We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). Methods The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle3® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V20 Gy and V30 Gy of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. Results Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V20 Gy, and heart V30 Gy in the DV-gEUD plan were lower than those in the DV plan (p<0.05). Conclusions A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV. PMID:23091290

TU-H-BRC-07: Therapeutic Benefit in Spatially Fractionated Radiotherapy (GRID) Using Helical Tomotherapy

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

Narayanasamy, G; Zhang, X; Paudel, N

Purpose: The aim of this project is to study the therapeutic ratio (TR) for helical Tomotherapy (HT) based spatially fractionated radiotherapy (GRID). Estimation of TR was based on the linear-quadratic cell survival model by comparing the normal cell survival in a HT GRID to that of a uniform dose delivery in an open-field for the same tumor survival. Methods: HT GRID plan was generated using a patient specific virtual GRID block pattern of non-divergent, cylinder shaped holes using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT GRID irradiation to an open field irradiationmore » with an equivalent dose that result in the same tumor cell SF. The ratio was estimated from DVH data on ten patient plans with deep seated, bulky tumor approved by the treating radiation oncologist. Dependence of the TR values on radio-sensitivity of the tumor cells and prescription dose were also analyzed. Results: The mean ± standard deviation (SD) of TR was 4.0±0.7 (range: 3.1 to 5.5) for the 10 patients with single fraction dose of 20 Gy and tumor cell SF of 0.5 at 2 Gy. In addition, mean±SD of TR = 1±0.1 and 18.0±5.1 were found for tumor with SF of 0.3 and 0.7, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the TR to 2.0±0.2 and 1.2±0.04 for a tumor cell SF of 0.5 at 2 Gy. In this study, the SF of normal cells was assumed to be 0.5 at 2 Gy. Conclusion: HT GRID displayed a significant therapeutic advantage over uniform dose from an open field irradiation. TR increases with the radioresistance of the tumor cells and with prescription dose.« less

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

PubMed

Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

2018-03-15

Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV vaccine is immunogenic and provides lasting protection against HPV 16 and 18 infections similar to the three- and two-dose vaccine schedules, although the study suffer from some limitations. Data on long term protection beyond 7 years against HPV infection and cervical precancerous lesions are needed before policy guidelines regarding a single dose can be formulated and implemented. Significant and long-lasting protective effect of a single dose can be a strong argument to introduce one dose of the HPV vaccine in many low income countries where the current standard of care for cervical cancer prevention is 'no intervention'. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Radiobiological effects on plants and animals within Semipalatinsk Test Site (Kazakhstan)].

PubMed

Mozolin, E M; Geras'kin, S A; Minkenova, K S

2008-01-01

The Semipalatinsk Test Site (STS) was the main place of nuclear devices tests in the former Soviet Union. From 1949 to 1989 about 460 nuclear explosions have been carried out at STS. Radioactive contamination of STS territory has the extremely non-uniform character. The main dose-forming radionuclides are 137Cs, 90Sr, 152Eu, as well as 154Eu, 60CO, 239,240Pu and 241Am. The greatest specific activity of 137Cs and 239,240Pu in ground are n x 10(3) kBk/kg, 152Eu - 96 kBk/kg, 154Eu - 10.4 kBk/kg, 60Co - 20.5 kBk/kg, 241Am - 15 kBk/kg. However, up to now, within STS sites exists where gamma-dose rate comes to 60 microGy/h, that is enough for induction reliable biological effects in animals and plants. Inhabiting territory of STS plants and animals are characterized by increased level of mutagenesis, changes of morpho-anatomic indices and parameters of peripheral blood, by the increase of asymmetry bilateral indices, change of composition and structure of communities.

Effect of processing time delay on the dose response of Kodak EDR2 film.

PubMed

Childress, Nathan L; Rosen, Isaac I

2004-08-01

Kodak EDR2 film is a widely used two-dimensional dosimeter for intensity modulated radiotherapy (IMRT) measurements. Our clinical use of EDR2 film for IMRT verifications revealed variations and uncertainties in dose response that were larger than expected, given that we perform film calibrations for every experimental measurement. We found that the length of time between film exposure and processing can affect the absolute dose response of EDR2 film by as much as 4%-6%. EDR2 films were exposed to 300 cGy using 6 and 18 MV 10 x 10 cm2 fields and then processed after time delays ranging from 2 min to 24 h. An ion chamber measured the relative dose for these film exposures. The ratio of optical density (OD) to dose stabilized after 3 h. Compared to its stable value, the film response was 4%-6% lower at 2 min and 1% lower at 1 h. The results of the 4 min and 1 h processing time delays were verified with a total of four different EDR2 film batches. The OD/dose response for XV2 films was consistent for time periods of 4 min and 1 h between exposure and processing. To investigate possible interactions of the processing time delay effect with dose, single EDR2 films were irradiated to eight different dose levels between 45 and 330 cGy using smaller 3 x 3 cm2 areas. These films were processed after time delays of 1, 3, and 6 h, using 6 and 18 MV photon qualities. The results at all dose levels were consistent, indicating that there is no change in the processing time delay effect for different doses. The difference in the time delay effect between the 6 and 18 MV measurements was negligible for all experiments. To rule out bias in selecting film regions for OD measurement, we compared the use of a specialized algorithm that systematically determines regions of interest inside the 10 x 10 cm2 exposure areas to manually selected regions of interest. There was a maximum difference of only 0.07% between the manually and automatically selected regions, indicating that the use of a systematic algorithm to determine regions of interest in large and fairly uniform areas is not necessary. Based on these results, we recommend a minimum time of 1 h between exposure and processing for all EDR2 film measurements.

Characterization of total ionizing dose damage in COTS pinned photodiode CMOS image sensors

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Ma, Wuying; Huang, Shaoyan

The characterization of total ionizing dose (TID) damage in COTS pinned photodiode (PPD) CMOS image sensors (CISs) is investigated. The radiation experiments are carried out at a {sup 60}Co γ-ray source. The CISs are produced by 0.18-μm CMOS technology and the pixel architecture is 8T global shutter pixel with correlated double sampling (CDS) based on a 4T PPD front end. The parameters of CISs such as temporal domain, spatial domain, and spectral domain are measured at the CIS test system as the EMVA 1288 standard before and after irradiation. The dark current, random noise, dark signal non-uniformity (DSNU), photo responsemore » non-uniformity (PRNU), overall system gain, saturation output, dynamic range (DR), signal to noise ratio (SNR), quantum efficiency (QE), and responsivity versus the TID are reported. The behaviors of the tested CISs show remarkable degradations after radiation. The degradation mechanisms of CISs induced by TID damage are also analyzed.« less

A universal sample manipulator with 50 kV negative bias

NASA Astrophysics Data System (ADS)

Kenny, M. J.; Wielunski, L. S.; Scott, M. D.; Clissold, R. A.; Stevenson, D.; Baxter, G.

1991-04-01

A manipulator incorporating a number of novel features has been built for a research ion implanter. The system is designed to enable uniform dose implantation of both planar and nonplanar surfaces by incorporating one translational and two rotational degrees of freedom. Negative target bias of up to 50 kV may be applied to the target, thus increasing the ion energy by this amount. The target chamber and all external manipulator controls are grounded. With the exception of the high voltage power supply, cable and feedthrough, all high voltage components are within the vacuum system. A secondary electron suppression cage which can be held at a negative bias of up to 60 kV relative to the chamber (i.e. 10 kV relative to the manipulator) surrounds the manipulator. Performance has been evaluated using 15N ions and nuclear reaction analysis through 15N(p,α) 12C to profile ion concentrations for dose uniformity and for ion depth at elevated target potentials.

Characterization of total ionizing dose damage in COTS pinned photodiode CMOS image sensors

NASA Astrophysics Data System (ADS)

Wang, Zujun; Ma, Wuying; Huang, Shaoyan; Yao, Zhibin; Liu, Minbo; He, Baoping; Liu, Jing; Sheng, Jiangkun; Xue, Yuan

2016-03-01

The characterization of total ionizing dose (TID) damage in COTS pinned photodiode (PPD) CMOS image sensors (CISs) is investigated. The radiation experiments are carried out at a 60Co γ-ray source. The CISs are produced by 0.18-μm CMOS technology and the pixel architecture is 8T global shutter pixel with correlated double sampling (CDS) based on a 4T PPD front end. The parameters of CISs such as temporal domain, spatial domain, and spectral domain are measured at the CIS test system as the EMVA 1288 standard before and after irradiation. The dark current, random noise, dark signal non-uniformity (DSNU), photo response non-uniformity (PRNU), overall system gain, saturation output, dynamic range (DR), signal to noise ratio (SNR), quantum efficiency (QE), and responsivity versus the TID are reported. The behaviors of the tested CISs show remarkable degradations after radiation. The degradation mechanisms of CISs induced by TID damage are also analyzed.

Risk-adaptive radiotherapy

NASA Astrophysics Data System (ADS)

Kim, Yusung

Currently, there is great interest in integrating biological information into intensity-modulated radiotherapy (IMRT) treatment planning with the aim of boosting high-risk tumor subvolumes. Selective boosting of tumor subvolumes can be accomplished without violating normal tissue complication constraints using information from functional imaging. In this work we have developed a risk-adaptive optimization-framework that utilizes a nonlinear biological objective function. Employing risk-adaptive radiotherapy for prostate cancer, it is possible to increase the equivalent uniform dose (EUD) by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing normal tissue complications. Subsequently, we have studied the impact of functional imaging accuracy, and found on the one hand that loss in sensitivity had a large impact on expected local tumor control, which was maximal when a low-risk classification for the remaining low risk PTV was chosen. While on the other hand loss in specificity appeared to have a minimal impact on normal tissue sparing. Therefore, it appears that in order to improve the therapeutic ratio a functional imaging technique with a high sensitivity, rather than specificity, is needed. Last but not least a comparison study between selective boosting IMRT strategies and uniform-boosting IMRT strategies yielding the same EUD to the overall PTV was carried out, and found that selective boosting IMRT considerably improves expected TCP compared to uniform-boosting IMRT, especially when lack of control of the high-risk tumor subvolumes is the cause of expected therapy failure. Furthermore, while selective boosting IMRT, using physical dose-volume objectives, did yield similar rectal and bladder sparing when compared its equivalent uniform-boosting IMRT plan, risk-adaptive radiotherapy, utilizing biological objective functions, did yield a 5.3% reduction in NTCP for the rectum. Hence, in risk-adaptive radiotherapy the therapeutic ratio can be increased over that which can be achieved with conventional selective boosting IMRT using physical dose-volume objectives. In conclusion, a novel risk-adaptive radiotherapy strategy is proposed and promises increased expected local control for locoregionally advanced tumors with equivalent or better normal tissue sparing.

Interplay effects in proton scanning for lung: a 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters.

PubMed

Dowdell, S; Grassberger, C; Sharp, G C; Paganetti, H

2013-06-21

Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of five lung cancer patients of varying tumor size (50.4-167.1 cc) and motion amplitude (2.9-30.1 mm). Treatments were planned assuming delivery in 35 × 2.5 Gy(RBE) fractions. The spot size, time to change the beam energy (τes), time required for magnet settling (τss), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the five patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior-inferior motion amplitude alone. Larger spot sizes (σ ~ 9-16 mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0 ± 4.4% (1 standard deviation) in a single fraction compared to 86.1 ± 13.1% for smaller spots (σ ~ 2-4 mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively. The interplay effect is highly patient specific, depending on the motion amplitude, tumor location and the delivery parameters. Large degradations of the dose distribution in a single fraction were observed, but improved significantly using conventional fractionation.

Interplay effects in proton scanning for lung: A 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters

PubMed Central

Dowdell, S; Grassberger, C; Sharp, G C; Paganetti, H

2013-01-01

Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of 5 lung cancer patients of varying tumor size (50.4–167.1cc) and motion amplitude (2.9–30.1mm). Treatments were planned assuming delivery in 35×2.5Gy(RBE) fractions. The spot size, time to change the beam energy (τes), time required for magnet settling (τss), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the 5 patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior-inferior (SI) motion amplitude alone. Larger spot sizes (σ ~9–16mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0±4.4% (1 standard deviation) in a single fraction compared to 86.1±13.1% for smaller spots (σ ~2–4mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively. The interplay effect is highly patient specific, depending on the motion amplitude, tumor location and the delivery parameters. Large degradations of the dose distribution in a single fraction were observed, but improved significantly using conventional fractionation. PMID:23689035

Evaluation of the radiological risks associated with the routine transport of radioactive material within Michigan

NASA Astrophysics Data System (ADS)

Steinman, Rebecca Lee

Radioactive materials play an important role in modern society. In addition to providing electrical power and supporting national defense, radioisotopes play significant roles in the fields of medicine, research, manufacturing, and industry. Since most of these materials are not manufactured or disposed of at the site where they are used, they must be transported between various processing, use, storage, and disposal facilities. This dissertation examines the mathematical model used to predict the collective dose to the population that resides along a potential transport route, commonly called the off-link dose. The currently accepted RADTRAN and RISKIND transient dose models are reviewed. Then three new individual transient dose models are derived by assuming that a point, line, or surface cylinder can approximate the actual transport package. Groundscatter effects were investigated using a Monte Carlo simulation of the surface cylinder model and found to contribute no more than 12% to the total individual dose from a passing shipment of radioactive material, thus not warranting explicit inclusion in the newly derived transient dose models. All five of the individual transient dose models were evaluated for representative shipments of spent nuclear fuel and low-level waste within the State of Michigan and compared to experimentally measured doses. The individual dose for the Michigan shipment scenarios was found to be on the order of 1 murem. Comparison to the experimental measurements revealed that RISKIND consistently predicts the best estimate of the measured dose, followed closely by the surface cylinder model. RADTRAN consistently over predicted the measured dose by at least a factor of two. Finally, the line dose model is integrated over strips of uniform population along the transport route to arrive at the collective off-link population dose. This off-link dose model was incorporated into an ArcView application using the Avenue scripting language. Then this script was used to investigate the off-link dose to Michigan residents for the previously mentioned representative transport scenarios. The off-link dose was found to be less than 3 person-rem for all of the scenarios investigated.

Dose uniformity analysis among ten 16-slice same-model CT scanners.

PubMed

Erdi, Yusuf Emre

2012-01-01

With the introduction of multislice scanners, computed tomographic (CT) dose optimization has become important. The patient-absorbed dose may differ among the scanners although they are the same type and model. To investigate the dose output variation of the CT scanners, we designed the study to analyze dose outputs of 10 same-model CT scanners using 3 clinical protocols. Ten GE Lightspeed (GE Healthcare, Waukesha, Wis) 16-slice scanners located at main campus and various satellite locations of our institution have been included in this study. All dose measurements were performed using poly (methyl methacrylate) (PMMA) head (diameter, 16 cm) and body (diameter, 32 cm) phantoms manufactured by Radcal (RadCal Corp, Monrovia, Calif) using a 9095 multipurpose analyzer with 10 × 9-3CT ion chamber both from the same manufacturer. Ion chamber is inserted into the peripheral and central axis locations and volume CT dose index (CTDIvol) is calculated as weighted average of doses at those locations. Three clinical protocol settings for adult head, high-resolution chest, and adult abdomen are used for dose measurements. We have observed up to 9.4% CTDIvol variation for the adult head protocol in which the largest variation occurred among the protocols. However, head protocol uses higher milliampere second values than the other 2 protocols. Most of the measured values were less than the system-stored CTDIvol values. It is important to note that reduction in dose output from tubes as they age is expected in addition to the intrinsic radiation output fluctuations of the same scanner. Although the same model CT scanners were used in this study, it is possible to see CTDIvol variation in standard patient scanning protocols of head, chest, and abdomen. The compound effect of the dose variation may be larger with higher milliampere and multiphase and multilocation CT scans.

Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

NASA Astrophysics Data System (ADS)

Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

2013-06-01

In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less smoothing at early time points post-radiopharmaceutical administration but more smoothing and fewer iterations at later time points when the total organ activity was lower. The results of this study demonstrate the importance of using optimal reconstruction and regularization parameters. Optimal results were obtained with different parameters at each time point, but using a single set of parameters for all time points produced near-optimal dose-volume histograms.

Microporous structure with layered interstitial surface treatment, and method and apparatus for preparation thereof

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

1994-01-01

A microporous structure with layered interstitial surface treatments, and method and apparatus for preparation thereof is presented. The structure is prepared by sequentially subjecting a uniformly surface-treated structure to atomic oxygen treatment to remove an outer layer of surface treatment to a generally uniform depth, and then surface treating the so exposed layer with another surface treating agent. The atomic oxygen/surface treatment steps may optionally be repeated, each successive time to a lesser depth, to produce a microporous structure having multilayered surface treatments. The apparatus employs at least one side arm from a main atomic oxygen-containing chamber. The side arm has characteristic relaxation times such that a uniform atomic oxygen dose rate is delivered to a specimen positioned transversely in the side arm spaced from the main gas chamber.

Microporous structure with layered interstitial surface treatment, and method and apparatus for preparation thereof

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

1992-01-01

A microporous structure with layered interstitial surface treatments, and the method and apparatus for its preparation are disclosed. The structure is prepared by sequentially subjecting a uniformly surface treated structure to atomic oxygen treatment to remove an outer layer of surface treatment to a generally uniform depth, and then surface treating the so exposed layer with another surface treating agent. The atomic oxygen/surface treatment steps may optionally be repeated, each successive time to a lesser depth, to produce a microporous structure having multilayered surface treatments. The apparatus employs at least one side arm from a main oxygen-containing chamber. The side arm has characteristic relaxation times such that a uniform atomic oxygen dose rate is delivered to a specimen positioned transversely in the side arm spaced from the main gas chamber.

Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity modulated proton therapy treatment planning

PubMed Central

Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

2014-01-01

The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization in intensity modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the spot intensity optimization (SIO) routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming (LP) approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable spot intensity optimization (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming (QP) based model without MU constraints, i.e., a conventional spot intensity optimization (CSIO) model, was also implemented to emulate the commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 mm to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO- than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post-processing procedure required by the TPS as well as the resultant deteriorating effect on ultimate dose distributions. This approach therefore allows IMPT plans to adopt all possible spot spacings optimally. Moreover, dosimetric benefits can be achieved using smaller spot spacings. PMID:23835656

The ion environment near Europa and its role in surface energetics

NASA Astrophysics Data System (ADS)

Paranicas, C.; Ratliff, J. M.; Mauk, B. H.; Cohen, C.; Johnson, R. E.

2002-03-01

This paper gives the composition, energy spectra, and time variability of energetic ions measured just upstream of Europa. From 100 keV to 100 MeV, ion intensities vary by less than a factor of ~5 among Europa passes considered between 1997 and 2000. We use the data to estimate the radiation dose rate into Europa's surface for depths 0.01 mm - 1 m. We find that in a critical fraction of the upper layer on Europa's trailing hemisphere, energetic electrons are the principal agent for radiolysis, and their bremsstrahlung photon products, not included in previous studies, dominate the dose below about 1 m. Because ion bombardment is more uniform across Europa's surface, the radiation dose on the leading hemisphere is dominated by the proton flux. Differences exist between this calculation and published doses based on the E4 wake pass. For instance, proton doses presented here are much greater below 1 mm.

Specific issues in small animal dosimetry and irradiator calibration

PubMed Central

Yoshizumi, Terry; Brady, Samuel L.; Robbins, Mike E.; Bourland, J. Daniel

2013-01-01

Purpose In response to the increased risk of radiological terrorist attack, a network of Centers for Medical Countermeasures against Radiation (CMCR) has been established in the United States, focusing on evaluating animal model responses to uniform, relatively homogenous whole- or partial-body radiation exposures at relatively high dose rates. The success of such studies is dependent not only on robust animal models but on accurate and reproducible dosimetry within and across CMCR. To address this issue, the Education and Training Core of the Duke University School of Medicine CMCR organised a one-day workshop on small animal dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics and differences of cesium-137 and X-ray irradiators, methods for dose measurement, and design of experimental irradiation geometries for uniform dose distributions. This paper summarises the information presented and discussed. Conclusions Without ensuring accurate and reproducible dosimetry the development and assessment of the efficacy of putative countermeasures will not prove successful. Radiation physics support is needed, but is often the weakest link in the small animal dosimetry chain. We recommend: (i) A user training program for new irradiator users, (ii) subsequent training updates, and (iii) the establishment of a national small animal dosimetry center for all CMCR members. PMID:21961967

Characterization of XR-RV3 GafChromic{sup ®} films in standard laboratory and in clinical conditions and means to evaluate uncertainties and reduce errors

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

Farah, J., E-mail: jad.farah@irsn.fr; Clairand, I.; Huet, C.

2015-07-15

Purpose: To investigate the optimal use of XR-RV3 GafChromic{sup ®} films to assess patient skin dose in interventional radiology while addressing the means to reduce uncertainties in dose assessment. Methods: XR-Type R GafChromic films have been shown to represent the most efficient and suitable solution to determine patient skin dose in interventional procedures. As film dosimetry can be associated with high uncertainty, this paper presents the EURADOS WG 12 initiative to carry out a comprehensive study of film characteristics with a multisite approach. The considered sources of uncertainties include scanner, film, and fitting-related errors. The work focused on studying filmmore » behavior with clinical high-dose-rate pulsed beams (previously unavailable in the literature) together with reference standard laboratory beams. Results: First, the performance analysis of six different scanner models has shown that scan uniformity perpendicular to the lamp motion axis and that long term stability are the main sources of scanner-related uncertainties. These could induce errors of up to 7% on the film readings unless regularly checked and corrected. Typically, scan uniformity correction matrices and reading normalization to the scanner-specific and daily background reading should be done. In addition, the analysis on multiple film batches has shown that XR-RV3 films have generally good uniformity within one batch (<1.5%), require 24 h to stabilize after the irradiation and their response is roughly independent of dose rate (<5%). However, XR-RV3 films showed large variations (up to 15%) with radiation quality both in standard laboratory and in clinical conditions. As such, and prior to conducting patient skin dose measurements, it is mandatory to choose the appropriate calibration beam quality depending on the characteristics of the x-ray systems that will be used clinically. In addition, yellow side film irradiations should be preferentially used since they showed a lower dependence on beam parameters compared to white side film irradiations. Finally, among the six different fit equations tested in this work, typically used third order polynomials and more rational and simplistic equations, of the form dose inversely proportional to pixel value, were both found to provide satisfactory results. Fitting-related uncertainty was clearly identified as a major contributor to the overall film dosimetry uncertainty with up to 40% error on the dose estimate. Conclusions: The overall uncertainty associated with the use of XR-RV3 films to determine skin dose in the interventional environment can realistically be estimated to be around 20% (k = 1). This uncertainty can be reduced to within 5% if carefully monitoring scanner, film, and fitting-related errors or it can easily increase to over 40% if minimal care is not taken. This work demonstrates the importance of appropriate calibration, reading, fitting, and other film-related and scan-related processes, which will help improve the accuracy of skin dose measurements in interventional procedures.« less

Development and validation of an UPLC method for determination of content uniformity in low-dose solid drugs products using the design space approach.

PubMed

Oliva, Alexis; Fariña, José B; Llabrés, Matías

2013-10-15

A simple and reproducible UPLC method was developed and validated for the quantitative analysis of finasteride in low-dose drug products. Method validation demonstrated the reliability and consistency of analytical results. Due to the regulatory requirements of pharmaceutical analysis in particular, evaluation of robustness is vital to predict how small variations in operating conditions affect the responses. Response surface methodology as an optimization technique was used to evaluate the robustness. For this, a central composite design was implemented around the nominal conditions. Statistical treatment of the responses (retention factor and drug concentrations expressed as percentage of label claim) showed that methanol content in mobile-phase and flow rate were the most influential factors. In the optimization process, the compromise decision support problem (cDSP) strategy was used. Construction of the robust domain from response-surfaces provided tolerance windows for the factors affecting the effectiveness of the method. The specified limits for the USP uniformity of dosage units assay (98.5-101.5%) and the purely experimental variations based on the repeatability test for center points (nominal conditions repetitions) were used as criteria to establish the tolerance windows, which allowed definition design space (DS) of analytical method. Thus, the acceptance criteria values (AV) proposed by the USP-uniformity of assay only depend on the sampling error. If the variation in the responses corresponded to approximately twice the repeatability standard deviation, individual values for percentage label claim (%LC) response may lie outside the specified limits; this implies the data are not centered between the specified limits, and that this term plus the sampling error affects the AV value. To avoid this fact, the limits specified by the Uniformity of Dosage Form assay (i.e., 98.5-101.5%) must be taken into consideration to fix the tolerance windows for each factor. All these results were verified by the Monte Carlo simulation. In conclusion, the level of variability for different factors must be calculated for each case, and not arbitrary way, provided a variation is found higher than the repeatability for center points and secondly, the %LC response must lie inside the specified limits i.e., 98.5-101.5%. If not the UPLC method must be re-developed. © 2013 Elsevier B.V. All rights reserved.

An investigation into factors affecting the precision of CT radiation dose profile width measurements using radiochromic films

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

Li, Baojun, E-mail: Baojunli@bu.edu; Behrman, Richard H.

Purpose: To investigate the impact of x-ray beam energy, exposure intensity, and flat-bed scanner uniformity and spatial resolution on the precision of computed tomography (CT) beam width measurements using Gafchromic XR-QA2 film and an off-the-shelf document scanner. Methods: Small strips of Gafchromic film were placed at isocenter in a CT scanner and exposed at various x-ray beam energies (80–140 kVp), exposure levels (50–400 mA s), and nominal beam widths (1.25, 5, and 10 mm). The films were scanned in reflection mode on a Ricoh MP3501 flat-bed document scanner using several spatial resolution settings (100 to 400 dpi) and at differentmore » locations on the scanner bed. Reflection measurements were captured in digital image files and radiation dose profiles generated by converting the image pixel values to air kerma through film calibration. Beam widths were characterized by full width at half maximum (FWHM) and full width at tenth maximum (FWTM) of dose profiles. Dependences of these parameters on the above factors were quantified in percentage change from the baselines. Results: The uncertainties in both FWHM and FWTM caused by varying beam energy, exposure level, and scanner uniformity were all within 4.5% and 7.6%, respectively. Increasing scanner spatial resolution significantly increased the uncertainty in both FWHM and FWTM, with FWTM affected by almost 8 times more than FWHM (48.7% vs 6.5%). When uncalibrated dose profiles were used, FWHM and FWTM were over-estimated by 11.6% and 7.6%, respectively. Narrower beam width appeared more sensitive to the film calibration than the wider ones (R{sup 2} = 0.68 and 0.85 for FWHM and FWTM, respectively). The global and maximum local background variations of the document scanner were 1.2%. The intrinsic film nonuniformity for an unexposed film was 0.3%. Conclusions: Measurement of CT beam widths using Gafchromic XR-QA2 films is robust against x-ray energy, exposure level, and scanner uniformity. With proper film calibration and scanner resolution setting, it can provide adequate precision for meeting ACR and manufacturer’s tolerances for the measurement of CT dose profiles.« less

Development of sustained and dual drug release co-extrusion formulations for individual dosing.

PubMed

Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

2015-01-01

In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Alqathami, M; Lee, H; Ibbott, G

Purpose: To develop and evaluate novel radiochromic films for quality assurance in radiotherapy dosimetry. Materials and Methods: Novel radiochromic film compositions were formulated using leuco crystal violet (LCV) as a reporting system and tetrabromoethane as a free radical source. The film matrix used consisted of polyurethane polymer mixed with dibutyl phthalate plasticizer (20 wt%). The concentration of the radical initiator was kept constant at 10 wt% and the concentration of the LCV dye varied (1 and 2 wt%). To ensure uniform thickness of the film, its precursors were sandwiched between two pieces of glass separated by a 1 mm gapmore » between during the curing process. The films were cut into pieces and were irradiated with a 6 MV X-ray beam to selected doses. The change in optical density was measured using a flatbed scanner and a spectrophotometer. Results: The results showed that all film formulations exhibited a linear response with dose and an absorption maximum at ∼ 590 nm. The formulation with 2 wt% LCV was ∼ 30% more sensitive to dose than the formulation with 1 wt% LCV. Both films were very deformable. In addition, the radiochromic response of the film was found to bleach over a short period of time (few weeks) allowing the film to be reused for dose verification measurements. Conclusion: Both film formulations displayed excellent sensitivity and linearity to radiation dose and thus can be used for the 2D dosimetry of clinical megavoltage and kilovoltage X-ray beams. In addition, the thickness of the film could easily be increased allowing for their potential use as a deformable bolus material. However, thicker films would need more optimization of the manufacturing procedure to ensure consistent material uniformity and sensitivity are recommended.« less

Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

NASA Astrophysics Data System (ADS)

Medina, Daniel C.; Li, Xin; Springer, Charles S., Jr.

2005-05-01

In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against γ-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 ± 2% (p-value <0.001) was observed in the rat brain—this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as ~10% in the presence of a 9% water volume increase (oedema). All three authors have contributed equally to this work.

Microtomographic studies of subdivision of modified-release tablets.

PubMed

Wilczyński, Sławomir; Koprowski, Robert; Duda, Piotr; Banyś, Anna; Błońska-Fajfrowska, Barbara

2016-09-25

The uniformity of dosage units within a certain batch is ensured when each unit contains the active pharmaceutical ingredient (API) within a narrow range around the label claim. For tablets containing a score-line authorised for dose reductions, the European Pharmacopoeia (Ph. Eur.) considers that the uniformity of the tablet parts may be based on weight measurements regardless of the tablet type (immediate or modified release). This is because it is up to the regulatory authorities first to assess whether the tablet may contain a score-line for such use. X-ray microtomography was applied to assess the symmetry of 36 modified release tablets, containing 300mg of theophylline. The sum of the volume and surface area of the pellets in the subdivided tablets were compared. Simulations were carried out to identify the optimal amount of pellets in the tablet mass. The maximum difference in the API content between two subdivided halves was 165.18mg vs 133.83mg. If the amount of pellets in the tablet mass would drop below 13% on the basis of the pellet surface area, then the Ph. Eur. requirements would be exceeded. The amount of pellets in the tablet halves resulting in the greatest variability in API content was 38%. The results of this study indicate that the pellets were not distributed uniformly in the tablet mass. Thus, the uniformity of the dose in both halves of a tablet containing pellets cannot be based on the weight measurements i.e. it is necessary to develop further standards for tablet subdivision. Microtomographic methods are a very interesting alternative to expensive and time-consuming pharmacokinetic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Process variation challenges and resolution in the negative-tone develop double patterning for 20nm and below technology node

NASA Astrophysics Data System (ADS)

Mehta, Sohan S.; Ganta, Lakshmi K.; Chauhan, Vikrant; Wu, Yixu; Singh, Sunil; Ann, Chia; Subramany, Lokesh; Higgins, Craig; Erenturk, Burcin; Srivastava, Ravi; Singh, Paramjit; Koh, Hui Peng; Cho, David

2015-03-01

Immersion based 20nm technology node and below becoming very challenging to chip designers, process and integration due to multiple patterning to integrate one design layer . Negative tone development (NTD) processes have been well accepted by industry experts for enabling technologies 20 nm and below. 193i double patterning is the technology solution for pitch down to 80 nm. This imposes tight control in critical dimension(CD) variation in double patterning where design patterns are decomposed in two different masks such as in litho-etch-litho etch (LELE). CD bimodality has been widely studied in LELE double patterning. A portion of CD tolerance budget is significantly consumed by variations in CD in double patterning. The objective of this work is to study the process variation challenges and resolution in the Negative Tone Develop Process for 20 nm and Below Technology Node. This paper describes the effect of dose slope on CD variation in negative tone develop LELE process. This effect becomes even more challenging with standalone NTD developer process due to q-time driven CD variation. We studied impact of different stacks with combination of binary and attenuated phase shift mask and estimated dose slope contribution individually from stack and mask type. Mask 3D simulation was carried out to understand theoretical aspect. In order to meet the minimum insulator requirement for the worst case on wafer the overlay and critical dimension uniformity (CDU) budget margins have slimmed. Besides the litho process and tool control using enhanced metrology feedback, the variation control has other dependencies too. Color balancing between the two masks in LELE is helpful in countering effects such as iso-dense bias, and pattern shifting. Dummy insertion and the improved decomposition techniques [2] using multiple lower priority constraints can help to a great extent. Innovative color aware routing techniques [3] can also help with achieving more uniform density and color balanced layouts.

Antispermatogenic and antifertility effects of fruits of Piper nigrum L. in mice.

PubMed

Mishra, Raghav Kumar; Singh, Shio Kumar

2009-09-01

Effect of oral administration (25 and 100 mg/kg body wt/day, for 20 and 90 days) of fruit powder of Piper nigrum L. on the male reproductive organs of mice, Parkes strain, was investigated. Various reproductive end points such as organs weight, histopathology, sperm parameters, sialic acid and fructose contents, and fertility indices were assessed. Histologically, testes in treated mice, except in those treated with 100 mg of dose for 90 days, showed non-uniform degenerative changes in the seminiferous tubules, as both affected and normal tubules were observed in the same section. In mice treated with 100 mg dose for 90 days, degenerative changes were observed in all the tubules. Affected seminiferous tubules showed intraepithelial vacuolation, loosening of germinal epithelium, occurrence of giant cells, and mixing of spermatids of different stages of spermatogenesis; in severe cases, the tubules were lined by mainly a layer of Sertoli cells. Percentage of affected tubules in testes of Piper-treated mice was dose-and duration-related. Further, Piper nigrum treatment for 20 days did not cause appreciable alterations in histological appearance of the epididymis, while the treatment for 90 days caused detectable alterations in the duct. The treatment also had adverse effects on sperm parameters, levels of sialic acid and fructose, and on litter size. Fifty six days after cessation of treatment, the alterations induced in the reproductive organs recovered to control levels, though the litter size in females impregnated by Piper-treated males remained significantly decreased compared to controls.

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

PubMed Central

Hrycushko, Brian A.; Li, Shihong; Goins, Beth; Otto, Randal A.; Bao, Ande

2011-01-01

Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods:99mTc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186Re∕188Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy∕MBq (318.2 Gy∕mCi) and 5.7 Gy∕MBq (209.1 Gy∕mCi) could be delivered with this protocol of radiation delivery for 186Re∕188Re liposomes, respectively, and 37–92 MBq (1–2.5 mCi)∕g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. Conclusions: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy. PMID:21520844

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

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

Hrycushko, Brian A.; Li Shihong; Goins, Beth

2011-03-15

Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods: {sup 99m}Tc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts inmore » nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, {sup 186}Re/{sup 188}Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for {sup 186}Re/{sup 188}Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. Conclusions: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.« less

Analysis method to determine and characterize the mask mean-to-target and uniformity specification

NASA Astrophysics Data System (ADS)

Lee, Sung-Woo; Leunissen, Leonardus H. A.; Van de Kerkhove, Jeroen; Philipsen, Vicky; Jonckheere, Rik; Lee, Suk-Joo; Woo, Sang-Gyun; Cho, Han-Ku; Moon, Joo-Tae

2006-06-01

The specification of the mask mean-to-target (MTT) and uniformity is related to functions as: mask error enhancement factor, dose sensitivity and critical dimension (CD) tolerances. The mask MTT shows a trade-off relationship with the uniformity. Simulations for the mask MTT and uniformity (M-U) are performed for LOGIC devices of 45 and 37 nm nodes according to mask type, illumination condition and illuminator polarization state. CD tolerances and after develop inspection (ADI) target CD's in the simulation are taken from the 2004 ITRS roadmap. The simulation results allow for much smaller tolerances in the uniformity and larger offsets in the MTT than the values as given in the ITRS table. Using the parameters in the ITRS table, the mask uniformity contributes to nearly 95% of total CDU budget for the 45 nm node, and is even larger than the CDU specification of the ITRS for the 37 nm node. We also compared the simulation requirements with the current mask making capabilities. The current mask manufacturing status of the mask uniformity is barely acceptable for the 45 nm node, but requires process improvements towards future nodes. In particular, for the 37 nm node, polarized illumination is necessary to meet the ITRS requirements. The current mask linearity deviates for pitches smaller than 300 nm, which is not acceptable even for the 45 nm node. More efforts on the proximity correction method are required to improve the linearity behavior.

Assessment of individual organ doses in a realistic human phantom from neutron and gamma stimulated spectroscopy of the breast and liver

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

Belley, Matthew D.; Segars, William Paul; Kapadia, Anuj J., E-mail: anuj.kapadia@duke.edu

2014-06-15

Purpose: Understanding the radiation dose to a patient is essential when considering the use of an ionizing diagnostic imaging test for clinical diagnosis and screening. Using Monte Carlo simulations, the authors estimated the three-dimensional organ-dose distribution from neutron and gamma irradiation of the male liver, female liver, and female breasts for neutron- and gamma-stimulated spectroscopic imaging. Methods: Monte Carlo simulations were developed using the Geant4 GATE application and a voxelized XCAT human phantom. A male and a female whole body XCAT phantom was voxelized into 256 × 256 × 600 voxels (3.125 × 3.125 × 3.125 mm{sup 3}). A monoenergeticmore » rectangular beam of 5.0 MeV neutrons or 7.0 MeV photons was made incident on a 2 cm thick slice of the phantom. The beam was rotated at eight different angles around the phantom ranging from 0° to 180°. Absorbed dose was calculated for each individual organ in the body and dose volume histograms were computed to analyze the absolute and relative doses in each organ. Results: The neutron irradiations of the liver showed the highest organ dose absorption in the liver, with appreciably lower doses in other proximal organs. The dose distribution within the irradiated slice exhibited substantial attenuation with increasing depth along the beam path, attenuating to ∼15% of the maximum value at the beam exit side. The gamma irradiation of the liver imparted the highest organ dose to the stomach wall. The dose distribution from the gammas showed a region of dose buildup at the beam entrance, followed by a relatively uniform dose distribution to all of the deep tissue structures, attenuating to ∼75% of the maximum value at the beam exit side. For the breast scans, both the neutron and gamma irradiation registered maximum organ doses in the breasts, with all other organs receiving less than 1% of the breast dose. Effective doses ranged from 0.22 to 0.37 mSv for the neutron scans and 41 to 66 mSv for the gamma scans. Conclusions: Neutron and gamma irradiation of a primary target organ was found to impart the majority of the total dose to the primary target organ (and other large organs) within the beam plane and considerably lower dose to proximal organs outside of the beam. These results also indicate that despite the use of a highly scattering particle such as a neutron, the dose from neutron stimulated emission computed tomography scans is on par with other clinical imaging techniques such as x-ray computed tomography (x-ray CT). Given the high nonuniformity in the dose across an organ during the neutron scan, care must be taken when computing average doses from neutron irradiations. The effective doses from neutron scanning were found to be comparable to x-ray CT. Further technique modifications are needed to reduce the effective dose levels from the gamma scans.« less

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

PubMed

Boepple, P A; Mansfield, M J; Wierman, M E; Rudlin, C R; Bode, H H; Crigler, J F; Crawford, J D; Crowley, W F

1986-02-01

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Immune globulins are effective in severe pediatric Guillain-Barré syndrome.

PubMed

Shahar, E; Shorer, Z; Roifman, C M; Levi, Y; Brand, N; Ravid, S; Murphy, E G

1997-01-01

The effect of high-dose intravenous immune globulins was evaluated in an open prospective multicenter study of 26 children with severe Guillain-Barré syndrome. They presented with mild to moderate flaccid weakness of extremities, with cranial nerve involvement (20) and sensory impairment (22). All children rapidly deteriorated in 2-16 days (mean 6) to become bedridden, and 2 children also developed respiratory failure requiring artificial ventilation (Disability Grading Scale 4-5). Immune globulins were then administered at a total dose of 2 gm/kg, on 2 consecutive days, without adverse effects requiring discontinuation of therapy. Marked and rapid improvement was noted in 25 children, who improved by 1 to 2 Disability Grade Scales < or = 2 weeks after the infusion. Twenty were able to walk independently by 1 week, and 1 could be weaned off a ventilator. Eighteen children recovered by 2 weeks. The rest recuperated in a period of four months, including a child who was artificially ventilated for 4 weeks. The uniform rapid improvement and recovery associated with immune globulins contrasts with the slow recovery course in severe natural cases. We conclude that immune globulins are effective and safe in severe childhood-onset Guillain-Barré syndrome and therefore may serve as the initial treatment of choice.

Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature

PubMed Central

Kavanagh, David; Jury, Alexa; Williams, Jac; Scolding, Neil; Bellamy, Chris; Gunther, Claudia; Ritchie, Diane; Gale, Daniel P.; Kanwar, Yashpal S.; Challis, Rachel; Buist, Holly; Overell, James; Weller, Belinda; Flossmann, Oliver; Blunden, Mark; Meyer, Eric P.; Krucker, Thomas; Evans, Stephen J. W.; Campbell, Iain L.; Jackson, Andrew P.; Chandran, Siddharthan

2016-01-01

Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation. PMID:27663672

Studies on high electronic energy deposition in transparent conducting indium tin oxide thin films

NASA Astrophysics Data System (ADS)

Deshpande, N. G.; Gudage, Y. G.; Ghosh, A.; Vyas, J. C.; Singh, F.; Tripathi, A.; Sharma, Ramphal

2008-02-01

We have examined the effect of swift heavy ions using 100 MeV Au8+ ions on the electrical properties of transparent, conducting indium tin oxide polycrystalline films with resistivity of 0.58 × 10-4 Ω cm and optical transmission greater than 78% (pristine). We report on the modifications occurring after high electronic energy deposition. With the increase in fluency, x-ray line intensity of the peaks corresponding to the planes (1 1 0), (4 0 0), (4 4 1) increased, while (3 3 1) remained constant. Surface morphological studies showed a pomegranate structure of pristine samples, which was highly disturbed with a high dose of irradiation. For the high dose, there was a formation of small spherical domes uniformly distributed over the entire surface. The transmittance was seen to be decreasing with the increase in ion fluency. At higher doses, the resistivity and photoluminescence intensity was seen to be decreased. In addition, the carrier concentration was seen to be increased, which was in accordance with the decrease in resistivity. The observed modifications after high electronic energy deposition in these films may lead to fruitful device applications.

Method for simulating dose reduction in digital mammography using the Anscombe transformation

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

Borges, Lucas R., E-mail: lucas.rodrigues.borges@usp.br; Oliveira, Helder C. R. de; Nunes, Polyana F.

2016-06-15

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtainedmore » by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

PubMed Central

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2016-01-01

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID:27277017

Optima HD Imax: Molecular Implant

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

Tieger, D. R.; Splinter, P. R.; Hsieh, T. J.

2008-11-03

Molecular implantation offers semiconductor device manufacturers multiple advantages over traditional high current ion implanters. The dose multiplication due to implanting more than one atom per molecule and the transport of beams at higher energies relative to the effective particle energies result in significant throughput enhancements without risk of energy contamination. The Optima HD Imax is introduced with molecular implant capability and the ability to reach up to 4.2 keV effective {sup 11}B from octadecaborane (B{sub 18}H{sub 22}). The ion source and beamline are optimized for molecular species ionization and transport. The beamline is coupled to the Optima HD mechanically scannedmore » endstation. The use of spot beam technology with ionized molecules maximizes the throughput potential and produces uniform implants with fast setup time and with superior angle control. The implanter architecture is designed to run multiple molecular species; for example, in addition to B{sub 18}H{sub 22} the system is capable of implanting carbon molecules for strain engineering and shallow junction engineering. Source lifetime data and typical operating conditions are described both for high dose, memory applications such as dual poly gate as well as lower energy implants for source drain extension and contact implants. Throughputs have been achieved in excess of 50 wafers per hour at doses up to 1x10{sup 16} ions/cm{sup 2} and for energies as low as 1 keV.« less

THE INFLUENCE OF ENDOTOXIN ADMINISTRATION ON THE NUTRITIONAL REQUIREMENTS OF MICE

PubMed Central

Dubos, René; Costello, Richard; Schaedler, Russell W.

1965-01-01

Albino mice lose weight within 24 hours following administration of bacterial endotoxin. The initial weight loss is proportional to the dose of endotoxin injected only when this dose is very small. The loss during the 1st day reaches a maximum with 10 to 30 µg of endotoxin; larger doses increase the duration of the overall effect. The rate at which mice regain weight after administration of endotoxin is markedly influenced by the composition of the diet. Recovery was rapid and complete within a few days when the animals were fed commercial pellets or a semisynthetic diet containing casein. In contrast, recovery was slow and incomplete when wheat gluten was used instead of casein in the diet. The deleterious effect of the gluten diet was less marked in older than in younger animals, probably because the latter have less exacting nutritional requirements. It was postulated that the failure of endotoxin-treated mice to regain weight when fed the gluten diet was due to the fact that this protein is low in certain amino acids. In fact, rapid and complete recovery from the weight loss uniformly occurred when the gluten diet was supplemented with proper amounts of lysine and threonine. The composition of the diet did not influence the extent of the initial loss of weight caused by endotoxin, nor did it prevent the animals from developing tolerance to this substance. PMID:5322368

Dosimetric treatment course simulation based on a statistical model of deformable organ motion

NASA Astrophysics Data System (ADS)

Söhn, M.; Sobotta, B.; Alber, M.

2012-06-01

We present a method of modeling dosimetric consequences of organ deformation and correlated motion of adjacent organ structures in radiotherapy. Based on a few organ geometry samples and the respective deformation fields as determined by deformable registration, principal component analysis (PCA) is used to create a low-dimensional parametric statistical organ deformation model (Söhn et al 2005 Phys. Med. Biol. 50 5893-908). PCA determines the most important geometric variability in terms of eigenmodes, which represent 3D vector fields of correlated organ deformations around the mean geometry. Weighted sums of a few dominating eigenmodes can be used to simulate synthetic geometries, which are statistically meaningful inter- and extrapolations of the input geometries, and predict their probability of occurrence. We present the use of PCA as a versatile treatment simulation tool, which allows comprehensive dosimetric assessment of the detrimental effects that deformable geometric uncertainties can have on a planned dose distribution. For this, a set of random synthetic geometries is generated by a PCA model for each simulated treatment course, and the dose of a given treatment plan is accumulated in the moving tissue elements via dose warping. This enables the calculation of average voxel doses, local dose variability, dose-volume histogram uncertainties, marginal as well as joint probability distributions of organ equivalent uniform doses and thus of TCP and NTCP, and other dosimetric and biologic endpoints. The method is applied to the example of deformable motion of prostate/bladder/rectum in prostate IMRT. Applications include dosimetric assessment of the adequacy of margin recipes, adaptation schemes, etc, as well as prospective ‘virtual’ evaluation of the possible benefits of new radiotherapy schemes.

Automatic exposure control at single- and dual-heartbeat CTCA on a 320-MDCT volume scanner: effect of heart rate, exposure phase window setting, and reconstruction algorithm.

PubMed

Funama, Yoshinori; Utsunomiya, Daisuke; Taguchi, Katsuyuki; Oda, Seitaro; Shimonobo, Toshiaki; Yamashita, Yasuyuki

2014-05-01

To investigate whether electrocardiogram (ECG)-gated single- and dual-heartbeat computed tomography coronary angiography (CTCA) with automatic exposure control (AEC) yields images with uniform image noise at reduced radiation doses. Using an anthropomorphic chest CT phantom we performed prospectively ECG-gated single- and dual-heartbeat CTCA on a second-generation 320-multidetector CT volume scanner. The exposure phase window was set at 75%, 70-80%, 40-80%, and 0-100% and the heart rate at 60 or 80 or corr80 bpm; images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR, adaptive iterative dose reduction 3D). We applied AEC and set the image noise level to 20 or 25 HU. For each technique we determined the image noise and the radiation dose to the phantom center. With half-scan reconstruction at 60 bpm, a 70-80% phase window- and a 20-HU standard deviation (SD) setting, the imagenoise level and -variation along the z axis manifested similar curves with FBP and IR. With half-scan reconstruction, the radiation dose to the phantom center with 70-80% phase window was 18.89 and 12.34 mGy for FBP and 4.61 and 3.10 mGy for IR at an SD setting SD of 20 and 25 HU, respectively. At 80 bpm with two-segment reconstruction the dose was approximately twice that of 60 bpm at both SD settings. However, increasing radiation dose at corr80 bpm was suppressed to 1.39 times compared to 60 bpm. AEC at ECG-gated single- and dual-heartbeat CTCA controls the image noise at different radiation dose. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Poster — Thur Eve — 38: Feasibility of a Table-Top Total Body Irradiation Technique using Robotic Couch Motion

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

Chin, Erika; Otto, Karl; Hoppe, Richard

Purpose: To develop and test the feasibility of a table-top implementation for total body irradiation (TBI) via robotic couch motion and coordinated monitor unit modulation on a standard C-arm linac geometry. Methods: To allow for collision free delivery and to maximize the effective field size, the couch was rotated to 270° IEC and dropped to 150 cm from the vertical radiation source. The robotic delivery was programmed using the TrueBeam STx Developer Mode using custom XML scripting. To assess the dosimetry of a sliding 30×20 cm{sup 2} field, irradiation on a solid water phantom of varying thickness was analyzed usingmore » EDR2 radiographic film and OSLDs. Beam modulation was achieved by dividing the couch path into multiple segments of varying dose rates and couch speeds in order to deliver 120 cGy to the midline. Results: The programmed irradiation in conjunction with coordinated couch motion was successfully delivered on a TrueBeam linac. When no beam modulation was employed, the dose difference between two different phantom sections was 17.0%. With simple beam modulation via changing dose rates and couch speeds, the desired prescription dose can be achieved at the centre of each phantom section within 1.9%. However, dose deviation at the junction was 9.2% due to the nonphysical change in the phantom thickness. Conclusions: The feasibility of robotic table-top TBI on a C-arm linac geometry was experimentally demonstrated. To achieve a more uniform dose distribution, inverse-planning allowing for a combination of dose rate modulation, jaw tracking and MLC motion is under investigation.« less

Dosimetric treatment course simulation based on a statistical model of deformable organ motion.

PubMed

Söhn, M; Sobotta, B; Alber, M

2012-06-21

We present a method of modeling dosimetric consequences of organ deformation and correlated motion of adjacent organ structures in radiotherapy. Based on a few organ geometry samples and the respective deformation fields as determined by deformable registration, principal component analysis (PCA) is used to create a low-dimensional parametric statistical organ deformation model (Söhn et al 2005 Phys. Med. Biol. 50 5893-908). PCA determines the most important geometric variability in terms of eigenmodes, which represent 3D vector fields of correlated organ deformations around the mean geometry. Weighted sums of a few dominating eigenmodes can be used to simulate synthetic geometries, which are statistically meaningful inter- and extrapolations of the input geometries, and predict their probability of occurrence. We present the use of PCA as a versatile treatment simulation tool, which allows comprehensive dosimetric assessment of the detrimental effects that deformable geometric uncertainties can have on a planned dose distribution. For this, a set of random synthetic geometries is generated by a PCA model for each simulated treatment course, and the dose of a given treatment plan is accumulated in the moving tissue elements via dose warping. This enables the calculation of average voxel doses, local dose variability, dose-volume histogram uncertainties, marginal as well as joint probability distributions of organ equivalent uniform doses and thus of TCP and NTCP, and other dosimetric and biologic endpoints. The method is applied to the example of deformable motion of prostate/bladder/rectum in prostate IMRT. Applications include dosimetric assessment of the adequacy of margin recipes, adaptation schemes, etc, as well as prospective 'virtual' evaluation of the possible benefits of new radiotherapy schemes.

Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy.

PubMed

Deveau, Michael A; Gutiérrez, Alonso N; Mackie, Thomas R; Tomé, Wolfgang A; Forrest, Lisa J

2010-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5 mm (0-10.0 mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9 +/- 3.3 mm. Due to variations, a loss of equivalent uniform dose for target volumes of up to 5.6% was noted which corresponded to a potential loss in tumor control probability of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose and highest normalized dose given to 2% of the volume. Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain.

DOSIMETRIC IMPACT OF DAILY SETUP VARIATIONS DURING TREATMENT OF CANINE NASAL TUMORS USING INTENSITY-MODULATED RADIATION THERAPY

PubMed Central

Deveau, Michael A.; Gutiérrez, Alonso N.; Mackie, Thomas R.; Tomé, Wolfgang A.; Forrest, Lisa J.

2009-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5mm (0-10.0mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9±3.3mm. Due to variations, a loss of equivalent uniform dose (EUD) for target volumes of up to 5.6% was noted which corresponded to a potential loss in TCP of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose (NTDmean) and highest normalized dose given to 2% of the volume (NTD2%). Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain. PMID:20166402

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

Zheng, Y; Chang, A; Liu, Y

Purpose: Electron beams are commonly used for boost radiation following whole breast irradiation (WBI) to improve the in-breast local control. Proton beams have a finite range and a sharper distal dose falloff compared to electron beams, thus potentially sparing more heart and lung in breast treatment. The purpose of the study is to compare protons with electrons for boost breast treatment in terms of target coverage and normal tissue sparing. Methods: Six breast cancer patients were included in this study. All women received WBI to 45–50 Gy, followed by a 10–16.2 Gy boost with standard fractionation. If proton beams weremore » used for the boost treatment, an electron plan was retrospectively generated for comparison using the same CT set and structures, and vice versa if electron beams were used for treatment. Proton plans were generated using the treatment planning system (TPS) with two to three uniform scanning proton beams. Electron plans were generated using the Pinnacle TPS with one single en face beam. Dose-volume histograms (DVH) were calculated and compared between proton and electron boost plans. Results: Proton plans show a similar boost target coverage, similar skin dose, and much better heart and lung sparing. For an example patient, V95% for PTV was 99.98% and skin (5 mm shell) received a max dose close to the prescription dose for both protons and electrons; however, V2 and V5 for the ipsilateral lung and heart were 37.5%, 17.9% and 19.9%, 4.9% respectively for electrons, but were essentially 0 for protons. Conclusions: This dosimetric comparison demonstrates that while both proton therapy and electron therapy provided similar coverage and skin dose, proton therapy could largely reduce the dose to lung and heart, thus leading to potential less side effects.« less

Methodology for worker neutron exposure evaluation in the PDCF facility design.

PubMed

Scherpelz, R I; Traub, R J; Pryor, K H

2004-01-01

A project headed by Washington Group International is meant to design the Pit Disassembly and Conversion Facility (PDCF) to convert the plutonium pits from excessed nuclear weapons into plutonium oxide for ultimate disposition. Battelle staff are performing the shielding calculations that will determine appropriate shielding so that the facility workers will not exceed target exposure levels. The target exposure levels for workers in the facility are 5 mSv y(-1) for the whole body and 100 mSv y(-1) for the extremity, which presents a significant challenge to the designers of a facility that will process tons of radioactive material. The design effort depended on shielding calculations to determine appropriate thickness and composition for glove box walls, and concrete wall thicknesses for storage vaults. Pacific Northwest National Laboratory (PNNL) staff used ORIGEN-S and SOURCES to generate gamma and neutron source terms, and Monte Carlo (computer code for) neutron photon (transport) (MCNP-4C) to calculate the radiation transport in the facility. The shielding calculations were performed by a team of four scientists, so it was necessary to develop a consistent methodology. There was also a requirement for the study to be cost-effective, so efficient methods of evaluation were required. The calculations were subject to rigorous scrutiny by internal and external reviewers, so acceptability was a major feature of the methodology. Some of the issues addressed in the development of the methodology included selecting appropriate dose factors, developing a method for handling extremity doses, adopting an efficient method for evaluating effective dose equivalent in a non-uniform radiation field, modelling the reinforcing steel in concrete, and modularising the geometry descriptions for efficiency. The relative importance of the neutron dose equivalent compared with the gamma dose equivalent varied substantially depending on the specific shielding conditions and lessons were learned from this effect. This paper addresses these issues and the resulting methodology.

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

A risk index for pediatric patients undergoing diagnostic imaging with 99mTc-dimercaptosuccinic acid that accounts for body habitus

NASA Astrophysics Data System (ADS)

O'Reilly, Shannon E.; Plyku, Donika; Sgouros, George; Fahey, Frederic H.; Treves, S. Ted; Frey, Eric C.; Bolch, Wesley E.

2016-03-01

Published guidelines for administered activity to pediatric patients undergoing diagnostic nuclear medicine imaging are currently obtained through expert consensus of the minimum values as a function of body weight as required to yield diagnostic quality images. We have previously shown that consideration of body habitus is also important in obtaining diagnostic quality images at the lowest administered activity. The objective of this study was to create a series of computational phantoms that realistically portray the anatomy of the pediatric patient population which can be used to develop and validate techniques to minimize radiation dose while maintaining adequate image quality. To achieve this objective, we have defined an imaging risk index that may be used in future studies to develop pediatric patient dosing guidelines. A population of 48 hybrid phantoms consisting of non-uniform B-spline surfaces and polygon meshes was generated. The representative ages included the newborn, 1 year, 5 year, 10 year and 15 year male and female. For each age, the phantoms were modeled at their 10th, 50th, and 90th height percentile each at a constant 50th weight percentile. To test the impact of kidney size, the newborn phantoms were modeled with the following three kidney volumes:  -15%, average, and  +15%. To illustrate the impact of different morphologies on dose optimization, we calculated the effective dose for each phantom using weight-based 99mTc-DMSA activity administration. For a given patient weight, body habitus had a considerable effect on effective dose. Substantial variations were observed in the risk index between the 10th and 90th percentile height phantoms from the 50th percentile phantoms for a given age, with the greatest difference being 18%. There was a dependence found between kidney size and risk of radiation induced kidney cancer, with the highest risk indices observed in newborns with the smallest kidneys. Overall, the phantoms and techniques in this study can be used to provide data to refine dosing guidelines for pediatric nuclear imaging studies while taking into account the effects on both radiation dose and image quality. This work was supported by:R01 EB013558 with the National Institute for Biomedical Imaging and Bioengineering (NIBIB).

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.

PubMed

Yazici, Cemal; Yanoso, Laura; Xie, Chao; Reynolds, David G; Samulski, R Jude; Samulski, Jade; Yannariello-Brown, Judith; Gertzman, Arthur A; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M

2008-10-01

Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; p<0.001) increase in percent surface area coating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

Evaluation of a commercial flatbed document scanner and radiographic film scanner for radiochromic EBT film dosimetry

PubMed Central

Parker, Brent C.; Neck, Daniel W.; Henkelmann, Greg; Rosen, Isaac I.

2010-01-01

The purpose of this study was to quantify the performance and assess the utility of two different types of scanners for radiochromic EBT film dosimetry: a commercial flatbed document scanner and a widely used radiographic film scanner. We evaluated the Epson Perfection V700 Photo flatbed scanner and the Vidar VXR Dosimetry Pro Advantage scanner as measurement devices for radiochromic EBT film. Measurements were made of scan orientation effects, response uniformity, and scanner noise. Scanners were tested using films irradiated with eight separate 3×3 cm2 fields to doses ranging from 0.115–5.119 Gy. ImageJ and RIT software was used for analyzing the Epson and Vidar scans, respectively. For repeated scans of a single film, the measurements in each dose region were reproducible to within ±0.3% standard deviation (SD) with both scanners. Film‐to‐film variations for corresponding doses were measured to be within ±0.4% SD for both Epson scanner and Vidar scanners. Overall, the Epson scanner showed a 10% smaller range of pixel value compared to the Vidar scanner. Scanner noise was small: ±0.3% SD for the Epson and ±0.2% for the Vidar. Overall measurement uniformity for blank film in both systems was better than ±0.2%, provided that the leading and trailing 2 cm film edges were neglected in the Vidar system. In this region artifacts are attributed to the film rollers. Neither system demonstrated a clear measurement advantage. The Epson scanner is a relatively inexpensive method for analyzing radiochromic film, but there is a lack of commercially available software. For a clinic already using a Vidar scanner, applying it to radiochromic film is attractive because commercial software is available. However, care must be taken to avoid using the leading and trailing film edges. PACS number: 87.55.Qr

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE PAGES

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan; ...

2017-03-03

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

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

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Automated registration of large deformations for adaptive radiation therapy of prostate cancer

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

Godley, Andrew; Ahunbay, Ergun; Peng Cheng

2009-04-15

Available deformable registration methods are often inaccurate over large organ variation encountered, for example, in the rectum and bladder. The authors developed a novel approach to accurately and effectively register large deformations in the prostate region for adaptive radiation therapy. A software tool combining a fast symmetric demons algorithm and the use of masks was developed in C++ based on ITK libraries to register CT images acquired at planning and before treatment fractions. The deformation field determined was subsequently used to deform the delivered dose to match the anatomy of the planning CT. The large deformations involved required that themore » bladder and rectum volume be masked with uniform intensities of -1000 and 1000 HU, respectively, in both the planning and treatment CTs. The tool was tested for five prostate IGRT patients. The average rectum planning to treatment contour overlap improved from 67% to 93%, the lowest initial overlap is 43%. The average bladder overlap improved from 83% to 98%, with a lowest initial overlap of 60%. Registration regions were set to include a volume receiving 4% of the maximum dose. The average region was 320x210x63, taking approximately 9 min to register on a dual 2.8 GHz Linux system. The prostate and seminal vesicles were correctly placed even though they are not masked. The accumulated doses for multiple fractions with large deformation were computed and verified. The tool developed can effectively supply the previously delivered dose for adaptive planning to correct for interfractional changes.« less

Development of a novel method to enhance the therapeutic effect on tumours by simultaneous action of radiation and heating.

PubMed

Kosterev, Vladimir V; Kramer-Ageev, Evgeny A; Mazokhin, Vladimir N; van Rhoon, Gerard C; Crezee, Johannes

2015-06-01

This paper describes the development of a new type of electromagnetic hyperthermia applicator delivering dose control within large application fields and increased effectiveness by providing simultaneous action of radiation and heating (SRH) in malignant tumours, and development of a dosimetric feedback method to support SRH. Single and phased arrays of flexible applicators have been developed to allow simultaneous hyperthermia and external beam therapy. A frequency of 434 MHz is used to heat near-surface and moderately deep-seated tumours and 70 MHz for deep-seated tumours. Phase and amplitude control allows focusing of electromagnetic energy (EM) to deep-seated tumours. The specific absorption rate (SAR) dose distribution can be modified to achieve uniform heating of tumours with complex shapes and heterogeneous tissue properties. A lithium fluoride thermoluminescent dosimeter (TLD) in a flexible film cassette has been developed for real-time dose measurement. Four types of 434 MHz applicators were manufactured with 3, 4, 9 or 12 independent applicators. Two types of 70 MHz applicators were made with 4 or 6 independent applicators. Phantom tests demonstrated the ability to control the SAR pattern by phase and amplitude control. Placement of the dosimeter between bolus and phantom increased the phantom surface temperature up to 3 °C and showed that the ratio of absorbed energy in TLD to dose in water approaches (0.83 ± 3%) for photon energies >60 keV. Simultaneous and controlled radiation and local hyperthermia is technically feasible in a preclinical setting, a clinical feasibility test is the next step.

Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.

PubMed

Zhang, Yong; Sadgrove, Matthew P; Sueda, Katsuhiko; Yang, Yu-Tsai; Pacyniak, Erik K; Kagel, John R; Braun, Brenda A; Zamboni, William C; Mumper, Russell J; Jay, Michael

2013-04-01

Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.

A Toolbox to Improve Algorithms for Insulin-Dosing Decision Support

PubMed Central

Donsa, K.; Plank, J.; Schaupp, L.; Mader, J. K.; Truskaller, T.; Tschapeller, B.; Höll, B.; Spat, S.; Pieber, T. R.

2014-01-01

Summary Background Standardized insulin order sets for subcutaneous basal-bolus insulin therapy are recommended by clinical guidelines for the inpatient management of diabetes. The algorithm based GlucoTab system electronically assists health care personnel by supporting clinical workflow and providing insulin-dose suggestions. Objective To develop a toolbox for improving clinical decision-support algorithms. Methods The toolbox has three main components. 1) Data preparation: Data from several heterogeneous sources is extracted, cleaned and stored in a uniform data format. 2) Simulation: The effects of algorithm modifications are estimated by simulating treatment workflows based on real data from clinical trials. 3) Analysis: Algorithm performance is measured, analyzed and simulated by using data from three clinical trials with a total of 166 patients. Results Use of the toolbox led to algorithm improvements as well as the detection of potential individualized subgroup-specific algorithms. Conclusion These results are a first step towards individualized algorithm modifications for specific patient subgroups. PMID:25024768

Nanomedicine in pulmonary delivery

PubMed Central

Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

2009-01-01

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

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

Sudhyadhom, A; McGuinness, C; Descovich, M

Purpose: To develop a methodology for validation of a Monte-Carlo dose calculation model for robotic small field SRS/SBRT deliveries. Methods: In a robotic treatment planning system, a Monte-Carlo model was iteratively optimized to match with beam data. A two-part analysis was developed to verify this model. 1) The Monte-Carlo model was validated in a simulated water phantom versus a Ray-Tracing calculation on a single beam collimator-by-collimator calculation. 2) The Monte-Carlo model was validated to be accurate in the most challenging situation, lung, by acquiring in-phantom measurements. A plan was created and delivered in a CIRS lung phantom with film insert.more » Separately, plans were delivered in an in-house created lung phantom with a PinPoint chamber insert within a lung simulating material. For medium to large collimator sizes, a single beam was delivered to the phantom. For small size collimators (10, 12.5, and 15mm), a robotically delivered plan was created to generate a uniform dose field of irradiation over a 2×2cm{sup 2} area. Results: Dose differences in simulated water between Ray-Tracing and Monte-Carlo were all within 1% at dmax and deeper. Maximum dose differences occurred prior to dmax but were all within 3%. Film measurements in a lung phantom show high correspondence of over 95% gamma at the 2%/2mm level for Monte-Carlo. Ion chamber measurements for collimator sizes of 12.5mm and above were within 3% of Monte-Carlo calculated values. Uniform irradiation involving the 10mm collimator resulted in a dose difference of ∼8% for both Monte-Carlo and Ray-Tracing indicating that there may be limitations with the dose calculation. Conclusion: We have developed a methodology to validate a Monte-Carlo model by verifying that it matches in water and, separately, that it corresponds well in lung simulating materials. The Monte-Carlo model and algorithm tested may have more limited accuracy for 10mm fields and smaller.« less

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

Moteabbed, M; Depauw, N; Kooy, H

Purpose: To investigate the dosimetric benefits of pencil beam scanning (PBS) compared with passive scattered (PS) proton therapy for treatment of pediatric head&neck patients as a function of the PBS spot size and explore the advantages of using apertures in PBS. Methods: Ten pediatric patients with head&neck cancers treated by PS proton therapy at our institution were retrospectively selected. The histologies included rhabdomyosarcoma, ependymoma, astrocytoma, craniopharyngioma and germinoma. The prescribed dose ranged from 36 to 54 Gy(RBE). Five PBS plans were created for each patient using variable spot size (average sigma at isocenter) and choice of beam specific apertures: (1)more » 10mm spots, (2) 10mm spots with apertures, (3) 6mm spots, (4) 6mm spots with apertures, and (5) 3mm spots. The plans were optimized for intensity modulated proton therapy (IMPT) with no single beam uniformity constraints. Dose volume indices as well as equivalent uniform dose (EUD) were compared between PS and PBS plans. Results: Although target coverage was clinically adequate for all cases, the plans with largest (10mm) spots provide inferior quality compared with PS in terms of dose to organs-at-risk (OAR). However, adding apertures to these plans ensured lower OAR dose than PS. The average EUD difference between PBS and PS plans over all patients and organs at risk were (1) 2.5%, (2) −5.1%, (3) -5%, (4) −7.8%, and (5) −9.5%. As the spot size decreased, more conformal plans were achieved that offered similar target coverage but lower dose to the neighboring healthy organs, while alleviating the need for using apertures. Conclusion: The application of PBS does not always translate to better plan qualities compared to PS depending on the available beam spot size. We recommend that institutions with spot size larger than ∼6mm at isocenter consider using apertures to guarantee clinically comparable or superior dosimetric efficacy to PS treatments.« less

Individual Genetic Susceptibility

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

Eric J. Hall

2008-12-08

Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimentalmore » radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.« less

EUD-based biological optimization for carbon ion therapy

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

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

2015-11-15

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalentmore » uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Liquid scintillator tiles for calorimetry

DOE PAGES

Amouzegar, M.; Belloni, A.; Bilki, B.; ...

2016-11-28

Future experiments in high energy and nuclear physics may require large, inexpensive calorimeters that can continue to operate after receiving doses of 50 Mrad or more. Also, the light output of liquid scintillators suffers little degradation under irradiation. However, many challenges exist before liquids can be used in sampling calorimetry, especially regarding developing a packaging that has sufficient efficiency and uniformity of light collection, as well as suitable mechanical properties. We present the results of a study of a scintillator tile based on the EJ-309 liquid scintillator using cosmic rays and test beam on the light collection efficiency and uniformity,more » and some preliminary results on radiation hardness.« less

Liquid scintillator tiles for calorimetry

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

Amouzegar, M.; Belloni, A.; Bilki, B.

Future experiments in high energy and nuclear physics may require large, inexpensive calorimeters that can continue to operate after receiving doses of 50 Mrad or more. Also, the light output of liquid scintillators suffers little degradation under irradiation. However, many challenges exist before liquids can be used in sampling calorimetry, especially regarding developing a packaging that has sufficient efficiency and uniformity of light collection, as well as suitable mechanical properties. We present the results of a study of a scintillator tile based on the EJ-309 liquid scintillator using cosmic rays and test beam on the light collection efficiency and uniformity,more » and some preliminary results on radiation hardness.« less

EMBOLIZATION OF DOG PROSTATES WITH YTTRIUM-90 MICROSPHERES

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

Greene, W.M.

1963-10-01

Experiments exploring means for the protection of adjacent normal tissue while delivering a destructive dose of radiation to malignant tissue were conducted. By injection of radioactive ceramic spheres or particles, too large to pass through capillaries or arteriovenous shunts, relatively high doses of radiation can be distributed homogeneously to a circumscribed area. Attempts were made to determine the uniformity of distribution and the radiation effect of varying doses of spheres injected into the arterial supply of the dog prostate. Nonradioactive and radioactive ceramic microspheres of 60 mu dia were used since this size exceeds the diameter of capillaries and arteriovenousmore » shunts. Yttrium-90 microspheres of varying radioactivity were used. Doses injected into right and left hypogastric arteries varied from 0.69 to 28.4 mc/side (92-1260 mc/ g prostate). Homogeneous distribution of radioactivity within the prostate was demonstrated by autoradiography. Distribution to some other organs (rectum, penis, and bladder) occurred because arterial supply to these structures was not isolated and occluded. The amount of radioactivity found in the lungs suggested more venous drainage in some cases than seemed apparent, and because of the infarctions of pelvic organs may have leaked radioactive spheres into the venous circuit. In 6 of the 8 dogs which died prematurely (2 to 7 days after surgery) obvious infarction of the prostate and in some other pelvic structures had occurred. That the radioactivity contributed to the infarction is suggested by the results in the dogs which received large doses of radioactivity (18.9 and 28.4 mc per side) in minimal amounts of spheres (100to 150 mg per side). The intensely concentrated radioactivity within the arteriolar lumens may have caused vasculitis and subsequent thrombosis. Although homogeneous destruction of the prostate gland occurred, the effect of a given dose ranged unpredictably through three groups: no apparent effect at all, destruction of the prostate, and early death with infarction of the prostate and other pelvic organs. It was concluded that with the present technique the range between the dose of radioactivity which caused no obvious response and the dose which is related to acute death is too narrow to allow reasonably predictable results, but that further refinement of technique might increase control over tissue destruction.« less

An IR Navigation System for Pleural PDT

NASA Astrophysics Data System (ADS)

Zhu, Timothy; Liang, Xing; Kim, Michele; Finlay, Jarod; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Friedberg, Joseph; Cengel, Keith

2015-03-01

Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

Optimal design and management of chlorination in drinking water networks: a multi-objective approach using Genetic Algorithms and the Pareto optimality concept

NASA Astrophysics Data System (ADS)

Nouiri, Issam

2017-11-01

This paper presents the development of multi-objective Genetic Algorithms to optimize chlorination design and management in drinking water networks (DWN). Three objectives have been considered: the improvement of the chlorination uniformity (healthy objective), the minimization of chlorine booster stations number, and the injected chlorine mass (economic objectives). The problem has been dissociated in medium and short terms ones. The proposed methodology was tested on hypothetical and real DWN. Results proved the ability of the developed optimization tool to identify relationships between the healthy and economic objectives as Pareto fronts. The proposed approach was efficient in computing solutions ensuring better chlorination uniformity while requiring the weakest injected chlorine mass when compared to other approaches. For the real DWN studied, chlorination optimization has been crowned by great improvement of free-chlorine-dosing uniformity and by a meaningful chlorine mass reduction, in comparison with the conventional chlorination.

Treatment of extensive scalp lesions with segmental intensity-modulated photon therapy.

PubMed

Bedford, James L; Childs, Peter J; Hansen, Vibeke Nordmark; Warrington, Alan P; Mendes, Ruheena L; Glees, John P

2005-08-01

To compare static electron therapy, electron arc therapy, and photon intensity-modulated radiation therapy (IMRT) for treatment of extensive scalp lesions and to examine the dosimetric accuracy of the techniques. A retrospective treatment-planning study was performed to evaluate the relative merits of static electron fields, arcing electron fields, and five-field photon IMRT. Thermoluminescent dosimeters (TLD) were used to verify the accuracy of the techniques. The required thickness of bolus was investigated, and an anthropomorphic phantom was also used to examine the effects of air gaps between the wax bolus used for the IMRT technique and the patient's scalp. Neither static nor arcing electron techniques were able to provide a reliable coverage of the planning target volume (PTV), owing to obliquity of the fields in relation to the scalp. The IMRT technique considerably improved PTV dose uniformity, though it irradiated a larger volume of brain. Either 0.5 cm or 1.0 cm of wax bolus was found to be suitable. Air gaps of up to 1 cm between the bolus and the patient's scalp were correctly handled by the treatment-planning system and had negligible influence on the dose to the scalp. Photon IMRT provides a feasible alternative to electron techniques for treatment of large scalp lesions, resulting in improved homogeneity of dose to the PTV but with a moderate increase in dose to the brain.

Characterisation of neutron-sensitive bubble detectors for application in the measurement of jet aircrew exposure to natural background radiation.

PubMed

Tume, P; Lewis, B J; Bennett, L G; Cousins, T

1998-01-01

A survey of the natural background dose equivalent received by Canadian Forces aircrew was conducted using neutron-sensitive bubble detectors (BDs) as the primary detection tool. Since this study was a new application for these detectors, the BD response to neutron dose equivalent (RD) was extended from thermal to 500 MeV in neutron energy. Based upon the extended RD, it was shown that the manufacturer's calibration can be scaled by 1.5 +/- 0.5 to give a BD sensitivity that takes into account recently recommended fluence-to-neutron dose equivalent conversion functions and the cosmogenic neutron spectrum encountered at jet altitudes. An investigation of the effects of systematic bias caused by the cabin environment (i.e., temperature, pressure and relative humidity) on the in-flight measurements was also conducted. Both simulated and actual aircraft climate tests indicated that the detectors are insensitive to the pressure and relative humidity variations encountered during routine jet aircraft operations. Long term conditioning tests also confirmed that the BD-PND model of detector is sensitive to variations in temperature to within +/- 20%. As part of the testing process, the in-flight measurements also demonstrated that the neutron dose equivalent is distributed uniformly throughout a Boeing 707 jet aircraft, indicating that both pilots and flight attendants are exposed to the same neutron field intensity to within experimental uncertainty.

Simple Carotid-Sparing Intensity-Modulated Radiotherapy Technique and Preliminary Experience for T1-2 Glottic Cancer

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

Rosenthal, David I., E-mail: dirosenthal@mdanderson.or; Fuller, Clifton D.; Barker, Jerry L.

2010-06-01

Purpose: To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience. Methods and Materials: Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique. Results: Intensity-modulated radiotherapymore » consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far. Conclusions: Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.« less

Pulmonary deposition modeling with airborne fiber exposure data: a study of workers manufacturing refractory ceramic fibers.

PubMed

Lentz, Thomas J; Rice, Carol H; Succop, Paul A; Lockey, James E; Dement, John M; LeMasters, Grace K

2003-04-01

Increasing production of refractory ceramic fiber (RCF), a synthetic vitreous material with industrial applications (e.g., kiln insulation), has created interest in potential respiratory effects of exposure to airborne fibers during manufacturing. An ongoing study of RCF manufacturing workers in the United States has indicated an association between cumulative fiber exposure and pleural plaques. Fiber sizing data, obtained from electron microscopy analyses of 118 air samples collected in three independent studies over a 20-year period (1976-1995), were used with a computer deposition model to estimate pulmonary dose of fibers of specified dimensions for 652 former and current RCF production workers. Separate dose correction factors reflecting differences in fiber dimensions in six uniform job title groups were used with data on airborne fiber concentration and employment duration to calculate cumulative dose estimates for each worker. From review of the literature, critical dimensions (diameter <0.4 microm, length <10 microm) were defined for fibers that may translocate to the parietal pleura. Each of three continuous exposure/dose metrics analyzed in separate logistic regression models was significantly related to plaques, even after adjusting for possible past asbestos exposure: cumulative fiber exposure, chi(2) = 15.2 (p < 0.01); cumulative pulmonary dose (all fibers), chi(2) = 14.6 (p < 0.01); cumulative pulmonary dose (critical dimension fibers), chi(2) = 12.4 (p < 0.01). Odds ratios (ORs) were calculated for levels of each metric. Increasing ORs were statistically significant for the two highest dose levels of critical dimension fibers (level three, OR = 11, 95%CI = [1.4, 98]; level four, OR = 25, 95%CI = [3.2, 190]). Similar associations existed for all metrics after adjustment for possible asbestos exposure. It was concluded that development of pleural plaques follows exposure- and dose-response patterns, and that airborne fibers in RCF manufacturing facilities include those with critical dimensions associated with pleural plaque formation. Analysis of additional air samples may improve estimates of the dose-response relationship.

Current status of intravenous thrombolysis for acute ischemic stroke in Asia.

PubMed

Sharma, Vijay K; Ng, Kay W P; Venketasubramanian, Narayanaswamy; Saqqur, Maher; Teoh, Hock L; Kaul, Subash; Srivastava, Padma M V; Sergentanis, Theodoris; Suwanwela, Nijasri; Nguyen, Thang H; Lawrence Wong, K S; Chan, Bernard P L

2011-12-01

Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0.6 mg/kg body weight; max 60 mg) comparable to standard dose (0.9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis

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

Mahan, Stephen L.; Ramsey, Chester R.; Scaperoth, Daniel D.

Introduction: Patients with vertebral metastasis that receive radiation therapy are typically treated to the spinal cord tolerance dose. As such, it is difficult to successfully deliver a second course of radiation therapy for patients with overlapping treatment volumes. In this study, an image-guided helical tomotherapy system was evaluated for the retreatment of previously irradiated vertebral metastasis. Methods and Materials: Helical tomotherapy dose gradients and maximum cord doses were measured in a cylindrical phantom for geometric test cases with separations between the planning target volume (PTV) and the spinal cord organ at risk (OAR) of 2 mm, 4 mm, 6 mm,more » 8 mm, and 10 mm. Megavoltage computed tomography (CT) images were examined for their ability to localize spinal anatomy for positioning purposes by repeat imaging of the cervical spine in an anthropomorphic phantom. In addition to the phantom studies, 8 patients with cord compressions that had received previous radiation therapy were retreated to a mean dose of 28 Gy using conventional fractionation. Results and Discussion: Megavoltage CT images were capable of positioning an anthropomorphic phantom to within {+-}1.2 mm (2{sigma}) superior-inferiorly and within {+-}0.6 mm (2{sigma}) anterior-posteriorly and laterally. Dose gradients of 10% per mm were measured in phantom while PTV uniformity indices of less than 11% were maintained. The calculated maximum cord dose was 25% of the prescribed dose for a 10-mm PTV-to-OAR separation and 71% of the prescribed dose for a PTV-to-OAR separation of 2 mm. Eight patients total have been treated without radiation-induced myelopathy or any other adverse effects from treatment. Conclusions: A technique has been evaluated for the retreatment of vertebral metastasis using image-guided helical tomotherapy. Phantom and patient studies indicated that a tomotherapy system is capable of delivering dose gradients of 10% per mm and positioning the patient within 1.2 mm without the use of special stereotactic immobilization.« less

FDG-PET Assessment of the Effect of Head and Neck Radiotherapy on Parotid Gland Glucose Metabolism

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

Roach, Michael C.; Turkington, Timothy G.; Department of Biomedical Engineering, Duke University Medical Center, Duke University, Durham, NC

Purpose: Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded tomore » paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. Results: The average parotid gland volume was 30.7 mL and contracted 3.9 {+-} 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% {+-} 7.3% regardless of dose. The average SUV{sub mean} of the glands was 1.63 {+-} 0.48 pretreatment and declined by 5.2% {+-} 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV{sub max} was 4.07 {+-} 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV{sub max} declined rapidly. Conclusion: Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning.« less

The impact of different dose response parameters on biologically optimized IMRT in breast cancer

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

Datamining approaches for modeling tumor control probability.

PubMed

Naqa, Issam El; Deasy, Joseph O; Mu, Yi; Huang, Ellen; Hope, Andrew J; Lindsay, Patricia E; Apte, Aditya; Alaly, James; Bradley, Jeffrey D

2010-11-01

Tumor control probability (TCP) to radiotherapy is determined by complex interactions between tumor biology, tumor microenvironment, radiation dosimetry, and patient-related variables. The complexity of these heterogeneous variable interactions constitutes a challenge for building predictive models for routine clinical practice. We describe a datamining framework that can unravel the higher order relationships among dosimetric dose-volume prognostic variables, interrogate various radiobiological processes, and generalize to unseen data before when applied prospectively. Several datamining approaches are discussed that include dose-volume metrics, equivalent uniform dose, mechanistic Poisson model, and model building methods using statistical regression and machine learning techniques. Institutional datasets of non-small cell lung cancer (NSCLC) patients are used to demonstrate these methods. The performance of the different methods was evaluated using bivariate Spearman rank correlations (rs). Over-fitting was controlled via resampling methods. Using a dataset of 56 patients with primary NCSLC tumors and 23 candidate variables, we estimated GTV volume and V75 to be the best model parameters for predicting TCP using statistical resampling and a logistic model. Using these variables, the support vector machine (SVM) kernel method provided superior performance for TCP prediction with an rs=0.68 on leave-one-out testing compared to logistic regression (rs=0.4), Poisson-based TCP (rs=0.33), and cell kill equivalent uniform dose model (rs=0.17). The prediction of treatment response can be improved by utilizing datamining approaches, which are able to unravel important non-linear complex interactions among model variables and have the capacity to predict on unseen data for prospective clinical applications.

Measurement and simulation of the TRR BNCT beam parameters

NASA Astrophysics Data System (ADS)

Bavarnegin, Elham; Sadremomtaz, Alireza; Khalafi, Hossein; Kasesaz, Yaser; Golshanian, Mohadeseh; Ghods, Hossein; Ezzati, Arsalan; Keyvani, Mehdi; Haddadi, Mohammad

2016-09-01

Recently, the configuration of the Tehran Research Reactor (TRR) thermal column has been modified and a proper thermal neutron beam for preclinical Boron Neutron Capture Therapy (BNCT) has been obtained. In this study, simulations and experimental measurements have been carried out to identify the BNCT beam parameters including the beam uniformity, the distribution of the thermal neutron dose, boron dose, gamma dose in a phantom and also the Therapeutic Gain (TG). To do this, the entire TRR structure including the reactor core, pool, the thermal column and beam tubes have been modeled using MCNPX Monte Carlo code. To measure in-phantom dose distribution a special head phantom has been constructed and foil activation techniques and TLD700 dosimeter have been used. The results show that there is enough uniformity in TRR thermal BNCT beam. TG parameter has the maximum value of 5.7 at the depth of 1 cm from the surface of the phantom, confirming that TRR thermal neutron beam has potential for being used in treatment of superficial brain tumors. For the purpose of a clinical trial, more modifications need to be done at the reactor, as, for example design, and construction of a treatment room at the beam exit which is our plan for future. To date, this beam is usable for biological studies and animal trials. There is a relatively good agreement between simulation and measurement especially within a diameter of 10 cm which is the dimension of usual BNCT beam ports. This relatively good agreement enables a more precise prediction of the irradiation conditions needed for future experiments.

Construction of anthropomorphic hybrid, dual-lattice voxel models for optimizing image quality and dose in radiography

NASA Astrophysics Data System (ADS)

Petoussi-Henss, Nina; Becker, Janine; Greiter, Matthias; Schlattl, Helmut; Zankl, Maria; Hoeschen, Christoph

2014-03-01

In radiography there is generally a conflict between the best image quality and the lowest possible patient dose. A proven method of dosimetry is the simulation of radiation transport in virtual human models (i.e. phantoms). However, while the resolution of these voxel models is adequate for most dosimetric purposes, they cannot provide the required organ fine structures necessary for the assessment of the imaging quality. The aim of this work is to develop hybrid/dual-lattice voxel models (called also phantoms) as well as simulation methods by which patient dose and image quality for typical radiographic procedures can be determined. The results will provide a basis to investigate by means of simulations the relationships between patient dose and image quality for various imaging parameters and develop methods for their optimization. A hybrid model, based on NURBS (Non Linear Uniform Rational B-Spline) and PM (Polygon Mesh) surfaces, was constructed from an existing voxel model of a female patient. The organs of the hybrid model can be then scaled and deformed in a non-uniform way i.e. organ by organ; they can be, thus, adapted to patient characteristics without losing their anatomical realism. Furthermore, the left lobe of the lung was substituted by a high resolution lung voxel model, resulting in a dual-lattice geometry model. "Dual lattice" means in this context the combination of voxel models with different resolution. Monte Carlo simulations of radiographic imaging were performed with the code EGS4nrc, modified such as to perform dual lattice transport. Results are presented for a thorax examination.

Investigation into the Manufacture and Properties of Inhalable High-Dose Dry Powders Produced by Comilling API and Lactose with Magnesium Stearate.

PubMed

Lau, Michael; Young, Paul M; Traini, Daniela

2017-08-01

The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1-7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1-40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.

Effects of neuropeptide-Y on renal function and its interaction with sympathetic stimulation in conscious dogs.

PubMed Central

Persson, P B; Ehmke, H; Nafz, B; Lang, R; Hackenthal, E; Nobiling, R; Dietrich, M S; Kirchheim, H R

1991-01-01

1. The effects of neuropeptide-Y (NPY) on renal function were investigated in conscious foxhounds. 2. Dose-response curves (n = 7) were obtained for NPY by measuring renal blood flow (RBF), glomerular filtration rate (GFR), urine excretion (VU), sodium excretion (VNa), potassium excretion (VK) and plasma renin activity (PRA) at different infusion rates. All variables decreased with increasing infusion rates except for PRA, which surprisingly did not change during the different infusion rates. 3. The influence of the non-constrictor dose of NPY at control pressure, and after servo-controlling renal arterial pressure at 80 mmHg, was determined for these parameters (n = 6). 4. This was repeated during a reflex sympathetic activation via carotid sinus hypotension, in order to quantify a possible interaction between the sympathetic transmitter and co-transmitter (n = 6). 5. The subthreshold NPY dose raised plasma NPY-like immunoreactivity (NPY-LI IR) significantly (renal venous plasma: 54 +/- 13 vs. 405 +/- 117 pg ml-1; P less than 0.05) and enhanced the pressure-dependent (80 mmHg) antidiuresis (0.48 +/- 0.06 vs. 0.24 +/- 0.02 ml min-1; P less than 0.05), antinatriuresis (46 +/- 11 vs. 25 +/- 3 mumol min-1; P less than 0.05), antikaliuresis (19 +/- 4 vs. 9 +/- 0.7 mumol min-1; P less than 0.05) and pressure-dependent renin release (0.95 +/- 0.27 vs. 3.0 +/- 1.1 ng angiotensin I ml-1 h-1; P less than 0.05). These effects are consistent with a non-uniform vasoconstrictor action of NPY in the renal vascular bed (see accompanying papers). 6. The effects of NPY plus sympathetic activation were less than the sum of the two individual effects, which may rely on a presynaptic mechanism. PMID:1688030

Mice and the A-Bomb: Irradiation Systems for Realistic Exposure Scenarios.

PubMed

Garty, Guy; Xu, Yanping; Elliston, Carl; Marino, Stephen A; Randers-Pehrson, Gerhard; Brenner, David J

2017-04-01

Validation of biodosimetry assays is normally performed with acute exposures to uniform external photon fields. Realistically, exposure to a radiological dispersal device or reactor leak will include exposure to low dose rates and likely exposure to ingested radionuclides. An improvised nuclear device will likely include a significant neutron component in addition to a mixture of high- and low-dose-rate photons and ingested radionuclides. We present here several novel irradiation systems developed at the Center for High Throughput Minimally Invasive Radiation Biodosimetry to provide more realistic exposures for testing of novel biodosimetric assays. These irradiators provide a wide range of dose rates (from Gy/s to Gy/week) as well as mixed neutron/photon fields mimicking an improvised nuclear device.

Mice and the A-Bomb: Irradiation Systems for Realistic Exposure Scenarios

PubMed Central

Garty, Guy; Xu, Yanping; Elliston, Carl; Marino, Stephen A.; Randers-Pehrson, Gerhard; Brenner, David J.

2017-01-01

Validation of biodosimetry assays is normally performed with acute exposures to uniform external photon fields. Realistically, exposure to a radiological dispersal device or reactor leak will include exposure to low dose rates and likely exposure to ingested radionuclides. An improvised nuclear device will likely include a significant neutron component in addition to a mixture of high- and low-dose-rate photons and ingested radionuclides. We present here several novel irradiation systems developed at the Center for High Throughput Minimally Invasive Radiation Biodosimetry to provide more realistic exposures for testing of novel biodosimetric assays. These irradiators provide a wide range of dose rates (from Gy/s to Gy/week) as well as mixed neutron/photon fields mimicking an improvised nuclear device. PMID:28211757

X-ray mask and method for making

DOEpatents

Morales, Alfredo M.

2004-10-26

The present invention describes a method for fabricating an x-ray mask tool which is a contact lithographic mask which can provide an x-ray exposure dose which is adjustable from point-to-point. The tool is useful in the preparation of LIGA plating molds made from PMMA, or similar materials. In particular the tool is useful for providing an ability to apply a graded, or "stepped" x-ray exposure dose across a photosensitive substrate. By controlling the x-ray radiation dose from point-to-point, it is possible to control the development process for removing exposed portions of the substrate; adjusting it such that each of these portions develops at a more or less uniformly rate regardless of feature size or feature density distribution.

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

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

Yu, V; Nguyen, D; Pajonk, F

Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to exploremore » the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported by the NSF Graduate Research Fellowship (DGE-1144087)« less

Effects of ultrasound-induced inertial cavitation on enzymatic thrombolysis.

PubMed

Chuang, Yueh-Hsun; Cheng, Po-Wen; Chen, Szu-Chia; Ruan, Jia-Ling; Li, Pai-Chi

2010-04-01

Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing the transport of reactants. However, the effects of cavitation need to be fully understood before sonothrombolysis can be applied clinically. In order to understand the underlying mechanisms, we examined the effects of combining ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we evaluated the relations between inertial cavitation and the reduction in the weight of a blood clot. Inertial cavitation was varied by changing the amplitude and duration of the transmitted acoustic wave as well as the concentration of microbubbles used to induce cavitation. Second, we studied the combined effects of streptokinase and inertial cavitation on thrombolysis. The results show that inertial cavitation increases the weight reduction of a blood clot by up to 33.9%. With linear regression fitting, the measured differential inertial cavitation dose and the weight reduction had a correlation coefficient of 0.66. Microscopically, enzymatic thrombolysis effects manifest as multiple large cavities within the clot that are uniformly distributed on the side exposed to ultrasound. This suggests that inertial cavitation plays an important role in producing cavities, while microjetting of the microbubbles induces pits on the clot surface. These observations preliminarily demonstrate the clinical potential of sonothrombolysis. The use of the differential inertial cavitation dose as an indicator of blood clot weight loss for controlled sonothrombolysis is also possible and will be further explored.

Dosimetric study of uniform scanning proton therapy planning for prostate cancer patients with a metal hip prosthesis, and comparison with volumetric‐modulated arc therapy

PubMed Central

Cheng, ChihYao; Zheng, Yuanshui; Hsi, Wen; Zeidan, Omar; Schreuder, Niek; Vargas, Carlos; Larson, Gary

2014-01-01

The main purposes of this study were to 1) investigate the dosimetric quality of uniform scanning proton therapy planning (USPT) for prostate cancer patients with a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that of volumetric‐modulated arc therapy (VMAT). Proton plans for prostate cancer (four cases) were generated in XiO treatment planning system (TPS). The beam arrangement in each proton plan consisted of three fields (two oblique fields and one lateral or slightly angled field), and the proton beams passing through a metal hip prosthesis was avoided. Dose calculations in proton plans were performed using the pencil beam algorithm. From each proton plan, planning target volume (PTV) coverage value (i.e., relative volume of the PTV receiving the prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done using two arcs in the Eclipse TPS utilizing 6 MV X‐rays, and beam entrance through metallic hip prosthesis was avoided. Dose computation in the VMAT plans was done using anisotropic analytical algorithm, and calculated VMAT plans were then normalized such that the PTV coverage in the VMAT plan was the same as in the proton plan of the corresponding case. The dose‐volume histograms of calculated treatment plans were used to evaluate the dosimetric quality of USPT and VMAT. In comparison to the proton plans, on average, the maximum and mean doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively, whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton plans had lower (or better) average homogeneity index (HI) of 0.03 compared to the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was lower in the proton plan, with an average absolute difference ranging from 0.1% to 32.6%. In contrast, using proton planning, the relative bladder volume exposed to radiation was higher at high‐dose region with an average absolute difference ranging from 0.4% to 0.8%, and lower at low‐ and medium‐dose regions with an average absolute difference ranging from 2.7% to 10.1%. The average mean dose to the rectum and bladder was lower in the proton plans by 45.1% and 22.0%, respectively, whereas the mean dose to femoral head was lower in VMAT plans by an average difference of 79.6%. In comparison to the VMAT, the proton planning produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4 Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2 CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in this study show that the combination of lateral and oblique fields in USPT planning could potentially provide dosimetric advantage over the VMAT for prostate cancer involving a metallic hip prosthesis. PACS number: 87.55.D‐, 87.55.ne, 87.55.dk PMID:24892333

Longitudinal uniformity, time performances and irradiation test of pure CsI crystals

NASA Astrophysics Data System (ADS)

Angelucci, M.; Atanova, O.; Baccaro, S.; Cemmi, A.; Cordelli, M.; Donghia, R.; Giovannella, S.; Happacher, F.; Miscetti, S.; Sarra, I.; Soleti, S. R.

2016-07-01

To study an alternative to BaF2, as the crystal choice for the Mu2e calorimeter, 13 pure CsI crystals from Opto Materials and ISMA producers have been characterized by determining their light yield (LY) and longitudinal response uniformity (LRU), when read with a UV extended PMT. The crystals show a LY of 100 p.e./MeV ( 150 p.e./MeV) when wrapped with Tyvek and coupled to the PMT without (with) optical grease. The LRU is well represented by a linear slope that is on average δ -0.6%/cm. The timing performances of the Opto Materials crystal, read with a UV extended MPPC, have been evaluated with minimum ionizing particles. A timing resolution of 330 ps ( 440 ps) is achieved when connecting the photosensor to the MPPC with (without) optical grease. The crystal radiation hardness to a ionization dose has also been studied for one pure CsI crystal from SICCAS. After exposing it to a dose of 900 Gy, a decrease of 33% in the LY is observed while the LRU remains unchanged.

Computational and Experimental Evaluations of a Novel Thermo-Brachytherapy Seed for Treatment of Solid Tumors

NASA Astrophysics Data System (ADS)

Warrell, Gregory R.

Hyperthermia has long been known as a radiation therapy sensitizer of high potential; however successful delivery of this modality and integrating it with radiation have often proved technically difficult. We present the dual-modality thermobrachytherapy (TB) seed, based on the ubiquitous low dose-rate (LDR) brachytherapy permanent implant, as a simple and effective combination of hyperthermia and radiation therapy. Heat is generated from a ferromagnetic or ferrimagnetic core within the seed, which produces Joule heating by eddy currents. A strategically-selected Curie temperature provides thermal self-regulation. In order to obtain a uniform and sufficiently high temperature distribution, additional hyperthermia-only (HT-only) seeds are proposed to be used in vacant spots within the needles used to implant the TB seeds; this permits a high seed density without the use of additional needles. Experimental and computational studies were done both to optimize the design of the TB and HT-only seeds and to quantitatively assess their ability to heat and irradiate defined, patient-specific targets. Experiments were performed with seed-sized ferromagnetic samples in tissue-mimicking phantoms heated by an industrial induction heater. The magnetic and thermal properties of the seeds were studied computationally in the finite element analysis (FEA) solver COMSOL Multiphysics, modelling realistic patient-specific seed distributions. These distributions were derived from LDR permanent prostate implants previously conducted at our institution; various modifications of the seeds' design were studied. The calculated temperature distributions were analyzed by generating temperature-volume histograms, which were used to quantify coverage and temperature homogeneity for a range of blood perfusion rates, as well as for a range of seed Curie temperatures and thermal power production rates. The impact of the interseed attenuation and scatter (ISA) effect on radiation dose distributions of this seed was also quantified by Monte Carlo studies in the software package MCNP5. Experimental and computational analyses agree that the proposed seeds may heat a defined target with safe and attainable seed spacing and magnetic field parameters. These studies also point to the use of a ferrite-based ferrimagnetic core within the seeds, a design that would deliver hyperthermia of acceptable quality even for the high rate of blood perfusion in prostate tissue. The loss of radiation coverage due to the ISA effect of distributions of TB and HT-only seeds may be rectified by slightly increasing the prescribed dose in standard dose superposition-based treatment planning software. A systematic approach of combining LDR prostate brachytherapy with hyperthermia is thus described, and its ability to provide sufficient and uniform temperature distributions in realistic patient-specific implants evaluated. Potential improvements to the previously reported TB seed design are discussed based on quantitative evaluation of its operation and performance.

Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma

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

Lee, Young K., E-mail: Young.Lee@rmh.nhs.uk; Bedford, James L.; Taj, Mary

To evaluate volumetric-modulated arc therapy (VMAT) for treatment of Hodgkin lymphoma (HL) in patients where conventional radiotherapy was not deliverable. A planning computed tomography (CT) scan was acquired for a twelve-year-old boy with Stage IIIB nodular sclerosing HL postchemotherapy with positive positron emission tomography scan. VMAT was used for Phase 1 (19.8 Gy in 11 fractions) and Phase 2 (10.8 Gy in 6 fractions) treatment plans. Single anticlockwise arc plans were constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 4°. The inverse-planning objectives were to uniformly irradiate the planning target volume (PTV) with themore » prescription dose while keeping the volume of lung receiving greater than 20 Gy (V{sub 20} {sub Gy}) to less than 30% and minimize the dose to the other adjacent organs at risk (OAR). Pretreatment verification was conducted and the treatment delivery was on an MLCi Synergy linear accelerator (Elekta Ltd, Crawley, UK). The planning results were retrospectively confirmed in a further 4 patients using a single PTV with a prescribed dose of 19.8 Gy in 11 fractions. Acceptable dose coverage and homogeneity were achieved for both Phase 1 and 2 plans while keeping the lung V{sub 20} {sub Gy} at 22.5% for the composite plan. The beam-on times for Phase 1 and Phase 2 plans were 109 and 200 seconds, respectively, and the total monitor units were 337.2 MU and 292.5 MU, respectively. The percentage of measured dose points within 3% and 3 mm for Phase 1 and Phase 2 were 92% and 98%, respectively. Both plans were delivered successfully. The retrospective planning study showed that VMAT improved PTV dose uniformity and reduced the irradiated volume of heart and lung, although the volume of lung irradiated to low doses increased. Two-phased VMAT offers an attractive option for large volume sites, such as HL, giving a high level of target coverage and significant OAR sparing together with efficient delivery.« less

Formulation of a novel fixed dose combination of salmeterol xinafoate and mometasone furoate for inhaled drug delivery.

PubMed

Liu, Sha; Watts, Alan B; Du, Ju; Bui, Amanda; Hengsawas, Soraya; Peters, Jay I; Williams, Robert O

2015-10-01

Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC0-24h) of two APIs were higher for the BMP combination group exhibiting a significantly higher lung concentration of drugs than for the crystalline physical blend. While high system drug levels are generally undesirable in lung targeted therapies, high blood levels in this rodent study could be indicative of increased pulmonary tissue exposure using BMP formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.edu; Foster, Ryan D.; Kogel, Albert J. van der

2012-07-01

Purpose: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. Methods and Materials: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10%more » isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 {+-} 0.1 Gy (n = 2), 17.1 {+-} 0.3 Gy (n = 3), 19.0 {+-} 0.1 Gy (n = 5), 21.2 {+-} 0.1 Gy (n = 5), 23.4 {+-} 0.2 Gy (n = 5), and 25.4 {+-} 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 34% {+-} 1%, 40% {+-} 1%, 46% {+-} 3%, 52% {+-} 1%, 56 {+-} 3%, and 57% {+-} 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. Results: A steep dose-response curve was observed with a 50% incidence of paralysis (ED{sub 50}) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. Conclusion: Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.« less

Performance characteristics of dedicated molecular breast imaging systems at low doses

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

Long, Zaiyang; Conners, Amy L.; Hunt, Katie N.

Purpose: The purpose of this study was to compare the system performance characteristics and lesion detection capability of two molecular breast imaging (MBI) systems: a multicrystal sodium iodide (NaI)-based single-head system and a cadmium zinc telluride (CZT)-based dual-head system at low administered doses (150–300 MBq) of Tc-99m sestamibi. Methods: System performance characteristics including count sensitivity, uniformity, energy resolution, and spatial resolution were measured using standard NEMA methods, or a modified version thereof in cases where the standard NEMA protocol could not be applied. A contrast-detail phantom with 48 lesions at varying depths from the collimator surface was used to assessmore » lesion contrast-to-noise-ratio (CNR) using background count densities comparable to those observed in patient studies performed with administered doses of 150 MBq Tc-99m sestamibi. Lesions with CNR >3 were deemed to be detectable. Thirty patients undergoing MBI examinations with administered doses of 150–300 MBq were scanned for an additional view on the pixelated NaI system. CNR was calculated for lesions observed on patient images. Background count densities of patient images were measured and compared between the two systems. Results: Over the central field of view, integral and differential uniformity were 6.1% and 4.2%, respectively, for the pixelated NaI system, and 3.8% and 2.7%, respectively, for the CZT system. Count sensitivity was 10.8 kcts/min/MBq for the NaI system and 32.9 kcts/min/MBq for the CZT system. Energy resolution was 13.5% on the pixelated NaI system and 4.5% on the CZT system. Spatial resolution (full-width at half-maximum) for the pixelated NaI detector was 4.2 mm at a distance of 1.2 cm from the collimator and 5.2 mm at 3.1 cm. Spatial resolution of a single CZT detector was 2.9 mm at a distance of 1.2 cm from the collimator and 4.7 mm at 3.1 cm. Effective spatial resolution obtained with dual-head CZT was below 4.7 mm throughout a simulated breast thickness of 6 cm. From contrast-detail phantom images of lesions at distances of 1.5–4.5 cm from the collimator face, the CZT system detected 124 of 144 (86%) of lesions compared to 97 of 144 (67%) with the NaI system. In patient studies, from comparison of the same view with both systems, a total of 7 breast lesions were identified on CZT system in seven patients, and 4 of 7 (57%) were detected on NaI system. Patient image background count densities on the CZT system were on average 3.4 times higher than those on the NaI system. Conclusions: The CZT system demonstrated better uniformity, count sensitivity, spatial resolution, energy resolution, and lesion detection in phantom and patient studies compared to the NaI system. At administered doses of 150–300 MBq Tc-99m sestamibi, patient results obtained with CZT systems may not be directly translatable to NaI systems.« less

Do School Uniforms Fit?

ERIC Educational Resources Information Center

White, Kerry A.

2000-01-01

In 1994, Long Beach (California) Unified School District began requiring uniforms in all elementary and middle schools. Now, half of all urban school systems and many suburban schools have uniform policies. Research on uniforms' effectiveness is mixed. Tightened dress codes may be just as effective and less litigious. (MLH)

Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

PubMed

Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

2012-11-01

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Design and application of 3D-printed stepless beam modulators in proton therapy

NASA Astrophysics Data System (ADS)

Lindsay, C.; Kumlin, J.; Martinez, D. M.; Jirasek, A.; Hoehr, C.

2016-06-01

A new method for the design of stepless beam modulators for proton therapy is described and verified. Simulations of the classic designs are compared against the stepless method for various modulation widths which are clinically applicable in proton eye therapy. Three modulator wheels were printed using a Stratasys Objet30 3D printer. The resulting depth dose distributions showed improved uniformity over the classic stepped designs. Simulated results imply a possible improvement in distal penumbra width; however, more accurate measurements are needed to fully verify this effect. Lastly, simulations were done to model bio-equivalence to Co-60 cell kill. A wheel was successfully designed to flatten this metric.

SU-E-T-397: Evaluation of Planned Dose Distributions by Monte Carlo (0.5%) and Ray Tracing Algorithm for the Spinal Tumors with CyberKnife

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

Cho, H; Brindle, J; Hepel, J

2015-06-15

Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT) and Monte Carlo (MC) algorithms of 0.5% uncertainty on a critical structure of spinal cord and gross target volume and planning target volume. Methods: Twenty four spinal tumor patients were treated with stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The MC algorithm with 0.5% of uncertainty is used to recalculate the dose distribution for the treatment plan of the patients using the same beams, beam directions, and monitor units (MUs). Results: The prescription doses are uniformly larger for MC plans than RT except one case. Upmore » to a factor of 1.19 for 0.25cc threshold volume and 1.14 for 1.2cc threshold volume of dose differences are observed for the spinal cord. Conclusion: The MC recalculated dose distributions are larger than the original MC calculations for the spinal tumor cases. Based on the accuracy of the MC calculations, more radiation dose might be delivered to the tumor targets and spinal cords with the increase prescription dose.« less

A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance.

PubMed

Short, Steven M; Cogdill, Robert P; D'Amico, Frank; Drennen, James K; Anderson, Carl A

2010-12-01

The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Development of high performance ODS alloys

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

Shao, Lin; Gao, Fei; Garner, Frank

2018-01-29

This project aims to capitalize on insights developed from recent high-dose self-ion irradiation experiments in order to develop and test the next generation of optimized ODS alloys needed to meet the nuclear community's need for high strength, radiation-tolerant cladding and core components, especially with enhanced resistance to void swelling. Two of these insights are that ferrite grains swell earlier than tempered martensite grains, and oxide dispersions currently produced only in ferrite grains require a high level of uniformity and stability to be successful. An additional insight is that ODS particle stability is dependent on as-yet unidentified compositional combinations of dispersoidmore » and alloy matrix, such as dispersoids are stable in MA957 to doses greater than 200 dpa but dissolve in MA956 at doses less than 200 dpa. These findings focus attention on candidate next-generation alloys which address these concerns. Collaboration with two Japanese groups provides this project with two sets of first-round candidate alloys that have already undergone extensive development and testing for unirradiated properties, but have not yet been evaluated for their irradiation performance. The first set of candidate alloys are dual phase (ferrite + martensite) ODS alloys with oxide particles uniformly distributed in both ferrite and martensite phases. The second set of candidate alloys are ODS alloys containing non-standard dispersoid compositions with controllable oxide particle sizes, phases and interfaces.« less

Alternative stitching method for massively parallel e-beam lithography

NASA Astrophysics Data System (ADS)

Brandt, Pieter; Tranquillin, Céline; Wieland, Marco; Bayle, Sébastien; Milléquant, Matthieu; Renault, Guillaume

2015-07-01

In this study, a stitching method other than soft edge (SE) and smart boundary (SB) is introduced and benchmarked against SE. The method is based on locally enhanced exposure latitude without throughput cost, making use of the fact that the two beams that pass through the stitching region can deposit up to 2× the nominal dose. The method requires a complex proximity effect correction that takes a preset stitching dose profile into account. Although the principle of the presented stitching method can be multibeam (lithography) systems in general, in this study, the MAPPER FLX 1200 tool is specifically considered. For the latter tool at a metal clip at minimum half-pitch of 32 nm, the stitching method effectively mitigates beam-to-beam (B2B) position errors such that they do not induce an increase in critical dimension uniformity (CDU). In other words, the same CDU can be realized inside the stitching region as outside the stitching region. For the SE method, the CDU inside is 0.3 nm higher than outside the stitching region. A 5-nm direct overlay impact from the B2B position errors cannot be reduced by a stitching strategy.

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.

Animal models of transcranial direct current stimulation: Methods and mechanisms.

PubMed

Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

2016-11-01

The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding "functional targeting" suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Parametric Evaluation of SiC/SiC Composite Cladding with UO2 Fuel for LWR Applications: Fuel Rod Interactions and Impact of Nonuniform Power Profile in Fuel Rod

NASA Astrophysics Data System (ADS)

Singh, G.; Sweet, R.; Brown, N. R.; Wirth, B. D.; Katoh, Y.; Terrani, K.

2018-02-01

SiC/SiC composites are candidates for accident tolerant fuel cladding in light water reactors. In the extreme nuclear reactor environment, SiC-based fuel cladding will be exposed to neutron damage, significant heat flux, and a corrosive environment. To ensure reliable and safe operation of accident tolerant fuel cladding concepts such as SiC-based materials, it is important to assess thermo-mechanical performance under in-reactor conditions including irradiation and realistic temperature distributions. The effect of non-uniform dimensional changes caused by neutron irradiation with spatially varying temperatures, along with the closing of the fuel-cladding gap, on the stress development in the cladding over the course of irradiation were evaluated. The effect of non-uniform circumferential power profile in the fuel rod on the mechanical performance of the cladding is also evaluated. These analyses have been performed using the BISON fuel performance modeling code and the commercial finite element analysis code Abaqus. A constitutive model is constructed and solved numerically to predict the stress distribution in the cladding under normal operating conditions. The dependence of dimensions and thermophysical properties on irradiation dose and temperature has been incorporated into the models. Initial scoping results from parametric analyses provide time varying stress distributions in the cladding as well as the interaction of fuel rod with the cladding under different conditions of initial fuel rod-cladding gap and linear heat rate. It is found that a non-uniform circumferential power profile in the fuel rod may cause significant lateral bowing in the cladding, and motivates further analysis and evaluation.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

PubMed

Zitzmann, M; Rohayem, J; Raidt, J; Kliesch, S; Kumar, N; Sitruk-Ware, R; Nieschlag, E

2017-05-01

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone ® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m -2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception. © 2017 American Society of Andrology and European Academy of Andrology.

Comparative studies on the conformational change and aggregation behavior of irradiated carrageenans and agar by dynamic light scattering.

PubMed

Abad, Lucille; Okabe, Satoshi; Shibayama, Mitsuhiro; Kudo, Hisaaki; Saiki, Seiichi; Aranilla, Charito; Relleve, Lorna; de la Rosa, Alumanda

2008-01-01

The conformational associative properties of kappa-, iota-, and lambda-carrageenan and agar with irradiation dose were studied by dynamic light scattering. The random scission of the carrageenans and agar by gamma irradiation resulted in the formation of polydispersed lower molecular weight fragments. At high doses, the system moves towards uniformity. Conformational change from coil to helix was observed in all carrageenans and agar at doses up to 100 kGy. The conformational change in lambda-carrageenan may be due to the irregular and hybrid structure of this polysaccharide. Only agar and lambda-carrageenan still undergo conformational transition at a high dose of 200 kGy. Gelation is observed for kappa-, iota-carrageenan up to a dose of 50 kGy while gelation is still observed at 100 kGy for agar. Increase in the hydrodynamic radius with decreasing temperatures for the non-irradiated carrageenans follows this order: lambda-carrageenan>kappa-carrageenan>iota-carrageenan. Slight increases in hydrodynamic radius were observed with irradiation.