Image guided IMRT dosimetry using anatomy specific MOSFET configurations.

PubMed

Amin, Md Nurul; Norrlinger, Bern; Heaton, Robert; Islam, Mohammad

2008-06-23

We have investigated the feasibility of using a set of multiple MOSFETs in conjunction with the mobile MOSFET wireless dosimetry system, to perform a comprehensive and efficient quality assurance (QA) of IMRT plans. Anatomy specific MOSFET configurations incorporating 5 MOSFETs have been developed for a specially designed IMRT dosimetry phantom. Kilovoltage cone beam computed tomography (kV CBCT) imaging was used to increase the positional precision and accuracy of the detectors and phantom, and so minimize dosimetric uncertainties in high dose gradient regions. The effectiveness of the MOSFET based dose measurements was evaluated by comparing the corresponding doses measured by an ion chamber. For 20 head and neck IMRT plans the agreement between the MOSFET and ionization chamber dose measurements was found to be within -0.26 +/- 0.88% and 0.06 +/- 1.94% (1 sigma) for measurement points in the high dose and low dose respectively. A precision of 1 mm in detector positioning was achieved by using the X-Ray Volume Imaging (XVI) kV CBCT system available with the Elekta Synergy Linear Accelerator. Using the anatomy specific MOSFET configurations, simultaneous measurements were made at five strategically located points covering high dose and low dose regions. The agreement between measurements and calculated doses by the treatment planning system for head and neck and prostate IMRT plans was found to be within 0.47 +/- 2.45%. The results indicate that a cylindrical phantom incorporating multiple MOSFET detectors arranged in an anatomy specific configuration, in conjunction with image guidance, can be utilized to perform a comprehensive and efficient quality assurance of IMRT plans.

Clinical outcome after high-precision radiotherapy for skull base meningiomas: Pooled data from three large German centers for radiation oncology.

PubMed

Combs, Stephanie E; Farzin, Mostafa; Boehmer, Julia; Oehlke, Oliver; Molls, Michael; Debus, Jürgen; Grosu, Anca-Ligia

2018-05-01

To evaluate outcome in patients with base of skull meningiomas treated with modern high precision radiation therapy (RT) techniques. 927 patients from three centers were treated with either radiosurgery or fractionated high-precision RT for meningiomas. Treatment planning was based on CT and MRI following institutional guidelines. For radiosurgery, a median dose of 13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy single fractions was prescribed. Follow-up included a clinical examination as well as contrast-enhanced imaging. All patients were followed up prospectively after radiotherapy in the three departments within a strict follow-up regimen. The median follow-up time was 81 months (range 1-348 months). Median local control was 79 months (range 1-348 months). Local control (LC) was 98% at 1 year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference between radiosurgery and fractionated RT. We analyzed the influence of higher doses on LC and could show that dose did not impact LC. Moreover, there was no difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were below 5% in both groups without any severe treatment-related complications. Based on the pooled data analysis this manuscript provides a large series of meningiomas of the skull base treated with modern high precision RT demonstrating excellent local control and low rates of side effects. Such data support the recommendation of RT for skull base meningiomas in the interdisciplinary tumor board discussions. The strong role of RT must influence treatment recommendations keeping in mind the individual risk-benefit profile of treatment alternatives. Copyright © 2018 Elsevier B.V. All rights reserved.

Dedicated Linac for Radioneurosurgery at the National Institute of Neurology and Neurosurgery of Mexico

NASA Astrophysics Data System (ADS)

Celis-López, Miguel A.; Lárraga-Gutiérrez, José M.

2003-09-01

The objective is to present a description and the main clinical applications of this dedicated Linac for benign and malignant tumors in the central nervous system. The Novalis (BrainLab, Germany) is a 6 MV dedicated linac for a single high dose Radiosurgery (RS) and for fractionated doses in Stereotactic Radiotherapy with a high level of precision at the isocenter.

Clinical Ion Beam Applications: Basic Properties, Application, Quality Control, Planning

NASA Astrophysics Data System (ADS)

Kraft, Gerhard

2009-03-01

Heavy-ion therapy using beam scanning and biological dose optimization is a novel technique of high-precision external radiotherapy. It yields a better perspective for tumor cure of radio-resistant tumors. However, heavy-ion therapy is not a general solution for all types of tumors. As compared to conventional radiotherapy, heavy-ion radiotherapy has the advantages of higher tumor dose, improved sparing of normal tissue in the entrance channel, a more precise concentration of the dose in the target volume with steeper gradients to the normal tissue, and a higher radiobiological effectiveness for tumors which are radio-resistant in conventional therapy. These properties make it possible to treat radio-resistant tumors with great success, including those in close vicinity to critical organs.

Optically Stimulated Luminescence Analysis Method for High Dose Rate Using an Optical Fiber Type Dosimeter

NASA Astrophysics Data System (ADS)

Ueno, Katsunori; Tominaga, Kazuo; Tadokoro, Takahiro; Ishizawa, Koji; Takahashi, Yoshinori; Kuwabara, Hitoshi

2016-08-01

The investigation of air dose rates at locations in the Fukushima Dai-ichi Nuclear Power Station is necessary for safe removal of the molten nuclear fuel. The target performance for the investigation is to analyze a dose rate in the range of 10-3 Gy/h to 102 Gy/h with a measurement precision of ±4.0% full scale (F.S.) at a measurement interval of 60 s. In order to achieve this target, the authors proposed an optically stimulated luminescence (OSL) analysis method using prompt OSL for a wide dynamic range of dose rates; the OSL is generated using BaFBr:Eu with a fast decay time constant. The luminescence intensity by prompt OSL was formulated by the electron concentration of the trapping state during gamma ray and stimulation light irradiations. The prototype OSL monitor using BaFBr:Eu was manufactured for investigation of prompt OSL and evaluation of the measurement precision. The time dependence of the luminescence intensity by prompt OSL was analyzed by irradiating the OSL sensor in a 60Co irradiation facility. The measured dose rates were obtained in a prompt mode and an accumulating mode with a precision of ±3.3% F.S. for the dose rate range of 9.5 ×10-4 Gy/h to 1.2 ×102 Gy/h.

Development of a Method to Assess the Precision Of the z-axis X-ray Beam Collimation in a CT Scanner

NASA Astrophysics Data System (ADS)

Kim, Yon-Min

2018-05-01

Generally X-ray equipment specifies the beam collimator for the accuracy measurement as a quality control item, but the computed tomography (CT) scanner with high dose has no collimator accuracy measurement item. If the radiation dose is to be reduced, an important step is to check if the beam precisely collimates at the body part for CT scan. However, few ways are available to assess how precisely the X-ray beam is collimated. In this regard, this paper provides a way to assess the precision of z-axis X-ray beam collimation in a CT scanner. After the image plate cassette had been exposed to the X-ray beam, the exposed width was automatically detected by using a computer program developed by the research team to calculate the difference between the exposed width and the imaged width (at isocenter). The result for the precision of z-axis X-ray beam collimation showed that the exposed width was 3.8 mm and the overexposure was high at 304% when a narrow beam of a 1.25 mm imaged width was used. In this study, the precision of the beam collimation of the CT scanner, which is frequently used for medical services, was measured in a convenient way by using the image plate (IP) cassette.

Image guided IMRT dosimetry using anatomy specific MOSFET configurations

PubMed Central

Norrlinger, Bern; Heaton, Robert; Islam, Mohammad

2008-01-01

We have investigated the feasibility of using a set of multiple MOSFETs in conjunction with the mobileMOSFET wireless dosimetry system, to perform a comprehensive and efficient quality assurance (QA) of IMRT plans. Anatomy specific MOSFET configurations incorporating 5 MOSFETs have been developed for a specially designed IMRT dosimetry phantom. Kilovoltage cone beam computed tomography (kV CBCT) imaging was used to increase the positional precision and accuracy of the detectors and phantom, and so minimize dosimetric uncertainties in high dose gradient regions. The effectiveness of the MOSFET based dose measurements was evaluated by comparing the corresponding doses measured by an ion chamber. For 20 head and neck IMRT plans the agreement between the MOSFET and ionization chamber dose measurements was found to be within −0.26±0.88% and 0.06±1.94% (1σ) for measurement points in the high dose and low dose respectively. A precision of 1 mm in detector positioning was achieved by using the X‐Ray Volume Imaging (XVI) kV CBCT system available with the Elekta Synergy Linear Accelerator. Using the anatomy specific MOSFET configurations, simultaneous measurements were made at five strategically located points covering high dose and low dose regions. The agreement between measurements and calculated doses by the treatment planning system for head and neck and prostate IMRT plans was found to be within 0.47±2.45%. The results indicate that a cylindrical phantom incorporating multiple MOSFET detectors arranged in an anatomy specific configuration, in conjunction with image guidance, can be utilized to perform a comprehensive and efficient quality assurance of IMRT plans. PACS number: 87.55.Qr

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

PubMed Central

Corre, Isabelle; Guillonneau, Maëva; Paris, François

2013-01-01

Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation. PMID:24252908

Multistep Lattice-Voxel method utilizing lattice function for Monte-Carlo treatment planning with pixel based voxel model.

PubMed

Kumada, H; Saito, K; Nakamura, T; Sakae, T; Sakurai, H; Matsumura, A; Ono, K

2011-12-01

Treatment planning for boron neutron capture therapy generally utilizes Monte-Carlo methods for calculation of the dose distribution. The new treatment planning system JCDS-FX employs the multi-purpose Monte-Carlo code PHITS to calculate the dose distribution. JCDS-FX allows to build a precise voxel model consisting of pixel based voxel cells in the scale of 0.4×0.4×2.0 mm(3) voxel in order to perform high-accuracy dose estimation, e.g. for the purpose of calculating the dose distribution in a human body. However, the miniaturization of the voxel size increases calculation time considerably. The aim of this study is to investigate sophisticated modeling methods which can perform Monte-Carlo calculations for human geometry efficiently. Thus, we devised a new voxel modeling method "Multistep Lattice-Voxel method," which can configure a voxel model that combines different voxel sizes by utilizing the lattice function over and over. To verify the performance of the calculation with the modeling method, several calculations for human geometry were carried out. The results demonstrated that the Multistep Lattice-Voxel method enabled the precise voxel model to reduce calculation time substantially while keeping the high-accuracy of dose estimation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sample size requirements for estimating effective dose from computed tomography using solid-state metal-oxide-semiconductor field-effect transistor dosimetry

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

Trattner, Sigal; Cheng, Bin; Pieniazek, Radoslaw L.

2014-04-15

Purpose: Effective dose (ED) is a widely used metric for comparing ionizing radiation burden between different imaging modalities, scanners, and scan protocols. In computed tomography (CT), ED can be estimated by performing scans on an anthropomorphic phantom in which metal-oxide-semiconductor field-effect transistor (MOSFET) solid-state dosimeters have been placed to enable organ dose measurements. Here a statistical framework is established to determine the sample size (number of scans) needed for estimating ED to a desired precision and confidence, for a particular scanner and scan protocol, subject to practical limitations. Methods: The statistical scheme involves solving equations which minimize the sample sizemore » required for estimating ED to desired precision and confidence. It is subject to a constrained variation of the estimated ED and solved using the Lagrange multiplier method. The scheme incorporates measurement variation introduced both by MOSFET calibration, and by variation in MOSFET readings between repeated CT scans. Sample size requirements are illustrated on cardiac, chest, and abdomen–pelvis CT scans performed on a 320-row scanner and chest CT performed on a 16-row scanner. Results: Sample sizes for estimating ED vary considerably between scanners and protocols. Sample size increases as the required precision or confidence is higher and also as the anticipated ED is lower. For example, for a helical chest protocol, for 95% confidence and 5% precision for the ED, 30 measurements are required on the 320-row scanner and 11 on the 16-row scanner when the anticipated ED is 4 mSv; these sample sizes are 5 and 2, respectively, when the anticipated ED is 10 mSv. Conclusions: Applying the suggested scheme, it was found that even at modest sample sizes, it is feasible to estimate ED with high precision and a high degree of confidence. As CT technology develops enabling ED to be lowered, more MOSFET measurements are needed to estimate ED with the same precision and confidence.« less

Sample size requirements for estimating effective dose from computed tomography using solid-state metal-oxide-semiconductor field-effect transistor dosimetry

PubMed Central

Trattner, Sigal; Cheng, Bin; Pieniazek, Radoslaw L.; Hoffmann, Udo; Douglas, Pamela S.; Einstein, Andrew J.

2014-01-01

Purpose: Effective dose (ED) is a widely used metric for comparing ionizing radiation burden between different imaging modalities, scanners, and scan protocols. In computed tomography (CT), ED can be estimated by performing scans on an anthropomorphic phantom in which metal-oxide-semiconductor field-effect transistor (MOSFET) solid-state dosimeters have been placed to enable organ dose measurements. Here a statistical framework is established to determine the sample size (number of scans) needed for estimating ED to a desired precision and confidence, for a particular scanner and scan protocol, subject to practical limitations. Methods: The statistical scheme involves solving equations which minimize the sample size required for estimating ED to desired precision and confidence. It is subject to a constrained variation of the estimated ED and solved using the Lagrange multiplier method. The scheme incorporates measurement variation introduced both by MOSFET calibration, and by variation in MOSFET readings between repeated CT scans. Sample size requirements are illustrated on cardiac, chest, and abdomen–pelvis CT scans performed on a 320-row scanner and chest CT performed on a 16-row scanner. Results: Sample sizes for estimating ED vary considerably between scanners and protocols. Sample size increases as the required precision or confidence is higher and also as the anticipated ED is lower. For example, for a helical chest protocol, for 95% confidence and 5% precision for the ED, 30 measurements are required on the 320-row scanner and 11 on the 16-row scanner when the anticipated ED is 4 mSv; these sample sizes are 5 and 2, respectively, when the anticipated ED is 10 mSv. Conclusions: Applying the suggested scheme, it was found that even at modest sample sizes, it is feasible to estimate ED with high precision and a high degree of confidence. As CT technology develops enabling ED to be lowered, more MOSFET measurements are needed to estimate ED with the same precision and confidence. PMID:24694150

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

On the use of particle filters for electromagnetic tracking in high dose rate brachytherapy.

PubMed

Götz, Th I; Lahmer, G; Brandt, T; Kallis, K; Strnad, V; Bert, Ch; Hensel, B; Tomé, A M; Lang, E W

2017-09-12

Modern radiotherapy of female breast cancers often employs high dose rate brachytherapy, where a radioactive source is moved inside catheters, implanted in the female breast, according to a prescribed treatment plan. Source localization relative to the patient's anatomy is determined with solenoid sensors whose spatial positions are measured with an electromagnetic tracking system. Precise sensor dwell position determination is of utmost importance to assure irradiation of the cancerous tissue according to the treatment plan. We present a hybrid data analysis system which combines multi-dimensional scaling with particle filters to precisely determine sensor dwell positions in the catheters during subsequent radiation treatment sessions. Both techniques are complemented with empirical mode decomposition for the removal of superimposed breathing artifacts. We show that the hybrid model robustly and reliably determines the spatial positions of all catheters used during the treatment and precisely determines any deviations of actual sensor dwell positions from the treatment plan. The hybrid system only relies on sensor positions measured with an EMT system and relates them to the spatial positions of the implanted catheters as initially determined with a computed x-ray tomography.

Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer

DTIC Science & Technology

2015-02-01

most dramatic example is stereotactic ablative radiotherapy ( SABR )/ stereotactic body radiation therapy (SBRT), highly focused and accurate...significant motion, thus increasing the precision and accuracy of lung SABR /SBRT. Objective: We propose to develop a new type of RT system for early stage

Treatment planning and delivery of shell dose distribution for precision irradiation

NASA Astrophysics Data System (ADS)

Matinfar, Mohammad; Iyer, Santosh; Ford, Eric; Wong, John; Kazanzides, Peter

2010-02-01

The motivation for shell dose irradiation is to deliver a high therapeutic dose to the surrounding supplying blood-vessels of a lesion. Our approach's main utility is in enabling laboratory experiments to test the much disputed hypothesis about tumor vascular damage. That is, at high doses, tumor control is driven by damage to the tumor vascular supply and not the damage to the tumor cells themselves. There is new evidence that bone marrow derived cells can reconstitute tumor blood vessels in mice after irradiation. Shell dosimetry is also of interest to study the effect of radiation on neurogenic stem cells that reside in small niche surface of the mouse ventricles, a generalized form of shell. The type of surface that we are considering as a shell is a sphere which is created by intersection of cylinders. The results are then extended to create the contours of different organ shapes. Specifically, we present a routine to identify the 3-D structure of a mouse brain, project it into 2-D contours and convert the contours into trajectories that can be executed by our platform. We use the Small Animal Radiation Research Platform (SARRP) to demonstrate the dose delivery procedure. The SARRP is a portable system for precision irradiation with beam sizes down to 0.5 mm and optimally planned radiation with on-board cone-beam CT guidance.

Results of heavy ion radiotherapy

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

Castro, J.R.

1994-04-01

The potential of heavy ion therapy for clinical use in cancer therapy stems from the biological parameters of heavy charged particles, and their precise dose localization. Biologically, carbon, neon and other heavy ion beams (up to about silicon) are clinically useful in overcoming the radioresistance of hypoxic tumors, thus increasing biological effectiveness relative to low-LET x-ray or electron beams. Cells irradiated by heavy ions show less variation in cell-cycle related radiosensitivity and decreased repair of radiation injury. The physical parameters of these heavy charged particles allow precise delivery of high radiation doses to tumors while minimizing irradiation of normal tissues.more » Clinical use requires close interaction between radiation oncologists, medical physicists, accelerator physicists, engineers, computer scientists and radiation biologists.« less

MONDO: a neutron tracker for particle therapy secondary emission characterisation

NASA Astrophysics Data System (ADS)

Marafini, M.; Gasparini, L.; Mirabelli, R.; Pinci, D.; Patera, V.; Sciubba, A.; Spiriti, E.; Stoppa, D.; Traini, G.; Sarti, A.

2017-04-01

Tumour control is performed in particle therapy using particles and ions, whose high irradiation precision enhances the effectiveness of the treatment, while sparing the healthy tissue surrounding the target volume. Dose range monitoring devices using photons and charged particles produced by the beam interacting with the patient’s body have already been proposed, but no attempt has been made yet to exploit the detection of the abundant neutron component. Since neutrons can release a significant dose far away from the tumour region, precise measurements of their flux, production energy and angle distributions are eagerly sought in order to improve the treatment planning system (TPS) software. It will thus be possible to predict not only the normal tissue toxicity in the target region, but also the risk of late complications in the whole body. The aforementioned issues underline the importance of an experimental effort devoted to the precise characterisation of neutron production, aimed at the measurement of their abundance, emission point and production energy. The technical challenges posed by a neutron detector aimed at high detection efficiency and good backtracking precision are addressed within the MONDO (monitor for neutron dose in hadrontherapy) project, whose main goal is to develop a tracking detector that can target fast and ultrafast neutrons. A full reconstruction of two consecutive elastic scattering interactions undergone by the neutrons inside the detector material will be used to measure their energy and direction. The preliminary results of an MC simulation performed using the FLUKA software are presented here, together with the DSiPM (digital SiPM) readout implementation. New detector readout implementations specifically tailored to the MONDO tracker are also discussed, and the neutron detection efficiency attainable with the proposed neutron tracking strategy are reported.

MONDO: a neutron tracker for particle therapy secondary emission characterisation.

PubMed

Marafini, M; Gasparini, L; Mirabelli, R; Pinci, D; Patera, V; Sciubba, A; Spiriti, E; Stoppa, D; Traini, G; Sarti, A

2017-04-21

Tumour control is performed in particle therapy using particles and ions, whose high irradiation precision enhances the effectiveness of the treatment, while sparing the healthy tissue surrounding the target volume. Dose range monitoring devices using photons and charged particles produced by the beam interacting with the patient's body have already been proposed, but no attempt has been made yet to exploit the detection of the abundant neutron component. Since neutrons can release a significant dose far away from the tumour region, precise measurements of their flux, production energy and angle distributions are eagerly sought in order to improve the treatment planning system (TPS) software. It will thus be possible to predict not only the normal tissue toxicity in the target region, but also the risk of late complications in the whole body. The aforementioned issues underline the importance of an experimental effort devoted to the precise characterisation of neutron production, aimed at the measurement of their abundance, emission point and production energy. The technical challenges posed by a neutron detector aimed at high detection efficiency and good backtracking precision are addressed within the MONDO (monitor for neutron dose in hadrontherapy) project, whose main goal is to develop a tracking detector that can target fast and ultrafast neutrons. A full reconstruction of two consecutive elastic scattering interactions undergone by the neutrons inside the detector material will be used to measure their energy and direction. The preliminary results of an MC simulation performed using the FLUKA software are presented here, together with the DSiPM (digital SiPM) readout implementation. New detector readout implementations specifically tailored to the MONDO tracker are also discussed, and the neutron detection efficiency attainable with the proposed neutron tracking strategy are reported.

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.

On the use of particle filters for electromagnetic tracking in high dose rate brachytherapy

NASA Astrophysics Data System (ADS)

Götz, Th I.; Lahmer, G.; Brandt, T.; Kallis, K.; Strnad, V.; Bert, Ch; Hensel, B.; Tomé, A. M.; Lang, E. W.

2017-10-01

Modern radiotherapy of female breast cancers often employs high dose rate brachytherapy, where a radioactive source is moved inside catheters, implanted in the female breast, according to a prescribed treatment plan. Source localization relative to the patient’s anatomy is determined with solenoid sensors whose spatial positions are measured with an electromagnetic tracking system. Precise sensor dwell position determination is of utmost importance to assure irradiation of the cancerous tissue according to the treatment plan. We present a hybrid data analysis system which combines multi-dimensional scaling with particle filters to precisely determine sensor dwell positions in the catheters during subsequent radiation treatment sessions. Both techniques are complemented with empirical mode decomposition for the removal of superimposed breathing artifacts. We show that the hybrid model robustly and reliably determines the spatial positions of all catheters used during the treatment and precisely determines any deviations of actual sensor dwell positions from the treatment plan. The hybrid system only relies on sensor positions measured with an EMT system and relates them to the spatial positions of the implanted catheters as initially determined with a computed x-ray tomography.

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)

Optimization of dual-energy CT acquisitions for proton therapy using projection-based decomposition.

PubMed

Vilches-Freixas, Gloria; Létang, Jean Michel; Ducros, Nicolas; Rit, Simon

2017-09-01

Dual-energy computed tomography (DECT) has been presented as a valid alternative to single-energy CT to reduce the uncertainty of the conversion of patient CT numbers to proton stopping power ratio (SPR) of tissues relative to water. The aim of this work was to optimize DECT acquisition protocols from simulations of X-ray images for the treatment planning of proton therapy using a projection-based dual-energy decomposition algorithm. We have investigated the effect of various voltages and tin filtration combinations on the SPR map accuracy and precision, and the influence of the dose allocation between the low-energy (LE) and the high-energy (HE) acquisitions. For all spectra combinations, virtual CT projections of the Gammex phantom were simulated with a realistic energy-integrating detector response model. Two situations were simulated: an ideal case without noise (infinite dose) and a realistic situation with Poisson noise corresponding to a 20 mGy total central dose. To determine the optimal dose balance, the proportion of LE-dose with respect to the total dose was varied from 10% to 90% while keeping the central dose constant, for four dual-energy spectra. SPR images were derived using a two-step projection-based decomposition approach. The ranges of 70 MeV, 90 MeV, and 100 MeV proton beams onto the adult female (AF) reference computational phantom of the ICRP were analytically determined from the reconstructed SPR maps. The energy separation between the incident spectra had a strong impact on the SPR precision. Maximizing the incident energy gap reduced image noise. However, the energy gap was not a good metric to evaluate the accuracy of the SPR. In terms of SPR accuracy, a large variability of the optimal spectra was observed when studying each phantom material separately. The SPR accuracy was almost flat in the 30-70% LE-dose range, while the precision showed a minimum slightly shifted in favor of lower LE-dose. Photon noise in the SPR images (20 mGy dose) had lower impact on the proton range accuracy as comparable results were obtained for the noiseless situation (infinite dose). Root-mean-square range errors averaged over all irradiation angles associated to dual-energy imaging were comprised between 0.50 mm and 0.72 mm for the noiseless situation and between 0.51 mm and 0.77 mm for the realistic scenario. The impact of the dual-energy spectra and the dose allocation between energy levels on the SPR accuracy and precision determined through a projection-based dual-energy algorithm were evaluated to guide the choice of spectra for dual-energy CT for proton therapy. The dose balance between energy levels was not found to be sensitive for the SPR estimation. The optimal pair of dual-energy spectra was material dependent but on a heterogeneous anthropomorphic phantom, there was no significant difference in range accuracy and the choice of spectra could be driven by the precision, i.e., the energy gap. © 2017 American Association of Physicists in Medicine.

Toddlers' choice: Yo-Yoing diabetes control or deci-unit insulin dosing?

PubMed

Abul-Ainine, Sarah Aa; Abul-Ainine, Ahmad Aa

2012-02-15

While the incidence of toddlers' diabetes is soaring, their mainstay insulins were withdrawn, namely the weak 10% or 20% insulin mixtures (WIM), which were injected only once or twice daily. Consequently, toddlers are coerced to use an insulin pump, multi-dose insulin regime (MuDIR), mix or dilute insulins. This paper highlights the difficulties and proposes a simple solution. While an insulin pump is the best available option, it is not readily available for everyone. Mixing insulins is not sufficiently precise in small doses. Although diluting insulin would allow precise dosing and reduce the dose variability secondary to dribbling after injections, it, like insulin mixing, deprives children from using the pen and related child-friendly accessories. In MuDIR, we inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM. Thus, on using a half unit (½unit) insulin pen, a dose of 0.5, 1, 1.5 and 2 units are adjusted in steps of 100%, 50%, 33% or 25%; unlike the advisable 5%-20%. This does not easily match the tiny erratic meals of grazing toddlers. Maternal anxiety peaks on watching yo-yoing glycemia. Carers have to accept either persistently high sugar or wild fluctuation. The risks of such poor glycemic pattern are increasingly recognized. Using insulin U20 in a ½unit disposable pen allows deci-unit dosing, with 5%-20% dose-tuning, greater accuracy on delivering small doses and reduction of dose variability from dribbling. Deci-unit dosing may help avoid wide glycemic swings and provide the affordable alternative to insulin pumps for toddlers. Deci-unit pen materializes the Human Rights of Children, a safer and effective treatment.

In vivo thermoluminescence dosimetry for total body irradiation.

PubMed

Palkosková, P; Hlavata, H; Dvorák, P; Novotný, J; Novotný, J

2002-01-01

An improvement in the clinical results obtained using total body irradiation (TBI) with photon beams requires precise TBI treatment planning, reproducible irradiation, precise in vivo dosimetry, accurate documentation and careful evaluation. In vivo dosimetry using LiF Harshaw TLD-100 chips was used during the TBI treatments performed in our department. The results of in vivo thermoluminescence dosimetry (TLD) show that using TLD measurements and interactive adjustment of some treatment parameters based on these measurements, like monitor unit calculations, lung shielding thickness and patient positioning, it is possible to achieve high precision in absorbed dose delivery (less than 0.5%) as well as in homogeneity of irradiation (less than 6%).

On the use of multi-dimensional scaling and electromagnetic tracking in high dose rate brachytherapy

NASA Astrophysics Data System (ADS)

Götz, Th I.; Ermer, M.; Salas-González, D.; Kellermeier, M.; Strnad, V.; Bert, Ch; Hensel, B.; Tomé, A. M.; Lang, E. W.

2017-10-01

High dose rate brachytherapy affords a frequent reassurance of the precise dwell positions of the radiation source. The current investigation proposes a multi-dimensional scaling transformation of both data sets to estimate dwell positions without any external reference. Furthermore, the related distributions of dwell positions are characterized by uni—or bi—modal heavy—tailed distributions. The latter are well represented by α—stable distributions. The newly proposed data analysis provides dwell position deviations with high accuracy, and, furthermore, offers a convenient visualization of the actual shapes of the catheters which guide the radiation source during the treatment.

Investigation of irradiation effects on highly integrated leading-edge electronic components of diagnostics and control systems for LHD deuterium operation

NASA Astrophysics Data System (ADS)

Ogawa, K.; Nishitani, T.; Isobe, M.; Murata, I.; Hatano, Y.; Matsuyama, S.; Nakanishi, H.; Mukai, K.; Sato, M.; Yokota, M.; Kobuchi, T.; Nishimura, T.; Osakabe, M.

2017-08-01

High-temperature and high-density plasmas are achieved by means of real-time control, fast diagnostic, and high-power heating systems. Those systems are precisely controlled via highly integrated electronic components, but can be seriously affected by radiation damage. Therefore, the effects of irradiation on currently used electronic components should be investigated for the control and measurement of Large Helical Device (LHD) deuterium plasmas. For the precise estimation of the radiation field in the LHD torus hall, the MCNP6 code is used with the cross-section library ENDF B-VI. The geometry is modeled on the computer-aided design. The dose on silicon, which is a major ingredient of electronic components, over nine years of LHD deuterium operation shows that the gamma-ray contribution is dominant. Neutron irradiation tests were performed in the OKTAVIAN at Osaka University and the Fast Neutron Laboratory at Tohoku University. Gamma-ray irradiation tests were performed at the Nagoya University Cobalt-60 irradiation facility. We found that there are ethernet connection failures of programmable logic controller (PLC) modules due to neutron irradiation with a neutron flux of 3  ×  106 cm-2 s-1. This neutron flux is equivalent to that expected at basement level in the LHD torus hall without a neutron shield. Most modules of the PLC are broken around a gamma-ray dose of 100 Gy. This is comparable with the dose in the LHD torus hall over nine years. If we consider the dose only, these components may survive more than nine years. For the safety of the LHD operation, the electronic components in the torus hall have been rearranged.

LiF TLD-100 as a Dosimeter in High Energy Proton Beam Therapy-Can It Yield Accurate Results?

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

Zullo, John R.; Kudchadker, Rajat J.; Zhu, X. Ronald

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly inmore » the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within {+-}5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within {+-} 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy.« less

Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

PubMed

Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2014-08-01

Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36-2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR, 3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index score (score 1: OR, 0.74; CI, 0.57-0.97; score ≥2: OR, 0.68; CI, 0.47-0.97). In conclusion, the majority of persons with AD used antipsychotics with low or medium dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics, which indicates a need for precise dosing instructions in the treatment of behavioral and psychological symptoms of dementia. Clinicians should regularly assess dosing levels especially among men and those with history of psychiatric disorder.

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

[Proton imaging applications for proton therapy: state of the art].

PubMed

Amblard, R; Floquet, V; Angellier, G; Hannoun-Lévi, J M; Hérault, J

2015-04-01

Proton therapy allows a highly precise tumour volume irradiation with a low dose delivered to the healthy tissues. The steep dose gradients observed and the high treatment conformity require a precise knowledge of the proton range in matter and the target volume position relative to the beam. Thus, proton imaging allows an improvement of the treatment accuracy, and thereby, in treatment quality. Initially suggested in 1963, radiographic imaging with proton is still not used in clinical routine. The principal difficulty is the lack of spatial resolution, induced by the multiple Coulomb scattering of protons with nuclei. Moreover, its realization for all clinical locations requires relatively high energies that are previously not considered for clinical routine. Abandoned for some time in favor of X-ray technologies, research into new imaging methods using protons is back in the news because of the increase of proton radiation therapy centers in the world. This article exhibits a non-exhaustive state of the art in proton imaging. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Dosimetric characterization of GafChromic EBT film and its implication on film dosimetry quality assurance.

PubMed

Fuss, Martina; Sturtewagen, Eva; De Wagter, Carlos; Georg, Dietmar

2007-07-21

The suitability of radiochromic EBT film was studied for high-precision clinical quality assurance (QA) by identifying the dose response for a wide range of irradiation parameters typically modified in highly-conformal treatment techniques. In addition, uncertainties associated with varying irradiation conditions were determined. EBT can be used for dose assessment of absorbed dose levels as well as relative dosimetry when compared to absolute absorbed dose calibrated using ionization chamber results. For comparison, a silver halide film (Kodak EDR-2) representing the current standard in film dosimetry was included. As an initial step a measurement protocol yielding accurate and precise results was established for a flatbed transparency scanner (Epson Expression 1680 Pro) that was utilized as a film reading instrument. The light transmission measured by the scanner was found to depend on the position of the film on the scanner plate. For three film pieces irradiated with doses of 0 Gy, approximately 1 Gy and approximately 7 Gy, the pixel values measured in portrait or landscape mode differed by 4.7%, 6.2% and 10.0%, respectively. A study of 200 film pieces revealed an excellent sheet-to-sheet uniformity. On a long time scale, the optical development of irradiated EBT film consisted of a slow but steady increase of absorbance which was not observed to cease during 4 months. Sensitometric curves of EBT films obtained under reference conditions (SSD = 95 cm, FS = 5 x 5 cm(2), d = 5 cm) for 6, 10 and 25 MV photon beams did not show any energy dependence. The average separation between all curves was only 0.7%. The variation of the depth d (range 2-25 cm) in the phantom did not affect the dose response of EBT film. Also the influence of the radiation field size (range 3 x 3-40 x 40 cm(2)) on the sensitometric curve was not significant. For EDR-2 films maximum differences between the calibration curves reached 7-8% for X6MV and X25MV. Radiochromic EBT film, in combination with a flatbed scanner, presents a versatile system for high-precision dosimetry in two dimensions, provided that the intrinsic behaviour of the film reading device is taken into account. EBT film itself presents substantial improvements on formerly available models of radiographic and a radiochromic film and its dosimetric characteristics allow us to measure absorbed dose levels in a large variety of situations with a single calibration curve.

Dosimetric characterization of GafChromic EBT film and its implication on film dosimetry quality assurance

NASA Astrophysics Data System (ADS)

Fuss, Martina; Sturtewagen, Eva; DeWagter, Carlos; Georg, Dietmar

2007-07-01

The suitability of radiochromic EBT film was studied for high-precision clinical quality assurance (QA) by identifying the dose response for a wide range of irradiation parameters typically modified in highly-conformal treatment techniques. In addition, uncertainties associated with varying irradiation conditions were determined. EBT can be used for dose assessment of absorbed dose levels as well as relative dosimetry when compared to absolute absorbed dose calibrated using ionization chamber results. For comparison, a silver halide film (Kodak EDR-2) representing the current standard in film dosimetry was included. As an initial step a measurement protocol yielding accurate and precise results was established for a flatbed transparency scanner (Epson Expression 1680 Pro) that was utilized as a film reading instrument. The light transmission measured by the scanner was found to depend on the position of the film on the scanner plate. For three film pieces irradiated with doses of 0 Gy, ~1 Gy and ~7 Gy, the pixel values measured in portrait or landscape mode differed by 4.7%, 6.2% and 10.0%, respectively. A study of 200 film pieces revealed an excellent sheet-to-sheet uniformity. On a long time scale, the optical development of irradiated EBT film consisted of a slow but steady increase of absorbance which was not observed to cease during 4 months. Sensitometric curves of EBT films obtained under reference conditions (SSD = 95 cm, FS = 5 × 5 cm2, d = 5 cm) for 6, 10 and 25 MV photon beams did not show any energy dependence. The average separation between all curves was only 0.7%. The variation of the depth d (range 2-25 cm) in the phantom did not affect the dose response of EBT film. Also the influence of the radiation field size (range 3 × 3-40 × 40 cm2) on the sensitometric curve was not significant. For EDR-2 films maximum differences between the calibration curves reached 7-8% for X6MV and X25MV. Radiochromic EBT film, in combination with a flatbed scanner, presents a versatile system for high-precision dosimetry in two dimensions, provided that the intrinsic behaviour of the film reading device is taken into account. EBT film itself presents substantial improvements on formerly available models of radiographic and a radiochromic film and its dosimetric characteristics allow us to measure absorbed dose levels in a large variety of situations with a single calibration curve.

A jaw calibration method to provide a homogeneous dose distribution in the matching region when using a monoisocentric beam split technique.

PubMed

Cenizo, E; García-Pareja, S; Galán, P; Bodineau, C; Caudepón, F; Casado, F J

2011-05-01

Asymmetric collimators are currently available in most of linear accelerators. They involve a lot of clinical improvements, such as the monoisocentric beam split technique that is more and more used in many external radiotherapy treatments. The tolerance established for each independent jaw positioning is 1 mm. Within this tolerance, a gap or overlap of the collimators up to 2 mm can occur in the half beams matching region, causing dose heterogeneities up to 40%. In order to solve this dosimetric problem, we propose an accurate jaw calibration method based on the Monte Carlo modeling of linac photon beams. Simulating different jaw misalignments, the dose distribution occurring in the matching region for each particular configuration is precisely known, so we can relate the misalignment of the jaws with the maximum heterogeneity produced. From experimental measurements using film dosimetry, and taking into account Monte Carlo results, we obtain the actual misalignment of each jaw. By direct inspection of the readings of the potentiometers that control the position of the jaws, high precision correction can be performed, adjusting the obtained misalignments. In the linac studied, the dose heterogeneity in the junction performed with X jaws (those farther from the source), and 6 MV photon beam was initially over 12%, although each jaw was within the tolerance in position. After jaw calibration, the heterogeneity was reduced to below 3%. With this method, we are able to reduce the positioning accuracy to 0.2 mm. Consequently, the dose distribution in the junction of abutted fields is highly smoothed, achieving the maximum dose heterogeneity to be less than 3%.

Feasibility Study on Cardiac Arrhythmia Ablation Using High-Energy Heavy Ion Beams

NASA Astrophysics Data System (ADS)

Lehmann, H. Immo; Graeff, Christian; Simoniello, Palma; Constantinescu, Anna; Takami, Mitsuru; Lugenbiel, Patrick; Richter, Daniel; Eichhorn, Anna; Prall, Matthias; Kaderka, Robert; Fiedler, Fine; Helmbrecht, Stephan; Fournier, Claudia; Erbeldinger, Nadine; Rahm, Ann-Kathrin; Rivinius, Rasmus; Thomas, Dierk; Katus, Hugo A.; Johnson, Susan B.; Parker, Kay D.; Debus, Jürgen; Asirvatham, Samuel J.; Bert, Christoph; Durante, Marco; Packer, Douglas L.

2016-12-01

High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40-55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Precision IORT - Image guided intraoperative radiation therapy (igIORT) using online treatment planning including tissue heterogeneity correction.

PubMed

Schneider, Frank; Bludau, Frederic; Clausen, Sven; Fleckenstein, Jens; Obertacke, Udo; Wenz, Frederik

2017-05-01

To the present date, IORT has been eye and hand guided without treatment planning and tissue heterogeneity correction. This limits the precision of the application and the precise documentation of the location and the deposited dose in the tissue. Here we present a set-up where we use image guidance by intraoperative cone beam computed tomography (CBCT) for precise online Monte Carlo treatment planning including tissue heterogeneity correction. An IORT was performed during balloon kyphoplasty using a dedicated Needle Applicator. An intraoperative CBCT was registered with a pre-op CT. Treatment planning was performed in Radiance using a hybrid Monte Carlo algorithm simulating dose in homogeneous (MCwater) and heterogeneous medium (MChet). Dose distributions on CBCT and pre-op CT were compared with each other. Spinal cord and the metastasis doses were evaluated. The MCwater calculations showed a spherical dose distribution as expected. The minimum target dose for the MChet simulations on pre-op CT was increased by 40% while the maximum spinal cord dose was decreased by 35%. Due to the artefacts on the CBCT the comparison between MChet simulations on CBCT and pre-op CT showed differences up to 50% in dose. igIORT and online treatment planning improves the accuracy of IORT. However, the current set-up is limited by CT artefacts. Fusing an intraoperative CBCT with a pre-op CT allows the combination of an accurate dose calculation with the knowledge of the correct source/applicator position. This method can be also used for pre-operative treatment planning followed by image guided surgery. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

MONDO: A neutron tracker for particle therapy secondary emission fluxes measurements

NASA Astrophysics Data System (ADS)

Marafini, M.; Patera, V.; Pinci, D.; Sarti, A.; Sciubba, A.; Spiriti, E.

2016-07-01

Cancer treatment is performed, in Particle Therapy, using accelerated charged particles whose high irradiation precision and conformity allows the tumor destruction while sparing the surrounding healthy tissues. Dose release monitoring devices using photons and charged particles produced by the beam interaction with the patient body have already been proposed, but no attempt based on the detection of the abundant secondary radiation neutron component has been made yet. The reduced attenuation length of neutrons yields a secondary particle sample that is larger in number when compared to photons and charged particles. Furthermore, neutrons allow for a backtracking of the emission point that is not affected by multiple scattering. Since neutrons can release a significant dose far away from the tumor region, a precise measurement of their flux, production energy and angle distributions is eagerly needed in order to improve the Treatment Planning Systems (TPS) software, so to predict not only the normal tissue toxicity in the target region but also the risk of late complications in the whole body. All the aforementioned issues underline the importance for an experimental effort devoted to the precise characterization of the neutron production gaining experimental access both to the emission point and production energy. The technical challenges posed by a neutron detector aiming for a high detection efficiency and good backtracking precision will be addressed within the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project. The MONDO's main goal is to develop a tracking detector targeting fast and ultrafast secondary neutrons. The tracker is composed by a scintillating fiber matrix (4 × 4 × 8cm3). The full reconstruction of protons, produced in elastic interactions, will be used to measure energy and direction of the impinging neutron. The neutron tracker will measure the neutron production yields, as a function of production angle and energy, using different therapeutic beams at CNAO in Pavia (protons, 12C ions and possibly 4He and 16O ions).

WE-DE-201-07: Measurement of Real-Time Dose for Tandem and Ovoid Brachytherapy Procedures Using a High Precision Optical Fiber Radiation Detector

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

Belley, MD; Current Address Rhode Island Hospital, Providence, RI; Faught, A

Purpose: Development of a novel on-line dosimetry tool is needed to move toward patient-specific quality assurance measurements for Ir-192 HDR brachytherapy to verify accurate dose delivery to the intended location. This work describes the development and use of a nano-crystalline yttrium oxide inorganic scintillator based optical-fiber detector capable of acquiring real-time high-precision dose measurements during tandem and ovoid (T&O) gynecological (GYN) applicator Ir-192 HDR brachytherapy procedures. Methods: An optical-fiber detector was calibrated by acquiring light output measurements in liquid water at 3, 5, 7, and 9cm radial source-detector-distances from an Ir-192 HDR source. A regression model was fit to themore » data to describe the relative light output per unit dose (TG-43 derived) as a function of source-detector-distance. Next, the optical-fiber detector was attached to a vaginal balloon fixed to a Varian Fletcher-Suit-Delclos-style applicator (to mimic clinical setup), and localized by acquiring high-resolution computed tomography (CT) images. To compare the physical point dose to the TPS calculated values (TG-43 and Acuros-BV), a phantom measurement was performed, by submerging the T&O applicator in a liquid water bath and delivering a treatment template representative of a clinical T&O procedure. The fiber detector collected scintillation signal as a function of time, and the calibration data was applied to calculate both real-time dose rate, and cumulative dose. Results: Fiber cumulative dose values were 100.0cGy, 94.3cGy, and 348.9cGy from the tandem, left ovoid, and right ovoid dwells, respectively (total of 443.2cGy). A plot of real time dose rate during the treatment was also acquired. The TPS values at the fiber location were 458.4cGy using TG-43, and 437.6cGy using Acuros-BV calculated as Dm,m (per TG-186). Conclusion: The fiber measured dose value agreement was 3% vs TG-43 and −1% vs Acuros-BV. This fiber detector opens up new possibilities for performing patient-specific quality assurance for Ir-192 HDR GYN procedures. Funding from Coulter Foundation, Duke Bio-medical Engineering. Company is being created around the detector technology. Duke holds patents on the technology.« less

COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1.

PubMed

Kaiser, Franz-Joachim; Bassler, Niels; Jäkel, Oliver

2010-08-01

Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy.

Precision radiotherapy for cancer of the pancreas: technique and results. [Photons and electrons

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

Dobelbower, R.R. Jr.; Borgelt, B.B.; Strubler, K.A.

1980-09-01

Forty patients with locally extensive, unresectable adenocarcinoma of the pancreas received precision high dose (PHD) radiation therapy with a 45 MeV betatron. PHD radiotherapy was generally well tolerated. During treatment, only 7 patients experienced significant nausea, vomiting, diarrhea or anorexia. Late gastrointestinal radiation reactions were observed in 7 patients. Twelve patients received adjuvant chemotherapy. The projected survival of patients with unresectable pancreatic cancer treated with PHD radiotherapy is comparable to that of patients with resectable disease operated on for cure. The projected one year survival rate is 49%.

Benchmark dose and the three Rs. Part I. Getting more information from the same number of animals.

PubMed

Slob, Wout

2014-08-01

Evaluating dose-response data using the Benchmark dose (BMD) approach rather than by the no observed adverse effect (NOAEL) approach implies a considerable step forward from the perspective of the Reduction, Replacement, and Refinement, three Rs, in particular the R of reduction: more information is obtained from the same number of animals, or, vice versa, similar information may be obtained from fewer animals. The first part of this twin paper focusses on the former, the second on the latter aspect. Regarding the former, the BMD approach provides more information from any given dose-response dataset in various ways. First, the BMDL (= BMD lower confidence bound) provides more information by its more explicit definition. Further, as compared to the NOAEL approach the BMD approach results in more statistical precision in the value of the point of departure (PoD), for deriving exposure limits. While part of the animals in the study do not directly contribute to the numerical value of a NOAEL, all animals are effectively used and do contribute to a BMDL. In addition, the BMD approach allows for combining similar datasets for the same chemical (e.g., both sexes) in a single analysis, which further increases precision. By combining a dose-response dataset with similar historical data for other chemicals, the precision can even be substantially increased. Further, the BMD approach results in more precise estimates for relative potency factors (RPFs, or TEFs). And finally, the BMD approach is not only more precise, it also allows for quantification of the precision in the BMD estimate, which is not possible in the NOAEL approach.

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Surface dose measurement for helical tomotherapy.

PubMed

Snir, Jonatan A; Mosalaei, Homeira; Jordan, Kevin; Yartsev, Slav

2011-06-01

To compare the surface dose measurements made by different dosimeters for the helical tomotherapy (HT) plan in the case of the target close to the surface. Surface dose measurements in different points for the HT plan to deliver 2 Gy to the planning target volume (PTV) at 5 mm below the surface of the cylindrical phantom were performed by radiochromic films, single use metal oxide semiconductor field-effect transistor (MOSFET) dosimeters, silicon IVD QED diode, and optically stimulated luminescence (OSL) dosimeters. The measured doses by all dosimeters were within 12 +/- 8% difference of each other. Radiochromic films, EBT, and EBT2, provide high spatial resolution, although it is difficult to get accurate measurements of dose. Both the OSL and QED measured similar dose to that of the MOSFET detectors. The QED dosimeter is promising as a reusable on-line wireless dosimeter, while the OSL dosimeters are easier to use, require minimum setup time and are very precise.

Toward a real-time in vivo dosimetry system using plastic scintillation detectors

PubMed Central

Archambault, Louis; Briere, Tina M.; Pönisch, Falk; Beaulieu, Luc; Kuban, Deborah A.; Lee, Andrew; Beddar, Sam

2010-01-01

Purpose In this work, we present and validate a plastic scintillation detector (PSD) system designed for real-time multi-probe in vivo measurements. Methods and Materials The PSDs were built with a dose-sensitive volume of 0.4 mm3. PSDs were assembled into modular detector patches, each containing 5 closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of less than 0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. Results The PSDs are compatible with clinical rectal balloons and are easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal-to-noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. Conclusion Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiation therapy should help radiation oncologists protect this sensitive normal structure. PMID:20231074

WE-F-16A-04: Micro-Irradiator Treatment Verification with High-Resolution 3D-Printed Rodent-Morphic Dosimeters

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

Bache, S; Belley, M; Benning, R

2014-06-15

Purpose: Pre-clinical micro-radiation therapy studies often utilize very small beams (∼0.5-5mm), and require accurate dose delivery in order to effectively investigate treatment efficacy. Here we present a novel high-resolution absolute 3D dosimetry procedure, capable of ∼100-micron isotopic dosimetry in anatomically accurate rodent-morphic phantoms Methods: Anatomically accurate rat-shaped 3D dosimeters were made using 3D printing techniques from outer body contours and spinal contours outlined on CT. The dosimeters were made from a radiochromic plastic material PRESAGE, and incorporated high-Z PRESASGE inserts mimicking the spine. A simulated 180-degree spinal arc treatment was delivered through a 2 step process: (i) cone-beam-CT image-guided positioningmore » was performed to precisely position the rat-dosimeter for treatment on the XRad225 small animal irradiator, then (ii) treatment was delivered with a simulated spine-treatment with a 180-degree arc with 20mm x 10mm cone at 225 kVp. Dose distribution was determined from the optical density change using a high-resolution in-house optical-CT system. Absolute dosimetry was enabled through calibration against a novel nano-particle scintillation detector positioned in a channel in the center of the distribution. Results: Sufficient contrast between regular PRESAGE (tissue equivalent) and high-Z PRESAGE (spinal insert) was observed to enable highly accurate image-guided alignment and targeting. The PRESAGE was found to have linear optical density (OD) change sensitivity with respect to dose (R{sup 2} = 0.9993). Absolute dose for 360-second irradiation at isocenter was found to be 9.21Gy when measured with OD change, and 9.4Gy with nano-particle detector- an agreement within 2%. The 3D dose distribution was measured at 500-micron resolution Conclusion: This work demonstrates for the first time, the feasibility of accurate absolute 3D dose measurement in anatomically accurate rat phantoms containing variable density PRESAGE material (tissue equivalent and bone equivalent). This method enables precise treatment verification of micro-radiation therapies, and enhances the robustness of tumor radio-response studies. This work was supported by NIH R01CA100835.« less

Evaluation of polymer gels and MRI as a 3-D dosimeter for intensity-modulated radiation therapy.

PubMed

Low, D A; Dempsey, J F; Venkatesan, R; Mutic, S; Markman, J; Mark Haacke, E; Purdy, J A

1999-08-01

BANG gel (MGS Research, Inc., Guilford, CT) has been evaluated for measuring intensity-modulated radiation therapy (IMRT) dose distributions. Treatment plans with target doses of 1500 cGy were generated by the Peacock IMRT system (NOMOS Corp., Sewickley, PA) using test target volumes. The gels were enclosed in 13 cm outer diameter cylindrical glass vessels. Dose calibration was conducted using seven smaller (4 cm diameter) cylindrical glass vessels irradiated to 0-1800 cGy in 300 cGy increments. Three-dimensional maps of the proton relaxation rate R2 were obtained using a 1.5 T magnetic resonance imaging (MRI) system (Siemens Medical Systems, Erlangen, Germany) and correlated with dose. A Hahn spin echo sequence was used with TR = 3 s, TE = 20 and 100 ms, NEX = 1, using 1 x 1 x 3 mm3 voxels. The MRI measurements were repeated weekly to identify the gel-aging characteristics. Ionization chamber, thermoluminescent dosimetry (TLD), and film dosimetry measurements of the IMRT dose distributions were obtained to compare against the gel results. The other dosimeters were used in a phantom with the same external cross-section as the gel phantom. The irradiated R2 values of the large vessels did not precisely track the smaller vessels, so the ionization chamber measurements were used to normalize the gel dose distributions. The point-to-point standard deviation of the gel dose measurements was 7.0 cGy. When compared with the ionization chamber measurements averaged over the chamber volume, 1% agreement was obtained. Comparisons against radiographic film dose distribution measurements and the treatment planning dose distribution calculation were used to determine the spatial localization accuracy of the gel and MRI. Spatial localization was better than 2 mm, and the dose was accurately determined by the gel both within and outside the target. The TLD chips were placed throughout the phantom to determine gel measurement precision in high- and low-dose regions. A multidimensional dose comparison tool that simultaneously examines the dose-difference and distance-to-agreement was used to evaluate the gel in both low-and high-dose gradient regions. When 3% and 3 mm criteria were used for the comparisons, more than 90% of the TLD measurements agreed with the gel, with the worst of 309 TLD chip measurements disagreeing by 40% of the criteria. All four MRI measurement session gel-measured dose distributions were compared to evaluate the time behavior of the gel. The low-dose regions were evaluated by comparison with TLD measurements at selected points, while high-dose regions were evaluated by directly comparing measured dose distributions. Tests using the multidimensional comparison tool showed detectable degradation beyond one week postirradiation, but all low-dose measurements passed relative to the test criteria and the dose distributions showed few regions that failed.

Towards high-throughput automated targeted femtosecond laser-based transfection of adherent cells

NASA Astrophysics Data System (ADS)

Antkowiak, Maciej; Torres-Mapa, Maria Leilani; Gunn-Moore, Frank; Dholakia, Kishan

2011-03-01

Femtosecond laser induced cell membrane poration has proven to be an attractive alternative to the classical methods of drug and gene delivery. It is a selective, sterile, non-contact technique that offers a highly localized operation, low toxicity and consistent performance. However, its broader application still requires the development of robust, high-throughput and user-friendly systems. We present a system capable of unassisted enhanced targeted optoinjection and phototransfection of adherent mammalian cells with a femtosecond laser. We demonstrate the advantages of a dynamic diffractive optical element, namely a spatial light modulator (SLM) for precise three dimensional positioning of the beam. It enables the implementation of a "point-and-shoot" system in which using the software interface a user simply points at the cell and a predefined sequence of precisely positioned doses can be applied. We show that irradiation in three axial positions alleviates the problem of exact beam positioning on the cell membrane and doubles the number of viably optoinjected cells when compared with a single dose. The presented system enables untargeted raster scan irradiation which provides transfection of adherent cells at the throughput of 1 cell per second.

LiF TLD-100 as a dosimeter in high energy proton beam therapy--can it yield accurate results?

PubMed

Zullo, John R; Kudchadker, Rajat J; Zhu, X Ronald; Sahoo, Narayan; Gillin, Michael T

2010-01-01

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within +/-5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within +/- 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy. Copyright 2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Medical imaging dose optimisation from ground up: expert opinion of an international summit.

PubMed

Samei, Ehsan; Järvinen, Hannu; Kortesniemi, Mika; Simantirakis, George; Goh, Charles; Wallace, Anthony; Vano, Eliseo; Bejan, Adrian; Rehani, Madan; Vassileva, Jenia

2018-05-17

As in any medical intervention, there is either a known or an anticipated benefit to the patient from undergoing a medical imaging procedure. This benefit is generally significant, as demonstrated by the manner in which medical imaging has transformed clinical medicine. At the same time, when it comes to imaging that deploys ionising radiation, there is a potential associated risk from radiation. Radiation risk has been recognised as a key liability in the practice of medical imaging, creating a motivation for radiation dose optimisation. The level of radiation dose and risk in imaging varies but is generally low. Thus, from the epidemiological perspective, this makes the estimation of the precise level of associated risk highly uncertain. However, in spite of the low magnitude and high uncertainty of this risk, its possibility cannot easily be refuted. Therefore, given the moral obligation of healthcare providers, 'first, do no harm,' there is an ethical obligation to mitigate this risk. Precisely how to achieve this goal scientifically and practically within a coherent system has been an open question. To address this need, in 2016, the International Atomic Energy Agency (IAEA) organised a summit to clarify the role of Diagnostic Reference Levels to optimise imaging dose, summarised into an initial report (Järvinen et al 2017 Journal of Medical Imaging 4 031214). Through a consensus building exercise, the summit further concluded that the imaging optimisation goal goes beyond dose alone, and should include image quality as a means to include both the benefit and the safety of the exam. The present, second report details the deliberation of the summit on imaging optimisation.

SU-F-J-127: Multi-Institutional Evaluation of Setup, Organ Deformation, Precision Dosimetry in Total Marrow Irradiation

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

Zuro, D; Hui, S

Purpose: Totals Marrow Irradiation (TMI) is a highly focused radiation delivery to the human skeleton structure therefore requiring a high amount of precision and accuracy for a quality treatment. Not much is known on how the patient position varies across multiple treatment fractions and how that positioning impacts the dose delivery. Currently TMI is studied as an international collaboration with multiple centers around the world; however, many of these centers used different pretreatment techniques. The goal of this work is to measure the accuracy of patient positioning, its impact on dose delivery and compare the impact of each technique formore » multiple institutions. Methods: Using Tomotherapy pretreatment MVCTs and the planning KVCTs measurements are made of the 3D setup uncertainties of the TMI treatment. Then, using the dose and plan files of the treatment impact of patient position on dose can be measured. Measurement of organ deformation and center of mass change were done using the Velocity AI program from Varian. We are looking at four the boney targets (skull, spine, pelvis, and femur) and three key sensitive tissues (eyes, lungs, kidneys). Results: Position measurements have been made for 3 different institutions using 3 different pre-treatment techniques. Comparing the translation motion we can observe the greatest change in the Y and Z direction of patient set up. For intra-fractional motion the shoulder and clavicle represent the greatest potential for motion and therefore most likely to have a dose change. Conclusion: All centers use different techniques for their treatment and this study shows that these techniques do not produce the same pretreatment results. We hope to expand this study further. Currently we have 3 centers participating in this study with more centers joining every day.« less

[Radiation therapy for cancer--challenges and opportunities].

PubMed

Specht, Lena

2010-02-01

Radiotherapy for cancer previously employed large treatment fields whereby cures were obtained. However, long-term follow-up documented serious long-term complications due to irradiation of normal tissues. Modern technology makes it possible to very accurately shape the high-dose volume. However, new problems emerge. Organ movement must be managed and the precise definition of the extent of the tumour tissue is crucial. Positron emission tomography and magnetic resonance imaging are increasingly used. Biological imaging may enable us to image tumour biology more accurately and modify radiation doses accordingly.

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

Magallanes, L., E-mail: lorena.magallanes@med.uni-heidelberg.de; Rinaldi, I., E-mail: ilaria.rinaldi@med.uni-heidelberg.de; Brons, S., E-mail: stephan.brons@med.uni-heidelberg.de

External beam radiotherapy techniques have the common aim to maximize the radiation dose to the target while sparing the surrounding healthy tissues. The inverted and finite depth-dose profile of ion beams (Bragg peak) allows for precise dose delivery and conformai dose distribution. Furthermore, increased radiobiological effectiveness of ions enhances the capability to battle radioresistant tumors. Ion beam therapy requires a precise determination of the ion range, which is particularly sensitive to range uncertainties. Therefore, novel imaging techniques are currently investigated as a tool to improve the quality of ion beam treatments. Approaches already clinically available or under development are basedmore » on the detection of secondary particles emitted as a result of nuclear reactions (e.g., positron-annihilation or prompt gammas, charged particles) or transmitted high energy primary ion beams. Transmission imaging techniques make use of the beams exiting the patient, which have higher initial energy and lower fluence than the therapeutic ones. At the Heidelberg Ion Beam Therapy Center, actively scanned energetic proton and carbon ion beams provide an ideal environment for the investigation of ion-based radiography and tomography. This contribution presents the rationale of ion beam therapy, focusing on the role of ion-based transmission imaging methods towards the reduction of range uncertainties and potential improvement of treatment planning.« less

Feasibility study of a photoconductor based dosimeter for quality assurance in radiotherapy

NASA Astrophysics Data System (ADS)

Lee, Y. K.; Kim, S. W.; Kim, J. N.; Kang, Y. N.; Kim, J. Y.; Lee, D. S.; Kim, K. T.; Han, M. J.; Ahn, K. J.; Park, S. K.

2017-09-01

With the recent market entries of new types of linear accelerators (LINACs) with a multi leaf collimator (MLC) mounted on them, high-precision radiosurgery applying a LINAC to measure high-dose radiation on the target region has been gaining popularity. Systematic and accurate quality assurance (QA) is of vital important for high-precision radiosurgery because of its increased risk of side effects including life-threatening ones such as overexposure of healthy tissues to high-dose radiation beams concentrated on small areas. Therefore, accurate dose and dose-distribution measurements are crucial in the treatment procedure. The accurate measurement of the properties of beams concentrated on small areas requires high-precision dosimeters capable of high-resolution output and dose mapping as well as accurate dosimetry in penumbra regions. In general, the properties of beams concentrated on small areas are measured using thermos luminescent dosimeters (TLD), diode detectors, ion chambers, diamond detectors, or films, and many papers have presented the advantages and disadvantages of each of these detectors for dosimetry. In this study, a solid-state photoconductor dosimeter was developed, and its clinical usability was tested by comparing its relative dosimetric performance with that of a conventional ion chamber. As materials best-suited for radiation dosimeters, four candidates namely lead (II) iodide (PbI2), lead (II) oxide (PbO), mercury (II) iodide (HgI2), and HgI2/ titanium dioxide (TiO2) composite, the performances of which were proved in previous studies, were used. The electrical properties of each candidate material were examined using the sedimentation method, one of the particle-in-binder (PIB) methods, and unit-cell-type prototypes were fabricated. The unit-cell samples thus prepared were cut into specimens of area 1 × 1 cm2 with 400-μ m thickness. The electrical properties of each sample, such as sensitivity, dark current, output current, rising time, falling time, and response delay, were then measured, in addition to the consistency, reproducibility and linearity of each unit-cell. According to the measurement results, HgI2/TiO2 composite outperformed the other candidate materials. A radiation dosimeter with a chamber-type structure was fabricated in this study using a LINAC under accelerating voltages of 6, and 15 MV and compared with a commercial ion chamber. Percent depth dose (PDD) and beam profile were measured on a water phantom at a fixed area of 10 × 10 cm2 by using the fabricated chamber-type dosimeter, and the values were compared with those measured by a commercial ion chamber. Additionally, a homogeneous phantom was fabricated, and the exposure doses of the center points were measured according to a real treatment plan, followed by a comparison of the measured values as relative values. In this paper, we report that the manufactured dosimeter shows similar characteristics in terms of PDD and beam profile and results for the conventional ion chamber. Based on these results, it is demonstrated that the HgI2/TiO2-based dosimeter complies with radiotherapy QA requirements, namely Superior detection characteristics, consistency, dose linearity, reproducibility. Thus, we expect the HgI2/TiO2-based dosimeter to be used commercially in the future.

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.

PubMed

Du, Shisuo; Lockamy, Virginia; Zhou, Lin; Xue, Christine; LeBlanc, Justin; Glenn, Shonna; Shukla, Gaurav; Yu, Yan; Dicker, Adam P; Leeper, Dennis B; Lu, You; Lu, Bo

2016-11-01

To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics. Copyright © 2016. Published by Elsevier Inc.

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

Du, Shisuo; Lockamy, Virginia; Zhou, Lin

Purpose: To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. Methods and Materials: A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOGmore » protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. Results: The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. Conclusions: It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics.« less

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PubMed

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

PubMed Central

Shuryak, Igor; Loucas, Bradford D.; Cornforth, Michael N.

2017-01-01

Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one) large dose(s) per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ) formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts) exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions). This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction. PMID:29312888

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

Evaluation of film and thermoluminescent dosimetry of high-energy electron beams in heterogeneous phantoms.

PubMed

el-Khatib, E; Antolak, J; Scrimger, J

1992-01-01

Film and thermoluminescent dosimetry (TLD) are investigated in heterogeneous phantoms irradiated by high-energy electron beams. Both film and TLD are practical dosimeters for multiple and moving beam radiotherapy. The accuracy and precision of these dosimeters for radiation dose measurements in homogeneous water-equivalent phantoms has been discussed in the literature. However, film and TLD are often used for dose measurements in heterogeneous phantoms. In those situations perturbations are produced which are related to the density and atomic number of the phantom material and the physical size and orientation of the dosimeter. In our experiments the relative dose measurements in homogeneous phantoms were the same regardless of dosimeter or dosimeter orientation. However, significant differences were observed between the dose measurements within the inhomogeneity. These differences were influenced by the type and orientation of the dosimeter in addition to the properties of the heterogeneity. These differences could be reproduced with Monte Carlo calculations and modeling of the experimental conditions.

SR-TXRF analysis of trace elements in whole blood and heart of rats: effects of irradiation with low and high doses

NASA Astrophysics Data System (ADS)

Mota, C. L.; Pickler, A.; Braz, D.; Barroso, R. C.; Mantuano, A.; Salata, C.; Ferreira-Machado, S. C.; Lau, C. C.; de Almeida, C. E.

2018-04-01

In the last decades, studies showed that the exposure to low doses of ionizing radiation of the body could sense and activate the cell signaling pathways needed to respond to any induced cellular damage. This procedure reduces cell killing compared with a single dose of high radiation dose. Damage to the vasculature can affect the function of most body organs by restricting blood flow and oxygen to tissues; however, the heart and brain are of main concern. The precise relationship between long-term health effects and low-dose exposures remain poorly understood. Biological markers are powerful tools that can be used to determine dose- response relationships and to estimate risk, especially when dealing with, the effects of low dose exposures in humans. These markers should be specific, sensitive, as well as easy and fast to quantify. Various types of biologic specimens are potential candidates for identifying biomarkers but blood has the advantage of being minimally invasive to obtain. In this study, we propose to apply total reflection X-ray fluorescence to quantify possible chemical elemental concentration (sulfer, iron, zinc, potassium and calcium) changes in blood and heart tissues of Wistar rats after total body irradiation with low (0.1 Gy) and high (2.5 Gy) doses. The fluorescence measurements were carried out at the X-ray Fluorescence beamline in the Brazilian Synchrotron Light Laboratory. The results showed that the irradiated animals with low doses have significant alterations in blood and cardiac tissue when compared with animals that received high doses of radiation. Taken together the analysis of all the elements, we can observe that the radiation induced oxidative stress may be the leading cause for alteration of the elemental level in the studied samples.

Clinical trial tests precision radiotherapy for recurrent prostate cancer | Center for Cancer Research

Cancer.gov

CCR investigators are leading a trial of stereotactic body radiation therapy (SBRT) to treat localized prostate cancer that has recurred after standard radiation therapy. The technique uses advanced molecular imaging to guide the delivery of high doses of radiation just to tumors that have recurred, potentially leading to fewer side effects. Read more…

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

A quantified dosing ALD reactor with in-situ diagnostics for surface chemistry studies

NASA Astrophysics Data System (ADS)

Larrabee, Thomas J.

A specialized atomic layer deposition (ALD) reactor has been constructed to serve as an instrument to simultaneously study the surface chemistry of the ALD process, and perform ALD as is conventionally done in continuum flow of inert gas. This reactor is uniquely useful to gain insight into the ALD process because of the combination of its precise, controllable, and quantified dosing/microdosing capability; its in-situ quadrupole mass spectrometer for gas composition analysis; its pair of highly-sensitive in-situ quartz crystal microbalances (QCMs); and its complete spectrum of pressures and operating conditions --- from viscous to molecular flow regimes. Control of the dose is achieved independently of the conditions by allowing a reactant gas to fill a fixed volume and measured pressure, which is held at a controlled temperature, and subsequently dosed into the system by computer controlled pneumatic valves. Absolute reactant exposure to the substrate and QCMs is unambiguously calculated from the molecular impingement flux, and its relationship to dose size is established, allowing means for easily intentionally reproducing specific exposures. Methods for understanding atomic layer growth and adsorption phenomena, including the precursor sticking probability, dynamics of molecular impingement, size of dose, and other operating variables are for the first time quantitatively related to surface reaction rates by mass balance. Extensive characterization of the QCM as a measurement tool for adsorption under realistic ALD conditions has been examined, emphasizing the state-of-the-art and importance of QCM system features required. Finally, the importance of dose-quantification and microdosing has been contextualized in view of the ALD literature, underscoring the significance of more precise condition specification in establishing a better basis for reactor and reactant comparison.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

Characterization of a commercial multileaf collimator used for intensity modulated radiation therapy.

PubMed

Low, D A; Sohn, J W; Klein, E E; Markman, J; Mutic, S; Dempsey, J F

2001-05-01

The characteristics of a commercial multileaf collimator (MLC) to deliver static and dynamic multileaf collimation (SMLC and DMLC, respectively) were investigated to determine their influence on intensity modulated radiation therapy (IMRT) treatment planning and quality assurance. The influence of MLC leaf positioning accuracy on sequentially abutted SMLC fields was measured by creating abutting fields with selected gaps and overlaps. These data were also used to measure static leaf positioning precision. The characteristics of high leaf-velocity DMLC delivery were measured with constant velocity leaf sequences starting with an open field and closing a single leaf bank. A range of 1-72 monitor units (MU) was used providing a range of leaf velocities. The field abutment measurements yielded dose errors (as a percentage of the open field max dose) of 16.7+/-0.7% mm(-1) and 12.8+/-0.7% mm(-1) for 6 MV and 18 MV photon beams, respectively. The MLC leaf positioning precision was 0.080+/-0.018 mm (single standard deviation) highlighting the excellent delivery hardware tolerances for the tested beam delivery geometry. The high leaf-velocity DMLC measurements showed delivery artifacts when the leaf sequence and selected monitor units caused the linear accelerator to move the leaves at their maximum velocity while modulating the accelerator dose rate to deliver the desired leaf and MU sequence (termed leaf-velocity limited delivery). According to the vendor, a unique feature to their linear accelerator and MLC is that the dose rate is reduced to provide the correct cm MU(-1) leaf velocity when the delivery is leaf-velocity limited. However, it was found that the system delivered roughly 1 MU per pulse when the delivery was leaf-velocity limited causing dose profiles to exhibit discrete steps rather than a smooth dose gradient. The root mean square difference between the steps and desired linear gradient was less than 3% when more than 4 MU were used. The average dose per MU was greater and less than desired for closing and opening leaf patterns, respectively, when the delivery was leaf-velocity limited. The results indicated that the dose delivery artifacts should be minor for most clinical cases, but limit the assumption of dose linearity when significantly reducing the delivered dose for dosimeter characterization studies or QA measurements.

Absolute dose calibration of an X-ray system and dead time investigations of photon-counting techniques

NASA Astrophysics Data System (ADS)

Carpentieri, C.; Schwarz, C.; Ludwig, J.; Ashfaq, A.; Fiederle, M.

2002-07-01

High precision concerning the dose calibration of X-ray sources is required when counting and integrating methods are compared. The dose calibration for a dental X-ray tube was executed with special dose calibration equipment (dosimeter) as function of exposure time and rate. Results were compared with a benchmark spectrum and agree within ±1.5%. Dead time investigations with the Medipix1 photon-counting chip (PCC) have been performed by rate variations. Two different types of dead time, paralysable and non-paralysable will be discussed. The dead time depends on settings of the front-end electronics and is a function of signal height, which might lead to systematic defects of systems. Dead time losses in excess of 30% have been found for the PCC at 200 kHz absorbed photons per pixel.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors.

PubMed

Pham, Trang T B; Oue, Naohide; Yamamoto, Manabu; Fujihara, Megumu; Ishida, Teruyoshi; Mukai, Shoichiro; Sakamoto, Naoya; Sentani, Kazuhiro; Yasui, Wataru

2017-02-01

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of FKTN , which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases. In the first cohort from Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital (Hiroshima, Japan; n=92), 102 (53%) of the GC cases were positive for fukutin. Expression of fukutin was not associated with exposure status, but was associated with CD10 expression (P=0.0001). The second cohort was from Hiroshima University Hospital (Hiroshima, Japan; n=86), and these patients were also in the Life Span Study cohort, in which atomic bomb radiation doses were precisely estimated using the DS02 system. Expression of fukutin was detected in 58 (67%) of GC cases. GC cases positive for fukutin were observed more frequently in the low dose-exposed group than in the high dose-exposed group (P=0.0001). Further studies with a larger cohort, including precise radiation dose estimation, may aid in clarifying whether fukutin could serve as a potential biomarker to define radiation-induced GC in atomic-bomb survivors.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors

PubMed Central

Pham, Trang T.B.; Oue, Naohide; Yamamoto, Manabu; Fujihara, Megumu; Ishida, Teruyoshi; Mukai, Shoichiro; Sakamoto, Naoya; Sentani, Kazuhiro; Yasui, Wataru

2017-01-01

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of FKTN, which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases. In the first cohort from Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital (Hiroshima, Japan; n=92), 102 (53%) of the GC cases were positive for fukutin. Expression of fukutin was not associated with exposure status, but was associated with CD10 expression (P=0.0001). The second cohort was from Hiroshima University Hospital (Hiroshima, Japan; n=86), and these patients were also in the Life Span Study cohort, in which atomic bomb radiation doses were precisely estimated using the DS02 system. Expression of fukutin was detected in 58 (67%) of GC cases. GC cases positive for fukutin were observed more frequently in the low dose-exposed group than in the high dose-exposed group (P=0.0001). Further studies with a larger cohort, including precise radiation dose estimation, may aid in clarifying whether fukutin could serve as a potential biomarker to define radiation-induced GC in atomic-bomb survivors. PMID:28356981

Identifying optimal dosage regimes under safety constraints: An application to long term opioid treatment of chronic pain.

PubMed

Laber, Eric B; Wu, Fan; Munera, Catherine; Lipkovich, Ilya; Colucci, Salvatore; Ripa, Steve

2018-04-30

There is growing interest and investment in precision medicine as a means to provide the best possible health care. A treatment regime formalizes precision medicine as a sequence of decision rules, one per clinical intervention period, that specify if, when and how current treatment should be adjusted in response to a patient's evolving health status. It is standard to define a regime as optimal if, when applied to a population of interest, it maximizes the mean of some desirable clinical outcome, such as efficacy. However, in many clinical settings, a high-quality treatment regime must balance multiple competing outcomes; eg, when a high dose is associated with substantial symptom reduction but a greater risk of an adverse event. We consider the problem of estimating the most efficacious treatment regime subject to constraints on the risk of adverse events. We combine nonparametric Q-learning with policy-search to estimate a high-quality yet parsimonious treatment regime. This estimator applies to both observational and randomized data, as well as settings with variable, outcome-dependent follow-up, mixed treatment types, and multiple time points. This work is motivated by and framed in the context of dosing for chronic pain; however, the proposed framework can be applied generally to estimate a treatment regime which maximizes the mean of one primary outcome subject to constraints on one or more secondary outcomes. We illustrate the proposed method using data pooled from 5 open-label flexible dosing clinical trials for chronic pain. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons, Ltd.

Biodosimetry estimate for high-LET irradiation.

PubMed

Wang, Z Z; Li, W J; Zhi, D J; Jing, X G; Wei, W; Gao, Q X; Liu, B

2007-08-01

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV microm(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

Image Guidance in Radiation Therapy: Techniques and Applications

PubMed Central

Kataria, Tejinder

2014-01-01

In modern day radiotherapy, the emphasis on reduction on volume exposed to high radiotherapy doses, improving treatment precision as well as reducing radiation-related normal tissue toxicity has increased, and thus there is greater importance given to accurate position verification and correction before delivering radiotherapy. At present, several techniques that accomplish these goals impeccably have been developed, though all of them have their limitations. There is no single method available that eliminates treatment-related uncertainties without considerably adding to the cost. However, delivering “high precision radiotherapy” without periodic image guidance would do more harm than treating large volumes to compensate for setup errors. In the present review, we discuss the concept of image guidance in radiotherapy, the current techniques available, and their expected benefits and pitfalls. PMID:25587445

DOSESCREEN: a computer program to aid dose placement

Treesearch

Kimberly C. Smith; Jacqueline L. Robertson

1984-01-01

Careful selection of an experimental design for a bioassay substantially improves the precision of effective dose (ED) estimates. Design considerations typically include determination of sample size, dose selection, and allocation of subjects to doses. DOSESCREEN is a computer program written to help investigators select an efficient design for the estimation of an...

Changing paradigm of cancer therapy: precision medicine by next-generation sequencing

PubMed Central

Xue, Yuan; Wilcox, William R.

2016-01-01

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been long-standing challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing (NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials. PMID:27144059

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

NASA Technical Reports Server (NTRS)

Williams, J. R.; Zhang, Y.; Zhou, H.; Osman, M.; Cha, D.; Kavet, R.; Cuccinotta, F.; Dicello, J. F.; Dillehay, L. E.

1999-01-01

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Determining the mechanical properties of a radiochromic silicone-based 3D dosimeter

NASA Astrophysics Data System (ADS)

Kaplan, L. P.; Høye, E. M.; Balling, P.; Muren, L. P.; Petersen, J. B. B.; Poulsen, P. R.; Yates, E. S.; Skyt, P. S.

2017-07-01

New treatment modalities in radiotherapy (RT) enable delivery of highly conformal dose distributions in patients. This creates a need for precise dose verification in three dimensions (3D). A radiochromic silicone-based 3D dosimetry system has recently been developed. Such a dosimeter can be used for dose verification in deformed geometries, which requires knowledge of the dosimeter’s mechanical properties. In this study we have characterized the dosimeter’s elastic behaviour under tensile and compressive stress. In addition, the dose response under strain was determined. It was found that the dosimeter behaved as an incompressible hyperelastic material with a non-linear stress/strain curve and with no observable hysteresis or plastic deformation even at high strains. The volume was found to be constant within a 2% margin at deformations up to 60%. Furthermore, it was observed that the dosimeter returned to its original geometry within a 2% margin when irradiated under stress, and that the change in optical density per centimeter was constant regardless of the strain during irradiation. In conclusion, we have shown that this radiochromic silicone-based dosimeter’s mechanical properties make it a viable candidate for dose verification in deformable 3D geometries.

CPU time optimization and precise adjustment of the Geant4 physics parameters for a VARIAN 2100 C/D gamma radiotherapy linear accelerator simulation using GAMOS.

PubMed

Arce, Pedro; Lagares, Juan Ignacio

2018-01-25

We have verified the GAMOS/Geant4 simulation model of a 6 MV VARIAN Clinac 2100 C/D linear accelerator by the procedure of adjusting the initial beam parameters to fit the percentage depth dose and cross-profile dose experimental data at different depths in a water phantom. Thanks to the use of a wide range of field sizes, from 2  ×  2 cm 2 to 40  ×  40 cm 2 , a small phantom voxel size and high statistics, fine precision in the determination of the beam parameters has been achieved. This precision has allowed us to make a thorough study of the different physics models and parameters that Geant4 offers. The three Geant4 electromagnetic physics sets of models, i.e. Standard, Livermore and Penelope, have been compared to the experiment, testing the four different models of angular bremsstrahlung distributions as well as the three available multiple-scattering models, and optimizing the most relevant Geant4 electromagnetic physics parameters. Before the fitting, a comprehensive CPU time optimization has been done, using several of the Geant4 efficiency improvement techniques plus a few more developed in GAMOS.

Exposing exposure: automated anatomy-specific CT radiation exposure extraction for quality assurance and radiation monitoring.

PubMed

Sodickson, Aaron; Warden, Graham I; Farkas, Cameron E; Ikuta, Ichiro; Prevedello, Luciano M; Andriole, Katherine P; Khorasani, Ramin

2012-08-01

To develop and validate an informatics toolkit that extracts anatomy-specific computed tomography (CT) radiation exposure metrics (volume CT dose index and dose-length product) from existing digital image archives through optical character recognition of CT dose report screen captures (dose screens) combined with Digital Imaging and Communications in Medicine attributes. This institutional review board-approved HIPAA-compliant study was performed in a large urban health care delivery network. Data were drawn from a random sample of CT encounters that occurred between 2000 and 2010; images from these encounters were contained within the enterprise image archive, which encompassed images obtained at an adult academic tertiary referral hospital and its affiliated sites, including a cancer center, a community hospital, and outpatient imaging centers, as well as images imported from other facilities. Software was validated by using 150 randomly selected encounters for each major CT scanner manufacturer, with outcome measures of dose screen retrieval rate (proportion of correctly located dose screens) and anatomic assignment precision (proportion of extracted exposure data with correctly assigned anatomic region, such as head, chest, or abdomen and pelvis). The 95% binomial confidence intervals (CIs) were calculated for discrete proportions, and CIs were derived from the standard error of the mean for continuous variables. After validation, the informatics toolkit was used to populate an exposure repository from a cohort of 54 549 CT encounters; of which 29 948 had available dose screens. Validation yielded a dose screen retrieval rate of 99% (597 of 605 CT encounters; 95% CI: 98%, 100%) and an anatomic assignment precision of 94% (summed DLP fraction correct 563 in 600 CT encounters; 95% CI: 92%, 96%). Patient safety applications of the resulting data repository include benchmarking between institutions, CT protocol quality control and optimization, and cumulative patient- and anatomy-specific radiation exposure monitoring. Large-scale anatomy-specific radiation exposure data repositories can be created with high fidelity from existing digital image archives by using open-source informatics tools.

SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

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

Yan, D; Chen, S; Krauss, D

Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function ofmore » pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.« less

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation

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

Yang, Feng; Waters, Katrina M.; Miller, John H.

2010-11-30

Background: High doses of ionizing radiation result in biological damage, however the precise relationships between long term health effects, including cancer, and low dose exposures remain poorly understood and are currently extrapolated using high dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose dependent responses to radiation. Principle Findings: We have identified 6845 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts one hour post-exposure. Dual statistical analyses based on spectral counts and peakmore » intensities identified 287 phosphopeptides (from 231 proteins) and 244 phosphopeptides (from 182 proteins) that varied significantly following exposure to 2 and 50 cGy respectively. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatics analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role of MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conlcusions: Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provides a basis for the systems level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low dose radiation exposure on human health.« less

Affordable CZT SPECT with dose-time minimization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hugg, James W.; Harris, Brian W.; Radley, Ian

2017-03-01

PURPOSE Pixelated CdZnTe (CZT) detector arrays are used in molecular imaging applications that can enable precision medicine, including small-animal SPECT, cardiac SPECT, molecular breast imaging (MBI), and general purpose SPECT. The interplay of gamma camera, collimator, gantry motion, and image reconstruction determines image quality and dose-time-FOV tradeoffs. Both dose and exam time can be minimized without compromising diagnostic content. METHODS Integration of pixelated CZT detectors with advanced ASICs and readout electronics improves system performance. Because historically CZT was expensive, the first clinical applications were limited to small FOV. Radiation doses were initially high and exam times long. Advances have significantly improved efficiency of CZT-based molecular imaging systems and the cost has steadily declined. We have built a general purpose SPECT system using our 40 cm x 53 cm CZT gamma camera with 2 mm pixel pitch and characterized system performance. RESULTS Compared to NaI scintillator gamma cameras: intrinsic spatial resolution improved from 3.8 mm to 2.0 mm; energy resolution improved from 9.8% to <4 % at 140 keV; maximum count rate is <1.5 times higher; non-detection camera edges are reduced 3-fold. Scattered photons are greatly reduced in the photopeak energy window; image contrast is improved; and the optimal FOV is increased to the entire camera area. CONCLUSION Continual improvements in CZT detector arrays for molecular imaging, coupled with optimal collimator and image reconstruction, result in minimized dose and exam time. With CZT cost improving, affordable whole-body CZT general purpose SPECT is expected to enable precision medicine applications.

Fricke-gel dosimetry in epithermal or thermal neutron beams of a research reactor

NASA Astrophysics Data System (ADS)

Gambarini, G.; Artuso, E.; Giove, D.; Volpe, L.; Agosteo, S.; Barcaglioni, L.; Campi, F.; Garlati, L.; Pola, A.; Durisi, E.; Borroni, M.; Carrara, M.; Klupak, V.; Marek, M.; Viererbl, L.; Vins, M.; d'Errico, F.

2015-11-01

Fricke-xylenol-orange gel has shown noticeable potentiality for in-phantom dosimetry in epithermal or thermal neutron fields with very high fluence rate, as those characteristic of nuclear research reactors. Fricke gels in form of layers give the possibility of achieving spatial distribution of gamma dose, fast neutron dose and dose due to charged particles generated by thermal neutron reactions. The thermal neutron fluence has been deduced from the dose coming from the charge particles emitted by neutron reactions with the isotope 10B. Some measurements have been performed for improving the information on the relative sensitivity of Fricke gel dosimeters to the particles produced by 10B reactions, because at present the precision of dose evaluations is limited by the scanty knowledge about the dependence of the dosimeter sensitivity on the radiation LET. For in-air measurements, the dosimeter material can produce an enhancement of thermal neutron fluence. Measurements and Monte Carlo calculations have been developed to investigate the importance of this effect.

Design and implementation of a film dosimetry audit tool for comparison of planned and delivered dose distributions in high dose rate (HDR) brachytherapy

NASA Astrophysics Data System (ADS)

Palmer, Antony L.; Lee, Chris; Ratcliffe, Ailsa J.; Bradley, David; Nisbet, Andrew

2013-10-01

A novel phantom is presented for ‘full system’ dosimetric audit comparing planned and delivered dose distributions in HDR gynaecological brachytherapy, using clinical treatment applicators. The brachytherapy applicator dosimetry test object consists of a near full-scatter water tank with applicator and film supports constructed of Solid Water, accommodating any typical cervix applicator. Film dosimeters are precisely held in four orthogonal planes bisecting the intrauterine tube, sampling dose distributions in the high risk clinical target volume, points A and B, bladder, rectum and sigmoid. The applicator position is fixed prior to CT scanning and through treatment planning and irradiation. The CT data is acquired with the applicator in a near clinical orientation to include applicator reconstruction in the system test. Gamma analysis is used to compare treatment planning system exported RTDose grid with measured multi-channel film dose maps. Results from two pilot audits are presented, using Ir-192 and Co-60 HDR sources, with a mean gamma passing rate of 98.6% using criteria of 3% local normalization and 3 mm distance to agreement (DTA). The mean DTA between prescribed dose and measured film dose at point A was 1.2 mm. The phantom was funded by IPEM and will be used for a UK national brachytherapy dosimetry audit.

Design and implementation of a film dosimetry audit tool for comparison of planned and delivered dose distributions in high dose rate (HDR) brachytherapy.

PubMed

Palmer, Antony L; Lee, Chris; Ratcliffe, Ailsa J; Bradley, David; Nisbet, Andrew

2013-10-07

A novel phantom is presented for 'full system' dosimetric audit comparing planned and delivered dose distributions in HDR gynaecological brachytherapy, using clinical treatment applicators. The brachytherapy applicator dosimetry test object consists of a near full-scatter water tank with applicator and film supports constructed of Solid Water, accommodating any typical cervix applicator. Film dosimeters are precisely held in four orthogonal planes bisecting the intrauterine tube, sampling dose distributions in the high risk clinical target volume, points A and B, bladder, rectum and sigmoid. The applicator position is fixed prior to CT scanning and through treatment planning and irradiation. The CT data is acquired with the applicator in a near clinical orientation to include applicator reconstruction in the system test. Gamma analysis is used to compare treatment planning system exported RTDose grid with measured multi-channel film dose maps. Results from two pilot audits are presented, using Ir-192 and Co-60 HDR sources, with a mean gamma passing rate of 98.6% using criteria of 3% local normalization and 3 mm distance to agreement (DTA). The mean DTA between prescribed dose and measured film dose at point A was 1.2 mm. The phantom was funded by IPEM and will be used for a UK national brachytherapy dosimetry audit.

Temperature mapping and thermal dose calculation in combined radiation therapy and 13.56 MHz radiofrequency hyperthermia for tumor treatment

NASA Astrophysics Data System (ADS)

Kim, Jung Kyung; Prasad, Bibin; Kim, Suzy

2017-02-01

To evaluate the synergistic effect of radiotherapy and radiofrequency hyperthermia therapy in the treatment of lung and liver cancers, we studied the mechanism of heat absorption and transfer in the tumor using electro-thermal simulation and high-resolution temperature mapping techniques. A realistic tumor-induced mouse anatomy, which was reconstructed and segmented from computed tomography images, was used to determine the thermal distribution in tumors during radiofrequency (RF) heating at 13.56 MHz. An RF electrode was used as a heat source, and computations were performed with the aid of the multiphysics simulation platform Sim4Life. Experiments were carried out on a tumor-mimicking agar phantom and a mouse tumor model to obtain a spatiotemporal temperature map and thermal dose distribution. A high temperature increase was achieved in the tumor from both the computation and measurement, which elucidated that there was selective high-energy absorption in tumor tissue compared to the normal surrounding tissues. The study allows for effective treatment planning for combined radiation and hyperthermia therapy based on the high-resolution temperature mapping and high-precision thermal dose calculation.

A protocol for EBT3 radiochromic film dosimetry using reflection scanning

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

Papaconstadopoulos, Pavlos, E-mail: pavpapac@gmail.com; Hegyi, Gyorgy; Seuntjens, Jan

2014-12-15

Purpose: To evaluate the performance of the EBT3 radiochromic film dosimetry system using reflection measurements and to suggest a calibration protocol for precise and accurate reflection film dosimetry. Methods: A set of 14 Gafchromic EBT3 film pieces were irradiated to various doses ranging from 0 to 8 Gy and subsequently scanned using both the reflection and transmission mode. Scanning resolution varied from 50 to 508 dpi (0.5–0.05 mm/pixel). Both the red and green color channels of scanned images were used to relate the film response to the dose. A sensitivity, uncertainty, and accuracy analysis was performed for all scanning modesmore » and color channels. The total uncertainty, along with the fitting and experimental uncertainty components, was identified and analyzed. A microscope resolution target was used to evaluate possible resolution losses under reflection scanning. The calibration range was optimized for reflection scanning in the low (<2 Gy) and high (>2 Gy) dose regions based on the reported results. Results: Reflection scanning using the red channel exhibited the highest sensitivity among all modes, being up to 150% higher than transmission mode in the red channel for the lowest dose level. Furthermore, there was no apparent loss in resolution between the two modes. However, higher uncertainties and reduced accuracy were observed for the red channel under reflection mode, especially at dose levels higher than 2 Gy. These uncertainties were mainly attributed to saturation effects which were translated in poor fitting results. By restricting the calibration to the 0–2 Gy dose range, the situation is reversed and the red reflection mode was superior to the transmission mode. For higher doses, the green channel in reflection mode presented comparable results to the red transmission. Conclusions: A two-color reflection scanning protocol can be suggested for EBT3 radiochromic film dosimetry using the red channel for doses less than 2 Gy and the green channel for higher doses. The precision and accuracy are significantly improved in the low dose region following such a protocol.« less

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

Yang, Y M; Bush, K; Han, B

Purpose: Accurate and fast dose calculation is a prerequisite of precision radiation therapy in modern photon and particle therapy. While Monte Carlo (MC) dose calculation provides high dosimetric accuracy, the drastically increased computational time hinders its routine use. Deterministic dose calculation methods are fast, but problematic in the presence of tissue density inhomogeneity. We leverage the useful features of deterministic methods and MC to develop a hybrid dose calculation platform with autonomous utilization of MC and deterministic calculation depending on the local geometry, for optimal accuracy and speed. Methods: Our platform utilizes a Geant4 based “localized Monte Carlo” (LMC) methodmore » that isolates MC dose calculations only to volumes that have potential for dosimetric inaccuracy. In our approach, additional structures are created encompassing heterogeneous volumes. Deterministic methods calculate dose and energy fluence up to the volume surfaces, where the energy fluence distribution is sampled into discrete histories and transported using MC. Histories exiting the volume are converted back into energy fluence, and transported deterministically. By matching boundary conditions at both interfaces, deterministic dose calculation account for dose perturbations “downstream” of localized heterogeneities. Hybrid dose calculation was performed for water and anthropomorphic phantoms. Results: We achieved <1% agreement between deterministic and MC calculations in the water benchmark for photon and proton beams, and dose differences of 2%–15% could be observed in heterogeneous phantoms. The saving in computational time (a factor ∼4–7 compared to a full Monte Carlo dose calculation) was found to be approximately proportional to the volume of the heterogeneous region. Conclusion: Our hybrid dose calculation approach takes advantage of the computational efficiency of deterministic method and accuracy of MC, providing a practical tool for high performance dose calculation in modern RT. The approach is generalizable to all modalities where heterogeneities play a large role, notably particle therapy.« less

Two-dimensional silicon-based detectors for ion beam therapy

NASA Astrophysics Data System (ADS)

Martišíková, M.; Granja, C.; Jakůbek, J.; Hartmann, B.; Telsemeyer, J.; Huber, L.; Brons, S.; Pospíšil, S.; Jäkel, O.

2012-02-01

Radiation therapy with ion beams is a highly precise kind of cancer treatment. As ion beams traverse material, the highest ionization density occurs at the end of their path. Due to this Bragg-peak, ion beams enable higher dose conformation to the tumor and increased sparing of the surrounding tissue, in comparison to standard radiation therapy using high energy photons. Ions heavier than protons offer in addition increased biological effectiveness and lower scattering. The Heidelberg Ion Beam Therapy Center (HIT) is a state-of-the-art ion beam therapy facility and the first hospital-based facility in Europe. It provides proton and carbon ion treatments. A synchrotron is used for ion acceleration. For dose delivery to the patient, narrow pencil-like beams are scanned over the target volume.

SU-E-T-451: Accuracy and Application of the Standard Imaging W1 Scintillator Dosimeter

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

Kowalski, M; McEwen, M

2014-06-01

Purpose: To evaluate the Standard Imaging W1 scintillator dosimeter in a range of clinical radiation beams to determine its range of possible applications. Methods: The W1 scintillator is a small perturbation-free dosimeter which is of interest in absolute and relative clinical dosimetry due to its small size and water equivalence. A single version of this detector was evaluated in Co-60 and linac photon and electron beams to investigate the following: linearity, sensitivity, precision, and dependence on electrometer type. In addition, depth-dose and cross-plane profiles were obtained in both photon and electron beams and compared with data obtained with wellbehaved ionizationmore » chambers. Results: In linac beams the precision and linearity was very impressive, with typical values of 0.3% and 0.1% respectively. Performance in a Co-60 beam was much poorer (approximately three times worse) and it is not clear whether this is due to the lower signal current or the effect of the continuous beam (rather than pulsed beam of the linac measurements). There was no significant difference in the detector reading when using either the recommended SI Supermax electrometer or two independent high-quality electrometers, except for low signal levels, where the Supermax exhibited an apparent threshold effect, preventing the measurement of the bremsstrahlung background in electron depth-dose curves. Comparisons with ion chamber measurements in linac beams were somewhat variable: good agreement was seen for cross-profiles (photon and electron beams) and electron beam depth-dose curves, generally within the 0.3% precision of the scintillator but systematic differences were observed as a function of measurement depth in photon beam depth-dose curves. Conclusion: A first look would suggest that the W1 scintillator has applications beyond small field dosimetry but performance appears to be limited to higher doserate and/or pulsed radiation beams. Further work is required to resolve discrepancies compared to ion chambers.« less

Impact of the Lok-bar for High-precision Radiotherapy with Tomotherapy.

PubMed

Hirata, Makoto; Monzen, Hajime; Tamura, Mikoto; Kubo, Kazuki; Matsumoto, Kenji; Hanaoka, Kohei; Okumura, Masahiko; Nishimura, Yasumasa

2018-05-01

Patient immobilization systems are used to establish a reproducible patient position relative to the couch. In this study, the impact of conventional lok-bars for CT-simulation (CIVCO-bar) and treatment (iBEAM-bar) were compared with a novel lok-bar (mHM-bar) in tomotherapy. Verification was obtained as follows: i. artifacts in CT images; ii. dose attenuation rate of lok-bar, compared to without lok-bar; and iii. dose differences between the calculated and measured absorbed doses. With the CIVCO-bar, there were obvious metal artifacts, while there were nearly no artifacts with the mHM-bar. The mean dose attenuation rates with the mHM-bar and iBEAM-bar were 1.31% and 2.28%, and the mean dose difference was 1.55% and 1.66% for mHM-bar and iBEAM-bar. Using the mHM-bar reduced artifacts on the CT image and improved dose attenuation are obtained. The lok-bar needs to be inserted as a structure set in treatment planning with tomotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

High resolution MR based polymer dosimetry versus film densitometry: a systematic study based on the modulation transfer function approach.

PubMed

Berg, A; Pernkopf, M; Waldhäusl, C; Schmidt, W; Moser, E

2004-09-07

Precise methods of modem radiation therapy such as intensity modulated radiotherapy (IMRT), brachytherapy (BT) and high LET irradiation allow for high dose localization in volumes of a few mm3. However, most dosimetry methods-ionization chambers, TLD arrangements or silicon detectors, for example-are not capable of detecting sub-mm dose variations or do not allow for simple dose imaging. Magnetic resonance based polymer dosimetry (MRPD) appears to be well suited to three-dimensional high resolution relative dosimetry but the spatial resolution based on a systematic modulation transfer function (MTF) approach has not yet been investigated. We offer a theoretical construct for addressing the spatial resolution in different dose imaging systems, i.e. the dose modulation transfer function (DMTF) approach, an experimental realization of this concept with a phantom and quantitative comparisons between two dosimetric systems: polymer gel and film dosimetry. Polymer gel samples were irradiated by Co-60 photons through an absorber grid which is characterized by periodic structures of different spatial period (a), the smallest one at width of a/2 = 280 microm. The modulation in dose under the grid is visualized via calibrated, high resolution, parameter-selective (T2) and dose images based on multi-echo MR imaging. The DMTF is obtained from the modulation depth of the spin-spin relaxation time (T2) after calibration. Voxel sizes below 0.04 mm3 could be achieved, which are significantly smaller than those reported in MR based dose imaging on polymer gels elsewhere, using a powerful gradient system and a highly sensitive small birdcage resonator on a whole-body 3T MR scanner. Dose modulations at 22% of maximum dose amplitude could be observed at about 2 line pairs per mm. The polymer DMTF results are compared to those of a typical clinical film-scanner system. This study demonstrates that MR based gel dosimetry at 200 microm pixel resolution might even be superior, with reference to relative spatial resolution, to the results of a standard film-scanner system offering a nominal scan resolution of 200 microm.

Characterizing a pulse-resolved dosimetry system for complex radiotherapy beams using organic scintillators.

PubMed

Beierholm, Anders R; Ottosson, Rickard O; Lindvold, Lars R; Behrens, Claus F; Andersen, Claus E

2011-05-21

A fast-readout dosimetry system based on fibre-coupled organic scintillators has been developed for the purpose of conducting point measurements of absorbed dose in radiotherapy beams involving high spatial and temporal dose gradients. The system measures the dose for each linac radiation pulse with millimetre spatial resolution. To demonstrate the applicability of the system in complex radiotherapy fields, output factors and per cent depth dose measurements were performed in solid water for a 6 MV photon beam and compared with Monte Carlo simulated doses for square fields down to 0.6 cm × 0.6 cm size. No significant differences between measurements and simulations were observed. The temporal resolution of the system was demonstrated by measuring dose per pulse, beam start-up transients and the quality factor for 6 MV. The precision of dose per pulse measurements was within 2.7% (1 SD) for a 10 cm × 10 cm field at 10 cm depth. The dose per pulse behaviour compared well with linac target current measurements and accumulated dose measurements, and the system was able to resolve transient dose delivery differences between two Varian linac builds. The system therefore shows promise for reference dosimetry and quality assurance of complex radiotherapy treatments.

Protons and more: state of the art in radiotherapy.

PubMed

Hoskin, Peter J; Bhattacharya, Indrani S

2014-12-01

The purpose of modern radiotherapy is to deliver a precise high dose of radiation which will result in reproductive death of the cells. Radiation should transverse within the tumour volume whilst minimising damage to surrounding normal tissue. Overall 40% of cancers which are cured will have received radiotherapy. Current state of the art treatment will incorporate cross-sectional imaging and multiple high energy X-ray beams in processes called intensity modulated radiotherapy and image guided radiotherapy. Brachytherapy enables very high radiation doses to be delivered by the direct passage of a radiation source through or within the tumour volume and similar results can be achieved using rotational stereotactic X-ray beam techniques. Protons have the characteristics of particle beams which deposit their energy in a finite fixed peak at depth in tissue with no dose beyond this point - the Bragg peak. This has advantages in certain sites such as the spine adjacent to the spinal cord and particularly in children when the overall volume of tissue receiving radiation can be minimised. © 2014 Royal College of Physicians.

Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study.

PubMed

Abend, M; Badie, C; Quintens, R; Kriehuber, R; Manning, G; Macaeva, E; Njima, M; Oskamp, D; Strunz, S; Moertl, S; Doucha-Senf, S; Dahlke, S; Menzel, J; Port, M

2016-02-01

The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.

The range and intensity of backscattered electrons for use in the creation of high fidelity electron beam lithography patterns.

PubMed

Czaplewski, David A; Holt, Martin V; Ocola, Leonidas E

2013-08-02

We present a set of universal curves that predict the range and intensity of backscattered electrons which can be used in conjunction with electron beam lithography to create high fidelity nanoscale patterns. The experimental method combines direct write dose, backscattered dose, and a self-reinforcing pattern geometry to measure the dose provided by backscattered electrons to a nanoscale volume on the substrate surface at various distances from the electron source. Electron beam lithography is used to precisely control the number and position of incident electrons on the surface of the material. Atomic force microscopy is used to measure the height of the negative electron beam lithography resist. Our data shows that the range and the intensity of backscattered electrons can be predicted using the density and the atomic number of any solid material, respectively. The data agrees with two independent Monte Carlo simulations without any fitting parameters. These measurements are the most accurate electron range measurements to date.

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PubMed

Di Venanzio, C; Marinelli, Marco; Tonnetti, A; Verona-Rinati, G; Falco, M D; Pimpinella, M; Ciccotelli, A; De Stefano, S; Felici, G; Marangoni, F

2015-12-01

To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Statistical analysis of radioimmunoassay. In comparison with bioassay (in Japanese)

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

Nakano, R.

1973-01-01

Using the data of RIA (radioimmunoassay), statistical procedures for dealing with two problems of the linearization of dose response curve and calculation of relative potency were described. There were three methods for linearization of dose response curve of RIA. In each method, the following parameters were shown on the horizontal and vertical axis: dose x, (B/T)/sup -1/; c/x + c, B/T (C: dose which makes B/T 50%); log x, logit B/T. Among them, the last method seems to be most practical. The statistical procedures for bioassay were employed for calculating the relative potency of unknown samples compared to the standardmore » samples from dose response curves of standand and unknown samples using regression coefficient. It is desirable that relative potency is calculated by plotting more than 5 points in the standard curve and plotting more than 2 points in unknow samples. For examining the statistical limit of precision of measuremert, LH activity of gonadotropin in urine was measured and relative potency, precision coefficient and the upper and lower limits of relative potency at 95% confidence limit were calculated. On the other hand, bioassay (by the ovarian ascorbic acid reduction method and anteriol lobe of prostate weighing method) was done in the same samples, and the precision was compared with that of RIA. In these examinations, the upper and lower limits of the relative potency at 95% confidence limit were near each other, while in bioassay, a considerable difference was observed between the upper and lower limits. The necessity of standardization and systematization of the statistical procedures for increasing the precision of RIA was pointed out. (JA)« less

Effect of low-dose CT and iterative reconstruction on trabecular bone microstructure assessment

NASA Astrophysics Data System (ADS)

Kopp, Felix K.; Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Bauer, Jan S.; Noël, Peter B.

2016-03-01

The trabecular bone microstructure is an important factor in the development of osteoporosis. It is well known that its deterioration is one effect when osteoporosis occurs. Previous research showed that the analysis of trabecular bone microstructure enables more precise diagnoses of osteoporosis compared to a sole measurement of the mineral density. Microstructure parameters are assessed on volumetric images of the bone acquired either with high-resolution magnetic resonance imaging, high-resolution peripheral quantitative computed tomography or high-resolution computed tomography (CT), with only CT being applicable to the spine, which is one of clinically most relevant fracture sites. However, due to the high radiation exposure for imaging the whole spine these measurements are not applicable in current clinical routine. In this work, twelve vertebrae from three different donors were scanned with standard and low radiation dose. Trabecular bone microstructure parameters were assessed for CT images reconstructed with statistical iterative reconstruction (SIR) and analytical filtered backprojection (FBP). The resulting structure parameters were correlated to the biomechanically determined fracture load of each vertebra. Microstructure parameters assessed for low-dose data reconstructed with SIR significantly correlated with fracture loads as well as parameters assessed for standard-dose data reconstructed with FBP. Ideal results were achieved with low to zero regularization strength yielding microstructure parameters not significantly different from those assessed for standard-dose FPB data. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis

PubMed Central

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.

2015-01-01

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation. PMID:26107175

Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

DOE PAGES

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; ...

2015-06-24

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were ablemore » to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm 2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Furthermore, such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.« less

Flexible and precise dosing of enalapril maleate for all paediatric age groups utilizing orodispersible minitablets.

PubMed

Thabet, Yasmin; Walsh, Jennifer; Breitkreutz, Joerg

2018-04-25

Enalapril is an off-patent angiotensin-converting enzyme inhibitor for which no paediatric age-appropriate formulation is commercially available in Europe, and enalapril maleate (EM) orodispersible minitablets (ODMTs) have previously been formulated within the LENA (labelling enalapril from neonates to adolescents) project. In this study, a dilution method has been developed by dispersing the lowest dose strength ODMTs to enable flexible and precise EM dosing during the dose titration phase of the therapy. Furthermore, the physicochemical stability of the ODMTs has been investigated in child-friendly beverages and the administration of ODMTs via nasogastric tubes (NGT) of different sizes and materials has been evaluated. The results for the ODMT dilution procedure reveal that dispersion within an oral syringe is preferred over dispersion in a separate container, leading to flexible and precise dosing down to 0.025 mg EM. Although ODMTs were stable in the beverages over the investigated time period, dispersion in tap water only is recommended due to prolonged disintegration times within the other beverages. Dispersed ODMTs can be administered through NGTs of CH5. Almost no adsoprtion of EM on silicone, polyurethane or polyvinyl chloride could be observed. The ODMT concept together with the investigated dispersion method enables the safe administration of EM for all paediatric subpopulations from new-borns to adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.

Process Performance of Optima XEx Single Wafer High Energy Implanter

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

Kim, J. H.; Yoon, Jongyoon; Kondratenko, S.

2011-01-07

To meet the process requirements for well formation in future CMOS memory production, high energy implanters require more robust angle, dose, and energy control while maintaining high productivity. The Optima XEx high energy implanter meets these requirements by integrating a traditional LINAC beamline with a robust single wafer handling system. To achieve beam angle control, Optima XEx can control both the horizontal and vertical beam angles to within 0.1 degrees using advanced beam angle measurement and correction. Accurate energy calibration and energy trim functions accelerate process matching by eliminating energy calibration errors. The large volume process chamber and UDC (upstreammore » dose control) using faraday cups outside of the process chamber precisely control implant dose regardless of any chamber pressure increase due to PR (photoresist) outgassing. An optimized RF LINAC accelerator improves reliability and enables singly charged phosphorus and boron energies up to 1200 keV and 1500 keV respectively with higher beam currents. A new single wafer endstation combined with increased beam performance leads to overall increased productivity. We report on the advanced performance of Optima XEx observed during tool installation and volume production at an advanced memory fab.« less

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment

NASA Astrophysics Data System (ADS)

Raaymakers, B. W.; Jürgenliemk-Schulz, I. M.; Bol, G. H.; Glitzner, M.; Kotte, A. N. T. J.; van Asselen, B.; de Boer, J. C. J.; Bluemink, J. J.; Hackett, S. L.; Moerland, M. A.; Woodings, S. J.; Wolthaus, J. W. H.; van Zijp, H. M.; Philippens, M. E. P.; Tijssen, R.; Kok, J. G. M.; de Groot-van Breugel, E. N.; Kiekebosch, I.; Meijers, L. T. C.; Nomden, C. N.; Sikkes, G. G.; Doornaert, P. A. H.; Eppinga, W. S. C.; Kasperts, N.; Kerkmeijer, L. G. W.; Tersteeg, J. H. A.; Brown, K. J.; Pais, B.; Woodhead, P.; Lagendijk, J. J. W.

2017-12-01

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Small Radiation Beam Dosimetry for Radiosurgery of Trigeminal Neuralgia: One Case Analysis

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

Garcia-Garduno, O. A.; Larraga-Gutierrez, J. M.; Unidad de Radioneurocirugia, Instituto Nacional de Neurologia y Neurocirugia. Insurgentes Sur 3677, Col. La Fama, C. P. 14269, Tlalpan, Mexico, D. F.

2008-08-11

The use of small radiation beams for trigeminal neuralgia (TN) treatment requires high precision and accuracy in dose distribution calculations and delivery. Special attention must be kept on the type of detector to be used. In this work, the use of GafChromic EBT registered radiochromic and X-OMAT V2 radiographic films for small radiation beam characterization is reported. The dosimetric information provided by the films (total output factors, tissue maximum ratios and off axis ratios) is compared against measurements with a shielded solid state (diode) reference detector. The film dosimetry was used for dose distribution calculations for the treatment of trigeminalmore » neuralgia radiosurgery. Comparison of the isodose curves shows that the dosimetry produced with the X-OMAT radiographic film overestimates the dose distributions in the penumbra region.« less

Quantification of Drug Choice with the Generalized Matching Law in Rhesus Monkeys

ERIC Educational Resources Information Center

Koffarnus, Mikhail N.; Woods, James H.

2008-01-01

The generalized matching law provides precise descriptions of choice, but has not been used to characterize choice between different doses of drugs or different classes of drugs. The current study examined rhesus monkeys' drug self-administration choices between identical drug doses, different doses, different drugs (cocaine, remifentanil, and…

Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems.

PubMed

Içten, Elçin; Purohit, Hitesh S; Wallace, Chelsey; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

2017-05-30

The improvements in healthcare systems and the advent of the precision medicine initiative have created the need to develop more innovative manufacturing methods for the delivery and production of individualized dosing and personalized treatments. In accordance with the changes observed in healthcare systems towards more innovative therapies, this paper presents dropwise additive manufacturing of pharmaceutical products (DAMPP) for small scale, distributed manufacturing of individualized dosing as an alternative to conventional manufacturing methods A dropwise additive manufacturing process for amorphous and self-emulsifying drug delivery systems is reported, which utilizes drop-on-demand printing technology for automated and controlled deposition of melt-based formulations onto inert tablets. The advantages of drop on demand technology include reproducible production of droplets with adjustable sizing and high placement accuracy, which enable production of individualized dosing even for low dose and high potency drugs. Flexible use of different formulations, such as lipid-based formulations, allows enhancement of the solubility of poorly water soluble and highly lipophilic drugs with DAMPP. Here, DAMPP is used to produce solid oral dosage forms from melts of an active pharmaceutical ingredient and a surfactant. The dosage forms are analyzed to show the amorphous nature, self-emulsifying drug delivery system characteristics and dissolution behavior of these formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Preventive Effect of Cashew-Derived Protein Hydrolysate with High Fiber on Cerebral Ischemia

PubMed Central

Thukham-mee, Wipawee; Wannanon, Panakaporn; Tiamkao, Somsak

2017-01-01

This study aimed to determine the protective effect of cashew nut-derived protein hydrolysate with high dietary fiber (AO) in cerebral ischemic rats induced by the occlusion of right middle cerebral artery (Rt.MCAO). Acute toxicity was determined and data showed that LD50 of AO > 5000 mg/kg BW. To determine the cerebroprotective effect of AO, male Wistar rats were orally given AO at doses of 2, 10, and 50 mg/kg for 14 days and subjected to Rt.MCAO. Brain infarction volume, neurological score, spatial memory, serum lipid profiles, and C-reactive protein together with the brain oxidative stress status were assessed. All doses of AO significantly decreased brain infarction in cortex, hippocampus, and striatum together with the decreased oxidative stress status. The improvement of spatial memory and serum C-reactive protein were also observed in MCAO rats which received AO at all doses. In addition, the decreased serum cholesterol, TG, and LDL but increased HDL were observed in MCAO rats which received high dose of AO. Taken all together, AO is the potential protectant against cerebral ischemia. The improvement of oxidative stress, inflammation, and dyslipidemia might play roles in the actions. However, further researches are required to understand the precise underlying mechanism. PMID:29457029

Development of Micro and Nano Crystalline CVD Diamond TL/OSL Radiation Detectors for Clinical Applications

NASA Astrophysics Data System (ADS)

Barboza-Flores, Marcelino

2015-03-01

Modern radiotherapy methods requires the use of high photon radiation doses delivered in a fraction to small volumes of cancer tumors. An accurate dose assessment for highly energetic small x-ray beams in small areas, as in stereotactic radiotherapy, is necessary to avoid damage to healthy tissue surrounding the tumor. Recent advances on the controlled synthesis of CVD diamond have demonstrated the possibility of using high quality micro and nano crystalline CVD as an efficient detector and dosimeter suitable for high energy photons and energetic particle beams. CVD diamond is a very attractive material for applications in ionizing radiation dosimetry, particularly in the biomedical field since the radiation absorption by a CVD diamond is very close to that of soft tissue. Furthermore, diamond is stable, non-toxic and radiation hard. In the present work we discuss the CVD diamond properties and dosimeter performance and discuss its relevance and advantages of various dosimetry methods, including thermally stimulated luminescence (TL) as well as optically stimulated luminescence (OSL). The recent CVD improved method of growth allows introducing precisely controlled impurities into diamond to provide it with high dosimetry sensitivity. For clinical dosimetry applications, high accuracy of dose measurements, low fading, high sensitivity, good reproducibility and linear dose response characteristics are very important parameters which all are found in CVD diamonds specimens. In some cases, dose linearity and reproducibility in CVD diamond have been found to be higher than standard commercial TLD materials like LiF. In the present work, we discuss the state-of-the art developments in dosimetry applications using CVD diamond. The financial support from Conacyt (Mexico) is greatly acknowledged

Application of TXRF for ion implanter dose matching experiments

NASA Astrophysics Data System (ADS)

Frost, M. R.; French, M.; Harris, W.

2004-06-01

Secondary ion mass spectrometry (SIMS) has been utilized for many years to measure the dose of ion implants in silicon for the purpose of verifying the ability of ion implantation equipment to accurately and reproducibly implant the desired species at the target dose. The development of statistically and instrumentally rigorous protocols has lead to high confidence levels, particularly with regard to accuracy and short-term repeatability. For example, high-dose, high-energy B implant dosimetry can be targeted to within ±1%. However, performing dose determination experiments using SIMS does have undesirable aspects, such as being highly labor intensive and sample destructive. Modern total reflection X-ray fluorescence (TXRF) instruments are equipped with capabilities for full 300 mm wafer handling, automated data acquisition software and intense X-ray sources. These attributes enable the technique to overcome the SIMS disadvantages listed above, as well as provide unique strengths that make it potentially highly amenable to implanter dose matching. In this paper, we report on data collected to date that provides confidence that TXRF is an effective and economical method to perform these measurements within certain limitations. We have investigated a number of ion implanted species that are within the "envelope" of TXRF application. This envelope is defined by a few important parameters. Species: For the anode materials used in the more common X-ray sources on the market, each has its own set of elements that can be detected. We have investigated W and Mo X-ray sources, which are the most common in use in commercial instrumentation. Implant energy: In general, if the energy of the implanted species is too high (or more specifically, the distribution of the implanted species is too deep), the amount of dopant not detected by TXRF may be significant, increasing the error of the measurement. Therefore, for each species investigated, the implant energy cannot exceed a certain level. Dose: Logically, as the implanted dose falls below a certain point, the concentration will be below the TXRF detection limit. In addition to the improved precision of TXRF over SIMS for dose matching, a number of other advantages will be discussed.

Fast CPU-based Monte Carlo simulation for radiotherapy dose calculation.

PubMed

Ziegenhein, Peter; Pirner, Sven; Ph Kamerling, Cornelis; Oelfke, Uwe

2015-08-07

Monte-Carlo (MC) simulations are considered to be the most accurate method for calculating dose distributions in radiotherapy. Its clinical application, however, still is limited by the long runtimes conventional implementations of MC algorithms require to deliver sufficiently accurate results on high resolution imaging data. In order to overcome this obstacle we developed the software-package PhiMC, which is capable of computing precise dose distributions in a sub-minute time-frame by leveraging the potential of modern many- and multi-core CPU-based computers. PhiMC is based on the well verified dose planning method (DPM). We could demonstrate that PhiMC delivers dose distributions which are in excellent agreement to DPM. The multi-core implementation of PhiMC scales well between different computer architectures and achieves a speed-up of up to 37[Formula: see text] compared to the original DPM code executed on a modern system. Furthermore, we could show that our CPU-based implementation on a modern workstation is between 1.25[Formula: see text] and 1.95[Formula: see text] faster than a well-known GPU implementation of the same simulation method on a NVIDIA Tesla C2050. Since CPUs work on several hundreds of GB RAM the typical GPU memory limitation does not apply for our implementation and high resolution clinical plans can be calculated.

Efficient Boar Semen Production and Genetic Contribution: The Impact of Low-Dose Artificial Insemination on Fertility.

PubMed

Broekhuijse, M L W J; Gaustad, A H; Bolarin Guillén, A; Knol, E F

2015-07-01

Diluting semen from high fertile breeding boars, and by that inseminating many sows, is the core business for artificial insemination (AI) companies worldwide. Knowledge about fertility results is the reason by which an AI company can lower the concentration of a dose. Efficient use of AI boars with high genetic merit by decreasing the number of sperm cells per insemination dose is important to maximize dissemination of the genetic progress made in the breeding nucleus. However, a potential decrease in fertility performance in the field should be weighed against the added value of improved genetics and, in general, is not tolerated in commercial production. This overview provides some important aspects that influence the impact of low-dose AI on fertility: (i) the importance of monitoring field fertility, (ii) the need for accurate and precise semen assessment, (iii) the parameters that are taken into account, (iv) the application of information from genetic and genomic selection and (v) the optimization when using different AI techniques. Efficient semen production, processing and insemination in combination with increasing use of genetic and genomic applications result in maximum impact of genetic trend. © 2015 Blackwell Verlag GmbH.

3D Printing Provides a Precise Approach in the Treatment of Tetralogy of Fallot, Pulmonary Atresia with Major Aortopulmonary Collateral Arteries.

PubMed

Anwar, Shafkat; Rockefeller, Toby; Raptis, Demetrios A; Woodard, Pamela K; Eghtesady, Pirooz

2018-02-03

Patients with tetralogy of Fallot, pulmonary atresia, and multiple aortopulmonary collateral arteries (Tet PA MAPCAs) have a wide spectrum of anatomy and disease severity. Management of these patients can be challenging and often require multiple high-risk surgical and interventional catheterization procedures. These interventions are made challenging by complex anatomy that require the proceduralist to mentally reconstruct three-dimensional anatomic relationships from two-dimensional images. Three-dimensional (3D) printing is an emerging medical technology that provides added benefits in the management of patients with Tet PA MAPCAs. When used in combination with current diagnostic modalities and procedures, 3D printing provides a precise approach to the management of these challenging, high-risk patients. Specifically, 3D printing enables detailed surgical and interventional planning prior to the procedure, which may improve procedural outcomes, decrease complications, and reduce procedure-related radiation dose and contrast load.

Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

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

Nakonechny, Keith; Tran, Muoi; Sasaki, David

Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 seriesmore » linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.« less

A method for depth-dose distribution measurements in tissue irradiated by a proton beam

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

Gambarini, G.; Birattari, C.; Bartolo, D. de

1994-12-31

The use of protons and heavy ions for the treatment of malignant and non-malignant disease has aroused a growing interest in the last decade. The notable advantage of heavy charged particles over photons in external beam radiotherapy lies in the possibility of irradiating a small localized region within the body, keeping a low value for the entrance dose. Owing to this high disuniformity of energy deposition, an essential requirement for treatment planning is a precise evaluation of the spatial distribution of absorbed dose. The proposed method for depth-dose distribution measurements utilizes a chemical dosimeter (ferrous sulphate solution plus sulfuric acidmore » and eventually xylenol orange) incorporated in a gelatine, whose role is the maintenance of spatial information. Ionizing radiation causes a variation in some parameters of the system such as the proton relaxation rates in the solution (measurable by NMR analysis) or the optical absorption of the gel in the visible spectrum (measurable by spectrophotometry).« less

EXPOSURE-DOSE-EFFECT LINKAGES FOR CHEMICALLY REACTIVE AIR TOXIC COMPOUNDS

EPA Science Inventory

This project represents a multidisciplinary collaboration to develop and test methods for more precisely predicting human exposure-dose-response relationships of respiratory tract irritants. These irritants have the unique property of reacting chemically with proteins and lipids ...

Final Aperture Superposition Technique applied to fast calculation of electron output factors and depth dose curves

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

Faddegon, B.A.; Villarreal-Barajas, J.E.; Mt. Diablo Regional Cancer Center, 2450 East Street, Concord, California

2005-11-15

The Final Aperture Superposition Technique (FAST) is described and applied to accurate, near instantaneous calculation of the relative output factor (ROF) and central axis percentage depth dose curve (PDD) for clinical electron beams used in radiotherapy. FAST is based on precalculation of dose at select points for the two extreme situations of a fully open final aperture and a final aperture with no opening (fully shielded). This technique is different than conventional superposition of dose deposition kernels: The precalculated dose is differential in position of the electron or photon at the downstream surface of the insert. The calculation for amore » particular aperture (x-ray jaws or MLC, insert in electron applicator) is done with superposition of the precalculated dose data, using the open field data over the open part of the aperture and the fully shielded data over the remainder. The calculation takes explicit account of all interactions in the shielded region of the aperture except the collimator effect: Particles that pass from the open part into the shielded part, or visa versa. For the clinical demonstration, FAST was compared to full Monte Carlo simulation of 10x10,2.5x2.5, and 2x8 cm{sup 2} inserts. Dose was calculated to 0.5% precision in 0.4x0.4x0.2 cm{sup 3} voxels, spaced at 0.2 cm depth intervals along the central axis, using detailed Monte Carlo simulation of the treatment head of a commercial linear accelerator for six different electron beams with energies of 6-21 MeV. Each simulation took several hours on a personal computer with a 1.7 Mhz processor. The calculation for the individual inserts, done with superposition, was completed in under a second on the same PC. Since simulations for the pre calculation are only performed once, higher precision and resolution can be obtained without increasing the calculation time for individual inserts. Fully shielded contributions were largest for small fields and high beam energy, at the surface, reaching a maximum of 5.6% at 21 MeV. Contributions from the collimator effect were largest for the large field size, high beam energy, and shallow depths, reaching a maximum of 4.7% at 21 MeV. Both shielding contributions and the collimator effect need to be taken into account to achieve an accuracy of 2%. FAST takes explicit account of the shielding contributions. With the collimator effect set to that of the largest field in the FAST calculation, the difference in dose on the central axis (product of ROF and PDD) between FAST and full simulation was generally under 2%. The maximum difference of 2.5% exceeded the statistical precision of the calculation by four standard deviations. This occurred at 18 MeV for the 2.5x2.5 cm{sup 2} field. The differences are due to the method used to account for the collimator effect.« less

Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

PubMed

Cologne, John; Preston, Dale L; Grant, Eric J; Cullings, Harry M; Ozasa, Kotaro

2018-03-01

It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), that the appearance of risk attenuation over time may be the result of less-precise risk estimation-in particular, imprecise estimation of effect-modification parameters-in the earlier periods. Longer follow-up, in addition to allowing more-precise estimation of risk due to larger numbers of radiation-related cases, provides more-precise adjustment for background mortality or incidence and more-accurate assessment of risk modification by age at exposure and attained age. It is concluded that the latest follow-up data are most appropriate for inferring low-dose risk. Furthermore, if researchers are interested in effects of time since exposure, the most-recent follow-up data should be considered rather than the results of earlier reports.

A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

NASA Astrophysics Data System (ADS)

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2015-12-01

Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ~87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Exposing Exposure: Automated Anatomy-specific CT Radiation Exposure Extraction for Quality Assurance and Radiation Monitoring

PubMed Central

Warden, Graham I.; Farkas, Cameron E.; Ikuta, Ichiro; Prevedello, Luciano M.; Andriole, Katherine P.; Khorasani, Ramin

2012-01-01

Purpose: To develop and validate an informatics toolkit that extracts anatomy-specific computed tomography (CT) radiation exposure metrics (volume CT dose index and dose-length product) from existing digital image archives through optical character recognition of CT dose report screen captures (dose screens) combined with Digital Imaging and Communications in Medicine attributes. Materials and Methods: This institutional review board–approved HIPAA-compliant study was performed in a large urban health care delivery network. Data were drawn from a random sample of CT encounters that occurred between 2000 and 2010; images from these encounters were contained within the enterprise image archive, which encompassed images obtained at an adult academic tertiary referral hospital and its affiliated sites, including a cancer center, a community hospital, and outpatient imaging centers, as well as images imported from other facilities. Software was validated by using 150 randomly selected encounters for each major CT scanner manufacturer, with outcome measures of dose screen retrieval rate (proportion of correctly located dose screens) and anatomic assignment precision (proportion of extracted exposure data with correctly assigned anatomic region, such as head, chest, or abdomen and pelvis). The 95% binomial confidence intervals (CIs) were calculated for discrete proportions, and CIs were derived from the standard error of the mean for continuous variables. After validation, the informatics toolkit was used to populate an exposure repository from a cohort of 54 549 CT encounters; of which 29 948 had available dose screens. Results: Validation yielded a dose screen retrieval rate of 99% (597 of 605 CT encounters; 95% CI: 98%, 100%) and an anatomic assignment precision of 94% (summed DLP fraction correct 563 in 600 CT encounters; 95% CI: 92%, 96%). Patient safety applications of the resulting data repository include benchmarking between institutions, CT protocol quality control and optimization, and cumulative patient- and anatomy-specific radiation exposure monitoring. Conclusion: Large-scale anatomy-specific radiation exposure data repositories can be created with high fidelity from existing digital image archives by using open-source informatics tools. ©RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111822/-/DC1 PMID:22668563

Volumetric quantification of lung nodules in CT with iterative reconstruction (ASiR and MBIR).

PubMed

Chen, Baiyu; Barnhart, Huiman; Richard, Samuel; Robins, Marthony; Colsher, James; Samei, Ehsan

2013-11-01

Volume quantifications of lung nodules with multidetector computed tomography (CT) images provide useful information for monitoring nodule developments. The accuracy and precision of the volume quantification, however, can be impacted by imaging and reconstruction parameters. This study aimed to investigate the impact of iterative reconstruction algorithms on the accuracy and precision of volume quantification with dose and slice thickness as additional variables. Repeated CT images were acquired from an anthropomorphic chest phantom with synthetic nodules (9.5 and 4.8 mm) at six dose levels, and reconstructed with three reconstruction algorithms [filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASiR), and model based iterative reconstruction (MBIR)] into three slice thicknesses. The nodule volumes were measured with two clinical software (A: Lung VCAR, B: iNtuition), and analyzed for accuracy and precision. Precision was found to be generally comparable between FBP and iterative reconstruction with no statistically significant difference noted for different dose levels, slice thickness, and segmentation software. Accuracy was found to be more variable. For large nodules, the accuracy was significantly different between ASiR and FBP for all slice thicknesses with both software, and significantly different between MBIR and FBP for 0.625 mm slice thickness with Software A and for all slice thicknesses with Software B. For small nodules, the accuracy was more similar between FBP and iterative reconstruction, with the exception of ASIR vs FBP at 1.25 mm with Software A and MBIR vs FBP at 0.625 mm with Software A. The systematic difference between the accuracy of FBP and iterative reconstructions highlights the importance of extending current segmentation software to accommodate the image characteristics of iterative reconstructions. In addition, a calibration process may help reduce the dependency of accuracy on reconstruction algorithms, such that volumes quantified from scans of different reconstruction algorithms can be compared. The little difference found between the precision of FBP and iterative reconstructions could be a result of both iterative reconstruction's diminished noise reduction at the edge of the nodules as well as the loss of resolution at high noise levels with iterative reconstruction. The findings do not rule out potential advantage of IR that might be evident in a study that uses a larger number of nodules or repeated scans.

A simple LC-MS/MS method using HILIC chromatography for the determination of fosfomycin in plasma and urine: application to a pilot pharmacokinetic study in humans.

PubMed

Parker, Suzanne L; Lipman, Jeffrey; Roberts, Jason A; Wallis, Steven C

2015-02-01

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using hydrophilic interaction liquid chromatography (HILIC) chromatography for the analysis of fosfomycin in human plasma and urine, has been developed and validated. The plasma method uses a simple protein precipitation using a low volume sample (10 μL) and is suitable for the concentration range of 1 to 2000 μg/mL. The urine method involves a simple dilution of 10 μL of sample and is suitable for a concentration range of 0.1 to 10 mg/mL. The plasma and urine results, reported, respectively, are for recovery (68, 72%), inter-assay precision (≤9.1%, ≤8.1%) and accuracy (range -7.2 to 3.3%, -1.9 to 1.6%), LLOQ precision (4.7%, 3.1%) and accuracy (1.7% and 1.2%), and includes investigations into the linearity, stability and matrix effects. The method was used in a pilot pharmacokinetic study of a critically ill patient receiving i.v. fosfomycin, which measured a maximum and minimum plasma concentration of 222 μg/mL and 172 μg/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868 μg/mL and 591μg/mL, respectively, after the fifth dose. The urine concentration was 2.03 mg/mL after the initial dose and 0.29 mg/mL after the fifth dose. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated extraction of radiation dose information from CT dose report images.

PubMed

Li, Xinhua; Zhang, Da; Liu, Bob

2011-06-01

The purpose of this article is to describe the development of an automated tool for retrieving texts from CT dose report images. Optical character recognition was adopted to perform text recognitions of CT dose report images. The developed tool is able to automate the process of analyzing multiple CT examinations, including text recognition, parsing, error correction, and exporting data to spreadsheets. The results were precise for total dose-length product (DLP) and were about 95% accurate for CT dose index and DLP of scanned series.

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.

PROGRAMMABLE TURBIDISTAT FOR SUSPENDED PARTICLES IN LABORATORY AQUARIA

EPA Science Inventory

A system for precise control of suspended particle concentrations in laboratory aquaria is described. It comprises an air-lift dosing system, a transmissometer to measure particle concentration, and a microcomputer which calculates the dose required to achieve a programmed turbid...

[Hypofractionation and radiotherapy: "the eternal return"].

PubMed

Cosset, J-M; Mornex, F; Eschwège, F

2013-10-01

Hypofractionation is not a new idea in radiotherapy. The use of a few high-dose fractions has been proposed by some pioneers of our specialty in the early years of the 20th century. Hypofractionation then reappeared several times in the next decades, based on successive radiobiological concepts, a number of them having been shown to be wrong. The nominal single dose (NSD), for example, so fashionable in the 1970's, dramatically underestimated the late toxicity of the high-dose fractions. Consequently, the NSD was directly responsible for a significant increase of the incidence and of the severity of late complications in large cohorts of patients. The linear-quadratic model (LQ) unequivocally improved our understanding of fractionation sensitivity, but one has to keep in mind its limitations, both in the areas of low and high doses per fraction. For more than a decade, prostate cancer has been the subject of fierce discussions about its sensitivity to fractionation. A number of studies have suggested an unusually low (for a malignant tumor) alpha/beta ratio. However, the available data do not allow a precise evaluation of this ratio; "very low" (1.5 Gy), with an advantage of hypofractionation in terms of local control? Or simply "low" (3-4 Gy), only allowing a reduction of the total number of fractions (with a dose adequately reduced)? While waiting for complementary data, it is advised to remain very careful when modifying the classical schemes towards hypofractionation. Copyright © 2013. Published by Elsevier SAS.

SU-E-T-269: Quality Assurance of Spine Volumetric Modulated Arc Therapy with Flattening Filter Free Beams Using Gafchromic EBT3 Films

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

Choi, Y; Cho, B; Kwak, J

2014-06-01

Purpose: We implemented the Gafchromic film-based patient specific QA of volumetric modulated arc therapy (VMAT) with flattening-filter free (FFF) beams for spine metastases and validated the accuracy of fast arc delivery. Methods: EBT3 films and a homemade cylindrical QA phantom were employed for dosimetric verification of VMATs. For 14 FFF VMAT plans (10 with 10-MV FFF beams and 4 with 6-MV FFF beams), the doses were recalculated on the phantom and delivered by a TrueBeam STx accelerator equipped with a high-definition 120 leaf MLC. The EBT3 films were scanned using an Epson 10000XL scanner through the FilmQA Pro software. Allmore » the irradiated film images were converted to dose map using a calibration response curve. The resulting dose map of film measurement was compared with treatment plan and evaluated using gamma analysis with dose tolerance of 2% within 2 mm. In addition, the point-dose measurement in the phantom using an ion chamber was evaluated as a reference in a ratio of measured and planned doses. Results: The gamma pass rates averaged over all FFF plans for composite-field measurements were 96.0 ± 3.6% (88.9%–99.5%). When adopting a tolerance level of 3% - 3 mm, the gamma pass rates were improved with the ranges from 98% to 100%. In addition, dose profiles and dose distributions showed that spinal cord was protected by the rapid dose fall-off and by delivering the treatment with high precision. In point-dose measurements, the average differences between the measured and planned doses were 0.5% ± 1.0% of the prescription dose. Conclusion: We demonstrated that Gafchromic EBT3 film would be an effective patient-specific QA tool, especially for VMAT of spine SBRT with treatment of small fields and highly gradient dose distributions. The results of film QA verified that the dosimetric accuracy of spine SBRT utilizing RapidArc with FFF beams in our institution is reliable.« less

A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

NASA Astrophysics Data System (ADS)

Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

2015-09-01

Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available: Synthesis procedure, 1HNMR, ESI-MS and additional data. See DOI: 10.1039/c5nr04045k

SU-F-T-255: Accuracy and Precision of Dynamic Tracking Irradiation with VERO-4DRT System

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

Hayashi, N; Takada, Y; Mizuno, T

2016-06-15

Purpose: The VERO-4DRT system is able to provide dynamic tracking irradiation (DTI) for the target with respiratory motion. This technique requires enough commissioning for clinical implementation. The purpose of this study is to make sure the accuracy and precision of DTI using VERO- 4DRT through commissioning from fundamental evaluation to end-to-end test. Method: We evaluated several contents for DTI commissioning: the accuracy of absorption dose at isocenter in DTI, the field size and penumbra of DTI, the accuracy of 4D modeling in DTI. All evaluations were performed by respiratory motion phantom (Quasar phantom). These contents were compared the results betweenmore » static irradiation and DTI. The shape of radiation field was set to square from 3 cm × 3 cm to 10 cm × 10 cm. The micro 3D chamber and Gafchromic EBT3 film were used for absorbed dose and relative dose distribution measurement, respectively. The sine and irregular shaped waves were used for demonstrative respiratory motion. The visicoil was implanted into the phantom for guidance of respiratory motion. The respiration patterns of frequency and motion amount were set to 10–15 BPM and 1–2 cm, respectively. Results: As the result of absorbed dose of DTI in comparison with static irradiation, the average dose error at isocenter was 0.5% even though various respiratory patterns were set on. As the result of relative dose distribution, the field size (set it on 50% dose line) was not significantly changed in all respiratory patterns. However, the penumbra was larger in greater respiratory motion (up to 4.1 mm). The 4D modeling coincidence between actual and created waves was within 1%. Conclusion: The DTI using VERO-4DRT can provide sufficient accuracy and precision in absorbed dose and distribution. However, the patientspecific quantitative internal margin corresponding respiratory motion should be taken into consideration with image guidance.« less

Neuroscience and Accelerator Mass Spectrometry

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

Palmblad, M N; Buchholz, B A; Hillegonds, D J

Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as {sup 3}H, {sup 14}C, {sup 26}Al, {sup 36}Cl and {sup 41}Ca, with zepto- or attomole sensitivity and high precision and throughput, enabling safe human pharmacokinetic studies involving: microgram doses, agents having low bioavailability, or toxicology studies where administered doses must be kept low (<1 {micro}g/kg). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets ofmore » neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the timescale of decades. We will here review how AMS is applied in neurotoxicology and neuroscience.« less

Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

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

Goody, Rebecca B.; MacKay, Helen; Pitcher, Bethany

Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m{sup 2}/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m{sup 2}) during weeks 1, 3, 5, and 7, and an additional week 9 dose in themore » final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m{sup 2} cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion: Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.« less

Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

PubMed

Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

2017-08-01

Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ 2 tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. The high-dose-requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low-dose-requiring women. Nine nonsynonymous variants were unique to the high-dose-requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173R were predicted by Scale-Invariant Feature Transform algorithm to damage oxytocin receptor function. There was no statistically significant association between the numbers of synonymous and nonsynonymous substitutions in the patient groups. Obesity, diabetes, and labor induction were associated with the requirement for high doses of oxytocin. We did not identify significant differences in the prevalence of oxytocin receptor variants between low-dose-requiring and high-dose-requiring women, but novel oxytocin receptor variants were enriched in the high-dose-requiring women. We also found 3 oxytocin receptor variants (2 novel, 1 known) that were predicted to damage oxytocin receptor function and would likely increase an individual's risk for requiring a high oxytocin dose. Further investigation of oxytocin receptor variants and their effects on protein function will inform precision medicine in pregnant women. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

OPTIMIZING THE PRECISION OF TOXICITY THRESHOLD ESTIMATION USING A TWO-STAGE EXPERIMENTAL DESIGN

EPA Science Inventory

An important consideration for risk assessment is the existence of a threshold, i.e., the highest toxicant dose where the response is not distinguishable from background. We have developed methodology for finding an experimental design that optimizes the precision of threshold mo...

3D Nanochannel Array Platform for High-throughput Cell Manipulation and Nano-electroporation

NASA Astrophysics Data System (ADS)

Chang, Lingqian

Electroporation is one of the most common non-viral methods for gene delivery. Recent progress in gene therapy has offered special opportunities to electroporation for in vitro and in vivo applications. However, conventional bulk electroporation (BEP) inevitably causes serious cell damage and stochastic transfection between cells. Microfluidic electroporation (MEP) has been claimed to provide benign single cell transfection for the last decade. Nevertheless, the intracellular transport in both MEP and BEP systems is highly diffusion-dominant, which prevents precise dose control and high uniformity. In this Ph.D. research, we developed a 3D nanochannel-electroporation (3D NEP) platform for mass cell transfection. A silicon-based nanochannel array (3D NEP) chip was designed and fabricated for cell manipulation and electroporation. The chip, designed as Z-directional microchannel - nanochannel array, was fabricated by clean room techniques including projection photolithography and deep reactive-ion etching (DRIE). The fabricated 3D NEP chip is capable of handling 40,000 cells per 1 cm2, up to 1 million per wafer (100 mm diameter). High-throughput cell manipulation technologies were investigated for precise alignment of individual cells to the nanochannel array, a key step for NEP to achieve dose control. We developed three techniques for cell trapping in this work. (1) Magnetic tweezers (MTs) were integrated on the chip to remotely control cells under a programmed magnetic field. (2) A positive dielectrophoresis (pDEP) power system was built as an alternative to trap cells onto the nanochannel array using DEP force. (3) A novel yet simple 'dipping-trap' method was used to rapidly trap cells onto a nanochannel array, aligned by a micro-cap array pattern on the 3D NEP chip, which eventually offered 70 - 90 % trapping efficiency and 90 % specificity. 3D NEP platforms were assembled for cell transfection based on the Si-based nanochannel array chip and cell manipulation techniques. Cells were patterned on the nanochannel array and collectively were electroporated in parallel, injected with cargo in Z-direction. Controlling the dose was demonstrated with the external pulse durations at high-throughput. The 'electrophoretic'- expedited delivery of large molecular weight plasmids were demonstrated with large numbers of primary cells simultaneously, which cannot be achieved in BEP and MEP. Two clinically valuable case studies were performed with our 3D NEP for living cell sensing / interrogation. (1) In the case of in vitro transfection of primary cardiomyocytes, we studied the dose-effects of miR-29 on mitochondrial changes and the suppression of the Mcl-1 gene in adult mouse cardiomyocytes by precisely controlling the miR-29 dose injected. (2) Glioma stem cells (GSCs), a type of cell hypothesized to be highly aggressive and to lead to the relapses of gliobastoma in human brain, was studied at single cell resolution on 3D NEP platform. The developed 3D NEP system moves towards clinically oriented and user-friendly tools for life science applications. The batch-treated cells with controlled dosage delivery provide a useful tool for single cell analysis. The pioneering experiments in this work have demonstrated the 3D NEP for the applications of cell reprogramming, adoptive immunotherapy, in vitro cardiomyocytes transfection and glioma stem cells study.

The relationship between carbohydrate and the mealtime insulin dose in type 1 diabetes.

PubMed

Bell, Kirstine J; King, Bruce R; Shafat, Amir; Smart, Carmel E

2015-01-01

A primary focus of the nutritional management of type 1 diabetes has been on matching prandial insulin therapy with carbohydrate amount consumed. Different methods exist to quantify carbohydrate including counting in one gram increments, 10g portions or 15g exchanges. Clinicians have assumed that counting in one gram increments is necessary to precisely dose insulin and optimize postprandial control. Carbohydrate estimations in portions or exchanges have been thought of as inadequate because they may result in less precise matching of insulin dose to carbohydrate amount. However, studies examining the impact of errors in carbohydrate quantification on postprandial glycemia challenge this commonly held view. In addition it has been found that a single mealtime bolus of insulin can cover a range of carbohydrate intake without deterioration in postprandial control. Furthermore, limitations exist in the accuracy of the nutrition information panel on a food label. This article reviews the relationship between carbohydrate quantity and insulin dose, highlighting limitations in the evidence for a linear association. These insights have significant implications for patient education and mealtime insulin dose calculations. Copyright © 2015 Elsevier Inc. All rights reserved.

Accuracy and Precision of Three-Dimensional Low Dose CT Compared to Standard RSA in Acetabular Cups: An Experimental Study.

PubMed

Brodén, Cyrus; Olivecrona, Henrik; Maguire, Gerald Q; Noz, Marilyn E; Zeleznik, Michael P; Sköldenberg, Olof

2016-01-01

Background and Purpose. The gold standard for detection of implant wear and migration is currently radiostereometry (RSA). The purpose of this study is to compare a three-dimensional computed tomography technique (3D CT) to standard RSA as an alternative technique for measuring migration of acetabular cups in total hip arthroplasty. Materials and Methods. With tantalum beads, we marked one cemented and one uncemented cup and mounted these on a similarly marked pelvic model. A comparison was made between 3D CT and standard RSA for measuring migration. Twelve repeated stereoradiographs and CT scans with double examinations in each position and gradual migration of the implants were made. Precision and accuracy of the 3D CT were calculated. Results. The accuracy of the 3D CT ranged between 0.07 and 0.32 mm for translations and 0.21 and 0.82° for rotation. The precision ranged between 0.01 and 0.09 mm for translations and 0.06 and 0.29° for rotations, respectively. For standard RSA, the precision ranged between 0.04 and 0.09 mm for translations and 0.08 and 0.32° for rotations, respectively. There was no significant difference in precision between 3D CT and standard RSA. The effective radiation dose of the 3D CT method, comparable to RSA, was estimated to be 0.33 mSv. Interpretation. Low dose 3D CT is a comparable method to standard RSA in an experimental setting.

Improved sulfide mitigation in sewers through on-line control of ferrous salt dosing.

PubMed

Ganigué, Ramon; Jiang, Guangming; Liu, Yiqi; Sharma, Keshab; Wang, Yue-Cong; Gonzalez, José; Nguyen, Tung; Yuan, Zhiguo

2018-05-15

Water utilities worldwide spend annually billions of dollars to control sulfide-induced corrosion in sewers. Iron salts chemically oxidize and/or precipitate dissolved sulfide in sewage and are especially used in medium- and large-size sewers. Iron salt dosing rates are defined ad hoc, ignoring variation in sewage flows and sulfide levels. This often results in iron overdosing or poor sulfide control. Online dosing control can adjust the chemical dosing rates to current (and future) state of the sewer system, allowing high-precision, stable and cost-effective sulfide control. In this paper, we report a novel and robust online control strategy for the dosing of ferrous salt in sewers. The control considers the fluctuation of sewage flow, pH, sulfide levels and also the perturbation from rainfall. Sulfide production in the pipe is predicted using auto-regressive models (AR) based on current flow measurements, which in turn can be used to determine the dose of ferrous salt required for cost-effective sulfide control. Following comprehensive model-based assesment, the control was successfully validated and its effectiveness demonstrated in a 3-week field trial. The online control algorithm controlled sulfide below the target level (0.5 mg S/L) while reducing chemical dosing up to 30%. Copyright © 2018 Elsevier Ltd. All rights reserved.

Validation of a virtual source model of medical linac for Monte Carlo dose calculation using multi-threaded Geant4

NASA Astrophysics Data System (ADS)

Aboulbanine, Zakaria; El Khayati, Naïma

2018-04-01

The use of phase space in medical linear accelerator Monte Carlo (MC) simulations significantly improves the execution time and leads to results comparable to those obtained from full calculations. The classical representation of phase space stores directly the information of millions of particles, producing bulky files. This paper presents a virtual source model (VSM) based on a reconstruction algorithm, taking as input a compressed file of roughly 800 kb derived from phase space data freely available in the International Atomic Energy Agency (IAEA) database. This VSM includes two main components; primary and scattered particle sources, with a specific reconstruction method developed for each. Energy spectra and other relevant variables were extracted from IAEA phase space and stored in the input description data file for both sources. The VSM was validated for three photon beams: Elekta Precise 6 MV/10 MV and a Varian TrueBeam 6 MV. Extensive calculations in water and comparisons between dose distributions of the VSM and IAEA phase space were performed to estimate the VSM precision. The Geant4 MC toolkit in multi-threaded mode (Geant4-[mt]) was used for fast dose calculations and optimized memory use. Four field configurations were chosen for dose calculation validation to test field size and symmetry effects, , , and for squared fields, and for an asymmetric rectangular field. Good agreement in terms of formalism, for 3%/3 mm and 2%/3 mm criteria, for each evaluated radiation field and photon beam was obtained within a computation time of 60 h on a single WorkStation for a 3 mm voxel matrix. Analyzing the VSM’s precision in high dose gradient regions, using the distance to agreement concept (DTA), showed also satisfactory results. In all investigated cases, the mean DTA was less than 1 mm in build-up and penumbra regions. In regards to calculation efficiency, the event processing speed is six times faster using Geant4-[mt] compared to sequential Geant4, when running the same simulation code for both. The developed VSM for 6 MV/10 MV beams widely used, is a general concept easy to adapt in order to reconstruct comparable beam qualities for various linac configurations, facilitating its integration for MC treatment planning purposes.

Development, Optimization, and Validation of a Microplate Bioassay for Relative Potency Determination of Linezolid Using a Design Space Concept, and its Measurement Uncertainty.

PubMed

Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello

2015-01-01

The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.

Comparison of two indices of exposure to polycyclic aromatic hydrocarbons in a retrospective aluminium smelter cohort.

PubMed

Friesen, Melissa C; Demers, Paul A; Spinelli, John J; Lorenzi, Maria F; Le, Nhu D

2007-04-01

The association between coal tar-derived substances, a complex mixture of polycyclic aromatic hydrocarbons, and cancer is well established. However, the specific aetiological agents are unknown. To compare the dose-response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo(a)pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes. The study population consisted of 6423 men with > or =3 years of work experience at an aluminium smelter (1954-97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose-response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log-log model). The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log-log dose-response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI. BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI. Similar conclusions regarding the associations could be made regardless of the exposure metric.

Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

PubMed

Eser, Alexander; Primas, Christian; Reinisch, Sieglinde; Vogelsang, Harald; Novacek, Gottfried; Mould, Diane R; Reinisch, Walter

2018-01-30

Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab. © 2018, The American College of Clinical Pharmacology.

Monitoring femtosecond laser microscopic photothermolysis with multimodal microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; McLean, David I.; Zeng, Haishan

2016-02-01

Photothermolysis induced by femtosecond (fs) lasers may be a promising modality in dermatology because of its advantages of high precision due to multiphoton absorption and deeper penetration due to the use of near infrared wavelengths. Although multiphoton absorption nonlinear effects are capable of precision targeting, the femtosecond laser photothermolysis could still have effects beyond the targeted area if a sufficiently high dose of laser light is used. Such unintended effects could be minimized by real time monitoring photothermolysis during the treatment. Targeted photothermolytic treatment of ex vivo mouse skin dermis was performed with tightly focused fs laser beams. Images of reflectance confocal microscopy (RCM), second harmonic generation (SHG), and two-photon fluorescence (TPF) of the mouse skins were obtained with integrated multimodal microscopy before, during, and after the laser treatment. The RCM, SHG, and TPF signal intensities of the treatment areas changed after high power femtosecond laser irradiation. The intensities of the RCM and SHG signals decreased when the tissue was damaged, while the intensity of the TPF signal increased when the photothermolysis was achieved. Moreover, the TPF signal was more susceptible to the degree of the photothermolysis than the RCM and SHG signals. The results suggested that multimodal microscopy is a potentially useful tool to monitor and assess the femtosecond laser treatment of the skin to achieve microscopic photothermolysis with high precision.

High-precision gamma-ray spectroscopy of 61Cu, an emerging medical isotope used in positron emission tomography

NASA Astrophysics Data System (ADS)

Nelson, N.; Ellison, P.; Nickles, R.; McCutchan, E.; Sonzogni, A.; Smith, S.; Greene, J.; Carpenter, M.; Zhu, S.; Lister, C.; Moran, K.

2017-09-01

61Cu (t1 / 2 = 3.339h) is an important medical isotope used in positron emission tomography (PET) tumor hypoxia imaging scans; however, its beta-plus decay and the subsequent gamma decay of 61Ni has not been studied in over 30 years. Therefore, high quality decay data of 61Cu is desired to determine the overall dose delivered to a patient. In this study, 61Cu was produced at the University of Wisconsin - Madison cyclotron and then assayed using the Gammasphere array at Argonne National Laboratory. Consisting of 70 Compton-suppressed high-purity germanium (HPGe) detectors, Gammasphere provides precise decay data that exceeds that of previous 61Cu studies. γ-ray singles and coincident data were recorded and then analyzed using Radware gf3m software. Through γ- γ coincidence techniques, new γ-ray transitions were identified and high precision determination of γ-ray intensities were made. These modifications and additions to the current decay scheme will be presented, and their impact on the resulting does estimates will be discussed. DOE Isotope Program is acknowledged for funding ST5001030. Work supported by the U.S. DOE under Grant No. DE-FG02-94ER40848 and Contract Nos. DE-AC02-98CH10946 and DE-AC02-06CH11357 and by the Science Undergraduate Laboratory Internship Program (SULI).

Detecting and locating light atoms from high-resolution STEM images: The quest for a single optimal design.

PubMed

Gonnissen, J; De Backer, A; den Dekker, A J; Sijbers, J; Van Aert, S

2016-11-01

In the present paper, the optimal detector design is investigated for both detecting and locating light atoms from high resolution scanning transmission electron microscopy (HR STEM) images. The principles of detection theory are used to quantify the probability of error for the detection of light atoms from HR STEM images. To determine the optimal experiment design for locating light atoms, use is made of the so-called Cramér-Rao Lower Bound (CRLB). It is investigated if a single optimal design can be found for both the detection and location problem of light atoms. Furthermore, the incoming electron dose is optimised for both research goals and it is shown that picometre range precision is feasible for the estimation of the atom positions when using an appropriate incoming electron dose under the optimal detector settings to detect light atoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses

PubMed Central

Kringel, D; Ultsch, A; Zimmermann, M; Jansen, J-P; Ilias, W; Freynhagen, R; Griessinger, N; Kopf, A; Stein, C; Doehring, A; Resch, E; Lötsch, J

2017-01-01

Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces ‘big data’ exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics. PMID:27139154

Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses.

PubMed

Kringel, D; Ultsch, A; Zimmermann, M; Jansen, J-P; Ilias, W; Freynhagen, R; Griessinger, N; Kopf, A; Stein, C; Doehring, A; Resch, E; Lötsch, J

2017-10-01

Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces 'big data' exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics.

Repeated application of Modafinil and Levodopa reveals a drug-independent precise timing of spatial working memory modulation.

PubMed

Bezu, M; Shanmugasundaram, B; Lubec, G; Korz, V

2016-10-01

Cognition enhancing drugs often target the dopaminergic system, which is involved in learning and memory, including working memory that in turn involves mainly the prefrontal cortex and the hippocampus. In most animal models for modulations of working memory animals are pre-trained to a certain criterion and treated then acutely to test drugs effects on working memory. Thus, little is known regarding subchronic or chronic application of cognition enhancing drugs and working memory performance. Therefore we trained male rats over six days in a rewarded alternation test in a T-maze. Rats received daily injections of either modafinil or Levodopa (L-Dopa) at a lower and a higher dose 30min before training. Levodopa but not modafinil increased working memory performance during early training significantly at day 3 when compared to vehicle controls. Both drugs induced dose dependent differences in working memory with significantly better performance at low doses compared to high doses for modafinil, in contrast to L-Dopa where high dose treated rats performed better than low dose rats. Strikingly, these effects appeared only at day 3 for both drugs, followed by a decline in behavioral performance. Thus, a critical drug independent time window for dopaminergic effects upon working memory could be revealed. Evaluating the underlying mechanisms contributes to the understanding of temporal effects of dopamine on working memory performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

PubMed Central

Meier, Robert

2015-01-01

Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system

NASA Astrophysics Data System (ADS)

Sportelli, G.; Belcari, N.; Camarlinghi, N.; Cirrone, G. A. P.; Cuttone, G.; Ferretti, S.; Kraan, A.; Ortuño, J. E.; Romano, F.; Santos, A.; Straub, K.; Tramontana, A.; Del Guerra, A.; Rosso, V.

2014-01-01

During particle therapy irradiation, positron emitters with half-lives ranging from 2 to 20 min are generated from nuclear processes. The half-lives are such that it is possible either to detect the positron signal in the treatment room using an in-beam positron emission tomography (PET) system, right after the irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since the activity distribution is spatially correlated with the dose, it is possible to use PET imaging as an indirect method to assure the quality of the dose delivery. In this work, we present a new dedicated PET system able to operate in-beam. The PET apparatus consists in two 10 cm × 10 cm detector heads. Each detector is composed of four scintillating matrices of 23 × 23 LYSO crystals. The crystal size is 1.9 mm × 1.9 mm × 16 mm. Each scintillation matrix is read out independently with a modularized acquisition system. The distance between the two opposing detector heads was set to 20 cm. The system has very low dead time per detector area and a 3 ns coincidence window, which is capable to sustain high single count rates and to keep the random counts relatively low. This allows a new full-beam monitoring modality that includes data acquisition also while the beam is on. The PET system was tested during the irradiation at the CATANA (INFN, Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with different doses and dose rates were analysed. In all cases the random to total coincidences ratio was equal or less than 25%. For each measurement we estimated the accuracy and precision of the activity range on a set of voxel lines within an irradiated PMMA phantom. Results show that the inclusion of data acquired during the irradiation, referred to as beam-on data, improves both the precision and accuracy of the range measurement with respect to data acquired only after irradiation. Beam-on data alone are enough to give precisions better than 1 mm when at least 5 Gy are delivered.

Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer.

PubMed

Cui, Zhen; Tian, Ye; He, Bin; Li, Hongwei; Li, Duojie; Liu, Jingjing; Cai, Hanfei; Lou, Jianjun; Jiang, Hao; Shen, Xueming; Peng, Kaigui

2015-01-01

Radiation pneumonitis is one of the most severe complications of esophageal cancer. To explore the factors correlated to radiation pneumonitis induced by precise radiotherapy for elderly patients with esophageal cancer. The retrospective analysis was used to collect clinical data from 186 elderly patients with esophageal cancer. The incidence of radiation pneumonitis was observed, followed by statistical analysis through ANVON or multiple regression analysis. 27 in 186 cases of esophageal cancer suffered from radiation pneumonitis, with incidence of 14.52%. The single factor analysis showed that, Karnofsky performance status (KPS) score, chronic obstructive pulmonary disease, concurrent chemoradiotherapy, gross tumor volume (GTV) dose, lung V20, mean lung dose (MLD) and planning target volume (PTV) were associated with radiation pneumonitis. The logistic regression analysis indicated that, concurrent chemoradiotherapy, GTV dose, lung V20 and PTV were the independent factors of radiation pneumonitis. The concurrent chemoradiotherapy, GTV dose, lung V20, MLD and PTV are the major risk factors of radiation pneumonitis for elderly patients with esophageal cancer.

Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments.

PubMed

Ho, Lavine; White, Peter; Chan, Edward; Chan, Kim; Ng, Janet; Tam, Timothy

2012-01-01

Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. Two types of technique (anterior-posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. The highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

PubMed

Hishiki, Tomoro; Matsumoto, Kimikazu; Ohira, Miki; Kamijo, Takehiko; Shichino, Hiroyuki; Kuroda, Tatsuo; Yoneda, Akihiro; Soejima, Toshinori; Nakazawa, Atsuko; Takimoto, Tetsuya; Yokota, Isao; Teramukai, Satoshi; Takahashi, Hideto; Fukushima, Takashi; Kaneko, Takashi; Hara, Junichi; Kaneko, Michio; Ikeda, Hitoshi; Tajiri, Tatsuro; Nakagawara, Akira

2018-04-26

The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

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

Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.

2015-09-01

Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiationmore » therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.« less

Anisotropic pyrochemical microetching of poly(tetrafluoroethylene) initiated by synchrotron radiation-induced scission of molecule bonds

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

Yamaguchi, Akinobu, E-mail: yamaguti@lasti.u-hyogo.ac.jp, E-mail: utsumi@lasti.u-hyogo.ac.jp; Kido, Hideki; Utsumi, Yuichi, E-mail: yamaguti@lasti.u-hyogo.ac.jp, E-mail: utsumi@lasti.u-hyogo.ac.jp

2016-02-01

We developed a process for micromachining polytetrafluoroethylene (PTFE): anisotropic pyrochemical microetching induced by synchrotron X-ray irradiation. X-ray irradiation was performed at room temperature. Upon heating, the irradiated PTFE substrates exhibited high-precision features. Both the X-ray diffraction peak and Raman signal from the irradiated areas of the substrate decreased with increasing irradiation dose. The etching mechanism is speculated as follows: X-ray irradiation caused chain scission, which decreased the number-average degree of polymerization. The melting temperature of irradiated PTFE decreased as the polymer chain length decreased, enabling the treated regions to melt at a lower temperature. The anisotropic pyrochemical etching process enabledmore » the fabrication of PTFE microstructures with higher precision than simultaneously heating and irradiating the sample.« less

Radiation measurements aboard the fourth Gemini flight.

PubMed

Janni, J F; Schneider, M F

1967-01-01

Two special tissue-equivalent ionization chambers and 5 highly sensitive passive dosimetry packages were flown aboard the recent Gemini 4 flight for the purpose of obtaining precise values of instantaneous dose rate, accumulated dose. and shielding effectiveness. This experiment marked the first time that well-defined tissue dose and radiation survey measurements have been carried out in manned spaceflight operations. Since all measurements were accomplished under normal spacecraft environmental conditions, the biological dose resulted primarily from trapped inner Van Allen Belt radiation encountered by the spacecraft in the South Atlantic Anomaly. The experiment determined the particle type, ionizing and penetrating power, and variation with time and position within the Gemini spacecraft. Measured dose rates ranged from 100 mrad/hr for passes penetrating deeply into the South Atlantic Anomaly to less than 0.1 mrad/hr from lower latitude cosmic radiation. The accumulated tissue dose measured by the active ionization chambers, shielded by 0.4 gm/cm2 for the 4-day mission, was 82 mrad. Since the 5 passive dosimetry packages were each located in different positions within the spacecraft, the total mission surface dose measured by these detectors varied from 73 to 27 mrad, depending upon location and shielding. The particles within the spacecraft were recorded in nuclear emulsion, which established that over 90% of the tissue dose was attributable to penetrating protons. This experiment indicates that the radiation environment under shielded conditions at Gemini altitudes was not hazardous.

Standard and Nonstandard Craniospinal Radiotherapy Using Helical TomoTherapy

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

Parker, William, E-mail: william@medphys.mcgill.c; Brodeur, Marylene; Roberge, David

2010-07-01

Purpose: To show the advantages of planning and delivering craniospinal radiotherapy with helical TomoTherapy (TomoTherapy Inc., Madison, WI) by presenting 4 cases treated at our institution. Methods and Materials: We first present a standard case of craniospinal irradiation in a patient with recurrent myxopapillary ependymoma (MPE) and follow this with 2 cases requiring differential dosing to multiple target volumes. One of these, a patient with recurrent medulloblastoma, required a lower dose to be delivered to the posterior fossa because the patient had been previously irradiated to the full dose, and the other required concurrent boosts to leptomeningeal metastases as partmore » of his treatment for newly diagnosed MPE. The final case presented is a patient with pronounced scoliosis who required spinal irradiation for recurrent MPE. Results: The four cases presented were planned and treated successfully with Helical Tomotherapy. Conclusions: Helical TomoTherapy delivers continuous arc-based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Increased healthy tissue sparing is achieved at higher doses albeit at the expense of larger volumes of tissue receiving lower doses. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very elegant dose distributions. Daily megavoltage computed tomography imaging allows for precision of patient positioning, permitting a reduction in planning margins and increased healthy tissue sparing in comparison with standard techniques.« less

Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3.

PubMed

Harris, Ruth B S; Desai, Bhavna N

2016-12-01

Previous studies have shown that very low-dose infusions of leptin into the third or the fourth ventricle alone have little effect on energy balance, but simultaneous low-dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (p-STAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses of leptin into the fourth ventricle inhibits food intake and weight gain. Therefore, we tested whether fourth-ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus. In a dose response study 14-day infusions of increasing doses of leptin showed significant hypophagia, weight loss, and increased hypothalamic p-STAT3 in rats receiving at least 0.9 μg leptin/day. In a second study 0.6 μg leptin/day transiently inhibited food intake and reduced carcass fat, but had no significant effect on energy expenditure. In a final study, we identified the localization of STAT3 activation in the hypothalamus of rats receiving 0, 0.3, or 1.2 μg leptin/day. The high dose of leptin, which caused weight loss in the first experiment, increased p-STAT3 in the ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. The low dose that increased brown fat UCP1 but did not affect body composition in the first experiment had little effect on hypothalamic p-STAT3. We propose that hindbrain leptin increases the precision of control of energy balance by lowering the threshold for leptin signaling in the forebrain. Further studies are needed to directly test this hypothesis. Copyright © 2016 the American Physiological Society.

High density scintillating glass proton imaging detector

NASA Astrophysics Data System (ADS)

Wilkinson, C. J.; Goranson, K.; Turney, A.; Xie, Q.; Tillman, I. J.; Thune, Z. L.; Dong, A.; Pritchett, D.; McInally, W.; Potter, A.; Wang, D.; Akgun, U.

2017-03-01

In recent years, proton therapy has achieved remarkable precision in delivering doses to cancerous cells while avoiding healthy tissue. However, in order to utilize this high precision treatment, greater accuracy in patient positioning is needed. An accepted approximate uncertainty of +/-3% exists in the current practice of proton therapy due to conversions between x-ray and proton stopping power. The use of protons in imaging would eliminate this source of error and lessen the radiation exposure of the patient. To this end, this study focuses on developing a novel proton-imaging detector built with high-density glass scintillator. The model described herein contains a compact homogeneous proton calorimeter composed of scintillating, high density glass as the active medium. The unique geometry of this detector allows for the measurement of both the position and residual energy of protons, eliminating the need for a separate set of position trackers in the system. Average position and energy of a pencil beam of 106 protons is used to reconstruct the image rather than by analyzing individual proton data. Simplicity and efficiency were major objectives in this model in order to present an imaging technique that is compact, cost-effective, and precise, as well as practical for a clinical setting with pencil-beam scanning proton therapy equipment. In this work, the development of novel high-density glass scintillator and the unique conceptual design of the imager are discussed; a proof-of-principle Monte Carlo simulation study is performed; preliminary two-dimensional images reconstructed from the Geant4 simulation are presented.

Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma

PubMed Central

Sumino, Kaharu; Sugar, Elizabeth A.; Irvin, Charles G.; Kaminsky, David A.; Shade, Dave; Wei, Christine Y.; Holbrook, Janet T.; Wise, Robert A.; Castro, Mario

2014-01-01

Background The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose–response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established. Objectives To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20. Methods A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval. Results Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements. Conclusion The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20. PMID:24507830

Adaptation, Commissioning, and Evaluation of a 3D Treatment Planning System for High-Resolution Small-Animal Irradiation

PubMed Central

Jeong, Jeho; Chen, Qing; Febo, Robert; Yang, Jie; Pham, Hai; Xiong, Jian-Ping; Zanzonico, Pat B.; Deasy, Joseph O.; Humm, John L.; Mageras, Gig S.

2016-01-01

Although spatially precise systems are now available for small-animal irradiations, there are currently limited software tools available for treatment planning for such irradiations. We report on the adaptation, commissioning, and evaluation of a 3-dimensional treatment planning system for use with a small-animal irradiation system. The 225-kV X-ray beam of the X-RAD 225Cx microirradiator (Precision X-Ray) was commissioned using both ion-chamber and radiochromic film for 10 different collimators ranging in field size from 1 mm in diameter to 40 × 40 mm2. A clinical 3-dimensional treatment planning system (Metropolis) developed at our institution was adapted to small-animal irradiation by making it compatible with the dimensions of mice and rats, modeling the microirradiator beam orientations and collimators, and incorporating the measured beam data for dose calculation. Dose calculations in Metropolis were verified by comparison with measurements in phantoms. Treatment plans for irradiation of a tumor-bearing mouse were generated with both the Metropolis and the vendor-supplied software. The calculated beam-on times and the plan evaluation tools were compared. The dose rate at the central axis ranges from 74 to 365 cGy/min depending on the collimator size. Doses calculated with Metropolis agreed with phantom measurements within 3% for all collimators. The beam-on times calculated by Metropolis and the vendor-supplied software agreed within 1% at the isocenter. The modified 3-dimensional treatment planning system provides better visualization of the relationship between the X-ray beams and the small-animal anatomy as well as more complete dosimetric information on target tissues and organs at risk. It thereby enhances the potential of image-guided microirradiator systems for evaluation of dose–response relationships and for preclinical experimentation generally. PMID:25948321

PROPOSAL FOR A SIMPLE AND EFFICIENT MONTHLY QUALITY MANAGEMENT PROGRAM ASSESSING THE CONSISTENCY OF ROBOTIC IMAGE-GUIDED SMALL ANIMAL RADIATION SYSTEMS

PubMed Central

Brodin, N. Patrik; Guha, Chandan; Tomé, Wolfgang A.

2015-01-01

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and efficient QMP for image-guided robotic small animal irradiators used in pre-clinical RT research is described. Protocols were developed and implemented to assess the dose output constancy (based on the AAPM TG-61 protocol), cone-beam computed tomography (CBCT) image quality and object representation accuracy (using a custom-designed imaging phantom), CBCT-guided target localization accuracy and consistency of the CBCT-based dose calculation. To facilitate an efficient read-out and limit the user dependence of the QMP data analysis, a semi-automatic image analysis and data representation program was developed using the technical computing software MATLAB. The results of the first six months experience using the suggested QMP for a Small Animal Radiation Research Platform (SARRP) are presented, with data collected on a bi-monthly basis. The dosimetric output constancy was established to be within ±1 %, the consistency of the image resolution was within ±0.2 mm, the accuracy of CBCT-guided target localization was within ±0.5 mm, and dose calculation consistency was within ±2 s (± 3 %) per treatment beam. Based on these results, this simple quality assurance program allows for the detection of inconsistencies in dosimetric or imaging parameters that are beyond the acceptable variability for a reliable and accurate pre-clinical RT system, on a monthly or bi-monthly basis. PMID:26425981

Proposal for a Simple and Efficient Monthly Quality Management Program Assessing the Consistency of Robotic Image-Guided Small Animal Radiation Systems.

PubMed

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

2015-11-01

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and efficient QMP for image-guided robotic small animal irradiators used in pre-clinical RT research is described. Protocols were developed and implemented to assess the dose output constancy (based on the AAPM TG-61 protocol), cone-beam computed tomography (CBCT) image quality and object representation accuracy (using a custom-designed imaging phantom), CBCT-guided target localization accuracy and consistency of the CBCT-based dose calculation. To facilitate an efficient read-out and limit the user dependence of the QMP data analysis, a semi-automatic image analysis and data representation program was developed using the technical computing software MATLAB. The results of the first 6-mo experience using the suggested QMP for a Small Animal Radiation Research Platform (SARRP) are presented, with data collected on a bi-monthly basis. The dosimetric output constancy was established to be within ±1 %, the consistency of the image resolution was within ±0.2 mm, the accuracy of CBCT-guided target localization was within ±0.5 mm, and dose calculation consistency was within ±2 s (±3%) per treatment beam. Based on these results, this simple quality assurance program allows for the detection of inconsistencies in dosimetric or imaging parameters that are beyond the acceptable variability for a reliable and accurate pre-clinical RT system, on a monthly or bi-monthly basis.

Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

PubMed

Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

2015-07-08

Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P < 0.001). For high-risk PONV patients undergoing gynecological laparoscopic surgery, when used with dexamethasone, 1-mg haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

Bridging Adult Experience to Pediatrics in Oncology Drug Development.

PubMed

Leong, Ruby; Zhao, Hong; Reaman, Gregory; Liu, Qi; Wang, Yaning; Stewart, Clinton F; Burckart, Gilbert

2017-10-01

Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge. Potential approaches to pediatric dosing in oncology patients include extrapolation of efficacy from adult studies in those few cases where the disease is similar, inclusion of adolescent patients in adult trials when possible, and bridging the adult dose to the pediatric dose. An analysis of the recommended phase 2 dose for 40 molecularly targeted agents in pediatric patients provides some insight into current practices. Increased knowledge of tumor biology and efforts to identify and validate molecular targets and genetic abnormalities that drive childhood cancers can lead to increased opportunities for precision medicine in the treatment of pediatric cancers. © 2017, The American College of Clinical Pharmacology.

TU-H-CAMPUS-TeP2-03: High Sensitivity and High Resolution Fiber Based Micro-Detector for Sub-Millimeter Preclinical Dosimetry

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

Izaguirre, E; Pokhrel, S; Knewtson, T

2016-06-15

Purpose: Current precision of small animal and cell micro-irradiators has continuously increased during the past years. Currently, preclinical irradiators can deliver sub-millimeter fields with micrometric precision but there are no water equivalent dosimeters to determine small field profiles and dose in the orthovoltage range of energies with micrometric resolution and precision. We have developed a fiber based micro-dosimeter with the resolution and dosimetric accuracy required for radiobiological research. Methods: We constructed two prototypes of micro-dosimeters based on different compositions of fiber scintillators to study the spatial resolution and dosimetric precision of small animal and cell micro-irradiators. The first has greenmore » output and the second has blue output. The blue output dosimeter has the highest sensitivity because it matches the spectral sensitivity of silicon photomultipliers. A blue detector with 500um cross section was built and tested respect to a CC01 ion chamber, film, and the 1500um green output detector. Orthovoltage fields from 1×1mm2 to 5×5mm2 were used for detector characteristics comparison. Results: The blue fiber dosimeter shows great agreement with films and matches dose measurements with the gold-standard ion chamber for 5×5mm2 fields. The detector has the appropriate sensitivity to measure fields from 1×1mm2 to larger sizes with a 1% dosimetric accuracy. The spatial resolution is in the sub-millimeter range and the spectral matching with the photomultiplier allows reducing the sensor cross section even further than the presented prototype. These results suggest that scintillating fibers combined with silicon photomultipliers is the appropriate technology to pursue micro-dosimetry for small animals and disperse cell samples. Conclusion: The constructed detectors establish a new landmark for the resolution and sensitivity of fiber based microdetectors. The validation of the detector in our small animal and cell irradiator shows that they are appropriate for preclinical and micro single cell irradiation quality assurance and dosimetry.« less

[Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

PubMed

Hennequin, C; Cosset, J M; Cailleux, P E; Girinsky, T; Ganem, G; Hubert, D; Comoy, E; Dutreix, J

1989-01-01

The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

Simultaneous integrated protection : A new concept for high-precision radiation therapy.

PubMed

Brunner, Thomas B; Nestle, Ursula; Adebahr, Sonja; Gkika, Eleni; Wiehle, Rolf; Baltas, Dimos; Grosu, Anca-Ligia

2016-12-01

Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described. An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTV SIP ). The remainder of the PTV represented the dominant PTV (PTV dom ). Planning was performed using IMRT. Dose was prescribed to PTV dom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTV SIP was required to be as high as possible within the constraints to avoid local relapse. SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTV SIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low. SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

High-precision piezo-ejection ocular microdosing: Phase II study on local and systemic effects of topical phenylephrine.

PubMed

Ianchulev, Tsontcho; Weinreb, Robert; Tsai, James C; Lin, Shan; Pasquale, Louis R

2018-01-01

Conventional eyedropper-delivered volumes (25-50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.

A Fluorescent Tile DNA Diagnocode System for In Situ Rapid and Selective Diagnosis of Cytosolic RNA Cancer Markers

PubMed Central

Park, Kyung Soo; Shin, Seung Won; Jang, Min Su; Shin, Woojung; Yang, Kisuk; Min, Junhong; Cho, Seung-Woo; Oh, Byung-Keun; Bae, Jong Wook; Jung, Sunghwan; Choi, Jeong-Woo; Um, Soong Ho

2015-01-01

Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields. PMID:26678430

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

PubMed

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

2017-04-11

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

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

PubMed Central

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

2017-01-01

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

The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006.

PubMed

Chen, Lin; Ray, Shonket; Keller, Brad M; Pertuz, Said; McDonald, Elizabeth S; Conant, Emily F; Kontos, Despina

2016-09-01

Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI-RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88-0.95; weighted κ = 0.83-0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76-0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. (©) RSNA, 2016 Online supplemental material is available for this article.

The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006

PubMed Central

Chen, Lin; Ray, Shonket; Keller, Brad M.; Pertuz, Said; McDonald, Elizabeth S.; Conant, Emily F.

2016-01-01

Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI-RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88–0.95; weighted κ = 0.83–0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76–0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. © RSNA, 2016 Online supplemental material is available for this article. PMID:27002418

Composite x-ray image assembly for large-field digital mammography with one- and two-dimensional positioning of a focal plane array

NASA Technical Reports Server (NTRS)

Halama, G.; McAdoo, J.; Liu, H.

1998-01-01

To demonstrate the feasibility of a novel large-field digital mammography technique, a 1024 x 1024 pixel Loral charge-coupled device (CCD) focal plane array (FPA) was positioned in a mammographic field with one- and two-dimensional scan sequences to obtain 950 x 1800 pixel and 3600 x 3600 pixel composite images, respectively. These experiments verify that precise positioning of FPAs produced seamless composites and that the CCD mosaic concept has potential for high-resolution, large-field imaging. The proposed CCD mosaic concept resembles a checkerboard pattern with spacing left between the CCDs for the driver and readout electronics. To obtain a complete x-ray image, the mosaic must be repositioned four times, with an x-ray exposure at each position. To reduce the patient dose, a lead shield with appropriately patterned holes is placed between the x-ray source and the patient. The high-precision motorized translation stages and the fiber-coupled-scintillating-screen-CCD sensor assembly were placed in the position usually occupied by the film cassette. Because of the high mechanical precision, seamless composites were constructed from the subimages. This paper discusses the positioning, image alignment procedure, and composite image results. The paper only addresses the formation of a seamless composite image from subimages and will not consider the effects of the lead shield, multiple CCDs, or the speed of motion.

Verification of BWR Turbine Skyshine Dose with the MCNP5 Code Based on an Experiment Made at SHIMANE Nuclear Power Station

NASA Astrophysics Data System (ADS)

Tayama, Ryuichi; Wakasugi, Kenichi; Kawanaka, Ikunori; Kadota, Yoshinobu; Murakami, Yasuhiro

We measured the skyshine dose from turbine buildings at Shimane Nuclear Power Station Unit 1 (NS-1) and Unit 2 (NS-2), and then compared it with the dose calculated with the Monte Carlo transport code MCNP5. The skyshine dose values calculated with the MCNP5 code agreed with the experimental data within a factor of 2.8, when the roof of the turbine building was precisely modeled. We concluded that our MCNP5 calculation was valid for BWR turbine skyshine dose evaluation.

Pediatric chest HRCT using the iDose4 Hybrid Iterative Reconstruction Algorithm: Which iDose level to choose?

NASA Astrophysics Data System (ADS)

Smarda, M.; Alexopoulou, E.; Mazioti, A.; Kordolaimi, S.; Ploussi, A.; Priftis, K.; Efstathopoulos, E.

2015-09-01

Purpose of the study is to determine the appropriate iterative reconstruction (IR) algorithm level that combines image quality and diagnostic confidence, for pediatric patients undergoing high-resolution computed tomography (HRCT). During the last 2 years, a total number of 20 children up to 10 years old with a clinical presentation of chronic bronchitis underwent HRCT in our department's 64-detector row CT scanner using the iDose IR algorithm, with almost similar image settings (80kVp, 40-50 mAs). CT images were reconstructed with all iDose levels (level 1 to 7) as well as with filtered-back projection (FBP) algorithm. Subjective image quality was evaluated by 2 experienced radiologists in terms of image noise, sharpness, contrast and diagnostic acceptability using a 5-point scale (1=excellent image, 5=non-acceptable image). Artifacts existance was also pointed out. All mean scores from both radiologists corresponded to satisfactory image quality (score ≤3), even with the FBP algorithm use. Almost excellent (score <2) overall image quality was achieved with iDose levels 5 to 7, but oversmoothing artifacts appearing with iDose levels 6 and 7 affected the diagnostic confidence. In conclusion, the use of iDose level 5 enables almost excellent image quality without considerable artifacts affecting the diagnosis. Further evaluation is needed in order to draw more precise conclusions.

Concentration dependent requirement for local protein synthesis in motor neuron subtype specific response to axon guidance cues

PubMed Central

Nedelec, Stephane; Peljto, Mirza; Shi, Peng; Amoroso, Mackenzie W.; Kam, Lance C.; Wichterle, Hynek

2012-01-01

Formation of functional motor circuits relies on the ability of distinct spinal motor neuron subtypes to project their axons with high precision to appropriate muscle targets. While guidance cues contributing to motor axon pathfinding have been identified, the intracellular pathways underlying subtype specific responses to these cues remain poorly understood. In particular, it remains controversial whether responses to axon guidance cues depend on axonal protein synthesis. Using a growth cone collapse assay, we demonstrate that mouse embryonic stem cell (ESC) derived spinal motor neurons (ES-MNs) respond to ephrin-A5, Sema3f and Sema3a in a concentration dependent manner. At low doses, ES-MNs exhibit segmental or subtype specific responses, while this selectivity is lost at higher concentrations. Response to high doses of semaphorins and to all doses of ephrin-A5 is protein synthesis independent. In contrast, using microfluidic devices and stripe assays, we show that growth cone collapse and guidance at low concentrations of semaphorins relies on local protein synthesis in the axonal compartment. Similar bimodal response to low and high concentrations of guidance cues is observed in human ES-MNs, pointing to a general mechanism by which neurons increase their repertoire of responses to the limited set of guidance cues involved in neural circuit formation. PMID:22279234

Stability of compounded trilostane suspension in cod liver oil.

PubMed

Crosby, Jesse; Brown, Stacy

2017-10-01

Trilostane is a synthetic steroid analog used to treat canine hyperadrenocorticism. For small dogs, the dose found in commercially available dosage forms of trilostane is sometimes too high. Compounding trilostane in a liquid diluent provides an option for more precise dosing and adjustments, and can be easier to administer, versus a tablet or capsule. Trilostane suspends well in cod liver oil, which is generally palatable to dogs. The stability of a compounded trilostane suspension in cod liver oil stored at room temperature was investigated for 90 days. Compounded trilostane retained stability, defined as maintaining 90-105% labeled value, for 60 days when stored in amber glass bottles. However, drug potency fell >10% below the labeled value when stored in amber plastic bottles after 7 days. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of vitamin C on male fertility in rats subjected to forced swimming stress.

PubMed

Vijayprasad, Sanghishetti; Bb, Ghongane; Bb, Nayak

2014-07-01

Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. Recently, oxidative stress has become the focus of interest as a potential cause of male infertility. Normally, equilibrium exists between reactive oxygen species (ROS) production and antioxidant scavenging activities in the male reproductive organs. The ascorbic acid is a known antioxidant present in the testis with the precise role of protecting the latter from the oxidative damage. It also contributes to the support of spermatogensis at least in part through its capacity to maintain antioxidant in an active state. Group1: Normal Control animal received Distilled water, Group 2: Positive control (Only Stress), Group 3: Normal rats received an intermediate dose of Vitamin C (20mg/kg/day), Group 4: Stress + Low dose Vitamin C (10mg/kg/day), Group 5: Stress+ Intermediate dose Vitamin C (20mg/kg/day), Group 6: High dose Vitamin C (30mg/kg/day). On 16(th) day effect of stress on body weight, Reproductive organ weight, sperm parameters, and hormonal assay was studied. In the present context, in stress group the sperm count, motility, testicular weight declined significantly. The intermediate dose and high dose of vitamin C showed significantly increased effect on the sperm count and motility. Various physiological changes produced force swimming indicates that swimming is an effective model for producing stress in albino rats. The results suggest that Vitamin C supplementation improves the stress induced reproductive infertility due to both their testosterone increase effect and their antioxidant effect.

Deep Inspiration Breath Hold—Based Radiation Therapy: A Clinical Review

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

Boda-Heggemann, Judit, E-mail: judit.boda-heggemann@umm.de; Knopf, Antje-Christin; Simeonova-Chergou, Anna

Several recent developments in linear accelerator–based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effectsmore » in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.« less

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

PubMed

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

Determination of the efficiency of commercially available dose calibrators for beta-emitters.

PubMed

Valley, Jean-François; Bulling, Shelley; Leresche, Michel; Wastiel, Claude

2003-03-01

The goals of this investigation are to determine whether commercially available dose calibrators can be used to measure the activity of beta-emitting radionuclides used in pain palliation and to establish whether manufacturer-supplied calibration factors are appropriate for this purpose. Six types of commercially available dose calibrators were studied. Dose calibrator response was controlled for 5 gamma-emitters used for calibration or typically encountered in routine use. For the 4 most commonly used beta-emitters ((32)P, (90)Sr, (90)Y, and (169)Er) dose calibrator efficiency was determined in the syringe geometry used for clinical applications. Efficiency of the calibrators was also measured for (153)Sm and (186)Re, 2 beta-emitters with significant gamma-contributions. Source activities were traceable to national standards. All calibrators measured gamma-emitters with a precision of +/-10%, in compliance with Swiss regulatory requirements. For beta-emitters, dose calibrator intrinsic efficiency depends strongly on the maximal energy of the beta-spectrum and is notably low for (169)Er. Manufacturer-supplied calibration factors give accurate results for beta-emitters with maximal beta-energy in the middle-energy range (1 MeV) but are not appropriate for use with low-energy ((169)Er) or high-energy ((90)Y) beta-emitters. beta-emitters with significant gamma-contributions behave like gamma-emitters. Commercially available dose calibrators have an intrinsic efficiency that is sufficient for the measurement of beta-emitters, including beta-emitters with a low maximum beta-energy. Manufacturer-supplied calibration factors are reliable for gamma-emitters and beta-emitters in the middle-energy range. For low- and high-energy beta-emitters, the use of manufacturer-supplied calibration factors introduces significant measurement inaccuracy.

Calculations of dose distributions using a neural network model

NASA Astrophysics Data System (ADS)

Mathieu, R.; Martin, E.; Gschwind, R.; Makovicka, L.; Contassot-Vivier, S.; Bahi, J.

2005-03-01

The main goal of external beam radiotherapy is the treatment of tumours, while sparing, as much as possible, surrounding healthy tissues. In order to master and optimize the dose distribution within the patient, dosimetric planning has to be carried out. Thus, for determining the most accurate dose distribution during treatment planning, a compromise must be found between the precision and the speed of calculation. Current techniques, using analytic methods, models and databases, are rapid but lack precision. Enhanced precision can be achieved by using calculation codes based, for example, on Monte Carlo methods. However, in spite of all efforts to optimize speed (methods and computer improvements), Monte Carlo based methods remain painfully slow. A newer way to handle all of these problems is to use a new approach in dosimetric calculation by employing neural networks. Neural networks (Wu and Zhu 2000 Phys. Med. Biol. 45 913-22) provide the advantages of those various approaches while avoiding their main inconveniences, i.e., time-consumption calculations. This permits us to obtain quick and accurate results during clinical treatment planning. Currently, results obtained for a single depth-dose calculation using a Monte Carlo based code (such as BEAM (Rogers et al 2003 NRCC Report PIRS-0509(A) rev G)) require hours of computing. By contrast, the practical use of neural networks (Mathieu et al 2003 Proceedings Journées Scientifiques Francophones, SFRP) provides almost instant results and quite low errors (less than 2%) for a two-dimensional dosimetric map.

Calculations of dose distributions using a neural network model.

PubMed

Mathieu, R; Martin, E; Gschwind, R; Makovicka, L; Contassot-Vivier, S; Bahi, J

2005-03-07

The main goal of external beam radiotherapy is the treatment of tumours, while sparing, as much as possible, surrounding healthy tissues. In order to master and optimize the dose distribution within the patient, dosimetric planning has to be carried out. Thus, for determining the most accurate dose distribution during treatment planning, a compromise must be found between the precision and the speed of calculation. Current techniques, using analytic methods, models and databases, are rapid but lack precision. Enhanced precision can be achieved by using calculation codes based, for example, on Monte Carlo methods. However, in spite of all efforts to optimize speed (methods and computer improvements), Monte Carlo based methods remain painfully slow. A newer way to handle all of these problems is to use a new approach in dosimetric calculation by employing neural networks. Neural networks (Wu and Zhu 2000 Phys. Med. Biol. 45 913-22) provide the advantages of those various approaches while avoiding their main inconveniences, i.e., time-consumption calculations. This permits us to obtain quick and accurate results during clinical treatment planning. Currently, results obtained for a single depth-dose calculation using a Monte Carlo based code (such as BEAM (Rogers et al 2003 NRCC Report PIRS-0509(A) rev G)) require hours of computing. By contrast, the practical use of neural networks (Mathieu et al 2003 Proceedings Journees Scientifiques Francophones, SFRP) provides almost instant results and quite low errors (less than 2%) for a two-dimensional dosimetric map.

Cone beam computed tomography image guidance system for a dedicated intracranial radiosurgery treatment unit.

PubMed

Ruschin, Mark; Komljenovic, Philip T; Ansell, Steve; Ménard, Cynthia; Bootsma, Gregory; Cho, Young-Bin; Chung, Caroline; Jaffray, David

2013-01-01

Image guidance has improved the precision of fractionated radiation treatment delivery on linear accelerators. Precise radiation delivery is particularly critical when high doses are delivered to complex shapes with steep dose gradients near critical structures, as is the case for intracranial radiosurgery. To reduce potential geometric uncertainties, a cone beam computed tomography (CT) image guidance system was developed in-house to generate high-resolution images of the head at the time of treatment, using a dedicated radiosurgery unit. The performance and initial clinical use of this imaging system are described. A kilovoltage cone beam CT system was integrated with a Leksell Gamma Knife Perfexion radiosurgery unit. The X-ray tube and flat-panel detector are mounted on a translational arm, which is parked above the treatment unit when not in use. Upon descent, a rotational axis provides 210° of rotation for cone beam CT scans. Mechanical integrity of the system was evaluated over a 6-month period. Subsequent clinical commissioning included end-to-end testing of targeting performance and subjective image quality performance in phantoms. The system has been used to image 2 patients, 1 of whom received single-fraction radiosurgery and 1 who received 3 fractions, using a relocatable head frame. Images of phantoms demonstrated soft tissue contrast visibility and submillimeter spatial resolution. A contrast difference of 35 HU was easily detected at a calibration dose of 1.2 cGy (center of head phantom). The shape of the mechanical flex vs scan angle was highly reproducible and exhibited <0.2 mm peak-to-peak variation. With a 0.5-mm voxel pitch, the maximum targeting error was 0.4 mm. Images of 2 patients were analyzed offline and submillimeter agreement was confirmed with conventional frame. A cone beam CT image guidance system was successfully adapted to a radiosurgery unit. The system is capable of producing high-resolution images of bone and soft tissue. The system is in clinical use and provides excellent image guidance without invasive frames. Copyright © 2013 Elsevier Inc. All rights reserved.

Optima XE Single Wafer High Energy Ion Implanter

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

Satoh, Shu; Ferrara, Joseph; Bell, Edward

2008-11-03

The Optima XE is the first production worthy single wafer high energy implanter. The new system combines a state-of-art single wafer endstation capable of throughputs in excess of 400 wafers/hour with a production-proven RF linear accelerator technology. Axcelis has been evolving and refining RF Linac technology since the introduction of the NV1000 in 1986. The Optima XE provides production worthy beam currents up to energies of 1.2 MeV for P{sup +}, 2.9 MeV for P{sup ++}, and 1.5 MeV for B{sup +}. Energies as low as 10 keV and tilt angles as high as 45 degrees are also available., allowingmore » the implanter to be used for a wide variety of traditional medium current implants to ensure high equipment utilization. The single wafer endstation provides precise implant angle control across wafer and wafer to wafer. In addition, Optima XE's unique dose control system allows compensation of photoresist outgassing effects without relying on traditional pressure-based methods. We describe the specific features, angle control and dosimetry of the Optima XE and their applications in addressing the ever-tightening demands for more precise process controls and higher productivity.« less

Neutron skyshine measurements at Fermilab.

PubMed

Cossairt, J D; Coulson, L V

1985-02-01

Neutron skyshine has been a significant source of environmental radiation exposure at many high-energy proton accelerators. A particularly troublesome source of skyshine neutrons has existed at Fermilab during operation of the 400-GeV high-energy physics program. This paper reports on several measurements of this source made with a DePangher precision long counter at large distances. The spatial distribution of the neutron skyshine can approximately be described as an inverse square law dependence multiplied by an exponential with an approximate attenuation length of 1200 +/- 300 m. The absolute magnitude of the distributions can be matched directly to the conventionally measured absorbed dose distribution near the source.

Directional interstitial brachytherapy from simulation to application

NASA Astrophysics Data System (ADS)

Lin, Liyong

Organs at risk (OAR) are sometimes adjacent to or embedded in or overlap with the clinical target volume (CTV) to be treated. The purpose of this PhD study is to develop directionally low energy gamma-emitting interstitial brachytherapy sources. These sources can be applied between OAR to selectively reduce hot spots in the OARs and normal tissues. The reduction of dose over undesired regions can expand patient eligibility or reduce toxicities for the treatment by conventional interstitial brachytherapy. This study covers the development of a directional source from design optimization to construction of the first prototype source. The Monte Carlo code MCNP was used to simulate the radiation transport for the designs of directional sources. We have made a special construction kit to assemble radioactive and gold-shield components precisely into D-shaped titanium containers of the first directional source. Directional sources have a similar dose distribution as conventional sources on the treated side but greatly reduced dose on the shielded side, with a sharp dose gradient between them. A three-dimensional dose deposition kernel for the 125I directional source has been calculated. Treatment plans can use both directional and conventional 125I sources at the same source strength for low-dose-rate (LDR) implants to optimize the dose distributions. For prostate tumors, directional 125I LDR brachytherapy can potentially reduce genitourinary and gastrointestinal toxicities and improve potency preservation for low risk patients. The combination of better dose distribution of directional implants and better therapeutic ratio between tumor response and late reactions enables a novel temporary LDR treatment, as opposed to permanent or high-dose-rate (HDR) brachytherapy for the intermediate risk T2b and high risk T2c tumors. Supplemental external-beam treatments can be shortened with a better brachytherapy boost for T3 tumors. In conclusion, we have successfully finished the design optimization and construction of the first prototype directional source. Potential clinical applications and potential benefits of directional sources have been shown for prostate and breast tumors.

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes.

PubMed

Markstein, Michele; Pitsouli, Chrysoula; Villalta, Christians; Celniker, Susan E; Perrimon, Norbert

2008-04-01

A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression.

Validation of a virtual source model of medical linac for Monte Carlo dose calculation using multi-threaded Geant4.

PubMed

Aboulbanine, Zakaria; El Khayati, Naïma

2018-04-13

The use of phase space in medical linear accelerator Monte Carlo (MC) simulations significantly improves the execution time and leads to results comparable to those obtained from full calculations. The classical representation of phase space stores directly the information of millions of particles, producing bulky files. This paper presents a virtual source model (VSM) based on a reconstruction algorithm, taking as input a compressed file of roughly 800 kb derived from phase space data freely available in the International Atomic Energy Agency (IAEA) database. This VSM includes two main components; primary and scattered particle sources, with a specific reconstruction method developed for each. Energy spectra and other relevant variables were extracted from IAEA phase space and stored in the input description data file for both sources. The VSM was validated for three photon beams: Elekta Precise 6 MV/10 MV and a Varian TrueBeam 6 MV. Extensive calculations in water and comparisons between dose distributions of the VSM and IAEA phase space were performed to estimate the VSM precision. The Geant4 MC toolkit in multi-threaded mode (Geant4-[mt]) was used for fast dose calculations and optimized memory use. Four field configurations were chosen for dose calculation validation to test field size and symmetry effects, [Formula: see text] [Formula: see text], [Formula: see text] [Formula: see text], and [Formula: see text] [Formula: see text] for squared fields, and [Formula: see text] [Formula: see text] for an asymmetric rectangular field. Good agreement in terms of [Formula: see text] formalism, for 3%/3 mm and 2%/3 mm criteria, for each evaluated radiation field and photon beam was obtained within a computation time of 60 h on a single WorkStation for a 3 mm voxel matrix. Analyzing the VSM's precision in high dose gradient regions, using the distance to agreement concept (DTA), showed also satisfactory results. In all investigated cases, the mean DTA was less than 1 mm in build-up and penumbra regions. In regards to calculation efficiency, the event processing speed is six times faster using Geant4-[mt] compared to sequential Geant4, when running the same simulation code for both. The developed VSM for 6 MV/10 MV beams widely used, is a general concept easy to adapt in order to reconstruct comparable beam qualities for various linac configurations, facilitating its integration for MC treatment planning purposes.

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

Lou, K; Rice University, Houston, TX; Sun, X

Purpose: To study the feasibility of clinical on-line proton beam range verification with PET imaging Methods: We simulated a 179.2-MeV proton beam with 5-mm diameter irradiating a PMMA phantom of human brain size, which was then imaged by a brain PET with 300*300*100-mm{sup 3} FOV and different system sensitivities and spatial resolutions. We calculated the mean and standard deviation of positron activity range (AR) from reconstructed PET images, with respect to different data acquisition times (from 5 sec to 300 sec with 5-sec step). We also developed a technique, “Smoothed Maximum Value (SMV)”, to improve AR measurement under a givenmore » dose. Furthermore, we simulated a human brain irradiated by a 110-MeV proton beam of 50-mm diameter with 0.3-Gy dose at Bragg peak and imaged by the above PET system with 40% system sensitivity at the center of FOV and 1.7-mm spatial resolution. Results: MC Simulations on the PMMA phantom showed that, regardless of PET system sensitivities and spatial resolutions, the accuracy and precision of AR were proportional to the reciprocal of the square root of image count if image smoothing was not applied. With image smoothing or SMV method, the accuracy and precision could be substantially improved. For a cylindrical PMMA phantom (200 mm diameter and 290 mm long), the accuracy and precision of AR measurement could reach 1.0 and 1.7 mm, with 100-sec data acquired by the brain PET. The study with a human brain showed it was feasible to achieve sub-millimeter accuracy and precision of AR measurement with acquisition time within 60 sec. Conclusion: This study established the relationship between count statistics and the accuracy and precision of activity-range verification. It showed the feasibility of clinical on-line BR verification with high-performance PET systems and improved AR measurement techniques. Cancer Prevention and Research Institute of Texas grant RP120326, NIH grant R21CA187717, The Cancer Center Support (Core) Grant CA016672 to MD Anderson Cancer Center.« less

Design study of an in situ PET scanner for use in proton beam therapy

NASA Astrophysics Data System (ADS)

Surti, S.; Zou, W.; Daube-Witherspoon, M. E.; McDonough, J.; Karp, J. S.

2011-05-01

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr3) and our results indicate that 4 mm wide LYSO or LaBr3 crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π a partial ring TOF imaging with good timing resolution (<=600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision <=1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr3 or LYSO to accurately characterize the proton dose for therapy planning.

Sensitivity in error detection of patient specific QA tools for IMRT plans

NASA Astrophysics Data System (ADS)

Lat, S. Z.; Suriyapee, S.; Sanghangthum, T.

2016-03-01

The high complexity of dose calculation in treatment planning and accurate delivery of IMRT plan need high precision of verification method. The purpose of this study is to investigate error detection capability of patient specific QA tools for IMRT plans. The two H&N and two prostate IMRT plans with MapCHECK2 and portal dosimetry QA tools were studied. Measurements were undertaken for original and modified plans with errors introduced. The intentional errors composed of prescribed dose (±2 to ±6%) and position shifting in X-axis and Y-axis (±1 to ±5mm). After measurement, gamma pass between original and modified plans were compared. The average gamma pass for original H&N and prostate plans were 98.3% and 100% for MapCHECK2 and 95.9% and 99.8% for portal dosimetry, respectively. In H&N plan, MapCHECK2 can detect position shift errors starting from 3mm while portal dosimetry can detect errors started from 2mm. Both devices showed similar sensitivity in detection of position shift error in prostate plan. For H&N plan, MapCHECK2 can detect dose errors starting at ±4%, whereas portal dosimetry can detect from ±2%. For prostate plan, both devices can identify dose errors starting from ±4%. Sensitivity of error detection depends on type of errors and plan complexity.

Are bioequivalence studies of levothyroxine sodium formulations in euthyroid volunteers reliable?

PubMed

Blakesley, Vicky; Awni, Walid; Locke, Charles; Ludden, Thomas; Granneman, G Richard; Braverman, Lewis E

2004-03-01

Levothyroxine (LT4) has a narrow therapeutic index. Consequently, precise standards for assessing the bioequivalence of different LT4 products are vital. We examined the methodology that the Food and Drug Administration (FDA) recommends for comparing the bioavailability of LT4 products, as well as three modifications to correct for endogenous, thyroxine (T4) levels, to determine if the methodology could distinguish LT4 products that differ by 12.5%, 25%, or 33%. With no baseline correction for the endogenous T4 pool, differences in administered LT4 doses that differed by 25%-33% could not be detected (450 microg and 400 microg doses versus 600 microg dose, respectively). The three mathematical correction methods could distinguish the doses that differed by 25% and 33%. None of the correction methods could distinguish dosage strengths that differed by 12.5% (450 microg versus 400 microg). Dose differences within this range are known to result in clinically relevant differences in safety and effectiveness. Methods of analysis of bioequivalence data that do not consider endogenous T4 concentrations confound accurate quantitation and interpretation of LT4 bioavailability. As a result, products inappropriately deemed bioequivalent may put patients at risk for iatrogenic hyperthyroidism or hypothyroidism. More precise methods for defining bioequivalence are required in order to ensure that LT4 products accepted as bioequivalent will perform equivalently in patients without the need for further monitoring and retitration of their dose.

Bunch by bunch beam monitoring in 3rd and 4th generation light sources by means of single crystal diamond detectors and quantum well devices

NASA Astrophysics Data System (ADS)

Antonelli, M.; Di Fraia, M.; Tallaire, A.; Achard, J.; Carrato, S.; Menk, R. H.; Cautero, G.; Giuressi, D.; Jark, W. H.; Biasiol, G.; Ganbold, T.; Oliver, K.; Callegari, C.; Coreno, M.; De Sio, A.; Pace, E.

2012-10-01

New generation Synchrotron Radiation (SR) sources and Free Electron Lasers (FEL) require novel concepts of beam diagnostics to keep photon beams under surveillance, asking for simultaneous position and intensity monitoring. To deal with high power load and short time pulses provided by these sources, novel materials and methods are needed for the next generation BPMs. Diamond is a promising material for the production of semitransparent in situ X-ray BPMs withstanding the high dose rates of SR rings and high energy FELs. We report on the development of freestanding, single crystal CVD diamond detectors. Performances in both low and radio frequency SR beam monitoring are presented. For the former, sensitivity deviation was found to be approximately 2%; a 0.05% relative precision in the intensity measurements and a 0.1-μm precision in the position encoding have been estimated. For the latter, single-shot characterizations revealed sub-nanosecond rise-times and spatial precisions below 6 μm, which allowed bunch-by-bunch monitoring in multi-bunch operation. Preliminary measurements at the Fermi FEL have been performed with this detector, extracting quantitative intensity and position information for FEL pulses (~ 100 fs, energy 12 ÷ 60 eV), with a long-term spatial precision of about 85 μm results on FEL radiation damages are also reported. Due to their direct, low-energy band gap, InGaAs quantum well devices too may be used as fast detectors for photons ranging from visible to X-ray. Results are reported which show the capability of a novel InGaAs/InAlAs device to detect intensity and position of 100-fs-wide laser pulses.

Solid state neutron dosimeter for space applications

NASA Technical Reports Server (NTRS)

Entine, Gerald; Nagargar, Vivek; Sharif, Daud

1990-01-01

Personnel engaged in space flight are exposed to significant flux of high energy neutrons arising from both primary and secondary sources of ionizing radiation. Presently, there exist no compact neutron sensor capable of being integrated in a flight instrument to provide real time measurement of this radiation flux. A proposal was made to construct such an instrument using special PIN silicon diode which has the property of being insensitive to the other forms of ionizing radiation. Studies were performed to determine the design and construction of a better reading system to allow the PIN diode to be read with high precision. The physics of the device was studied, especially with respect to those factors which affect the sensitivity and reproducibility of the neutron response. This information was then used to develop methods to achieve high sensitivity at low neutron doses. The feasibility was shown of enhancing the PIN diode sensitivity to make possible the measurement of the low doses of neutrons encountered in space flights. The new PIN diode will make possible the development of a very compact, accurate, personal neutron dosimeter.

A tool to automatically analyze electromagnetic tracking data from high dose rate brachytherapy of breast cancer patients.

PubMed

Götz, Th I; Lahmer, G; Strnad, V; Bert, Ch; Hensel, B; Tomé, A M; Lang, E W

2017-01-01

During High Dose Rate Brachytherapy (HDR-BT) the spatial position of the radiation source inside catheters implanted into a female breast is determined via electromagnetic tracking (EMT). Dwell positions and dwell times of the radiation source are established, relative to the patient's anatomy, from an initial X-ray-CT-image. During the irradiation treatment, catheter displacements can occur due to patient movements. The current study develops an automatic analysis tool of EMT data sets recorded with a solenoid sensor to assure concordance of the source movement with the treatment plan. The tool combines machine learning techniques such as multi-dimensional scaling (MDS), ensemble empirical mode decomposition (EEMD), singular spectrum analysis (SSA) and particle filter (PF) to precisely detect and quantify any mismatch between the treatment plan and actual EMT measurements. We demonstrate that movement artifacts as well as technical signal distortions can be removed automatically and reliably, resulting in artifact-free reconstructed signals. This is a prerequisite for a highly accurate determination of any deviations of dwell positions from the treatment plan.

A tool to automatically analyze electromagnetic tracking data from high dose rate brachytherapy of breast cancer patients

PubMed Central

Lahmer, G.; Strnad, V.; Bert, Ch.; Hensel, B.; Tomé, A. M.; Lang, E. W.

2017-01-01

During High Dose Rate Brachytherapy (HDR-BT) the spatial position of the radiation source inside catheters implanted into a female breast is determined via electromagnetic tracking (EMT). Dwell positions and dwell times of the radiation source are established, relative to the patient’s anatomy, from an initial X-ray-CT-image. During the irradiation treatment, catheter displacements can occur due to patient movements. The current study develops an automatic analysis tool of EMT data sets recorded with a solenoid sensor to assure concordance of the source movement with the treatment plan. The tool combines machine learning techniques such as multi-dimensional scaling (MDS), ensemble empirical mode decomposition (EEMD), singular spectrum analysis (SSA) and particle filter (PF) to precisely detect and quantify any mismatch between the treatment plan and actual EMT measurements. We demonstrate that movement artifacts as well as technical signal distortions can be removed automatically and reliably, resulting in artifact-free reconstructed signals. This is a prerequisite for a highly accurate determination of any deviations of dwell positions from the treatment plan. PMID:28934238

A smart aminoglycoside hydrogel with tunable gel degradation, on-demand drug release, and high antibacterial activity.

PubMed

Hu, Jingjing; Quan, Yanchun; Lai, Yuping; Zheng, Zhao; Hu, Zhiqi; Wang, Xinyu; Dai, Tianjiao; Zhang, Qiang; Cheng, Yiyun

2017-02-10

Aminoglycosides are a family of critically important antibiotics for the treatment of serious infections including multidrug-resistant pathogens. However, clinical use of aminoglycoside antibiotics is compromised by bacterial biofilm formation at subinhibitory concentrations or adverse side effects such as ototoxicity and nephrotoxicity at high antibiotic doses. Preparation of aminoglycoside formulation that allows on-demand drug delivery is a solution to this sticky issue. Here, we designed a new type of aminoglycoside hydrogels by cross-linking oxidized polysaccharides such as dextran, carboxymethyl cellulose, alginate, and chondroitin using aminoglycosides as cross-linkers. The hydrogel modulus, degradation rate and release kinetics can be precisely modulated by tailoring the aminoglycoside dose during gel formation. The aminoglycoside hydrogel showed fast gelation, self-healing and on-demand drug release behaviors, and high antibacterial activities in vitro and in vivo against both Gram-positive and Gram-negative bacteria. This study provides a facile and promising strategy to develop smart hydrogels for topical administration of aminoglycoside antibiotics. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards ion beam therapy based on laser plasma accelerators.

PubMed

Karsch, Leonhard; Beyreuther, Elke; Enghardt, Wolfgang; Gotz, Malte; Masood, Umar; Schramm, Ulrich; Zeil, Karl; Pawelke, Jörg

2017-11-01

Only few ten radiotherapy facilities worldwide provide ion beams, in spite of their physical advantage of better achievable tumor conformity of the dose compared to conventional photon beams. Since, mainly the large size and high costs hinder their wider spread, great efforts are ongoing to develop more compact ion therapy facilities. One promising approach for smaller facilities is the acceleration of ions on micrometre scale by high intensity lasers. Laser accelerators deliver pulsed beams with a low pulse repetition rate, but a high number of ions per pulse, broad energy spectra and high divergences. A clinical use of a laser based ion beam facility requires not only a laser accelerator providing beams of therapeutic quality, but also new approaches for beam transport, dosimetric control and tumor conformal dose delivery procedure together with the knowledge of the radiobiological effectiveness of laser-driven beams. Over the last decade research was mainly focused on protons and progress was achieved in all important challenges. Although currently the maximum proton energy is not yet high enough for patient irradiation, suggestions and solutions have been reported for compact beam transport and dose delivery procedures, respectively, as well as for precise dosimetric control. Radiobiological in vitro and in vivo studies show no indications of an altered biological effectiveness of laser-driven beams. Laser based facilities will hardly improve the availability of ion beams for patient treatment in the next decade. Nevertheless, there are possibilities for a need of laser based therapy facilities in future.

How Advances in Imaging Will Affect Precision Radiation Oncology.

PubMed

Jaffray, David A; Das, Shiva; Jacobs, Paula M; Jeraj, Robert; Lambin, Philippe

2018-06-01

Radiation oncology is 1 of the most structured disciplines in medicine. It is of a highly technical nature with reliance on robotic systems to deliver intervention, engagement of diverse expertise, and early adoption of digital approaches to optimize and execute the application of this highly effective cancer treatment. As a localized intervention, the dependence on sensitive, specific, and accurate imaging to define the extent of disease, its heterogeneity, and adjacency to normal tissues directly affects the therapeutic ratio. Image-based in vivo temporal monitoring of the response to treatment enables adaptation and further affects the therapeutic ratio. Thus, more precise intervention will enable fractionation schedules that better interoperate with advances such as immunotherapy. In the data set-rich era that promises precision and personalized medicine, the radiation oncology field will integrate these new data into highly protocoled pathways of care that begin with multimodality prediction and enable patient-specific adaptation of therapy based on quantitative measures of the individual's dose-volume temporal trajectory and midtherapy predictions of response. In addition to advancements in computed tomography imaging, emerging technologies, such as ultra-high-field magnetic resonance and molecular imaging will bring new information to the design of treatments. Next-generation image guided radiation therapy systems will inject high specificity and sensitivity data and stimulate adaptive replanning. In addition, a myriad of pre- and peritherapeutic markers derived from advances in molecular pathology (eg, tumor genomics), automated and comprehensive imaging analytics (eg, radiomics, tumor microenvironment), and many other emerging biomarkers (eg, circulating tumor cell assays) will need to be integrated to maximize the benefit of radiation therapy for an individual patient. We present a perspective on the promise and challenges of fully exploiting imaging data in the pursuit of personalized radiation therapy, drawing from the presentations and broader discussions at the 2016 American Society of Therapeutic Radiation Oncology-National Cancer Institute workshop on Precision Medicine in Radiation Oncology (Bethesda, MD). Copyright © 2018. Published by Elsevier Inc.

Development of a stable and sensitive semiconductor detector by using a mixture of lead(II) iodide and lead monoxide for NDT radiation dose detection

NASA Astrophysics Data System (ADS)

Heo, Y. J.; Kim, K. T.; Han, M. J.; Moon, C. W.; Kim, J. E.; Park, J. K.; Park, S. K.

2018-03-01

Recently, high-energy radiation has been widely used in various industrial fields, including the medical industry, and increasing research efforts have been devoted to the development of radiation detectors to be used with high-energy radiation. In particular, nondestructive industrial applications use high-energy radiation for ships and multilayered objects for accurate inspection. Therefore, it is crucial to verify the accuracy of radiation dose measurements and evaluate the precision and reproducibility of the radiation output dose. Representative detectors currently used for detecting the dose in high-energy regions include Si diodes, diamond diodes, and ionization chambers. However, the process of preparing these detectors is complex in addition to the processes of conducting dosimetric measurements, analysis, and evaluation. Furthermore, the minimum size that can be prepared for a detector is limited. In the present study, the disadvantages of original detectors are compensated by the development of a detector made of a mixture of polycrystalline PbI2 and PbO powder, which are both excellent semiconducting materials suitable for detecting high-energy gamma rays and X-rays. The proposed detector shows characteristics of excellent reproducibility and stable signal detection in response to the changes in energy, and was analyzed for its applicability. Moreover, the detector was prepared through a simple process of particle-in-binder to gain control over the thickness and meet the specific value designated by the user. A mixture mass ratio with the highest reproducibility was determined through reproducibility testing with respect to changes in the photon energy. The proposed detector was evaluated for its detection response characteristics with respect to high-energy photon beam, in terms of dose-rate dependence, sensitivity, and linearity evaluation. In the reproducibility assessment, the detector made with 15 wt% PbO powder showed the best characteristics of 0.59% and 0.25% at 6 and 15 MV, respectively. Based on its selection in the reproducibility assessment, the 15 wt% PbO detector showed no dependence on the dose-rate changes, with R-SD < 1%. Finally, a coefficient of determination of 1 in the linearity assessment demonstrated very good linearity with regards to changes in dose. These results demonstrate the applicability and usefulness of the proposed detector made from a mixture of PbI2 and PbO semiconductors.

Testing the Crystalline Integrity of Baddeleyite: A Systematic EBSD and Confocal Laser-Raman Spectroscopy Study

NASA Astrophysics Data System (ADS)

DesOrmeau, J. W.; Ibanez-Mejia, M.; Lafuente Valverde, B.; Eddy, M. P.; Trail, D.; Wang, Y.

2017-12-01

The accessory mineral baddeleyite (monoclinic ZrO2) has great potential as a high-precision U-Pb geochronometer in silica-undersaturated rocks. However, due to a lack of understanding of alpha-recoil damage to the crystal structure and the influences on chemical diffusion properties and closed-system behavior, limitations still exist. Studies have shown phase transformations in baddeleyite (monoclinic to tetragonal) resulting from radiation damage due to ion bombardment [e.g., 1], but the effects of self-irradiation on the baddeleyite crystal structure over geologic timescales remain poorly understood. A recent study reported confocal laser-Raman spectra suggesting the presence of a tetragonal phase in a Phalaborwa baddeleyite [2], which has crucial implications for Pb mobility and high-precision U-Pb results. To better understand the physical effects of self-irradiation in baddeleyite over geologic timescales, samples of various ages (ca. 2060-32 Ma) and calculated alpha-doses (0.001-0.901 x 1016 α/mg) were imaged by cathodoluminescence (CL) and subsequently analyzed via electron backscatter diffraction (EBSD) and confocal laser-Raman spectroscopy. Synthetic baddeleyite grown in a one-atmosphere furnace was also analyzed to allow a comparison of EBSD and Raman results of the pure monoclinic phase and the natural unknown samples. Whole grain EBSD maps (n=75) of baddeleyite from the Phalabowra and Kovdor carbonatites, the Ammänpelto sill, and the Duluth, Ogden and Yinmawanshan gabbros show complex twinning that is loosely correlated to CL zoning and identification of the monoclinic phase only, suggesting no evidence for phase transformations within grains of contrasting age and amounts of alpha-doses. Preliminary Raman results show evidence of systematic shifts in the vibrational modes of Phalabowra baddeleyite with respect to the younger crystals, which may be the result of radiation-induced damage accumulation rather than phase transformation. These results aim to better characterize the poorly known effects of radiation damage in natural baddeleyite and assist in improving methods for high-precision U-Pb dating of mafic systems on Earth and other planetary bodies. [1] Valdez et al. (2008), J. Nucl. Mater. 381, pp. 259-266. [2[ Schaltegger and Davies (2017), RIMG 83, pp.297-328.

SU-F-T-559: High-Resolution Scintillating Fiber Array for In-Vivo Real-Time SRS and SBRT Patient QA

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

Knewtson, T; Pokhrel, S; University of Tennessee Health Science Center, Memphis, TN

2016-06-15

Purpose: A high-resolution scintillating fiber detector was built for in-vivo real-time patient specific quality assurance (QA). The detector is designed for stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) to monitor treatment delivery and detect real-time deviations from planned dose to increase patient safety and treatment accuracy. Methods: The detector consists of two high-density scintillating fiber arrays layered to form an X-Y grid which can be attached to the accessory tray of a medical linac for SBRT and cone SRS treatment QA. Fiber arrays consist of 128 scintillating fibers embedded within a precision-machined, high-transmission polymer substrate with 0.8mm pitch. Themore » fibers are coupled on both ends to high-sensitivity photodetectors and the output is recorded through a high-speed analog-to-digital converter to capture the linac pulse sequence as treatment delivery progresses. The detector has a software controlled 360 degree rotational system to capture angular beam projections for high-resolution beam profile reconstruction. Results: The detector was validated using SRS cone sizes from 6mm to 34mm and MLC defined field sizes from 5×5mm2 to 100×100mm2. The detector output response is linear with dose and is dose rate independent. Each field can be reconstructed accurately with a spatial resolution of 0.8mm and the current beam output is displayed every 50msec. Dosimetric errors of 1% with respect to the treatment plan can be identified and clinically significant deviations from the expected treatment can be displayed in real-time to alert the therapists. Conclusion: The high resolution detector is capable of reconstructing beam profiles in real-time with submillimeter resolution and 1% dose resolution. This system has the ability to project in-vivo both spatial and dosimetric errors during SBRT and SRS treatments when only a non-clinically significant fraction of the intended dose was delivered. The device has the potential to establish new standards for in-vivo patient specific QA.« less

Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

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

Tao, Yinghua; Chen, Guang-Hong; Hacker, Timothy A.

Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan wasmore » performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937.9% for the 500 mA FBP, 25 mA SIR, and 25 mA FBP, respectively. In numerical simulations, SIR mitigated streak artifacts in the low dose data and yielded flow maps with mean error <7% and standard deviation <9% of mean, for 30×30 pixel ROIs (12.9 × 12.9 mm{sup 2}). In comparison, low dose FBP flow errors were −38% to +258%, and standard deviation was 6%–93%. Additionally, low dose SIR achieved 4.6 times improvement in flow map CNR{sup 2} per unit input dose compared to low dose FBP. Conclusions: SIR reconstruction can reduce image noise and mitigate streaking artifacts caused by photon starvation in dynamic CT myocardial perfusion data sets acquired at low dose (low tube current), and improve perfusion map quality in comparison to FBP reconstruction at the same dose.« less

Postoperative irradiation of carcinoma of the head of the pancreas area: Short-time tolerance and results to precision high-dose technique in 18 patients

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

Nguyen, T.D.; Bugat, R.; Combes, P.F.

1982-07-01

During the period from January 1977-August 1979, 18 patients with biopsy-proven pancreas duct or ampullary adenocarcinoma with no distant or liver metastases underwent external beam radiation therapy following laparotomy. With the use of a 25 MEV photon beam and a four field ''box'' technique, the dose delivered to the target volume identified with radio-opaque clips at laparotomy was 6000 rad in six weeks, while largely sparing the spinal cord, kidney, liver and gut. All patients subjected to low fat, gluten free diet completed treatment as planned without any acute reaction. Three patients developed delayed pancreatic insufficiency. According to actuarial survivalmore » analysis and low morbidity such an approach may lead to increased survival in patients with pancreatic cancer.« less

Development and evaluation of multi-energy PbO dosimeter for quality assurance of image-guide radiation therapy devices

NASA Astrophysics Data System (ADS)

Kim, Kyo-Tae; Heo, Ye-Ji; Han, Moo-Jae; Oh, Kyung-Min; Lee, Young-Kyu; Kim, Shin-Wook; Park, Sung-Kwang

2017-04-01

In radiation therapy, accurate radiotherapy treatment plan (RTP) reproduction is necessary to optimize the clinical results. Thus, attempts have recently been made to ensure high RTP reproducibility using image-guide radiation therapy (IGRT) technology. However, the clinical use of digital X-ray equipment requires extended quality assurance (QA) for those devices, since the IGRT device quality determines the precision of intensity-modulated radiation therapy. The study described in this paper was focused on developing a multi-energy PbO dosimeter for IGRT device QA. The Schottky-type polycrystalline PbO dosimeter with a Au/PbO/ITO structure was evaluated by comparing its response coincidence, dose linearity, measurement reproducibility, linear attenuation coefficient, and percent depth dose with those of Si diode and standard ionization chamber dosimeters.

New stereotactic X-ray knife

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

Barish, R.J.; Barish, S.V.

1988-06-01

For many years, the irradiation of small volumes of tissue in the brain to necrotizing doses has been investigated as a non-invasive alternative to neurosurgery. We propose a new system in which a precisely machined helmet serves as a multi-port focussed X-ray collimator when it is itself irradiated by a conventional medical linear accelerator run in the electron mode. When the collimator is attached to a stereotactic frame, the geometric accuracy of delivering small radiation fields to the brain is limited primarily by the accuracy of the stereotactic localization, and is relatively independent of the positional stability of the accelerator.more » Field sizes as small as two millimeters are readily achievable. The problem of low dose rate associated with these small fields is overcome by the use of high electron beam currents.« less

Distribution of Chromosome Breakpoints in Human Epithelial Cells Exposed to Low- and High-LET Radiations

NASA Technical Reports Server (NTRS)

Hada, Megumi; Cucinotta, Francis; Wu, Honglu

2009-01-01

The advantage of the multicolor banding in situ hybridization (mBAND) technique is not only its ability to identify simultaneously both inter- and intrachromosome exchanges, but also the ability to measure the breakpoint location along the length of the chromosome in a precision that is unmatched with other traditional banding techniques. Breakpoints on specific regions of a chromosome have been known to associate with specific cancers. The breakpoint distribution in cells after low- and high-LET radiation exposures will also provide the data for biophysical modeling of the chromatin structure, as well as the data for the modeling the formation of radiation-induced chromosome aberrations. In a series of experiments, we studied low- and high-LET radiation-induced chromosome aberrations using the mBAND technique with chromosome 3 painted in 23 different colored bands. Human epithelial cells (CH1 84B5F5/M10) were exposed in vitro to Cs- 137 rays at both low and high dose rates, secondary neutrons with a broad energy spectrum at a low dose rate and 600 MeV/u Fe ions at a high dose rate. The data of both inter- and intrachromosome aberrations involving the painted chromosome have been reported previously. Here we present data of the location of the chromosome breaks along the length of chromosome 3 in the cells after exposures to each of the four radiation scenarios. In comparison to the expected breakpoint distribution based on the length of the bands, the observed distribution appeared to be non-random for both the low- and high-LET radiations. In particular, hot spots towards both ends of the chromosome were found after low-LET irradiations of either low or high dose rates. For both high-LET radiation types (Fe ions and neutrons), the breakpoint distributions were similar, and were much smoother than that for low-LET radiation. The dependence of the breakpoint distribution on the radiation quality requires further investigations.

Pharmaceutical spray drying: solid-dose process technology platform for the 21st century.

PubMed

Snyder, Herman E

2012-07-01

Requirement for precise control of solid-dosage particle properties created with a scalable process technology are continuing to expand in the pharmaceutical industry. Alternate methods of drug delivery, limited active drug substance solubility and the need to improve drug product stability under room-temperature conditions are some of the pharmaceutical applications that can benefit from spray-drying technology. Used widely for decades in other industries with production rates up to several tons per hour, pharmaceutical uses for spray drying are expanding beyond excipient production and solvent removal from crystalline material. Creation of active pharmaceutical-ingredient particles with combinations of unique target properties are now more common. This review of spray-drying technology fundamentals provides a brief perspective on the internal process 'mechanics', which combine with both the liquid and solid properties of a formulation to enable high-throughput, continuous manufacturing of precision powder properties.

Technical Note: Construction of heterogeneous head phantom for quality control in stereotactic radiosurgery.

PubMed

Najafi, Mohsen; Teimouri, Javad; Shirazi, Alireza; Geraily, Ghazale; Esfahani, Mahbod; Shafaei, Mostafa

2017-10-01

Stereotactic radiosurgery is a high precision modality for conformally delivering high doses of radiation to the brain lesion with a large dose volume. Several studies for the quality control of this technique were performed to measure the dose delivered to the target with a homogenous head phantom and some dosimeters. Some studies were also performed with one or two instances of heterogeneity in the head phantom to measure the dose delivered to the target. But these studies assumed the head as a sphere and simple shape heterogeneity. The construction of an adult human head phantom with the same size, shape, and real inhomogeneity as an adult human head is needed. Only then is measuring the accurate dose delivered to the area of interest and comparison with the calculated dose possible. According to the ICRU Report 44, polytetrafluoroethylene (PTFE) and methyl methacrylate were selected as a bone and soft tissue, respectively. A set of computed tomography (CT) scans from a standard human head were taken, and simplification of the CT images was used to design the layers of the phantom. The parts of each slice were cut and attached together. Tests of density and CT number were done to compare the material of the phantom with tissues of the head. The dose delivered to the target was measured with an EBT3 film. The density of the PTFE and Plexiglas that were inserted in the phantom are in good agreement with bone and soft tissue. Also, the CT numbers of these materials have a low difference. The dose distribution from the EBT3 film and the treatment planning system is similar. The constructed phantom with a size and inhomogeneity like an adult human head is suitable to measure the dose delivered to the area of interest. It also helps make an accurate comparison with the calculated dose by the treatment planning system. By using this phantom, the actual dose delivered to the target was obtained. This anthropomorphic head phantom can be used in other modalities of radiosurgery as well. © 2017 American Association of Physicists in Medicine.

Three dimensional image correlation of CT, MR, and PET studies in radiotherapy treatment planning of brain tumors.

PubMed

Schad, L R; Boesecke, R; Schlegel, W; Hartmann, G H; Sturm, V; Strauss, L G; Lorenz, W J

1987-01-01

A treatment planning system for stereotactic convergent beam irradiation of deeply localized brain tumors is reported. The treatment technique consists of several moving field irradiations in noncoplanar planes at a linear accelerator facility. Using collimated narrow beams, a high concentration of dose within small volumes with a dose gradient of 10-15%/mm was obtained. The dose calculation was based on geometrical information of multiplanar CT or magnetic resonance (MR) imaging data. The patient's head was fixed in a stereotactic localization system, which is usable at CT, MR, and positron emission tomography (PET) installations. Special computer programs for correction of the geometrical MR distortions allowed a precise correlation of the different imaging modalities. The therapist can use combinations of CT, MR, and PET data for defining target volume. For instance, the superior soft tissue contrast of MR coupled with the metabolic features of PET may be a useful addition in the radiation treatment planning process. Furthermore, other features such as calculated dose distribution to critical structures can also be transferred from one set of imaging data to another and can be displayed as three-dimensional shaded structures.

On the use of quality factors and fluence to dose rate conversion in human radiation exposures

NASA Technical Reports Server (NTRS)

Sondhaus, C. A.

1972-01-01

It is shown that various combinations of numbers and factors arrive at estimates of dose and dose effectiveness from values of fluence; but as yet it has not been possible to use biological data with the same degree of precision to estimate the physical data. It would seem that the most reasonable way to use the human data that exist is to apply them as far as possible to the human animal as a whole.

High Relative Biologic Effectiveness of Carbon Ion Radiation on Induction of Rat Mammary Carcinoma and its Lack of H-ras and Tp53 Mutations

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

Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko

2007-09-01

Purpose: The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model. Methods and Materials: We observed 7-8-week-old rats (ACI, F344, Wistar, and Sprague-Dawley) until 1 year of age after irradiation (0.05-2 Gy) with either 290 MeV/u carbon ions with a spread out Bragg peak (LET 40-90 keV/{mu}m) generated from the Heavy-Ion Medical Acceleratormore » in Chiba or {sup 137}Cs {gamma}-rays. Results: Carbon ions significantly induced mammary carcinomas in Sprague-Dawley rats but less so in other strains. The dose-effect relationship for carcinoma incidence in the Sprague-Dawley rats was concave downward, providing an RBE of 2 at a typical therapeutic dose per fraction. In contrast, {approx}10 should be considered for radiation protection at low doses. Immunohistochemically, 14 of 18 carcinomas were positive for estrogen receptor {alpha}. All carcinomas examined were free of common H-ras and Tp53 mutations. Importantly, lung metastasis (7%) was characteristic of carbon ion-irradiated rats. Conclusions: We found clear genetic variability in the susceptibility to carbon ion-induced mammary carcinomas. The high RBE for carbon ion radiation further supports the importance of precise dose localization in radiotherapy. Common point mutations in H-ras and Tp53 were not involved in carbon ion induction of rat mammary carcinomas.« less

High relative biologic effectiveness of carbon ion radiation on induction of rat mammary carcinoma and its lack of H-ras and Tp53 mutations.

PubMed

Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko; Hatano, Yukiko; Ohmachi, Yasushi; Yoshinaga, Shinji; Kawano, Akihiro; Maekawa, Akihiko; Shimada, Yoshiya

2007-09-01

The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model. We observed 7-8-week-old rats (ACI, F344, Wistar, and Sprague-Dawley) until 1 year of age after irradiation (0.05-2 Gy) with either 290 MeV/u carbon ions with a spread out Bragg peak (LET 40-90 keV/mum) generated from the Heavy-Ion Medical Accelerator in Chiba or (137)Cs gamma-rays. Carbon ions significantly induced mammary carcinomas in Sprague-Dawley rats but less so in other strains. The dose-effect relationship for carcinoma incidence in the Sprague-Dawley rats was concave downward, providing an RBE of 2 at a typical therapeutic dose per fraction. In contrast, approximately 10 should be considered for radiation protection at low doses. Immunohistochemically, 14 of 18 carcinomas were positive for estrogen receptor alpha. All carcinomas examined were free of common H-ras and Tp53 mutations. Importantly, lung metastasis (7%) was characteristic of carbon ion-irradiated rats. We found clear genetic variability in the susceptibility to carbon ion-induced mammary carcinomas. The high RBE for carbon ion radiation further supports the importance of precise dose localization in radiotherapy. Common point mutations in H-ras and Tp53 were not involved in carbon ion induction of rat mammary carcinomas.

Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams

PubMed Central

Niklas, Martin; Zimmermann, Ferdinand; Chaudhri, Naved; Krunic, Damir; Tessonnier, Thomas; Ferrari, Alfredo; Parodi, Katia; Jäkel, Oliver; Debus, Jürgen; Haberer, Thomas; Abdollahi, Amir

2016-01-01

The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy. PMID:27494855

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

NASA Astrophysics Data System (ADS)

Babic, Steven; Schreiner, L. John

2006-09-01

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters.

PubMed

Babic, Steven; Schreiner, L John

2006-09-07

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

Clinical Evaluation of Targeting Accuracy of Gamma Knife Radiosurgery in Trigeminal Neuralgia

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

Massager, Nicolas; Abeloos, Laurence; Devriendt, Daniel

2007-12-01

Purpose: The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgical treatment with the Leksell Gamma Knife for trigeminal neuralgia. We also studied the applied radiation dose within the area of focal contrast enhancement on the trigeminal nerve root following radiosurgery. Methods and Materials: From an initial group of 78 patients with trigeminal neuralgia treated with gamma knife radiosurgery using a 90-Gy dose, we analyzed a subgroup of 65 patients for whom 6-month follow-up MRI showed focal contrast enhancement of the trigeminal nerve. Follow-up MRI was spatially coregistered to the radiosurgicalmore » planning MRI. Target accuracy was assessed from deviation of the coordinates of the intended target compared with the center of enhancement on postoperative MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was 0.91 mm in Euclidean space. The radiation doses fitting within the borders of the contrast enhancement of the trigeminal nerve root ranged from 49 to 85 Gy (median value, 77 {+-} 8.7 Gy). Conclusions: The median deviation found in clinical assessment of gamma knife treatment for trigeminal neuralgia is low and compatible with its high rate of efficiency. Focal enhancement of the trigeminal nerve after radiosurgery occurred in 83% of our patients and was not associated with clinical outcome. Focal enhancement borders along the nerve root fit with a median dose of 77 {+-} 8.7 Gy.« less

Substitution of starch by soluble fiber and Saccharomyces cerevisiae dose response on nutrient digestion and blood metabolites for precision-fed dairy heifers.

PubMed

Lascano, G J; Heinrichs, A J; Tricarico, J M

2012-06-01

The objective of this experiment was to determine the effects of 2 levels of dietary starch and the dose at which the effects of yeast culture (YC) derived from Saccharomyces cerevisiae (Yea-Sacc¹⁰²⁶, Alltech Inc., Nicholasville, KY) were maximized based on nutrient total-tract digestibility (AD), N utilization, and blood metabolites of precision-fed dairy heifers. A split-plot design with starch level as the whole plot and YC dose as subplot was administered in a 4-period (21 d), 4 × 4 Latin square. Eight Holstein heifers (432.49 ± 6.81 kg of body weight) were allocated to 2 starch treatments (28% starch, high starch, HS, or 17% starch, low starch, LS) and to a sequence of YC doses (0, 10, 30, and 50 g/d). Dry matter (DM) and neutral detergent fiber (NDF) AD were not different between HS and LS; however, HS decreased acid detergent fiber (ADF) and increased hemicellulose AD. Digestibility of DM and organic matter (OM) increased quadratically in response to increasing YC dose. Hemicellulose, NDF, and ADF AD increased or tended to increase quadratically with increasing YC dose. No significant effects were noted on fecal or urine output between dietary starch concentrations; YC decreased wet and dry fecal output corresponding to the effect in DM and OM. Apparent N digestibility was greater in the LS group. As YC dose increased, fecal N output decreased quadratically and was lowest at 30 g/d YC. A corresponding quadratic increase was observed for N retention expressed as a percentage of N digested: N output in urine tended to increase with increasing YC dose, resulting in no differences in retained N (g/d). Dietary starch concentration did not affect blood glucose, triglyceride, creatinine, or lactate concentration. However, HS increased plasma urea N concentration. Glucose concentration tended to increase quadratically with daily YC dose in both starch treatments, with the greatest response at 30 g/d. For triglycerides, dietary starch concentration and YC dose interacted, decreasing quadratically in the LS group and increasing in the HS group (lowest and highest value for 10 g/d respectively). We observed a significant time effect for all blood metabolites measured. We conclude that starch level did not affect DM AD, but influenced ADF and hemicellulose AD. Yeast culture had the greatest effect on DM, NDF, ADF, and hemicellulose AD when added at 30 g/d. Addition of YC influenced glucose and triglyceride concentrations differently according to the dietary starch concentration of the diet. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Galactic cosmic ray-induced radiation dose on terrestrial exoplanets.

PubMed

Atri, Dimitra; Hariharan, B; Grießmeier, Jean-Mathias

2013-10-01

This past decade has seen tremendous advancements in the study of extrasolar planets. Observations are now made with increasing sophistication from both ground- and space-based instruments, and exoplanets are characterized with increasing precision. There is a class of particularly interesting exoplanets that reside in the habitable zone, which is defined as the area around a star where the planet is capable of supporting liquid water on its surface. Planetary systems around M dwarfs are considered to be prime candidates to search for life beyond the Solar System. Such planets are likely to be tidally locked and have close-in habitable zones. Theoretical calculations also suggest that close-in exoplanets are more likely to have weaker planetary magnetic fields, especially in the case of super-Earths. Such exoplanets are subjected to a high flux of galactic cosmic rays (GCRs) due to their weak magnetic moments. GCRs are energetic particles of astrophysical origin that strike the planetary atmosphere and produce secondary particles, including muons, which are highly penetrating. Some of these particles reach the planetary surface and contribute to the radiation dose. Along with the magnetic field, another factor governing the radiation dose is the depth of the planetary atmosphere. The higher the depth of the planetary atmosphere, the lower the flux of secondary particles will be on the surface. If the secondary particles are energetic enough, and their flux is sufficiently high, the radiation from muons can also impact the subsurface regions, such as in the case of Mars. If the radiation dose is too high, the chances of sustaining a long-term biosphere on the planet are very low. We have examined the dependence of the GCR-induced radiation dose on the strength of the planetary magnetic field and its atmospheric depth, and found that the latter is the decisive factor for the protection of a planetary biosphere.

Comparison of depth-dose distributions of proton therapeutic beams calculated by means of logical detectors and ionization chamber modeled in Monte Carlo codes

NASA Astrophysics Data System (ADS)

Pietrzak, Robert; Konefał, Adam; Sokół, Maria; Orlef, Andrzej

2016-08-01

The success of proton therapy depends strongly on the precision of treatment planning. Dose distribution in biological tissue may be obtained from Monte Carlo simulations using various scientific codes making it possible to perform very accurate calculations. However, there are many factors affecting the accuracy of modeling. One of them is a structure of objects called bins registering a dose. In this work the influence of bin structure on the dose distributions was examined. The MCNPX code calculations of Bragg curve for the 60 MeV proton beam were done in two ways: using simple logical detectors being the volumes determined in water, and using a precise model of ionization chamber used in clinical dosimetry. The results of the simulations were verified experimentally in the water phantom with Marcus ionization chamber. The average local dose difference between the measured relative doses in the water phantom and those calculated by means of the logical detectors was 1.4% at first 25 mm, whereas in the full depth range this difference was 1.6% for the maximum uncertainty in the calculations less than 2.4% and for the maximum measuring error of 1%. In case of the relative doses calculated with the use of the ionization chamber model this average difference was somewhat greater, being 2.3% at depths up to 25 mm and 2.4% in the full range of depths for the maximum uncertainty in the calculations of 3%. In the dose calculations the ionization chamber model does not offer any additional advantages over the logical detectors. The results provided by both models are similar and in good agreement with the measurements, however, the logical detector approach is a more time-effective method.

SU-E-T-627: Precision Modelling of the Leaf-Bank Rotation in Elekta’s Agility MLC: Is It Necessary?

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

Vujicic, M; Belec, J; Heath, E

Purpose: To demonstrate the method used to determine the leaf bank rotation angle (LBROT) as a parameter for modeling the Elekta Agility multi-leaf collimator (MLC) for Monte Carlo simulations and to evaluate the clinical impact of LBROT. Methods: A detailed model of an Elekta Infinity linac including an Agility MLC was built using the EGSnrc/BEAMnrc Monte Carlo code. The Agility 160-leaf MLC is modelled using the MLCE component module which allows for leaf bank rotation using the parameter LBROT. A precise value of LBROT is obtained by comparing measured and simulated profiles of a specific field, which has leaves arrangedmore » in a repeated pattern such that one leaf is opened and the adjacent one is closed. Profile measurements from an Agility linac are taken with gafchromic film, and an ion chamber is used to set the absolute dose. The measurements are compared to Monte Carlo (MC) simulations and the LBROT is adjusted until a match is found. The clinical impact of LBROT is evaluated by observing how an MC dose calculation changes with LBROT. A clinical Stereotactic Body Radiation Treatment (SBRT) plan is calculated using BEAMnrc/DOSXYZnrc simulations with different input values for LBROT. Results: Using the method outlined above, the LBROT is determined to be 9±1 mrad. Differences as high as 4% are observed in a clinical SBRT plan between the extreme case (LBROT not modeled) and the nominal case. Conclusion: In small-field radiation therapy treatment planning, it is important to properly account for LBROT as an input parameter for MC dose calculations with the Agility MLC. More work is ongoing to elucidate the observed differences by determining the contributions from transmission dose, change in field size, and source occlusion, which are all dependent on LBROT. This work was supported by OCAIRO (Ontario Consortium of Adaptive Interventions in Radiation Oncology), funded by the Ontario Research Fund.« less

SU-F-I-56: High-Precision Gamma-Ray Analysis of Medical Isotopes

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

Chopra, N; Chillery, T; Chowdhury, P

2016-06-15

Purpose: Advanced, time-resolved, Compton-suppressed gamma-ray spectroscopy with germanium detectors is implemented for assaying medical isotopes to study the radioactive decay process leading to a more accurate appraisal of the received dose and treatment planning. Lowell’s Array for Radiological Assay (LARA), a detector array that is comprised of six Compton-suppressed high-purity germanium detectors, is currently under development at UMass-Lowell which combines Compton-suppression and time-and-angle correlations to allow for highly efficient and highly sensitive measurements. Methods: Two isotopes produced Brookhaven Linac Isotope Producer (BLIP) were investigated. {sup 82}Sr which is the parent isotope for producing {sup 82}Rb is often used in cardiacmore » PET. {sup 82}Sr gamma-ray spectrum is dominated by the 511keV photons from positron annihilation which prevent precise measurement of co-produced contaminant isotopes. A second project was to investigate the production of platinum isotopes. Natural platinum was bombarded with protons from 53MeV to 200MeV. The resulting spectrum was complicated due to the large number of stable platinum isotopes in the target, the variety of open reaction channels (p,xn), (p,pxn), (p,axn). Results: By using face-to-face NaI(Tl) counters 90-degrees to the Compton-suppressed germaniums to detect the 511keV photons, a much cleaner and more sensitive measurement of {sup 85}Sr and other contaminants was obtained. For the platinum target, we identified the production of {sup 188–189–191–195}Pt, {sup 191–192–193–194–195–196}Au and {sup 186–188–189–190–192–194–189–190–192–194}Ir. For example, at the lower energies (53 and 65MeV), we measured {sup 191}Pt production cross-sections of 144mb and 157mb. Considerable care was needed in following the process of dissolving and diluting the samples to get consistent results. The new LARA array will help us better ascertain the absolute efficiency of the counting system and more reliable production cross-sections. Conclusion: Modern HPGe spectroscopic techniques provide enhanced sensitivity, promising precise quantification of the quality of radioisotopes used in medical physics. Using new decay information may have non-trivial impact on treatment planning and dose-assessment.« less

[Population pharmacokinetics applied to optimising cisplatin doses in cancer patients].

PubMed

Ramón-López, A; Escudero-Ortiz, V; Carbonell, V; Pérez-Ruixo, J J; Valenzuela, B

2012-01-01

To develop and internally validate a population pharmacokinetics model for cisplatin and assess its prediction capacity for personalising doses in cancer patients. Cisplatin plasma concentrations in forty-six cancer patients were used to determine the pharmacokinetic parameters of a two-compartment pharmacokinetic model implemented in NONMEN VI software. Pharmacokinetic parameter identification capacity was assessed using the parametric bootstrap method and the model was validated using the nonparametric bootstrap method and standardised visual and numerical predictive checks. The final model's prediction capacity was evaluated in terms of accuracy and precision during the first (a priori) and second (a posteriori) chemotherapy cycles. Mean population cisplatin clearance is 1.03 L/h with an interpatient variability of 78.0%. Estimated distribution volume at steady state was 48.3 L, with inter- and intrapatient variabilities of 31,3% and 11,7%, respectively. Internal validation confirmed that the population pharmacokinetics model is appropriate to describe changes over time in cisplatin plasma concentrations, as well as its variability in the study population. The accuracy and precision of a posteriori prediction of cisplatin concentrations improved by 21% and 54% compared to a priori prediction. The population pharmacokinetic model developed adequately described the changes in cisplatin plasma concentrations in cancer patients and can be used to optimise cisplatin dosing regimes accurately and precisely. Copyright © 2011 SEFH. Published by Elsevier Espana. All rights reserved.

Markov random field based automatic image alignment for electron tomography.

PubMed

Amat, Fernando; Moussavi, Farshid; Comolli, Luis R; Elidan, Gal; Downing, Kenneth H; Horowitz, Mark

2008-03-01

We present a method for automatic full-precision alignment of the images in a tomographic tilt series. Full-precision automatic alignment of cryo electron microscopy images has remained a difficult challenge to date, due to the limited electron dose and low image contrast. These facts lead to poor signal to noise ratio (SNR) in the images, which causes automatic feature trackers to generate errors, even with high contrast gold particles as fiducial features. To enable fully automatic alignment for full-precision reconstructions, we frame the problem probabilistically as finding the most likely particle tracks given a set of noisy images, using contextual information to make the solution more robust to the noise in each image. To solve this maximum likelihood problem, we use Markov Random Fields (MRF) to establish the correspondence of features in alignment and robust optimization for projection model estimation. The resulting algorithm, called Robust Alignment and Projection Estimation for Tomographic Reconstruction, or RAPTOR, has not needed any manual intervention for the difficult datasets we have tried, and has provided sub-pixel alignment that is as good as the manual approach by an expert user. We are able to automatically map complete and partial marker trajectories and thus obtain highly accurate image alignment. Our method has been applied to challenging cryo electron tomographic datasets with low SNR from intact bacterial cells, as well as several plastic section and X-ray datasets.

Parametric study of irradiation effects on the ductile damage and flow stress behavior in ferritic-martensitic steels

NASA Astrophysics Data System (ADS)

Chakraborty, Pritam; Biner, S. Bulent

2015-10-01

Ferritic-martensitic steels are currently being considered as structural materials in fusion and Gen-IV nuclear reactors. These materials are expected to experience high dose radiation, which can increase their ductile to brittle transition temperature and susceptibility to failure during operation. Hence, to estimate the safe operational life of the reactors, precise evaluation of the ductile to brittle transition temperatures of ferritic-martensitic steels is necessary. Owing to the scarcity of irradiated samples, particularly at high dose levels, micro-mechanistic models are being employed to predict the shifts in the ductile to brittle transition temperatures. These models consider the ductile damage evolution, in the form of nucleation, growth and coalescence of voids; and the brittle fracture, in the form of probabilistic cleavage initiation, to estimate the influence of irradiation on the ductile to brittle transition temperature. However, the assessment of irradiation dependent material parameters is challenging and influences the accuracy of these models. In the present study, the effects of irradiation on the overall flow stress and ductile damage behavior of two ferritic-martensitic steels is parametrically investigated. The results indicate that the ductile damage model parameters are mostly insensitive to irradiation levels at higher dose levels though the resulting flow stress behavior varies significantly.

Fast Track Characterization of Highly Radioactive Waste Pits Combining Off-the-Shelf Robotics with Innovative Investigation Protocols

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

Chabeuf, Jean-Michel; Boya, Didier

The investigation and characterization of radioactive waste pits and effluent storage tanks represents a substantial and challenging step in the overall decommissioning programme launched by AREVA NC in 1998 on the site of Marcoule on behalf of the French Atomic Energy commission. Physical ,radiological and regulatory constraints, combined with a tight schedule, have lead our teams to use proven conventional instrumentation and robotics in innovative configurations . One such investigation, conducted on a particularly challenging radioactive effluent storage pit, is described below. The 'H' pit is a stainless steel clad concrete cavity, located in the second basement of the de-claddingmore » building of Marcoule site. It was used for forty years as buffer storage for high activity effluents and has a length of 5 meters, a width of 3 meters , a height of 2.5 meters, and is topped by lead plates over 5 cm thick and The bottom of the cavity is covered with a layer of mud containing mainly graphite, diatoms and resins. The mud level ranges from about 20 centimeters to over 50 centimeters. The overall mud volume is around 2.4 cubic meters. Ambient dose rates above the lead plates exceed 10 mSv/h. The main purpose of our investigation was to characterize the muds for future recovery and conditioning prior to decontaminating the pit. The history of the pit together with the varying mud altimetry lead us to believe that sedimentation had probably occurred throughout the years. We thus decided to combine dose rate measurements using IF104 probes, gamma spectroscopy with CdTe probes and sample collections at different depths to ensure the representativeness and full characterization of the muds. Poor access, ambient dose rates have lead us to conceive a robotic arm, mounted on an shaft which can be modified to fit a wide range of pits and tanks. Custom built robotic tools with maximum manoeuvrability generally involve costs and delays far exceeding our purposes. SIT, a French manufacturer of high precision handling equipment for the nuclear industry, supplied us with a user customized 'Python' Robotic arm and the associated computerized command and control equipment within 6 months of the order. The arm allowed the necessary free movement for a precise characterization of the entire pit while being flexible enough to carry varying measuring and sample collection tools. Investigations included video imaging, precise dimensional checks, collection of effluent samples, gamma spectroscopy and collimated dose rate measurements. Specific tooling and arm extensions were created by SIT for each measurement type. The investigations were conducted successfully, providing a detailed view of the pit condition, a complete mapping of collimated dose rates, a grid of gamma spectroscopy, as well as 8 samples of radioactive mud which were subsequently analyzed in our laboratory . A simple yet innovative technology allowed us to fully characterize this pit and its content within a time frame of less than Eight months We subsequently developed a mud recovery scenario, a process for the conditioning of radioactive muds by cementation, and a complete scenario for the pit decontamination and dismantling. The robotic arm is now being used for the characterization and decontamination of other similar environments on the site of Marcoule.« less

Spot scanning proton therapy plan assessment: design and development of a dose verification application for use in routine clinical practice

NASA Astrophysics Data System (ADS)

Augustine, Kurt E.; Walsh, Timothy J.; Beltran, Chris J.; Stoker, Joshua B.; Mundy, Daniel W.; Parry, Mark D.; Bues, Martin; Fatyga, Mirek

2016-04-01

The use of radiation therapy for the treatment of cancer has been carried out clinically since the late 1800's. Early on however, it was discovered that a radiation dose sufficient to destroy cancer cells can also cause severe injury to surrounding healthy tissue. Radiation oncologists continually strive to find the perfect balance between a dose high enough to destroy the cancer and one that avoids damage to healthy organs. Spot scanning or "pencil beam" proton radiotherapy offers another option to improve on this. Unlike traditional photon therapy, proton beams stop in the target tissue, thus better sparing all organs beyond the targeted tumor. In addition, the beams are far narrower and thus can be more precisely "painted" onto the tumor, avoiding exposure to surrounding healthy tissue. To safely treat patients with proton beam radiotherapy, dose verification should be carried out for each plan prior to treatment. Proton dose verification systems are not currently commercially available so the Department of Radiation Oncology at the Mayo Clinic developed its own, called DOSeCHECK, which offers two distinct dose simulation methods: GPU-based Monte Carlo and CPU-based analytical. The three major components of the system include the web-based user interface, the Linux-based dose verification simulation engines, and the supporting services and components. The architecture integrates multiple applications, libraries, platforms, programming languages, and communication protocols and was successfully deployed in time for Mayo Clinic's first proton beam therapy patient. Having a simple, efficient application for dose verification greatly reduces staff workload and provides additional quality assurance, ultimately improving patient safety.

SU-E-T-50: Automatic Validation of Megavoltage Beams Modeled for Clinical Use in Radiation Therapy

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

Melchior, M; Salinas Aranda, F; 21st Century Oncology, Ft. Myers, FL

2014-06-01

Purpose: To automatically validate megavoltage beams modeled in XiO™ 4.50 (Elekta, Stockholm, Sweden) and Varian Eclipse™ Treatment Planning Systems (TPS) (Varian Associates, Palo Alto, CA, USA), reducing validation time before beam-on for clinical use. Methods: A software application that can automatically read and analyze DICOM RT Dose and W2CAD files was developed using MatLab integrated development environment.TPS calculated dose distributions, in DICOM RT Dose format, and dose values measured in different Varian Clinac beams, in W2CAD format, were compared. Experimental beam data used were those acquired for beam commissioning, collected on a water phantom with a 2D automatic beam scanningmore » system.Two methods were chosen to evaluate dose distributions fitting: gamma analysis and point tests described in Appendix E of IAEA TECDOC-1583. Depth dose curves and beam profiles were evaluated for both open and wedged beams. Tolerance parameters chosen for gamma analysis are 3% and 3 mm dose and distance, respectively.Absolute dose was measured independently at points proposed in Appendix E of TECDOC-1583 to validate software results. Results: TPS calculated depth dose distributions agree with measured beam data under fixed precision values at all depths analyzed. Measured beam dose profiles match TPS calculated doses with high accuracy in both open and wedged beams. Depth and profile dose distributions fitting analysis show gamma values < 1. Relative errors at points proposed in Appendix E of TECDOC-1583 meet therein recommended tolerances.Independent absolute dose measurements at points proposed in Appendix E of TECDOC-1583 confirm software results. Conclusion: Automatic validation of megavoltage beams modeled for their use in the clinic was accomplished. The software tool developed proved efficient, giving users a convenient and reliable environment to decide whether to accept or not a beam model for clinical use. Validation time before beam-on for clinical use was reduced to a few hours.« less

Parotid gland mean dose as a xerostomia predictor in low-dose domains.

PubMed

Gabryś, Hubert Szymon; Buettner, Florian; Sterzing, Florian; Hauswald, Henrik; Bangert, Mark

2017-09-01

Xerostomia is a common side effect of radiotherapy resulting from excessive irradiation of salivary glands. Typically, xerostomia is modeled by the mean dose-response characteristic of parotid glands and prevented by mean dose constraints to either contralateral or both parotid glands. The aim of this study was to investigate whether normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands are suitable for the prediction of xerostomia in a highly conformal low-dose regime of modern intensity-modulated radiotherapy (IMRT) techniques. We present a retrospective analysis of 153 head and neck cancer patients treated with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate predictive power of the parotid gland mean dose with respect to xerostomia at 6 and 12 months after the treatment. The predictive performance of the model was evaluated by receiver operating characteristic (ROC) curves and precision-recall (PR) curves. Average mean doses to ipsilateral and contralateral parotid glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in 74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12 months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to provide reliable G2 + xerostomia predictions at both time points. Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1 + xerostomia fairly well, however, failed to recognize patients at risk of G2 + xerostomia. There is a need for the development of more flexible models able to capture complexity of dose response in this dose regime.

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

Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org; Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne; Te Marvelde, Luc

Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predictmore » future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.« less

Combined experimental and Monte Carlo verification of brachytherapy plans for vaginal applicators

NASA Astrophysics Data System (ADS)

Sloboda, Ron S.; Wang, Ruqing

1998-12-01

Dose rates in a phantom around a shielded and an unshielded vaginal applicator containing Selectron low-dose-rate sources were determined by experiment and Monte Carlo simulation. Measurements were performed with thermoluminescent dosimeters in a white polystyrene phantom using an experimental protocol geared for precision. Calculations for the same set-up were done using a version of the EGS4 Monte Carlo code system modified for brachytherapy applications into which a new combinatorial geometry package developed by Bielajew was recently incorporated. Measured dose rates agree with Monte Carlo estimates to within 5% (1 SD) for the unshielded applicator, while highlighting some experimental uncertainties for the shielded applicator. Monte Carlo calculations were also done to determine a value for the effective transmission of the shield required for clinical treatment planning, and to estimate the dose rate in water at points in axial and sagittal planes transecting the shielded applicator. Comparison with dose rates generated by the planning system indicates that agreement is better than 5% (1 SD) at most positions. The precision thermoluminescent dosimetry protocol and modified Monte Carlo code are effective complementary tools for brachytherapy applicator dosimetry.

Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate data analysis.

PubMed

Yan, Hui; Qiao, Zheng; Shen, Baohua; Xiang, Ping; Shen, Min

2016-10-01

Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of brodifacoum induced toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interference experiment with asymmetric double slit by using 1.2-MV field emission transmission electron microscope.

PubMed

Harada, Ken; Akashi, Tetsuya; Niitsu, Kodai; Shimada, Keiko; Ono, Yoshimasa A; Shindo, Daisuke; Shinada, Hiroyuki; Mori, Shigeo

2018-01-17

Advanced electron microscopy technologies have made it possible to perform precise double-slit interference experiments. We used a 1.2-MV field emission electron microscope providing coherent electron waves and a direct detection camera system enabling single-electron detections at a sub-second exposure time. We developed a method to perform the interference experiment by using an asymmetric double-slit fabricated by a focused ion beam instrument and by operating the microscope under a "pre-Fraunhofer" condition, different from the Fraunhofer condition of conventional double-slit experiments. Here, pre-Fraunhofer condition means that each single-slit observation was performed under the Fraunhofer condition, while the double-slit observations were performed under the Fresnel condition. The interference experiments with each single slit and with the asymmetric double slit were carried out under two different electron dose conditions: high-dose for calculation of electron probability distribution and low-dose for each single electron distribution. Finally, we exemplified the distribution of single electrons by color-coding according to the above three types of experiments as a composite image.

Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats.

PubMed

Li, Chao; Song, Xiaowei; Song, Junke; Pang, Xiaocong; Wang, Zhe; Zhao, Ying; Lian, Wenwen; Liu, Ailin; Du, Guanhua

2016-01-01

The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C 0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0-t ) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688.

Improving external beam radiotherapy by combination with internal irradiation.

PubMed

Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

2015-07-01

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

Testing and linearity calibration of films of phenol compounds exposed to thermal neutron field for EPR dosimetry.

PubMed

Gallo, S; Panzeca, S; Longo, A; Altieri, S; Bentivoglio, A; Dondi, D; Marconi, R P; Protti, N; Zeffiro, A; Marrale, M

2015-12-01

This paper reports the preliminary results obtained by Electron Paramagnetic Resonance (EPR) measurements on films of IRGANOX® 1076 phenols with and without low content (5% by weight) of gadolinium oxide (Gd2O3) exposed in the thermal column of the Triga Mark II reactor of LENA (Laboratorio Energia Nucleare Applicata) of Pavia (Italy). Thanks to their size, the phenolic films here presented are good devices for the dosimetry of beams with high dose gradient and which require accurate knowledge of the precise dose delivered. The dependence of EPR signal as function of neutron dose was investigated in the fluence range between 10(11) cm(-2) and 10(14) cm(-2). Linearity of EPR response was found and the signal was compared with that of commercial alanine films. Our analysis showed that gadolinium oxide (5% by weight) can enhance the thermal neutron sensitivity more than 18 times. Irradiated dosimetric films of phenolic compound exhibited EPR signal fading of about 4% after 10 days from irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electronic Subsystem Analysis (ESA)

DTIC Science & Technology

1977-01-01

than aluminum for the gate material, 0 Ion implanted source and draia regions, 0 Dielectrically isolated transistors. The use of a doped polysilicon gate...second level of interconnect ( polysilicon ). Ion implantation is essentially a precisely controllable pre-deposition of the required dopants. It’s use...discussed below). Radiation effects on MOS devices include the following: 0 Total Dose ol Dose Rate o Neutrons Because MOS technology is based on

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

PubMed

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

2017-10-01

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

Rigorous-two-Steps scheme of TRIPOLI-4® Monte Carlo code validation for shutdown dose rate calculation

NASA Astrophysics Data System (ADS)

Jaboulay, Jean-Charles; Brun, Emeric; Hugot, François-Xavier; Huynh, Tan-Dat; Malouch, Fadhel; Mancusi, Davide; Tsilanizara, Aime

2017-09-01

After fission or fusion reactor shutdown the activated structure emits decay photons. For maintenance operations the radiation dose map must be established in the reactor building. Several calculation schemes have been developed to calculate the shutdown dose rate. These schemes are widely developed in fusion application and more precisely for the ITER tokamak. This paper presents the rigorous-two-steps scheme implemented at CEA. It is based on the TRIPOLI-4® Monte Carlo code and the inventory code MENDEL. The ITER shutdown dose rate benchmark has been carried out, results are in a good agreement with the other participant.

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays | NCI Technology Transfer Center | TTC

Cancer.gov

Pre-clinical radiotracer biomedical research involves the use of compounds labeled with radioisotopes, including cell binding studies, immune cell labeling techniques, and radio-ligand bio-distribution studies. Before this Micro-Dose Calibrator, measurement of pre-clinical level dosage for small animal studies was inaccurate and unreliable. This dose calibrator is a prototype ready for manufacturing. It is designed to accurately measure radioactive doses in the range of 50 nCi (1.8 kBq) to 100 µCi (3.7 MBq) with 1% precision. The NCI seeks co-development or licensing to commercialize it. Alternative uses will be considered.

On the use of an analytic source model for dose calculations in precision image-guided small animal radiotherapy.

PubMed

Granton, Patrick V; Verhaegen, Frank

2013-05-21

Precision image-guided small animal radiotherapy is rapidly advancing through the use of dedicated micro-irradiation devices. However, precise modeling of these devices in model-based dose-calculation algorithms such as Monte Carlo (MC) simulations continue to present challenges due to a combination of very small beams, low mechanical tolerances on beam collimation, positioning and long calculation times. The specific intent of this investigation is to introduce and demonstrate the viability of a fast analytical source model (AM) for use in either investigating improvements in collimator design or for use in faster dose calculations. MC models using BEAMnrc were developed for circular and square fields sizes from 1 to 25 mm in diameter (or side) that incorporated the intensity distribution of the focal spot modeled after an experimental pinhole image. These MC models were used to generate phase space files (PSFMC) at the exit of the collimators. An AM was developed that included the intensity distribution of the focal spot, a pre-calculated x-ray spectrum, and the collimator-specific entrance and exit apertures. The AM was used to generate photon fluence intensity distributions (ΦAM) and PSFAM containing photons radiating at angles according to the focal spot intensity distribution. MC dose calculations using DOSXYZnrc in a water and mouse phantom differing only by source used (PSFMC versus PSFAM) were found to agree within 7% and 4% for the smallest 1 and 2 mm collimator, respectively, and within 1% for all other field sizes based on depth dose profiles. PSF generation times were approximately 1200 times faster for the smallest beam and 19 times faster for the largest beam. The influence of the focal spot intensity distribution on output and on beam shape was quantified and found to play a significant role in calculated dose distributions. Beam profile differences due to collimator alignment were found in both small and large collimators sensitive to shifts of 1 mm with respect to the central axis.

Selective doping of silicon nanowires by means of electron beam stimulated oxide etching.

PubMed

Pennelli, G; Totaro, M; Piotto, M

2012-02-08

Direct patterning of silicon dioxide by means of electron beam stimulated etching is shown, and a full characterization of exposure dose is presented. For its high dose, this technique is unsuitable for large areas but can be usefully employed like a precision scalpel for removing silicon dioxide by well-localized points. In this work, this technique is applied to the definition of windows through the oxide surrounding top down fabricated n-doped silicon nanowires. These windows will be employed for a selective doping of the nanowire by boron diffusion. In this way, pn junctions can be fabricated in well-localized points in the longitudinal direction of the nanowire, and an electrical contact to the different junctions can be provided. Electrical I-V characteristics of a nanowire with pn longitudinal junctions are reported and discussed. © 2012 American Chemical Society

Simulation and experimental measurement of radon activity using a multichannel silicon-based radiation detector.

PubMed

Ozdemir, F B; Selcuk, A B; Ozkorucuklu, S; Alpat, A B; Ozdemir, T; Ӧzek, N

2018-05-01

In this study, high-precision radiation detector (HIPRAD), a new-generation semiconductor microstrip detector, was used for detecting radon (Rn-222) activity. The aim of this study was to detect radon (Rn-222) activity experimentally by measuring the energy of particles in this detector. Count-ADC channel, eta-charge, and dose-response values were experimentally obtained using HIPRAD. The radon simulation in the radiation detector was theoretically performed using the Geant4 software package. The obtained radioactive decay, energy generation, energy values, and efficiency values of the simulation were plotted using the root program. The new-generation radiation detector proved to have 95% reliability according to the obtained dose-response graphs. The experimental and simulation results were found to be compatible with each other and with the radon decays and literature studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thermoluminescence (TL) characteristics of perovskite-like KMgF 3 activated by La ions

NASA Astrophysics Data System (ADS)

Sepulveda, F.; Azorin, J.; Rivera, T.; Furetta, C.; Sanipoli, C.

2004-01-01

This paper reports the experimental results concerning the thermoluminescent characteristics of a new preparation of the fluoroperovskite KMgF 3:La + PTFE.The main thermoluminescent properties investigated were: the thermoluminescence (TL) response as a function of the absorbed dose, the precision obtainable in the dose measurement, the reproducibility of the TL readings and the threshold dose. The results obtained were then compared to the requirements of the ANSI protocol for thermoluminescent environmental dosimetry, resulting in a very good agreement with the required performances.

Imaging and characterization of primary and secondary radiation in ion beam therapy

NASA Astrophysics Data System (ADS)

Granja, Carlos; Martisikova, Maria; Jakubek, Jan; Opalka, Lukas; Gwosch, Klaus

2016-07-01

Imaging in ion beam therapy is an essential and increasingly significant tool for treatment planning and radiation and dose deposition verification. Efforts aim at providing precise radiation field characterization and online monitoring of radiation dose distribution. A review is given of the research and methodology of quantum-imaging, composition, spectral and directional characterization of the mixed-radiation fields in proton and light ion beam therapy developed by the IEAP CTU Prague and HIT Heidelberg group. Results include non-invasive imaging of dose deposition and primary beam online monitoring.

Clinical translation of photobiomodulation therapy using evidences from precision molecular pathway analyses (Conference Presentation)

NASA Astrophysics Data System (ADS)

Arany, Praveen

2017-02-01

Can `light' be a Drug? To satisfy this definition as a pharmaceutical agent, light must be absorbed and change bodily function. Much evidence from our understanding of our visual cycle and Vitamin D metabolism have all noted this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. The use of lasers and light devices at high doses in dermatology, ophthalmology, oncology and dentistry are now considered mainstream for certain clinical applications such as surgery, skin rejuvenation, ocular and soft tissue recontouring, anti-tumor and anti-microbial photodynamic therapy. In contrast, therapeutic use of low dose biophotonics devices is called Low Level Light / Laser Therapy (LLLT), now termed Photobiomodulation (PBM) Therapy. This therapy is defined as a non-thermal use of non-ionizing forms of electromagnetic radiation to alleviate pain, inflammation, modulating the immune responses and promoting wound healing and tissue regeneration. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, limited mechanistic insights have prevented the development of rigorous, reproducible clinical protocols. This presentation will outline our current efforts at ongoing efforts in our group to assess molecular pathways and precisely define clinical treatment variables to enable clinical translation with PBM therapies.

Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

PubMed Central

VanGuilder, Michael; Donnelly, J. Peter; Blijlevens, Nicole M. A.; Brüggemann, Roger J. M.; Jelliffe, Roger W.; Neely, Michael N.

2013-01-01

The efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice. PMID:23380734

Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram.

PubMed

Kasper, Siegfried; Sacher, Julia; Klein, Nikolas; Mossaheb, Nilufar; Attarbaschi-Steiner, Trawat; Lanzenberger, Rupert; Spindelegger, Christoph; Asenbaum, Susanne; Holik, Alexander; Dudczak, Robert

2009-05-01

Escitalopram the S-enantiomer of the racemate citalopram, is clinically more effective than citalopram in the treatment of major depressive disorder. However, the precise mechanism by which escitalopram achieves superiority over citalopram is yet to be determined. It has been hypothesized that the therapeutically inactive R-enantiomer competes with the serotonin-enhancing S-enantiomer at a low-affinity allosteric site on serotonin reuptake transporters (SERTs), and reduces the effectiveness of the S-enantiomer at the primary, high-affinity serotonin-binding site. This study summarizes the results of two recent single-photon emission computerized tomography studies measuring SERT occupancy in citalopram-treated and escitalopram-treated healthy volunteers, after a single dose and multiple doses (i.e. under steady-state conditions). The single-dose study showed no attenuating effect of R-citalopram. After multiple dosing, however, SERT occupancy was significantly reduced in the presence of R-citalopram. Under steady-state conditions, R-enantiomer concentrations were greater than for the S-enantiomer because of slower clearance of R-citalopram. A pooled analysis suggests that build-up of the R-enantiomer after repeated citalopram dosing may lead to increased inhibition of S-enantiomer occupancy of SERT. This review adds to the growing body of evidence regarding differences in the dynamics of SERT occupancy, that is, molecular mechanisms underlying the often-observed superior clinical efficacy of escitalopram compared with citalopram in major depressive disorder.

Analysis of measurement deviations for the patient-specific quality assurance using intensity-modulated spot-scanning particle beams

NASA Astrophysics Data System (ADS)

Li, Yongqiang; Hsi, Wen C.

2017-04-01

To analyze measurement deviations of patient-specific quality assurance (QA) using intensity-modulated spot-scanning particle beams, a commercial radiation dosimeter using 24 pinpoint ionization chambers was utilized. Before the clinical trial, validations of the radiation dosimeter and treatment planning system were conducted. During the clinical trial 165 measurements were performed on 36 enrolled patients. Two or three fields of particle beam were used for each patient. Measurements were typically performed with the dosimeter placed at special regions of dose distribution along depth and lateral profiles. In order to investigate the dosimeter accuracy, repeated measurements with uniform dose irradiations were also carried out. A two-step approach was proposed to analyze 24 sampling points over a 3D treatment volume. The mean value and the standard deviation of each measurement did not exceed 5% for all measurements performed on patients with various diseases. According to the defined intervention thresholds of mean deviation and the distance-to-agreement concept with a Gamma index analysis using criteria of 3.0% and 2 mm, a decision could be made regarding whether the dose distribution was acceptable for the patient. Based measurement results, deviation analysis was carried out. In this study, the dosimeter was used for dose verification and provided a safety guard to assure precise dose delivery of highly modulated particle therapy. Patient-specific QA will be investigated in future clinical operations.

Inkjet printing of drug substances and use of porous substrates-towards individualized dosing.

PubMed

Sandler, Niklas; Määttänen, Anni; Ihalainen, Petri; Kronberg, Leif; Meierjohann, Axel; Viitala, Tapani; Peltonen, Jouko

2011-08-01

Medicines are most often oral solid dosage forms made into tablets or capsules, and there is little room for individualized doses. The drug substance and additives are processed through multiple production phases, including complex powder handling steps. In drug manufacturing, the control of the solid-state properties of active pharmaceutical ingredient (API) is essential and it offers opportunities for enhancement of drug delivery systems. In this context, inkjet printing technologies have emerged over the last decades in pharmaceutical and biological applications and offer solutions for controlling material and product characteristics with high precision. Here we report the concept of conventional inkjet printing technology to produce printable pharmaceutical dosage forms on porous substrates. Data are shown to demonstrate inkjet printing of APIs into paper substrates, and how the model drug substances (paracetamol, theophylline, and caffeine) are penetrating the porous substrates used. The method enables controlling not only the deposition but also the crystallization of the drug substances. We anticipate that the inkjet printing approach has immense potential in making sophisticated drug delivery systems by use of porous substrates in the future. For example, it may offer new perspectives for solving problems around poorly soluble drugs and dosing low-dose medicines accurately. Furthermore, with the advent of genetic mapping of humans, controlled inkjet dosing can bring solutions to fabricate on-demand individualized medicines for patients. Copyright © 2011 Wiley-Liss, Inc.

Charge dynamics of MgO single crystals subjected to KeV electron irradiation

NASA Astrophysics Data System (ADS)

Boughariou, A.; Blaise, G.; Braga, D.; Kallel, A.

2004-04-01

A scanning electron microscope has been equipped to study the fundamental aspects of charge trapping in insulating materials, by measuring the secondary electron emission (SEE) yield σ with a high precision (a few percent), as a function of energy, electron current density, and dose. The intrinsic secondary electron emission yield σ0 of uncharged MgO single crystals annealed at 1000 °C, 2 h, has been studied at four energies 1.1, 5, 15, and 30 keV on three different crystal orientations (100), (110), and (111). At low energies (1.1 and 5 keV) σ0 depends on the crystalline orientation wheras at high energies (30 keV) no differentiation occurs. It is shown that the value of the second crossover energy E2, for which the intrinsic SEE yield σ0=1, is extremely delicate to measure with precision. It is about 15 keV±500 eV for the (100) orientation, 13.5 keV±500 eV for the (110), and 18.5 keV±500 eV for the (111) one. At low current density J⩽105 pA/cm2, the variation of σ with the injected dose makes possible the observation of a self-regulated regime characterized by a steady value of the SEE yield σst=1. At low energies 1.1 and 5 keV, there is no current density effects in MgO, but at high energies ≈30 keV, apparent current density effects come from a bad collect of secondary electrons, due to very high negative surface potential. At 30 keV energy, an intense erratic electron exoemission was observed on the MgO (110) orientation annealed at 1500 °C. This phenomenon is the result of a disruptive process similar to flashover, which takes place at the surface of the material.

Development of OSL system using two high-density blue LEDs equipped with liquid light guides

NASA Astrophysics Data System (ADS)

Choi, J. H.; Kim, M. J.; Cheong, C. S.; Hong, D. G.

2014-03-01

In recent years, considerable developments in optically stimulated luminescence (OSL) have been made in the fields of radiation dosimetry, age determination, and medical applications. A compact and economical OSL system comprising a precision x-y-z stage for loading 12 samples, a small X-ray generator for radiation dosing, and two powerful blue light emitting diodes (LEDs) for optical stimulation equipped with VIS liquid light guides (VIS-LLGs) has been developed. This paper describes the principal features of the system along with the examples of measurements performed by the system.

Homeopathic drug discovery: theory update and methodological aspect.

PubMed

Khuda-Bukhsh, Anisur Rahman; Pathak, Surajit

2008-08-01

Homeopathy treats patient on the basis of totality of symptoms and is based on the principle of 'like cures like'. It uses ultra-low doses of highly diluted natural substances as remedies that originate from plants, minerals or animals. The objectives of this review are to discuss concepts, controversies and research related to understanding homeopathy in the light of modern science. Attempts have been made to focus on current views of homeopathy and to delineate its most plausible mechanism(s) of action. Although some areas of concern remain, research carried out so far both in vitro and in vivo validates the effects of highly diluted homeopathic medicines in a wide variety of organisms. The precise mechanism(s) and pathway(s) of action of highly diluted homeopathic drugs are still unknown.

An international dosimetry exchange for BNCT part II: computational dosimetry normalizations.

PubMed

Riley, K J; Binns, P J; Harling, O K; Albritton, J R; Kiger, W S; Rezaei, A; Sköld, K; Seppälä, T; Savolainen, S; Auterinen, I; Marek, M; Viererbl, L; Nievaart, V A; Moss, R L

2008-12-01

The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of +/-2%-3%. These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron concentration of 15 microg g(-1) in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy(w) at the different facilities range between 7.6 and 13.2 Gy(w) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy(w) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.

Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1

PubMed Central

Smith, Andrew H.; Jensen, Kevin P.; Li, Jin; Nunez, Yaira; Farrer, Lindsay A.; Hakonarson, Hakon; Cook-Sather, Scott D.; Kranzler, Henry R.; Gelernter, Joel

2017-01-01

Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time-consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study (GWAS) of usual daily methadone dose. In African-American (AA) OD subjects (n = 383), we identified a genome-wide significant association between therapeutic methadone dose (mean = 68.0 mg, standard deviation (SD) = 30.1 mg) and rs73568641 (P = 2.8 × 10−8), the nearest gene (306 kilobases) being OPRM1. Each minor (C) allele corresponded to an additional ~20 mg/day of oral methadone, an effect specific to AAs. In European-Americans (EAs) (n = 1,027), no genome-wide significant associations with methadone dose (mean = 77.8 mg, SD = 33.9 mg) were observed. In an independent set of opioid-naïve AA children being treated for surgical pain, rs73568641-C was associated with a higher required dose of morphine (n = 241, P = 3.9 × 10−2). Similarly, independent genomic loci previously shown to associate with higher opioid analgesic dose were associated with higher methadone dose in the OD sample (AA and EA: n = 1,410, genetic score P = 1.3 × 10−3). The present results in AAs indicate that genetic variants influencing opioid sensitivity across different clinical settings could contribute to precision pharmacotherapy for pain and addiction. PMID:28115739

Tuning acoustic and mechanical properties of materials for ultrasound phantoms and smart substrates for cell cultures.

PubMed

Cafarelli, A; Verbeni, A; Poliziani, A; Dario, P; Menciassi, A; Ricotti, L

2017-02-01

Materials with tailored acoustic properties are of great interest for both the development of tissue-mimicking phantoms for ultrasound tests and smart scaffolds for ultrasound mediated tissue engineering and regenerative medicine. In this study, we assessed the acoustic properties (speed of sound, acoustic impedance and attenuation coefficient) of three different materials (agarose, polyacrylamide and polydimethylsiloxane) at different concentrations or cross-linking levels and doped with different concentrations of barium titanate ceramic nanoparticles. The selected materials, besides different mechanical features (stiffness from few kPa to 1.6MPa), showed a wide range of acoustic properties (speed of sound from 1022 to 1555m/s, acoustic impedance from 1.02 to 1.67MRayl and attenuation coefficient from 0.2 to 36.5dB/cm), corresponding to ranges in which natural soft tissues can fall. We demonstrated that this knowledge can be used to build tissue-mimicking phantoms for ultrasound-based medical procedures and that the mentioned measurements enable to stimulate cells with a highly controlled ultrasound dose, taking into account the attenuation due to the cell-supporting scaffold. Finally, we were able to correlate for the first time the bioeffect on human fibroblasts, triggered by piezoelectric barium titanate nanoparticles activated by low-intensity pulsed ultrasound, with a precise ultrasound dose delivered. These results may open new avenues for the development of both tissue-mimicking materials for ultrasound phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine. This study reports for the first time the results of a systematic acoustic characterization of agarose, polyacrylamide and polydimethylsiloxane at different concentrations and cross-linking extents and doped with different concentrations of barium titanate nanoparticles. These results can be used to build tissue-mimicking phantoms, useful for many ultrasound-based medical procedures, and to fabricate smart materials for stimulating cells with a highly controlled ultrasound dose. Thanks to this knowledge, we correlated for the first time a bioeffect (the proliferation increase) on human fibroblasts, triggered by piezoelectric nanoparticles, with a precise US dose delivered. These results may open new avenues for the development of both tissue-mimicking phantoms and smart triggerable scaffolds for tissue engineering and regenerative medicine. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characteristics and verification of a car-borne survey system for dose rates in air: KURAMA-II.

PubMed

Tsuda, S; Yoshida, T; Tsutsumi, M; Saito, K

2015-01-01

The car-borne survey system KURAMA-II, developed by the Kyoto University Research Reactor Institute, has been used for air dose rate mapping after the Fukushima Dai-ichi Nuclear Power Plant accident. KURAMA-II consists of a CsI(Tl) scintillation detector, a GPS device, and a control device for data processing. The dose rates monitored by KURAMA-II are based on the G(E) function (spectrum-dose conversion operator), which can precisely calculate dose rates from measured pulse-height distribution even if the energy spectrum changes significantly. The characteristics of KURAMA-II have been investigated with particular consideration to the reliability of the calculated G(E) function, dose rate dependence, statistical fluctuation, angular dependence, and energy dependence. The results indicate that 100 units of KURAMA-II systems have acceptable quality for mass monitoring of dose rates in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

MCNP5 evaluation of photoneutron production from the Alexandria University 15 MV Elekta Precise medical LINAC.

PubMed

Abou-Taleb, W M; Hassan, M H; El Mallah, E A; Kotb, S M

2018-05-01

Photoneutron production, and the dose equivalent, in the head assembly of the 15 MV Elekta Precise medical linac; operating in the faculty of Medicine at Alexandria University were estimated with the MCNP5 code. Photoneutron spectra were calculated in air and inside a water phantom to different depths as a function of the radiation field sizes. The maximum neutron fluence is 3.346×10 -9 n/cm 2 -e for a 30×30 cm 2 field size to 2-4 cm-depth in the phantom. The dose equivalent due to fast neutron increases as the field size increases, being a maximum of 0.912 ± 0.05 mSv/Gy at depth between 2 and 4 cm in the water phantom for 40×40 cm 2 field size. Photoneutron fluence and dose equivalent are larger to 100 cm from the isocenter than to 35 cm from the treatment room wall. Copyright © 2018 Elsevier Ltd. All rights reserved.

GEANT4 and PHITS simulations of the shielding of neutrons from the 252Cf source

NASA Astrophysics Data System (ADS)

Shin, Jae Won; Hong, Seung-Woo; Bak, Sang-In; Kim, Do Yoon; Kim, Chong Yeal

2014-09-01

Monte Carlo simulations are performed by using the GEANT4 and the PHITS for studying the neutron-shielding abilities of several materials, such as graphite, iron, polyethylene, NS-4-FR and KRAFTON-HB. As a neutron source, 252Cf is considered. For the Monte Carlo simulations by using the GEANT4, high precision (G4HP) models with the G4NDL 4.2 based on ENDF/B-VII data are used. For the simulations by using the PHITS, the JENDL-4.0 library is used. The neutron-dose-equivalent rates with or without five different shielding materials are estimated and compared with the experimental values. The differences between the shielding abilities calculated by using the GEANT4 with the G4NDL 4.2 and the PHITS with the JENDL-4.0 are found not to be significant for all the cases considered in this work. The neutron-dose-equivalent rates obtained by using the GEANT4 and the PHITS are compared with experimental data and other simulation results. Our neutron-dose-equivalent rates agree well with the experimental dose-equivalent rates, within 20% errors, except for polyethylene. For polyethylene, the discrepancies between our calculations and the experiments are less than 40%, as observed in other simulation results.

Dose accuracy of a reusable insulin pen using a cartridge system with an integrated plunger mechanism.

PubMed

Clarke, Alastair; Dain, Marie-Paule

2006-09-01

Pen injection devices are a common method of administering insulin for patients with diabetes. Pen devices must comply with guidelines prepared by the International Organization for Standardization, which include device dose accuracy and precision. OptiClik (sanofi-aventis) was developed to fulfil unmet needs of patients with diabetes, including: easier cartridge changing, clearer dose display and readability, and a larger dose of insulin to be delivered with a single injection. In this paper, the authors report on the dose accuracy of the OptiClik pen device, which uses a novel cartridge system with an integrated plunger for easier cartridge changing. The authors show that OptiClik accurately delivers a required dose of insulin, which is maintained over the lifetime of the pen. OptiClik offers a significant contribution to the treatment of diabetes.

Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

PubMed

Schuck, Robert N; Grillo, Joseph A

2016-05-01

Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels.

A Protein Turnover Signaling Motif Controls the Stimulus-Sensitivity of Stress Response Pathways

PubMed Central

Loriaux, Paul Michael; Hoffmann, Alexander

2013-01-01

Stimulus-induced perturbations from the steady state are a hallmark of signal transduction. In some signaling modules, the steady state is characterized by rapid synthesis and degradation of signaling proteins. Conspicuous among these are the p53 tumor suppressor, its negative regulator Mdm2, and the negative feedback regulator of NFκB, IκBα. We investigated the physiological importance of this turnover, or flux, using a computational method that allows flux to be systematically altered independently of the steady state protein abundances. Applying our method to a prototypical signaling module, we show that flux can precisely control the dynamic response to perturbation. Next, we applied our method to experimentally validated models of p53 and NFκB signaling. We find that high p53 flux is required for oscillations in response to a saturating dose of ionizing radiation (IR). In contrast, high flux of Mdm2 is not required for oscillations but preserves p53 sensitivity to sub-saturating doses of IR. In the NFκB system, degradation of NFκB-bound IκB by the IκB kinase (IKK) is required for activation in response to TNF, while high IKK-independent degradation prevents spurious activation in response to metabolic stress or low doses of TNF. Our work identifies flux pairs with opposing functional effects as a signaling motif that controls the stimulus-sensitivity of the p53 and NFκB stress-response pathways, and may constitute a general design principle in signaling pathways. PMID:23468615

High resolution ion chamber array delivery quality assurance for robotic radiosurgery: Commissioning and validation.

PubMed

Blanck, Oliver; Masi, Laura; Chan, Mark K H; Adamczyk, Sebastian; Albrecht, Christian; Damme, Marie-Christin; Loutfi-Krauss, Britta; Alraun, Manfred; Fehr, Roman; Ramm, Ulla; Siebert, Frank-Andre; Stelljes, Tenzin Sonam; Poppinga, Daniela; Poppe, Björn

2016-06-01

High precision radiosurgery demands comprehensive delivery-quality-assurance techniques. The use of a liquid-filled ion-chamber-array for robotic-radiosurgery delivery-quality-assurance was investigated and validated using several test scenarios and routine patient plans. Preliminary evaluation consisted of beam profile validation and analysis of source-detector-distance and beam-incidence-angle response dependence. The delivery-quality-assurance analysis is performed in four steps: (1) Array-to-plan registration, (2) Evaluation with standard Gamma-Index criteria (local-dose-difference⩽2%, distance-to-agreement⩽2mm, pass-rate⩾90%), (3) Dose profile alignment and dose distribution shift until maximum pass-rate is found, and (4) Final evaluation with 1mm distance-to-agreement criterion. Test scenarios consisted of intended phantom misalignments, dose miscalibrations, and undelivered Monitor Units. Preliminary method validation was performed on 55 clinical plans in five institutions. The 1000SRS profile measurements showed sufficient agreement compared with a microDiamond detector for all collimator sizes. The relative response changes can be up to 2.2% per 10cm source-detector-distance change, but remains within 1% for the clinically relevant source-detector-distance range. Planned and measured dose under different beam-incidence-angles showed deviations below 1% for angles between 0° and 80°. Small-intended errors were detected by 1mm distance-to-agreement criterion while 2mm criteria failed to reveal some of these deviations. All analyzed delivery-quality-assurance clinical patient plans were within our tight tolerance criteria. We demonstrated that a high-resolution liquid-filled ion-chamber-array can be suitable for robotic radiosurgery delivery-quality-assurance and that small errors can be detected with tight distance-to-agreement criterion. Further improvement may come from beam specific correction for incidence angle and source-detector-distance response. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Breath alcohol analysis incorporating standardization to water vapour is as precise as blood alcohol analysis.

PubMed

Grubb, D; Rasmussen, B; Linnet, K; Olsson, S G; Lindberg, L

2012-03-10

A novel breath-alcohol analyzer based on the standardization of the breath alcohol concentration (BrAC) to the alveolar-air water vapour concentration has been developed and evaluated. The present study compares results with this particular breath analyzer with arterial blood alcohol concentrations (ABAC), the most relevant quantitative measure of brain alcohol exposure. The precision of analysis of alcohol in arterial blood and breath were determined as well as the agreement between ABAC and BrAC over time post-dosing. Twelve healthy volunteers were administered 0.6g alcohol/kg bodyweight via an orogastric tube. Duplicate breath and arterial blood samples were obtained simultaneously during the absorption, distribution and elimination phases of the alcohol metabolism with particular emphasis on the absorption phase. The precision of the breath analyzer was similar to the determination of blood alcohol concentration by headspace gas chromatography (CV 2.40 vs. 2.38%, p=0.43). The ABAC/BrAC ratio stabilized 30min post-dosing (2089±99; mean±SD). Before this the BrAC tended to underestimate the coexisting ABAC. In conclusion, breath alcohol analysis utilizing standardization of alcohol to water vapour was as precise as blood alcohol analysis, the present "gold standard" method. The BrAC reliably predicted the coexisting ABAC from 30min onwards after the intake of alcohol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Advanced technologies and devices for inhalational anesthetic drug dosing.

PubMed

Meyer, J-U; Kullik, G; Wruck, N; Kück, K; Manigel, J

2008-01-01

Technological advances in micromechanics, optical sensing, and computing have led to innovative and reliable concepts of precise dosing and sensing of modern volatile anesthetics. Mixing of saturated desflurane flow with fresh gas flow (FGF) requires differential pressure sensing between the two circuits for precise delivery. The medical gas xenon is administered most economically in a closed circuit breathing system. Sensing of xenon in the breathing system is achieved with miniaturized and unique gas detector systems. Innovative sensing principles such as thermal conductivity and sound velocity are applied. The combination of direct injection of volatile anesthetics and low-flow in a closed circuit system requires simultaneous sensing of the inhaled and exhaled gas concentrations. When anesthetic conserving devices are used for sedation with volatile anesthetics, regular gas concentration monitoring is advised. High minimal alveolar concentration (MAC) of some anesthetics and low-flow conditions bear the risk of hypoxic gas delivery. Oxygen sensing based on paramagnetic thermal transduction has become the choice when long lifetime and one-time calibration are required. Compact design of beam splitters, infrared filters, and detectors have led to multiple spectra detector systems that fit in thimble-sized housings. Response times of less than 500 ms allow systems to distinguish inhaled from exhaled gas concentrations. The compact gas detector systems are a prerequisite to provide "quantitative anesthesia" in closed circuit feedback-controlled breathing systems. Advanced anesthesia devices in closed circuit mode employ multiple feedback systems. Multiple feedbacks include controls of volume, concentrations of anesthetics, and concentration of oxygen with a corresponding safety system. In the ideal case, the feedback system delivers precisely what the patient is consuming. In this chapter, we introduce advanced technologies and device concepts for delivering inhalational anesthetic drugs. First, modern vaporizers are described with special attention to the particularities of delivering desflurane. Delivery of xenon is presented, followed by a discussion of direct injection of volatile anesthetics and of a device designed to conserve anesthetic drugs. Next, innovative sensing technologies are presented for reliable control and precise metering of the delivered volatile anesthetics. Finally, we discuss the technical challenges of automatic control in low-flow and closed circuit breathing systems in anesthesia.

Characterization of conductive nanobiomaterials derived from viral assemblies by low-voltage STEM imaging and Raman scattering

NASA Astrophysics Data System (ADS)

Plascencia-Villa, Germán; Carreño-Fuentes, Liliana; Bahena, Daniel; José-Yacamán, Miguel; Palomares, Laura A.; Ramírez, Octavio T.

2014-09-01

New technologies require the development of novel nanomaterials that need to be fully characterized to achieve their potential. High-resolution low-voltage scanning transmission electron microscopy (STEM) has proven to be a very powerful technique in nanotechnology, but its use for the characterization of nanobiomaterials has been limited. Rotavirus VP6 self-assembles into nanotubular assemblies that possess an intrinsic affinity for Au ions. This property was exploited to produce hybrid nanobiomaterials by the in situ functionalization of recombinant VP6 nanotubes with gold nanoparticles. In this work, Raman spectroscopy and advanced analytical electron microscopy imaging with spherical aberration-corrected (Cs) STEM and nanodiffraction at low-voltage doses were employed to characterize nanobiomaterials. STEM imaging revealed the precise structure and arrangement of the protein templates, as well as the nanostructure and atomic arrangement of gold nanoparticles with high spatial sub-Angstrom resolution and avoided radiation damage. The imaging was coupled with backscattered electron imaging, ultra-high resolution scanning electron microscopy and x-ray spectroscopy. The hybrid nanobiomaterials that were obtained showed unique properties as bioelectronic conductive devices and showed enhanced Raman scattering by their precise arrangement into superlattices, displaying the utility of viral assemblies as functional integrative self-assembled nanomaterials for novel applications.

Printing of small molecular medicines from the vapor phase

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

Shalev, Olga; Raghavan, Shreya; Mazzara, J. Maxwell

There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitromore » treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. In conclusion, the demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.« less

CMOS Rad-Hard Front-End Electronics for Precise Sensors Measurements

NASA Astrophysics Data System (ADS)

Sordo-Ibáñez, Samuel; Piñero-García, Blanca; Muñoz-Díaz, Manuel; Ragel-Morales, Antonio; Ceballos-Cáceres, Joaquín; Carranza-González, Luis; Espejo-Meana, Servando; Arias-Drake, Alberto; Ramos-Martos, Juan; Mora-Gutiérrez, José Miguel; Lagos-Florido, Miguel Angel

2016-08-01

This paper reports a single-chip solution for the implementation of radiation-tolerant CMOS front-end electronics (FEE) for applications requiring the acquisition of base-band sensor signals. The FEE has been designed in a 0.35μm CMOS process, and implements a set of parallel conversion channels with high levels of configurability to adapt the resolution, conversion rate, as well as the dynamic input range for the required application. Each conversion channel has been designed with a fully-differential implementation of a configurable-gain instrumentation amplifier, followed by an also configurable dual-slope ADC (DS ADC) up to 16 bits. The ASIC also incorporates precise thermal monitoring, sensor conditioning and error detection functionalities to ensure proper operation in extreme environments. Experimental results confirm that the proposed topologies, in conjunction with the applied radiation-hardening techniques, are reliable enough to be used without loss in the performance in environments with an extended temperature range (between -25 and 125 °C) and a total dose beyond 300 krad.

Printing of small molecular medicines from the vapor phase

DOE PAGES

Shalev, Olga; Raghavan, Shreya; Mazzara, J. Maxwell; ...

2017-09-27

There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitromore » treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. In conclusion, the demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.« less

SU-E-J-116: Uncertainties Associated with Dose Summation of High-Dose Rate Brachytherapy and Intensity Modulated Radiotherapy for Gynecological Cases

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

Kauweloa, K; Bergamo, A; Gutierrez, A

Purpose: Determining the cumulative dose distribution (CDD) for gynecological patients treated with both high-dose rate (HDR) brachytherapy and intensity-modulated radiotherapy (IMRT) is challenging. The purpose of this work is to study the uncertainty of performing this with a structure-guided deformable (SGD) approach in Velocity. Methods: For SGD, the Hounsfield units inside specified contours are overridden to set uniform values. Deformable image registration (DIR) is the run on these process images, which forces the DIR to focus on these contour boundaries. 18 gynecological cancer patients were used in this study. The original bladder and rectum planning contours for these patients weremore » used to drive the SGD. A second set of contours were made of the bladder by the same person with the intent of carefully making them completely consistent with each other. This second set was utilized to evaluate the spatial accuracy of the SGD. The determined spatial accuracy was then multiplied by the local dose gradient to determine a dose uncertainty associated with the SGD dose warping. The normal tissue complication probability (NTCP) was then calculated for each dose volume histogram (DVH) that included four different probabilistic uncertainties associated with the spatial errors (e.g., 68.3% and 95.4%). Results: The NTCPs for each DVH (e.g., NTCP-−95.4%, NTCP-−68.3%, NTCP-68.3%, NTCP-95.4%) differed amongst patients. All patients had an NTCP-−95.4% close to 0%, while NTCP-95.4% ranged from 0.67% to 100%. Nine patients had an NTCP-−95.4% less than 50% while the remaining nine patients had NTCP-95.4% greater than 50%. Conclusion: The uncertainty associated with this CDD technique renders a large NTCP uncertainty. Thus, it is currently not practical for clinical use. The two ways to improve this would be to use more precise contours to drive the SGD and to use a more accurate DIR algorithm.« less

Dose verification for respiratory-gated volumetric modulated arc therapy (VMAT)

PubMed Central

Qian, Jianguo; Xing, Lei; Liu, Wu; Luxton, Gary

2011-01-01

A novel commercial medical linac system (TrueBeam™, Varian Medical Systems, Palo Alto, CA) allows respiratory-gated volumetric modulated arc therapy (VMAT), a new modality for treating moving tumors with high precision and improved accuracy by allowing for regular motion associated with a patient's breathing during VMAT delivery. The purpose of this work is to adapt a previously-developed dose reconstruction technique to evaluate the fidelity of VMAT treatment during gated delivery under clinic-relevant periodic motion related to patient breathing. A Varian TrueBeam system was used in this study. VMAT plans were created for three patients with lung or pancreas tumors. Conventional 6 MV and 15 MV beams with flattening filter and high dose-rate 10 MV beams with no flattening filter were used in these plans. Each patient plan was delivered to a phantom first without gating and then with gating for three simulated respiratory periods (3, 4.5 and 6 seconds). Using the adapted log file-based dose reconstruction procedure supplemented with ion chamber array (Seven29™, PTW, Freiburg, Germany) measurements, the delivered dose was used to evaluate the fidelity of gated VMAT delivery. Comparison of Seven29 measurements with and without gating showed good agreement with gamma-index passing rates above 99% for 1%/1mm dose accuracy/distance-to-agreement criteria. With original plans as reference, gamma-index passing rates were 100% for the reconstituted plans (1%/1 mm criteria) and 93.5–100% for gated Seven29 measurements (3%/3 mm criteria). In the presence of leaf error deliberately introduced into the gated delivery of a pancreas patient plan, both dose reconstruction and Seven29 measurement consistently indicated substantial dosimetric differences from the original plan. In summary, a dose reconstruction procedure was demonstrated for evaluating the accuracy of respiratory-gated VMAT delivery. This technique showed that under clinical operation, the TrueBeam system faithfully realized treatment plans with gated delivery. This methodology affords a useful tool for machine and patient-specific quality assurance of the newly available respiratory-gated VMAT. PMID:21753232

Sodium phenylbutyrate coated granules (Pheburane). Defective urea synthesis: a welcome formulation.

PubMed

2015-02-01

Compared with Ammonaps granules, Pheburane coated granules mask the unpleasant taste of sodium phenylbutyrate. A more precise dosing device is provided with the coated granules than with the uncoated granules (Ammonaps).

A comprehensive evaluation of the PRESAGE/optical-CT 3D dosimetry system

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

Sakhalkar, H. S.; Adamovics, J.; Ibbott, G.

2009-01-15

This work presents extensive investigations to evaluate the robustness (intradosimeter consistency and temporal stability of response), reproducibility, precision, and accuracy of a relatively new 3D dosimetry system comprising a leuco-dye doped plastic 3D dosimeter (PRESAGE) and a commercial optical-CT scanner (OCTOPUS 5x scanner from MGS Research, Inc). Four identical PRESAGE 3D dosimeters were created such that they were compatible with the Radiologic Physics Center (RPC) head-and-neck (H and N) IMRT credentialing phantom. Each dosimeter was irradiated with a rotationally symmetric arrangement of nine identical small fields (1x3 cm{sup 2}) impinging on the flat circular face of the dosimeter. A repetitiousmore » sequence of three dose levels (4, 2.88, and 1.28 Gy) was delivered. The rotationally symmetric treatment resulted in a dose distribution with high spatial variation in axial planes but only gradual variation with depth along the long axis of the dosimeter. The significance of this treatment was that it facilitated accurate film dosimetry in the axial plane, for independent verification. Also, it enabled rigorous evaluation of robustness, reproducibility and accuracy of response, at the three dose levels. The OCTOPUS 5x commercial scanner was used for dose readout from the dosimeters at daily time intervals. The use of improved optics and acquisition technique yielded substantially improved noise characteristics (reduced to {approx}2%) than has been achieved previously. Intradosimeter uniformity of radiochromic response was evaluated by calculating a 3D gamma comparison between each dosimeter and axially rotated copies of the same dosimeter. This convenient technique exploits the rotational symmetry of the distribution. All points in the gamma comparison passed a 2% difference, 1 mm distance-to-agreement criteria indicating excellent intradosimeter uniformity even at low dose levels. Postirradiation, the dosimeters were all found to exhibit a slight increase in opaqueness with time. However, the relative dose distribution was found to be extremely stable up to 90 h postirradiation indicating excellent temporal stability. Excellent interdosimeter reproducibility was also observed between the four dosimeters. Gamma comparison maps between each dosimeter and the average distribution of all four dosimeters showed full agreement at the 2% difference, 2 mm distance-to-agreement level. Dose readout from the 3D dosimetry system was found to agree better with independent film measurement than with treatment planning system calculations in penumbral regions and was generally accurate to within 2% dose difference and 2 mm distance-to-agreement. In conclusion, these studies demonstrate excellent precision, accuracy, robustness, and reproducibility of the PRESAGE/optical-CT system for relative 3D dosimetry and support its potential integration with the RPC H and N credentialing phantom for IMRT verification.« less

Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots

NASA Astrophysics Data System (ADS)

Lai, Priscilla; Cai, Zhongli; Pignol, Jean-Philippe; Lechtman, Eli; Mashouf, Shahram; Lu, Yijie; Winnik, Mitchell A.; Jaffray, David A.; Reilly, Raymond M.

2017-11-01

Permanent seed implantation (PSI) brachytherapy is a highly conformal form of radiation therapy but is challenged with dose inhomogeneity due to its utilization of low energy radiation sources. Gold nanoparticles (AuNP) conjugated with electron emitting radionuclides have recently been developed as a novel form of brachytherapy and can aid in homogenizing dose through physical distribution of radiolabeled AuNP when injected intratumorally (IT) in suspension. However, the distribution is unpredictable and precise placement of many injections would be difficult. Previously, we reported the design of a nanoparticle depot (NPD) that can be implanted using PSI techniques and which facilitates controlled release of AuNP. We report here the 3D dose distribution resulting from a NPD incorporating AuNP labeled with electron emitters (90Y, 177Lu, 111In) of different energies using Monte Carlo based voxel level dosimetry. The MCNP5 Monte Carlo radiation transport code was used to assess differences in dose distribution from simulated NPD and conventional brachytherapy sources, positioned in breast tissue simulating material. We further compare these dose distributions in mice bearing subcutaneous human breast cancer xenografts implanted with 177Lu-AuNP NPD, or injected IT with 177Lu-AuNP in suspension. The radioactivity distributions were derived from registered SPECT/CT images and time-dependent dose was estimated. Results demonstrated that the dose distribution from NPD reduced the maximum dose 3-fold when compared to conventional seeds. For simulated NPD, as well as NPD implanted in vivo, 90Y delivered the most homogeneous dose distribution. The tumor radioactivity in mice IT injected with 177Lu-AuNP redistributed while radioactivity in the NPD remained confined to the implant site. The dose distribution from radiolabeled AuNP NPD were predictable and concentric in contrast to IT injected radiolabeled AuNP, which provided irregular and temporally variant dose distributions. The use of NPD may serve as an intermediate between PSI and radiation delivered by radiolabeled AuNP by providing a controlled method to improve delivery of prescribed doses as well as homogenize dose from low penetrating electron sources.

PREFACE: Third International Conference on Radiotherapy Gel Dosimetry

NASA Astrophysics Data System (ADS)

DeDeene, Yves; Baldock, Clive

2004-01-01

Gel dosimetry is not merely another dosimetry technique. Gel dosimeters are integrating dosimeters that enable dose verification in three dimensions. The application of a 3D dosimetry technique in the clinic would give a real push to the implementation of advanced high-precision radiotherapy technologies in many institutes. It can be expected that with the recent developments in the field towards more user-friendly gel systems and imaging modalities, gel dosimetry will become a vital link in the chain of high-precision radiation cancer therapy in the near future. Many researchers all over the world have contributed to the emerging technology of gel dosimetry. The research field of gel dosimetry is recognized to be very broad from polymer and analytical chemistry and material research to imaging technologies. The DOSGEL conferences in the past have proven to be an important forum at which material scientists, chemists, medical physicists, magnetic resonance imaging and radiation specialists brought together a critical mass of thoughts, findings and considerations. DOSGEL 2004 has been endorsed by many international, supra-national and national medical physics organizations and publishers. These proceedings contain 51 papers that cover various aspects of gel dosimetry.

Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-beam computed tomography and its effect on planning target volume margins.

PubMed

Patni, Nidhi; Burela, Nagarjuna; Pasricha, Rajesh; Goyal, Jaishree; Soni, Tej Prakash; Kumar, T Senthil; Natarajan, T

2017-01-01

To achieve the best possible therapeutic ratio using high-precision techniques (image-guided radiation therapy/volumetric modulated arc therapy [IGRT/VMAT]) of external beam radiation therapy in cases of carcinoma cervix using kilovoltage cone-beam computed tomography (kV-CBCT). One hundred and five patients of gynecological malignancies who were treated with IGRT (IGRT/VMAT) were included in the study. CBCT was done once a week for intensity-modulated radiation therapy and daily in IGRT/VMAT. These images were registered with the planning CT scan images and translational errors were applied and recorded. In all, 2078 CBCT images were studied. The margins of planning target volume were calculated from the variations in the setup. The setup variation was 5.8, 10.3, and 5.6 mm in anteroposterior, superoinferior, and mediolateral direction. This allowed adequate dose delivery to the clinical target volume and the sparing of organ at risks. Daily kV-CBCT is a satisfactory method of accurate patient positioning in treating gynecological cancers with high-precision techniques. This resulted in avoiding geographic miss.

360-degree 3D transvaginal ultrasound system for high-dose-rate interstitial gynaecological brachytherapy needle guidance

NASA Astrophysics Data System (ADS)

Rodgers, Jessica R.; Surry, Kathleen; D'Souza, David; Leung, Eric; Fenster, Aaron

2017-03-01

Treatment for gynaecological cancers often includes brachytherapy; in particular, in high-dose-rate (HDR) interstitial brachytherapy, hollow needles are inserted into the tumour and surrounding area through a template in order to deliver the radiation dose. Currently, there is no standard modality for visualizing needles intra-operatively, despite the need for precise needle placement in order to deliver the optimal dose and avoid nearby organs, including the bladder and rectum. While three-dimensional (3D) transrectal ultrasound (TRUS) imaging has been proposed for 3D intra-operative needle guidance, anterior needles tend to be obscured by shadowing created by the template's vaginal cylinder. We have developed a 360-degree 3D transvaginal ultrasound (TVUS) system that uses a conventional two-dimensional side-fire TRUS probe rotated inside a hollow vaginal cylinder made from a sonolucent plastic (TPX). The system was validated using grid and sphere phantoms in order to test the geometric accuracy of the distance and volumetric measurements in the reconstructed image. To test the potential for visualizing needles, an agar phantom mimicking the geometry of the female pelvis was used. Needles were inserted into the phantom and then imaged using the 3D TVUS system. The needle trajectories and tip positions in the 3D TVUS scan were compared to their expected values and the needle tracks visualized in magnetic resonance images. Based on this initial study, 360-degree 3D TVUS imaging through a sonolucent vaginal cylinder is a feasible technique for intra-operatively visualizing needles during HDR interstitial gynaecological brachytherapy.

Low-dose radiosurgery or hypofractionated stereotactic radiotherapy as treatment option in refractory epilepsy due to epileptogenic lesions in eloquent areas - Preliminary report of feasibility and safety.

PubMed

Boström, Jan P; Delev, Daniel; Quesada, Carlos; Widman, Guido; Vatter, Hartmut; Elger, Christian E; Surges, Rainer

2016-03-01

The eradication of epileptogenic lesions (e.g. focal cortical dysplasia) can be used for treatment of drug-resistant focal epilepsy, but in highly eloquent cortex areas it can also lead to a permanent neurological deficit. In such cases the neuromodulation effect of low-dose high-precision irradiation of circumscribed lesions may represent an alternative therapy. A total of 10 patients with eloquent localized lesions causing pharmacoresistant focal epilepsy were prospectively identified. After informed consent, six patients agreed and were treated with risk adapted low-dose radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hfSRT). Comprehensive data concerning treatment modalities and outcome after short-term follow up (mean=16.3 months) were prospectively collected and evaluated. From the six patients, two patients were treated with hfSRT (marginal dose 36 Gy) and four with SRS (marginal dose 13 Gy). Clinical target volume (CTV) ranged from 0.70 ccm to 4.32 ccm. The short-term follow-up ranged from 6 to 27 months. There were no side effects or neurological deficits after treatment. At last available follow-up two patients were seizure-free, one of them being off antiepileptic drugs. The seizure frequency improved in one and remained unchanged in three patients. Treatment of eloquent localized epileptogenic lesions by SRS and hfSRT showed no adverse events and an acceptable seizure outcome in this small prospective patient series. The relatively short-term follow-up comprises one of the study's drawbacks and therefore a longer follow-up should be awaited in order to evaluate the neuromodulation effect of the treatment. These preliminary results may however justify the initiation of a larger prospective trial investigating whether focused low-dose stereotactic irradiation could be an option for lesions in eloquent brain areas. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.

PubMed

Livingstone, Jayde; Stevenson, Andrew W; Butler, Duncan J; Häusermann, Daniel; Adam, Jean-François

2016-07-01

Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.

IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases.

PubMed

Wen, Ning; Zhao, Bo; Kim, Jinkoo; Chin-Snyder, Karen; Bellon, Maria; Glide-Hurst, Carri; Barton, Kenneth; Chen, Daiquan; Chetty, Indrin J

2014-09-08

The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

Effect of Ion Flux (Dose Rate) in Source-Drain Extension Ion Implantation for 10-nm Node FinFET and Beyond on 300/450mm Platforms

NASA Astrophysics Data System (ADS)

Shen, Ming-Yi

The improvement of wafer equipment productivity has been a continuous effort of the semiconductor industry. Higher productivity implies lower product price, which economically drives more demand from the market. This is desired by the semiconductor manufacturing industry. By raising the ion beam current of the ion implanter for 300/450mm platforms, it is possible to increase the throughput of the ion implanter. The resulting dose rate can be comparable to the performance of conventional ion implanters or higher, depending on beam current and beam size. Thus, effects caused by higher dose rate must be investigated further. One of the major applications of ion implantation (I/I) is source-drain extension (SDE) I/I for the silicon FinFET device. This study investigated the dose rate effects on the material properties and device performance of the 10-nm node silicon FinFET. In order to gain better understanding of the dose rate effects, the dose rate study is based on Synopsys Technology CAD (TCAD) process and device simulations that are calibrated and validated using available structural silicon fin samples. We have successfully shown that the kinetic monte carlo (KMC) I/I simulation can precisely model both the silicon amorphization and the arsenic distribution in the fin by comparing the KMC simulation results with TEM images. The results of the KMC I/I simulation show that at high dose rate more activated arsenic dopants were in the source-drain extension (SDE) region. This finding matches with the increased silicon amorphization caused by the high dose-rate I/I, given that the arsenic atoms could be more easily activated by the solid phase epitaxial regrowth process. This increased silicon amorphization led to not only higher arsenic activation near the spacer edge, but also less arsenic atoms straggling into the channel. Hence, it is possible to improve the throughput of the ion implanter when the dopants are implanted at high dose rate if the same doping level with a lower wafer dose can be achieved. In addition, the leakage current might also be reduced due to less undesired dopants in the channel. However, the twin defects from the problematic Si{111} recrystallization is well-known to cause excessive leakage current to the FinFET. This drawback can offset the benefits of the high dose rate I/I mentioned above. This work produced the first attempt at simulating the electrical impact of twin defects on advanced-node (10 nm) FinFET device performance. It was found that the high dose-rate I/I causes more twin defects in the silicon fin, and the physical locations of these defects were close to the channel. The defects undesirably induced trap-assisted band-to-band tunneling near the drain, which increased the leakage current. This issue could be mitigated by using asymmetrical gate overlap/underlap design or thicker spacer for SDE I/I so that the twin defects are not located in the depletion region near the drain.

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.

In vivo dosimetry for external photon treatments of head and neck cancers by diodes and TLDS.

PubMed

Tung, C J; Wang, H C; Lo, S H; Wu, J M; Wang, C J

2004-01-01

In vivo dosimetry was implemented for treatments of head and neck cancers in the large fields. Diode and thermoluminescence dosemeter (TLD) measurements were carried out for the linear accelerators of 6 MV photon beams. ESTRO in vivo dosimetry protocols were followed in the determination of midline doses from measurements of entrance and exit doses. Of the fields monitored by diodes, the maximum absolute deviation of measured midline doses from planned target doses was 8%, with the mean value and the standard deviation of -1.0 and 2.7%. If planned target doses were calculated using radiological water equivalent thicknesses rather than patient geometric thicknesses, the maximum absolute deviation dropped to 4%, with the mean and the standard deviation of 0.7 and 1.8%. For in vivo dosimetry monitored by TLDs, the shift in mean dose remained small but the statistical precision became poor.

Poster – 13: Evaluation of an in-house CCD camera film dosimetry imaging system for small field deliveries

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

Lalonde, Michel; Alexander, Kevin; Olding, Tim

Purpose: Radiochromic film dosimetry is a standard technique used in clinics to verify modern conformal radiation therapy delivery, and sometimes in research to validate other dosimeters. We are using film as a standard for comparison as we improve high-resolution three-dimensional gel systems for small field dosimetry; however, precise film dosimetry can be technically challenging. We report here measurements for fractionated stereotactic radiation therapy (FSRT) delivered using volumetric modulated arc therapy (VMAT) to investigate the accuracy and reproducibility of film measurements with a novel in-house readout system. We show that radiochromic film can accurately and reproducibly validate FSRT deliveries and alsomore » benchmark our gel dosimetry work. Methods: VMAT FSRT plans for metastases alone (PTV{sub MET}) and whole brain plus metastases (WB+PTV{sub MET}) were delivered onto a multi-configurational phantom with a sheet of EBT3 Gafchromic film inserted mid-plane. A dose of 400 cGy was prescribed to 4 small PTV{sub MET} structures in the phantom, while a WB structure was prescribed a dose of 200 cGy in the WB+PTV{sub MET} iterations. Doses generated from film readout with our in-house system were compared to treatment planned doses. Each delivery was repeated multiple times to assess reproducibility. Results and Conclusions: The reproducibility of film optical density readout was excellent throughout all experiments. Doses measured from the film agreed well with plans for the WB+PTV{sub MET} delivery. But, film doses for PTV{sub MET} only deliveries were significantly below planned doses. This discrepancy is due to stray/scattered light perturbations in our system during readout. Corrections schemes will be presented.« less

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

Evaluation of alanine as a reference dosimeter for therapy level dose comparisons in megavoltage electron beams

NASA Astrophysics Data System (ADS)

McEwen, Malcolm; Sharpe, Peter; Vörös, Sándor

2015-04-01

When comparing absorbed dose standards from different laboratories (e.g. National Measurement Institutes, NMIs, for Key or Supplementary comparisons) it is rarely possible to carry out a direct comparison of primary standard instruments, and therefore some form of transfer detector is required. Historically, air-filled, unsealed ionization chambers have been used because of the long history of using these instruments, very good stability over many years, and ease of transport. However, the use of ion chambers for therapy-level comparisons is not without its problems. Findings from recent investigations suggest that ion chambers are prone to non-random variations, they are not completely robust to standard courier practices, and failure at any step in a comparison can render all measurements potentially useless. An alternative approach is to identify a transfer system that is insensitive to some of these concerns—effectively a dosimeter that is inexpensive, simple to use, robust, but with sufficient precision and of a size relevant to the disseminated quantity in question. The alanine dosimetry system has been successfully used in a number of situations as an audit dosimeter and therefore the purpose of this investigation was to determine whether alanine could also be used as the transfer detector for dosimetric comparisons, which require a lower value for the measurement uncertainty. A measurement protocol was developed for comparing primary standards of absorbed dose to water in high-energy electron beams using alanine pellets irradiated in a water-equivalent plastic phantom. A trial comparison has been carried out between three NMIs and has indicated that alanine is a suitable alternative to ion chambers, with the system used achieving a precision of 0.1%. Although the focus of the evaluation was on the performance of the dosimeter, the comparison results are encouraging, showing agreement at the level of the combined uncertainties (~0.6%). Based on this investigation, a large-scale comparison of primary standards for high-energy electron beams is currently being developed under the auspices of the BIPM.

Determination of 1-(4'-aminophenyl)-4-methyl-7,8-methylene-dioxy-2,3-benzodiazepine by high-performance liquid chromatography-diode array detection in plasma and brain in healthy and hypoxic-ischaemic rats.

PubMed

Nayak, P K; Zhang, H; Kerr, D S

2013-03-01

Previously we showed that 1-(4'-aminophenyl)-4-methyl-7,8-methylene-dioxy-2,3-benzodiazepine (GYKI-52466), an ionotropic AMPA receptor antagonist, can trigger strong, presumably metabotropic, protection against seizures and stroke at very low doses. To date, no study has determined brain and plasma concentrations of GYKI-52466 following subcutaneous administration in animals with or without brain damage. Here we developed and validated a rapid method of high-performance liquid chromatography with diode array detection. Chromatographic separation was achieved by a Luna C18 column using a mixture of 25 mM phosphate buffer (pH 7.0)-methanol-acetonitrile (40:37.5:22.5, v/v/v) as the mobile phase at a flow rate of 1.2 mL/min. The method showed acceptable precision and accuracy and allowed a precise quantification of 25 ng/mL GYKI-52466 in the plasma and brain. Recovery of GYKI-52466 from the plasma and brain was >87%, and GYKI was stable at room temperature and during prolonged storage at -20 °C. The method was successfully applied in measuring levels of GYKI-52466 following administration of 3 and 20 mg/kg of GYKI-52466 in control and brain damaged rats. A low brain concentration of 0.56 μM GYKI-52466 was observed with 3mg/kg compared to 10.7 μM with 20 mg/kg at 90 min post drug administration. Severe ataxia was observed with the 20mg/kg dose for up to 90 min. Furthermore, in ischaemic animals, there was no evidence of a 'surge' in brain GYKI concentrations at the injury site, confirming the integrity of the blood-brain barrier in the region of infarct. Taken together, our findings support a metabotropic mode of action underlying the low-dose neuroprotective efficacy of GYKI-52466. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Atomic-resolution transmission electron microscopy of electron beam–sensitive crystalline materials

NASA Astrophysics Data System (ADS)

Zhang, Daliang; Zhu, Yihan; Liu, Lingmei; Ying, Xiangrong; Hsiung, Chia-En; Sougrat, Rachid; Li, Kun; Han, Yu

2018-02-01

High-resolution imaging of electron beam–sensitive materials is one of the most difficult applications of transmission electron microscopy (TEM). The challenges are manifold, including the acquisition of images with extremely low beam doses, the time-constrained search for crystal zone axes, the precise image alignment, and the accurate determination of the defocus value. We develop a suite of methods to fulfill these requirements and acquire atomic-resolution TEM images of several metal organic frameworks that are generally recognized as highly sensitive to electron beams. The high image resolution allows us to identify individual metal atomic columns, various types of surface termination, and benzene rings in the organic linkers. We also apply our methods to other electron beam–sensitive materials, including the organic-inorganic hybrid perovskite CH3NH3PbBr3.

Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies

NASA Astrophysics Data System (ADS)

Wei, Jikun; Sandison, George A.; Hsi, Wen-Chien; Ringor, Michael; Lu, Xiaoyi

2006-10-01

Accurate dose calculation is essential to precision radiation treatment planning and this accuracy depends upon anatomic and tissue electron density information. Modern treatment planning inhomogeneity corrections use x-ray CT images and calibrated scales of tissue CT number to electron density to provide this information. The presence of metal in the volume scanned by an x-ray CT scanner causes metal induced image artefacts that influence CT numbers and thereby introduce errors in the radiation dose distribution calculated. This paper investigates the dosimetric improvement achieved by a previously proposed x-ray CT metal artefact suppression technique when the suppressed images of a patient with bilateral hip prostheses are used in commercial treatment planning systems for proton, electron or photon therapies. For all these beam types, this clinical image and treatment planning study reveals that the target may be severely underdosed if a metal artefact-contaminated image is used for dose calculations instead of the artefact suppressed one. Of the three beam types studied, the metal artefact suppression is most important for proton therapy dose calculations, intermediate for electron therapy and least important for x-ray therapy but still significant. The study of a water phantom having a metal rod simulating a hip prosthesis indicates that CT numbers generated after image processing for metal artefact suppression are accurate and thus dose calculations based on the metal artefact suppressed images will be of high fidelity.

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

PubMed Central

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

2015-01-01

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

IV busulfan dose individualization in children undergoing hematopoietic stem cell transplant: limited sampling strategies.

PubMed

Dupuis, L Lee; Sibbald, Cathryn; Schechter, Tal; Ansari, Marc; Gassas, Adam; Théorêt, Yves; Kassir, Nastya; Champagne, Martin A; Doyle, John

2008-05-01

We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busulfan concentrations (AUC7) drawn after the first of 16 i.v. busulfan doses given as a 2-hour infusion every 6 hours. The aim of this study was to develop and validate limited sampling strategies (LSSs) using 3 or fewer busulfan concentration values with which to reliably calculate AUC in children undergoing hematopoietic stem cell transplant (HSCT). Children in the development group (44) received i.v. busulfan at Sick Kids; the validation group consisted of 35 children who received care at CHU Ste-Justine. Busulfan doses given and subsequent plasma busulfan concentrations were recorded. LSSs using 1 to 3 concentration-time points were developed using multiple linear regression. LSS were considered to be acceptable when adjusted r(2) > 0.9, mean bias <15% and precision <15%. Extent of agreement between the AUC7 values and the LSS AUC was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Agreement was considered to be excellent when the lower limit of the 95% confidence limit of the ICC exceeded 0.9 and when the limits of agreement in the BA analysis were +/-15% for both AUC and dose. Administration of the theoretic adjusted busulfan doses based on each LSS was simulated and cases where the resulting AUC was >1500 or <900 microM x min were noted. LSSs using 1, 2, or 3 plasma busulfan concentrations were developed that showed excellent agreement with AUC7 and adjusted busulfan doses. In the validation sample, only the 2- and 3-point LSSs demonstrated acceptable precision and lack of bias. LSSs using 2 or 3 plasma busulfan concentrations can be used to reliably estimate busulfan AUC after IV administration in children undergoing HSCT.

Radon and thoron inhalation doses in dwellings with earthen architecture: Comparison of measurement methods.

PubMed

Meisenberg, Oliver; Mishra, Rosaline; Joshi, Manish; Gierl, Stefanie; Rout, Rajeswari; Guo, Lu; Agarwal, Tarun; Kanse, Sandeep; Irlinger, Josef; Sapra, Balvinder K; Tschiersch, Jochen

2017-02-01

The radioactive noble gas radon ( 222 Rn) and its decay products have been considered a health risk in the indoor environment for many years because of their contribution to the radiation dose of the lungs. The radioisotope thoron ( 220 Rn) and its decay products came into focus of being a health risk only recently. The reason for this is its short half-life, so only building material can become a significant source for indoor thoron. In this study, dwellings with earthen architecture were investigated with different independent measurement techniques in order to determine appropriate methods for reliable dose assessment of the dwellers. While for radon dose assessment, radon gas measurement and the assumption of a common indoor equilibrium factor often are sufficient, thoron gas has proven to be an unreliable surrogate for a direct measurement of thoron decay products. Active/time-resolved but also passive/integrating measurements of the total concentration of thoron decay products demonstrated being precise and efficient methods for determining the exposure and inhalation dose from thoron and its decay products. Exhalation rate measurements are a useful method for a rough dose estimate only if the exhalation rate is homogeneous throughout the house. Before the construction of a building in-vitro exhalation rate measurements on the building material can yield information about the exposure that is to be expected. Determining the unattached fraction of radon decay products and even more of thoron decay products leads to only a slightly better precision; this confirms the relative unimportance of the unattached thoron decay products due to their low concentration. The results of this study thereby give advice on the proper measurement method in similar exposure situations. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-C-201-02: Dosimetric Verification of SBRT with FFF-VMAT Using a 3-D Radiochromic/Optical-CT Dosimetry System

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

Na, Y; Black, P; Wuu, C

2016-06-15

Purpose: With an increasing use of small field size and high dose rate irradiation in the advances of radiotherapy techniques, such as stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS), an in-depth quality assurance (QA) system is required. The purpose of this study is to investigate a high resolution optical CT-based 3D radiochromic dosimetry system for SBRT with intensity modulated radiotherapy (IMRT) and flattening filter free (FFF) volumetric modulated arc therapy (VMAT). Methods: Cylindrical PRESAGE radiochromic dosimeters of 10cm height and 11cm diameter were used to validate SBRT. Four external landmarks were placed on the surface of each dosimeter tomore » define the isocenter of target. SBRT plans were delivered using a Varian TrueBeam™ linear accelerator (LINAC). Three validation plans, SBRT with IMRT (6MV 600MU/min), FFF-VMAT (10MV 2400MU/min), and mixed FFF-VMAT (6MV 1400MU/min, 10MV 2400MU/min), were delivered to the PRESAGE dosimeters. Each irradiated PRESAGE dosimeter was scanned using a single laser beam optical CT scanner and reconstructed with a 1mm × 1mm high spatial resolution. The comparison of measured dose distributions of irradiated PRESAGE dosimeters to those calculated by Pinnacle{sup 3} treatment planning system (TPS) were performed with a 10% dose threshold, 3% dose difference (DD), and 3mm distance-to-agreement (DTA) Gamma criteria. Results: The average pass rates for the gamma comparisons between PRESAGE and Pinnacle{sup 3} in the transverse, sagittal, coronal planes were 94.6%, 95.9%, and 96.4% for SBRT with IMRT, FFF-VMAT, and mixed FFF-VMAT plans, respectively. A good agreement of the isodose distributions of those comparisons were shown at the isodose lines 50%, 70%, 80%, 90% and 98%. Conclusion: This study demonstrates the feasibility of the high resolution optical CT-based 3D radiochromic dosimetry system for validation of SBRT with IMRT and FFF-VMAT. This dosimetry system offers higher precision QA with 3D dose information for small beams compared to what is currently available.« less

COBALT 60 KILOCURIE TELETHERAPY ADVANTAGES AND LIMITATIONS--TECHNICAL PROBLEMS

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

Patricio, M.B.

1961-12-01

The advantages of Co/sup 60/ therapy over conventional x-ray therapy, stemming from the fact that in the lst instance energy absorption within the tissues is by the Compton effect and in the 2nd case by the photoelectric effect, are: (1) increased skin tolerance, (2) reduced bone absorption, (3) increase in depth dose, (4) diminished radiation sickness, and (5) simplicity of operation. As a disadvantage, possibility of injury to adjacent organs is greater with Co/ sup 60/ therapy, since skin reactions, indicative of overdosage with x-ray therapy, may be absent. Some tumors at limited skin depth, such as in the larynx,more » are not amenable to Co/sup 60/ therapy because of the high exit dose. Various technical problems of Co/sup 60/ therapy are discussed, including precise localization of the tumor, calculation of dosage, use of filters to evenly distribute radiation and prevent hot spots, immobilization and positioning of the patient, and direct dosimetry for affirmation of calculated dosage. Favorable results are described in patients with urinary bladder tumors administered l50- to 200-rad daily doses, for a total of 6000 to 8000 rads over 6 to 8 weeks. (H.H.D.)« less

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The “La Cittadina Fondazione” Experience

PubMed Central

Dolera, Mario; Malfassi, Luca; Carrara, Nancy; Finesso, Sara; Marcarini, Silvia; Mazza, Giovanni; Pavesi, Simone; Sala, Massimo; Urso, Gaetano

2018-01-01

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets. PMID:29364837

Characterization of detector-systems based on CeBr3, LaBr3, SrI2 and CdZnTe for the use as dosemeters

NASA Astrophysics Data System (ADS)

Kessler, P.; Behnke, B.; Dombrowski, H.; Neumaier, S.

2017-11-01

For the upgrade of existing dosimetric early warning networks in Europe spectrometric detectors based on CeBr3, LaBr3, SrI2, and CdZnTe are investigated as possible substitutes for the current detector generation which is mainly based on gas filled detectors. The additional information on the nuclide vector which can be derived from the spectra of γ-radiation is highly useful for an appropriate response in case of a nuclear or radiological accident. The measured γ-spectra will be converted into ambient dose equivalent H* (10) using a method where the spectrum is subdivided into multiple energy bands. For each band the conversion coefficients from count rate to dose rate is determined. The derivation of these conversion coefficients is explained in this work. Both experimental and simulative approaches are investigated using quasi-mono-energetic γ-sources and synthetic spectra from Monte-Carlo simulations to determine the conversion coefficients for each detector type. Finally, precision of the obtained characterization is checked by irradiation of the detectors in different well-known photon fields with traceable dose rates.

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

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged usmore » in our activity in the battle against cancer.« less

[Polymer Gel Dosimeter].

PubMed

Hayashi, Shin-Ichiro

2017-01-01

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

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

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

Kroll, Florian; Karsch, Leonhard; Pawelke, Jörg

2013-08-15

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

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

PubMed

Kroll, Florian; Pawelke, Jörg; Karsch, Leonhard

2013-08-01

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

Analytical and quasi-Bayesian methods as development of the iterative approach for mixed radiation biodosimetry.

PubMed

Słonecka, Iwona; Łukasik, Krzysztof; Fornalski, Krzysztof W

2018-06-04

The present paper proposes two methods of calculating components of the dose absorbed by the human body after exposure to a mixed neutron and gamma radiation field. The article presents a novel approach to replace the common iterative method in its analytical form, thus reducing the calculation time. It also shows a possibility of estimating the neutron and gamma doses when their ratio in a mixed beam is not precisely known.

SU-C-BRE-04: Microbeam-Radiation-Therapy (MRT): Characterizing a Novel MRT Device Using High Resolution 3D Dosimetry

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

Li, Q; Juang, T; Bache, S

2014-06-15

Purpose: The feasibility of MRT has recently been demonstrated utilizing a new technology of Carbon-Nano-Tube(CNT) field emission x-ray sources.This approach can deliver very high dose(10's of Gy) in narrow stripes(sub-mm) of radiation which enables the study of novel radiation treatment approaches. Here we investigate the application of highresolution (50um isotropic) PRESAGE/Optical-CT 3D dosimetry techniques to characterize the radiation delivered in this extremely dosimetrically challenging scenario. Methods: The CNT field emission x-ray source irradiator comprises of a linear cathode array and a novel collimator alignment system. This allows a precise delivery of high-energy small beams up to 160 kVp. A cylindricalmore » dosimeter (∼2.2cm in height ∼2.5cm in diameter) was irradiated by CNT MRT delivering 3 strips of radiation with a nominal entrance dose of 32 Gy.A second dosimeter was irradiated with similar entrance dose, with a regular x-ray irradiator collimated to microscopical strip-beams. 50um (isotropic) 3D dosimetry was performed using an in-house optical-CT system designed and optimized for high resolution imaging (including a stray light deconvolution correction).The percentage depth dose (PDD), peak-to-valley ratio (PVR) and beam width (FWHM) data were obtained and analyzed in both cases. Results: High resolution 3D images were successfully achieved with the prototype system, enabling extraction of PDD and dose profiles. The PDDs for the CNT irradiation showed pronounced attenuation, but less build-up effect than that from the multibeam irradiation. The beam spacing between the three strips has an average value of 0.9mm while that for the 13 strips is 1.5 mm at a depth of 16.5 mm. The stray light corrected image shows line profiles with reduced noise and consistent PVR values. Conclusion: MRT dosimetry is extremely challenging due to the ultra small fields involved.This preliminary application of a novel, ultra-high resolution, optical-CT 3D dosimetry system shows promise, but further work is required to validate and investigate accuracy and artifacts. This work was supported by NIH R01CA100835.« less

The process evaluation of two alternative participatory ergonomics intervention strategies for construction companies.

PubMed

Visser, Steven; van der Molen, Henk F; Sluiter, Judith K; Frings-Dresen, Monique H W

2018-03-26

To gain insight into the process of applying two guidance strategies - face-to-face (F2F) or e-guidance strategy (EC) - of a Participatory Ergonomics (PE) intervention and whether differences between these guidance strategies occur, 12 construction companies were randomly assigned to a strategy. The process evaluation contained reach, dose delivered, dose received, precision, competence, satisfaction and behavioural change of individual workers. Data were assessed by logbooks, and questionnaires and interviews at baseline and/or after six months. Reach was low (1%). Dose delivered (F2F: 63%; EC: 44%), received (F2F: 42%; EC: 16%) were not sufficient. The precision and competence were sufficient for both strategies and satisfaction was strongly affected by dose received. For behavioural change, knowledge (F2F) and culture (EC) changed positively within companies. Neither strategy was delivered as intended. Compliance to the intervention was low, especially for EC. Starting with a face-to-face meeting might lead to higher compliance, especially in the EC group. Practitioner Summary: This study showed that compliance to a face-to-face and an e-guidance strategy is low. To improve the compliance, it is advised to start with a face-to-face meeting to see which parts of the intervention are needed and which guidance strategy can be used for these parts. ISRCTN73075751.

Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

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

Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.

2013-02-15

Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively,more » whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94.62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Conclusions: Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.« less

Validation of a method for quantitation of the clopidogrel active metabolite, clopidogrel, clopidogrel carboxylic acid, and 2-oxo-clopidogrel in feline plasma.

PubMed

Lyngby, Janne G; Court, Michael H; Lee, Pamela M

2017-08-01

The clopidogrel active metabolite (CAM) is unstable and challenging to quantitate. The objective was to validate a new method for stabilization and quantitation of CAM, clopidogrel, and the inactive metabolites clopidogrel carboxylic acid and 2-oxo-clopiodgrel in feline plasma. Two healthy cats administered clopidogrel to demonstrate assay in vivo utility. Stabilization of CAM was achieved by adding 2-bromo-3'methoxyacetophenone to blood tubes to form a derivatized CAM (CAM-D). Method validation included evaluation of calibration curve linearity, accuracy, and precision; within and between assay precision and accuracy; and compound stability using spiked blank feline plasma. Analytes were measured by high performance liquid chromatography with tandem mass spectrometry. In vivo utility was demonstrated by a pharmacokinetic study of cats given a single oral dose of 18.75mg clopidogrel. The 2-oxo-clopidogrel metabolite was unstable. Clopidogrel, CAM-D, and clopidogrel carboxylic acid appear stable for 1 week at room temperature and 9 months at -80°C. Standard curves showed linearity for CAM-D, clopidogrel, and clopidogrel carboxylic acid (r > 0.99). Between assay accuracy and precision was ≤2.6% and ≤7.1% for CAM-D and ≤17.9% and ≤11.3% for clopidogrel and clopidogrel carboxylic acid. Within assay precision for all three compounds was ≤7%. All three compounds were detected in plasma from healthy cats receiving clopidogrel. This methodology is accurate and precise for simultaneous quantitation of CAM-D, clopidogrel, and clopidogrel carboxylic acid in feline plasma but not 2-oxo-clopidogrel. Validation of this assay is the first step to more fully understanding the use of clopidogrel in cats. Copyright © 2017 Elsevier B.V. All rights reserved.

Replacing the Measles Ten-Dose Vaccine Presentation with the Single-Dose Presentation in Thailand

PubMed Central

Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Chen, Sheng-I; Bailey, Rachel R.; Wiringa, Ann E.; Wateska, Angela R.; Jana, Anirban; Van Panhuis, Willem G.; Burke, Donald S.

2011-01-01

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand is currently considering) and a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations’ storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage. PMID:21439313

SU-F-J-203: Retrospective Assessment of Delivered Proton Dose in Prostate Cancer Patients Based On Daily In-Room CT Imaging

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

Stuetzer, K; Paessler, T; Valentini, C

Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonalmore » X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%<107%), bladder (V75Gy<15%, V70Gy<25%, V65Gy<30%), rectum (V70Gy<10%, V50Gy<40%) and femoral heads (V50Gy<5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Results: No alarming differences were observed between planned and retrospectively accumulated dose: iCTV constraints were met, except for one patient (D98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (<11.3%) in two patients. First intra-therapy variability analysis in 4 patients showed no timedependent parameter drift, revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare interventions after daily 3D imaging of the first 12 patients, in-room CT frequency for prostate cancer patients was reduced. The presented study supports this decision. The authors acknowledge the German Federal Ministry for Education and Research for funding the High Precision Radiotherapy Group at the OncoRay - National Center for Radiation Research in Oncology (BMBF- 03Z1N51).« less

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PubMed

Rosenzweig, K E; Mychalczak, B; Fuks, Z; Hanley, J; Burman, C; Ling, C C; Armstrong, J; Ginsberg, R; Kris, M G; Raben, A; Leibel, S

2000-01-01

Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife.

PubMed

van Riet-Nales, Diana A; Doeve, Myrthe E; Nicia, Agnes E; Teerenstra, Steven; Notenboom, Kim; Hekster, Yechiel A; van den Bemt, Bart J F

2014-05-15

Tablets are frequently subdivided to lower the dose, to facilitate swallowing by e.g. children or older people or to save costs. Splitting devices are commonly used when hand breaking is difficult or painful. Three techniques for tablet subdivision were investigated: hand breaking, tablet splitter, kitchen knife. A best case drug (paracetamol), tablet (round, flat, uncoated, 500 mg) and operator (24-year student) were applied. Hundred tablets were subdivided by hand and by three devices of each of the following types: Fit & Healthy, Health Care Logistics, Lifetime, PillAid, PillTool, Pilomat tablet splitter; Blokker kitchen knife. The intra and inter device accuracy, precision and sustainability were investigated. The compliance to (adapted) regulatory requirements was investigated also. The accuracy and precision of hand broken tablets was 104/97% resp. 2.8/3.2% (one part per tablet considered; parts right/left side operator). The right/left accuracies of the splitting devices varied between 60 and 133%; the precisions 4.0 and 29.6%. The devices did not deteriorate over 100-fold use. Only hand broken tablets complied with all regulatory requirements. Health care professionals should realize that tablet splitting may result in inaccurate dosing. Authorities should undertake appropriate measures to assure good function of tablet splitters and, where feasible, to reduce the need for their use. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Incorporating lower grade toxicity information into dose finding designs

PubMed Central

Iasonos, Alexia; Zohar, Sarah; O’Quigley, John

2012-01-01

Background Toxicity grades underlie the definition of a dose limiting toxicity (DLT) but in the majority of phase I designs, the information contained in the individual grades is not used. Some authors have argued that it may be more appropriate to consider a polytomous rather than dichotomous response. Purpose We investigate whether the added information on individual grades can improve the operating characteristics of the Continual Reassessment Method (CRM). Methods We compare the original CRM design for a binary response with two stage CRM designs which make di erent use of lower-grade toxicity information via simulations. Specifically we study; a two-stage design that utilizes lower-grade toxicities in the first stage only, during the initial non model-based escalation, and two-stage designs where lower grades are used throughout the trial via explicit models. We postulate a model relating the rates of lower grade toxicities to the rate of DLTs, or assume the relative rates of low to high grade toxicities is unknown. The designs were compared in terms of accuracy, patient allocation and precision. Results Significant gains can be achieved when using grades in the first stage of a two-stage design. Otherwise, only modest improvements are seen when the information on grades is exploited via the use of explicit models, where the parameters are known precisely. CRM with some use of grade information, increases the number of patients treated at the MTD by approximately 5%. The additional information from lower grades can lead to a small increase in the precision of our estimate of the MTD. Limitations Our comparisons are not exhaustive and it would be worth studying other models and situations. Conclusions Although, the gains in performance were not as great as we had hoped, we observed no cases where the performance of CRM was poorer. Our recommendation is that investigators might consider using graded toxicities at the design stage. PMID:21835856

Complexity in estimation of esomeprazole and its related impurities' stability in various stress conditions in low-dose aspirin and esomeprazole magnesium capsules.

PubMed

Reddy, Palavai Sripal; Hotha, Kishore Kumar; Sait, Shakil

2013-01-01

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities' development in the presence of aspirin was traditionally difficult due to aspirin's sensitivity to basic conditions and esomeprazole's sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole's purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5μm) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min(-1) with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness.

SU-E-T-120: Dosimetric Characteristics Study of NanoDotâ,,¢ for In-Vivo Dosimetry

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

Hussain, A; Wasaye, A; Gohar, R

Purpose: The purpose of the study was to analyze the dosimetric characteristics (energy dependence, reproducibility and dose linearity) of nanoDot™ optically stimulated luminescence dosimeters (OSLDs) and validate their potential use during in-vivo dosimetry, specifically TBI. The manufacturer stated accuracy is ±10% for standard nanoDot™. Methods: At AKUH, the InLight microStar OSL dosimetry system for patient in-vivo dosimetry is in use since 2012. Twenty-five standard nanoDot™ were used in the analysis. Sensitivity and reproducibility was tested in the first part with 6MV and 18 MV Varian x-ray beams. Each OSLD was irradiated to 100cGy dose at nominal SSD (100 cm). Allmore » the OSLDs were read 3 times for average reading. Dose linearity and calibration were also performed with same beams in common clinical dose range of 0 - 500 cGy. In addition, verification of TBI absolute dose at extended SSD (500cm) was also performed. Results: The reproducibility observed with the OSLD was better than the manufacturer stated limits. Measured doses vary less than ±2% in 19(76%) OSLDs, whereas less than ±3% in 6(24%) OSLDs. Their sensitivity was approximately 525 counts per cGy. Better agreement was observed between measurements, with a standard deviation of 1.8%. A linear dose response was observed with OSLDs for both 6 and 18MV beams in 0 - 500 cGy dose range. TBI measured doses at 500 cm SSD were also confirmed to be within ±0.5% and ±1.3% of the ion chamber measured doses for 6 and 18MV beams respectively. Conclusion: The dosimetric results demonstrate that nanoDot™ can be potentially used for in-vivo dosimetry verification in various clinical situations, with a high degree of accuracy and precision. In addition OSLDs exhibit better dose reproducibility with standard deviation of 1.8%. There was no significant difference in their response to 6 and 18MV beams. The dose response was also linear.« less

MR-based source localization for MR-guided HDR brachytherapy

NASA Astrophysics Data System (ADS)

Beld, E.; Moerland, M. A.; Zijlstra, F.; Viergever, M. A.; Lagendijk, J. J. W.; Seevinck, P. R.

2018-04-01

For the purpose of MR-guided high-dose-rate (HDR) brachytherapy, a method for real-time localization of an HDR brachytherapy source was developed, which requires high spatial and temporal resolutions. MR-based localization of an HDR source serves two main aims. First, it enables real-time treatment verification by determination of the HDR source positions during treatment. Second, when using a dummy source, MR-based source localization provides an automatic detection of the source dwell positions after catheter insertion, allowing elimination of the catheter reconstruction procedure. Localization of the HDR source was conducted by simulation of the MR artifacts, followed by a phase correlation localization algorithm applied to the MR images and the simulated images, to determine the position of the HDR source in the MR images. To increase the temporal resolution of the MR acquisition, the spatial resolution was decreased, and a subpixel localization operation was introduced. Furthermore, parallel imaging (sensitivity encoding) was applied to further decrease the MR scan time. The localization method was validated by a comparison with CT, and the accuracy and precision were investigated. The results demonstrated that the described method could be used to determine the HDR source position with a high accuracy (0.4–0.6 mm) and a high precision (⩽0.1 mm), at high temporal resolutions (0.15–1.2 s per slice). This would enable real-time treatment verification as well as an automatic detection of the source dwell positions.

Lithography-based fabrication of nanopore arrays in freestanding SiN and graphene membranes

NASA Astrophysics Data System (ADS)

Verschueren, Daniel V.; Yang, Wayne; Dekker, Cees

2018-04-01

We report a simple and scalable technique for the fabrication of nanopore arrays on freestanding SiN and graphene membranes based on electron-beam lithography and reactive ion etching. By controlling the dose of the single-shot electron-beam exposure, circular nanopores of any size down to 16 nm in diameter can be fabricated in both materials at high accuracy and precision. We demonstrate the sensing capabilities of these nanopores by translocating dsDNA through pores fabricated using this method, and find signal-to-noise characteristics on par with transmission-electron-microscope-drilled nanopores. This versatile lithography-based approach allows for the high-throughput manufacturing of nanopores and can in principle be used on any substrate, in particular membranes made out of transferable two-dimensional materials.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

NASA Astrophysics Data System (ADS)

Toppi, M.; Battistoni, G.; Bellini, F.; Collamati, F.; De Lucia, E.; Durante, M.; Faccini, R.; Frallicciardi, P. M.; Marafini, M.; Mattei, I.; Morganti, S.; Muraro, S.; Paramatti, R.; Patera, V.; Pinci, D.; Piersanti, L.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Senzacqua, M.; Solfaroli Camillocci, E.; Traini, G.; Voena, C.

2016-05-01

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presented.

High quality high spatial resolution functional classification in low dose dynamic CT perfusion using singular value decomposition (SVD) and k-means clustering

NASA Astrophysics Data System (ADS)

Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

2017-03-01

Dynamic CT perfusion acquisitions are intrinsically high-dose examinations, due to repeated scanning. To keep radiation dose under control, relatively noisy images are acquired. Noise is then further enhanced during the extraction of functional parameters from the post-processing of the time attenuation curves of the voxels (TACs) and normally some smoothing filter needs to be employed to better visualize any perfusion abnormality, but sacrificing spatial resolution. In this study we propose a new method to detect perfusion abnormalities keeping both high spatial resolution and high CNR. To do this we first perform the singular value decomposition (SVD) of the original noisy spatial temporal data matrix to extract basis functions of the TACs. Then we iteratively cluster the voxels based on a smoothed version of the three most significant singular vectors. Finally, we create high spatial resolution 3D volumes where to each voxel is assigned a distance from the centroid of each cluster, showing how functionally similar each voxel is compared to the others. The method was tested on three noisy clinical datasets: one brain perfusion case with an occlusion in the left internal carotid, one healthy brain perfusion case, and one liver case with an enhancing lesion. Our method successfully detected all perfusion abnormalities with higher spatial precision when compared to the functional maps obtained with a commercially available software. We conclude this method might be employed to have a rapid qualitative indication of functional abnormalities in low dose dynamic CT perfusion datasets. The method seems to be very robust with respect to both spatial and temporal noise and does not require any special a priori assumption. While being more robust respect to noise and with higher spatial resolution and CNR when compared to the functional maps, our method is not quantitative and a potential usage in clinical routine could be as a second reader to assist in the maps evaluation, or to guide a dataset smoothing before the modeling part.

High-resolution Modeling Assisted Design of Customized and Individualized Transcranial Direct Current Stimulation Protocols

PubMed Central

Bikson, Marom; Rahman, Asif; Datta, Abhishek; Fregni, Felipe; Merabet, Lotfi

2012-01-01

Objectives Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS. Methods In this review, we discuss the following topics: (i) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; (ii) The protocols and the workflow for developing high-resolution models; (iii) The technical challenges and limitations of interpreting modeling predictions, and (iv) Real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy. Conclusions Though modeling for non-invasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy. PMID:22780230

Cellular Response to Reagent-Free Electron-Irradiated Gelatin Hydrogels.

PubMed

Wisotzki, Emilia I; Friedrich, Ralf P; Weidt, Astrid; Alexiou, Christoph; Mayr, Stefan G; Zink, Mareike

2016-06-01

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

XPS-XRF hybrid metrology enabling FDSOI process

NASA Astrophysics Data System (ADS)

Hossain, Mainul; Subramanian, Ganesh; Triyoso, Dina; Wahl, Jeremy; Mcardle, Timothy; Vaid, Alok; Bello, A. F.; Lee, Wei Ti; Klare, Mark; Kwan, Michael; Pois, Heath; Wang, Ying; Larson, Tom

2016-03-01

Planar fully-depleted silicon-on-insulator (FDSOI) technology potentially offers comparable transistor performance as FinFETs. pFET FDOSI devices are based on a silicon germanium (cSiGe) layer on top of a buried oxide (BOX). Ndoped interfacial layer (IL), high-k (HfO2) layer and the metal gate stacks are then successively built on top of the SiGe layer. In-line metrology is critical in precisely monitoring the thickness and composition of the gate stack and associated underlying layers in order to achieve desired process control. However, any single in-line metrology technique is insufficient to obtain the thickness of IL, high-k, cSiGe layers in addition to Ge% and N-dose in one single measurement. A hybrid approach is therefore needed that combines the capabilities of more than one measurement technique to extract multiple parameters in a given film stack. This paper will discuss the approaches, challenges, and results associated with the first-in-industry implementation of XPS-XRF hybrid metrology for simultaneous detection of high-k thickness, IL thickness, N-dose, cSiGe thickness and %Ge, all in one signal measurement on a FDSOI substrate in a manufacturing fab. Strong correlation to electrical data for one or more of these measured parameters will also be presented, establishing the reliability of this technique.

Radiobiological effectiveness of laser accelerated electrons in comparison to electron beams from a conventional linear accelerator.

PubMed

Laschinsky, Lydia; Baumann, Michael; Beyreuther, Elke; Enghardt, Wolfgang; Kaluza, Malte; Karsch, Leonhard; Lessmann, Elisabeth; Naumburger, Doreen; Nicolai, Maria; Richter, Christian; Sauerbrey, Roland; Schlenvoigt, Hans-Peter; Pawelke, Jörg

2012-01-01

The notable progress in laser particle acceleration technology promises potential medical application in cancer therapy through compact and cost effective laser devices that are suitable for already existing clinics. Previously, consequences on the radiobiological response by laser driven particle beams characterised by an ultra high peak dose rate have to be investigated. Therefore, tumour and non-malignant cells were irradiated with pulsed laser accelerated electrons at the JETI facility for the comparison with continuous electrons of a conventional therapy LINAC. Dose response curves were measured for the biological endpoints clonogenic survival and residual DNA double strand breaks. The overall results show no significant differences in radiobiological response for in vitro cell experiments between laser accelerated pulsed and clinical used electron beams. These first systematic in vitro cell response studies with precise dosimetry to laser driven electron beams represent a first step toward the long term aim of the application of laser accelerated particles in radiotherapy.

Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

NASA Astrophysics Data System (ADS)

Battistoni, G.; Bellini, F.; Bini, F.; Collamati, F.; Collini, F.; De Lucia, E.; Durante, M.; Faccini, R.; Ferroni, F.; Frallicciardi, P. M.; La Tessa, C.; Marafini, M.; Mattei, I.; Miraglia, F.; Morganti, S.; Ortega, P. G.; Patera, V.; Piersanti, L.; Pinci, D.; Russomando, A.; Sarti, A.; Schuy, C.; Sciubba, A.; Senzacqua, M.; Solfaroli Camillocci, E.; Vanstalle, M.; Voena, C.

2015-02-01

Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50-300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented.

Schedule Dependence in Cancer Therapy: Intravenous Vitamin C and the Systemic Saturation Hypothesis

PubMed Central

Miranda Massari, Jorge R.; Duconge, Jorge; Riordan, Neil H.; Ichim, Thomas

2013-01-01

Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do single continuous IV doses of the same total exposure. This approach would be expected to minimize saturation of renal reabsorption, providing a continuous “dynamic flow” of vitamin C in the body for optimal systemic exposure and clinical outcomes. This prevents the “systemic saturation” phenomena, which may recycle vitamin C and render it less effective as an anticancer agent. Nonetheless, more pharmacokinetic and pharmacodynamic studies are needed to fully understand this schedule-dependence phenomenon. PMID:24860238

Assessing Impact of High-Dose Pitavastatin on Carotid Artery Elasticity with Speckle-Tracking Strain Imaging.

PubMed

Kim, Chee Hae; Wang, Shuang; Park, Jun-Bean; Jung, Keun-Hwa; Yoon, Yeonyee E; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Cho, Goo-Yeong; Sohn, Dae-Won

2018-03-07

Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity. This study was a prospective study including 48 statin-naïve patients (age, 58.2±8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β 2 ) were measured using speckle-tracking imaging before and after 3 months of high-dose pitavastatin treatment (4 mg daily). For the comparison, we measured conventional carotid elasticity parameters and intima-media thickness using B-mode ultrasound at the same time points. Compared with baseline, there was significant improvement in circumferential CAS (2.98%±1.18% to 3.40%±1.43%, p=0.008) and β 2 (0.19±0.07 to 0.17±0.08, p=0.047) after statin therapy. Contrariwise, there were no significant changes in all conventional carotid elasticity metrics and intima-media thickness. When stratifying patients into two subgroups by 10 year atherosclerotic cardiovascular disease (ASCVD) risk, speckle-tracking-derived circumferential CAS and β 2 improved significantly only in patients with ASCVD risk ≥ 7.5%. Short-term treatment with high-dose pitavastatin improved carotid artery elasticity measured by speckle-tracking method, but not conventional parameters by B-mode ultrasound. Speckle-tracking-based measurements may allow the early noninvasive assessment of statin effects on vascular function in hypercholesterolemic patients.

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

dos Reis, Roberto; Yang, Hao; Ophus, Colin

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr 3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr 3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurementmore » of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). Finally, the approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.« less

Determination of the structural phase and octahedral rotation angle in halide perovskites

NASA Astrophysics Data System (ADS)

dos Reis, Roberto; Yang, Hao; Ophus, Colin; Ercius, Peter; Bizarri, Gregory; Perrodin, Didier; Shalapska, Tetiana; Bourret, Edith; Ciston, Jim; Dahmen, Ulrich

2018-02-01

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurement of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). The approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.

PubMed

Galaup, Ariane; Paci, Angelo

2013-03-01

Among the dimethanesulfonates, busulfan, in combination with other alkylating agents or nucleoside analogues, is the cornerstone of high-dose chemotherapy. It is used, and followed hematopoietic stem cell transplantation, for the treatment of various hematologic malignancies and immunodeficiencies. Treosulfan, which is a hydrophilic analogue of busulfan, was the first dimethanesufonate registered for the treatment of ovarian cancer. Recently, treosulfan has been investigated for the treatment of hematologic malignancies in combination with the same second agents before hematopoietic stem cell transplantation. This work reviews the pharmacological data of these two dimethanesulfonates alkylating agents. Specifically, the article looks at their chemistry, metabolism, anticancer activity, and their pharmacokinetics and pharmacodynamics. Busulfan has been investigated widely for more than three decades leading to a large and precise handling of this agent with numerous studies on activity and pharmacokinetics and pharmacodynamics. In contrast, the behavior of treosulfan is still under investigation and not fully described. The complexity of treosulfan's metabolism and mechanism of action gives rise to the need of a deeper understanding of its pharmacological activity in a context of high-dose chemotherapy. Specifically, there is a great need to better understand its pharmacokinetics/pharmacodynamics relationship.

Radiation-induced immune responses: mechanisms and therapeutic perspectives.

PubMed

Jeong, Hoibin; Bok, Seoyeon; Hong, Beom-Ju; Choi, Hyung-Seok; Ahn, G-One

2016-09-01

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

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

Zhu, Yuanyuan; Munro, Catherine J.; Olszta, Matthew J.

In this work, we showcase that through precise control of the electron dose rate, state-of-the-art large solid angle energy dispersive X-ray spectroscopy (EDS) mapping in aberration-corrected scanning transmission electron microscope (STEM) is capable of faithful and unambiguous chemical characterization of the Pt and Pd distribution in a peptide-mediated nanosystem. This low-dose-rate recording scheme adds another dimension of flexibility to the design of elemental mapping experiments, and holds significant potential for extending its application to a wide variety of beam sensitive hybrid nanostructures.

Lithium formate EPR dosimetry for verifications of planned dose distributions prior to intensity-modulated radiation therapy.

PubMed

Gustafsson, H; Lund, E; Olsson, S

2008-09-07

The objective of the present investigation was to evaluate lithium formate electron paramagnetic resonance (EPR) dosimetry for measurement of dose distributions in phantoms prior to intensity-modulated radiation therapy (IMRT). Lithium formate monohydrate tablets were carefully prepared, and blind tests were performed in clinically relevant situations in order to determine the precision and accuracy of the method. Further experiments confirmed that within the accuracy of the current method, the dosimeter response was independent of beam energies and dose rates used for IMRT treatments. The method was applied to IMRT treatment plans, and the dose determinations were compared to ionization chamber measurements. The experiments showed that absorbed doses above 3 Gy could be measured with an uncertainty of less than 2.5% of the dose (coverage factor kappa = 1.96). Measurement time was about 15 min using a well-calibrated dosimeter batch. The conclusion drawn from the investigation was that lithium formate EPR dosimetry is a promising new tool for absorbed dose measurements in external beam radiation therapy, especially for doses above 3 Gy.

Lithium formate EPR dosimetry for verifications of planned dose distributions prior to intensity-modulated radiation therapy

NASA Astrophysics Data System (ADS)

Gustafsson, H.; Lund, E.; Olsson, S.

2008-09-01

The objective of the present investigation was to evaluate lithium formate electron paramagnetic resonance (EPR) dosimetry for measurement of dose distributions in phantoms prior to intensity-modulated radiation therapy (IMRT). Lithium formate monohydrate tablets were carefully prepared, and blind tests were performed in clinically relevant situations in order to determine the precision and accuracy of the method. Further experiments confirmed that within the accuracy of the current method, the dosimeter response was independent of beam energies and dose rates used for IMRT treatments. The method was applied to IMRT treatment plans, and the dose determinations were compared to ionization chamber measurements. The experiments showed that absorbed doses above 3 Gy could be measured with an uncertainty of less than 2.5% of the dose (coverage factor k = 1.96). Measurement time was about 15 min using a well-calibrated dosimeter batch. The conclusion drawn from the investigation was that lithium formate EPR dosimetry is a promising new tool for absorbed dose measurements in external beam radiation therapy, especially for doses above 3 Gy.

Calcium kinetics with microgram stable isotope doses and saliva sampling

NASA Technical Reports Server (NTRS)

Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.

1996-01-01

Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

Optically stimulated luminescence (OSL) of carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for film dosimetry in radiotherapy

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

Schembri, V.; Heijmen, B. J. M.

2007-06-15

Introduction and Purpose: Conventional x-ray films and radiochromic films have inherent challenges for high precision radiotherapy dosimetry. Here we have investigated basic characteristics of optically stimulated luminescence (OSL) of irradiated films containing carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for dosimetry in therapeutic photon and electron beams. Materials and Methods: The OSL films consist of a polystyrene sheet, with a top layer of a mixture of single crystals of Al{sub 2}O{sub 3}:C, ground into a powder, and a polyester base. The total thickness of the films is 0.3 mm. Measurements have been performed in a water equivalent phantom, using 4, 6,more » 10, and 18 MV photon beams, and 6-22 MeV electron beams. The studies include assessment of the film response (acquired OSL signal/delivered dose) on delivered dose (linearity), dose rate (1-6 Gy/min), beam quality, field size and depth (6 MV, ranges 4x4-30x30 cm{sup 2}, d{sub max}-35 cm). Doses have been derived from ionization chamber measurements. OSL films have also been compared with conventional x-ray and GafChromic films for dosimetry outside the high dose area, with a high proportion of low dose scattered photons. In total, 787 OSL films have been irradiated. Results: Overall, the OSL response for electron beams was 3.6% lower than for photon beams. Differences between the various electron beam energies were not significant. The 6 and 18 MV photon beams differed in response by 4%. No response dependencies on dose rate were observed. For the 6 MV beam, the field size and depth dependencies of the OSL response were within {+-}2.5%. The observed inter-film response variation for films irradiated with the same dose varied from 1% to 3.2% (1 SD), depending on the measurement day. At a depth of 20 cm, 5 cm outside the 20x20 cm{sup 2} 6 and 18 MV beams, an over response of 17% was observed. In contrast to GafChromic and conventional x-ray films, the response of the Al{sub 2}O{sub 3}:C films is linear in the clinically relevant dose range 0-200 cGy. Conclusions: Measurement of the OSL signal of irradiated films containing Al{sub 2}O{sub 3}:C is a promising technique for film dosimetry in radiotherapy with no or small response variations with dose rate, beam quality, field size and depth, and a linear response from 0 to 200 cGy.« less

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

[Verification of the dose delivered to the patient by means of TLD, SC, PID. What future?].

PubMed

Noël, A

2003-11-01

Among the different possibilities to check the accuracy of the treatment delivered, only in vivo dosimetry ensures the precision of the dose delivered to the patient during the treatment. In 1970-1980, Ruden assessed the use of thermoluminescent dosimetry to perform in vivo measurements at Radiumemmet in Stockholm. Straightforward in its principle but demanding in its implementation, thermoluminescent dosimetry has largely been used. Today, thanks to the work of Rikner, the use of semiconductor detectors allows the general implementation of in vivo dosimetry. Tomorrow, we will use electronic portal imaging device to verify the geometrical patient setup and the dose delivery at the same time. Its implementation remains complex and will need the development of algorithms to compute exit dose or midplane dose using portal in vivo dosimetry. First clinical results show that portal imaging is an accurate alternative for conventional in vivo dosimetry using diodes.

Reference geometry-based detection of (4D-)CT motion artifacts: a feasibility study

NASA Astrophysics Data System (ADS)

Werner, René; Gauer, Tobias

2015-03-01

Respiration-correlated computed tomography (4D or 3D+t CT) can be considered as standard of care in radiation therapy treatment planning for lung and liver lesions. The decision about an application of motion management devices and the estimation of patient-specific motion effects on the dose distribution relies on precise motion assessment in the planning 4D CT data { which is impeded in case of CT motion artifacts. The development of image-based/post-processing approaches to reduce motion artifacts would benefit from precise detection and localization of the artifacts. Simple slice-by-slice comparison of intensity values and threshold-based analysis of related metrics suffer from- depending on the threshold- high false-positive or -negative rates. In this work, we propose exploiting prior knowledge about `ideal' (= artifact free) reference geometries to stabilize metric-based artifact detection by transferring (multi-)atlas-based concepts to this specific task. Two variants are introduced and evaluated: (S1) analysis and comparison of warped atlas data obtained by repeated non-linear atlas-to-patient registration with different levels of regularization; (S2) direct analysis of vector field properties (divergence, curl magnitude) of the atlas-to-patient transformation. Feasibility of approaches (S1) and (S2) is evaluated by motion-phantom data and intra-subject experiments (four patients) as well as - adopting a multi-atlas strategy- inter-subject investigations (twelve patients involved). It is demonstrated that especially sorting/double structure artifacts can be precisely detected and localized by (S1). In contrast, (S2) suffers from high false positive rates.

Evaluation of Al2O3:C optically stimulated luminescence (OSL) dosimeters for passive dosimetry of high-energy photon and electron beams in radiotherapy.

PubMed

Yukihara, E G; Mardirossian, G; Mirzasadeghi, M; Guduru, S; Ahmad, S

2008-01-01

This article investigates the performance of Al2O3: C optically stimulated luminescence dosimeters (OSLDs) for application in radiotherapy. Central-axis depth dose curves and optically stimulated luminescence (OSL) responses were obtained in a water phantom for 6 and 18 MV photons, and for 6, 9, 12, 16, and 20 MeV electron beams from a Varian 21EX linear accelerator. Single OSL measurements could be repeated with a precision of 0.7% (one standard deviation) and the differences between absorbed doses measured with OSLDs and an ionization chamber were within +/- 1% for photon beams. Similar results were obtained for electron beams in the low-gradient region after correction for a 1.9% photon-to-electron bias. The distance-to-agreement values were of the order of 0.5-1.0 mm for electrons in high dose gradient regions. Additional investigations also demonstrated that the OSL response dependence on dose rate, field size, and irradiation temperature is less than 1% in the conditions of the present study. Regarding the beam energy/quality dependence, the relative response of the OSLD for 18 MV was (0.51 +/- 0.48)% of the response for the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam was in average 1.9% higher, but this result requires further confirmation. The relative response did not seem to vary with electron energy at dmax within the experimental uncertainties (0.5% in average) and, therefore, a fixed correction factor of 1.9% eliminated the energy dependence in our experimental conditions.

Evaluation of Al{sub 2}O{sub 3}:C optically stimulated luminescence (OSL) dosimeters for passive dosimetry of high-energy photon and electron beams in radiotherapy

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

Yukihara, E. G.; Mardirossian, G.; Mirzasadeghi, M.

This article investigates the performance of Al{sub 2}O{sub 3}:C optically stimulated luminescence dosimeters (OSLDs) for application in radiotherapy. Central-axis depth dose curves and optically stimulated luminescence (OSL) responses were obtained in a water phantom for 6 and 18 MV photons, and for 6, 9, 12, 16, and 20 MeV electron beams from a Varian 21EX linear accelerator. Single OSL measurements could be repeated with a precision of 0.7% (one standard deviation) and the differences between absorbed doses measured with OSLDs and an ionization chamber were within {+-}1% for photon beams. Similar results were obtained for electron beams in the low-gradientmore » region after correction for a 1.9% photon-to-electron bias. The distance-to-agreement values were of the order of 0.5-1.0 mm for electrons in high dose gradient regions. Additional investigations also demonstrated that the OSL response dependence on dose rate, field size, and irradiation temperature is less than 1% in the conditions of the present study. Regarding the beam energy/quality dependence, the relative response of the OSLD for 18 MV was (0.51{+-}0.48)% of the response for the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam. The OSLD response for the electron beams relative to the 6 MV photon beam was in average 1.9% higher, but this result requires further confirmation. The relative response did not seem to vary with electron energy at d{sub max} within the experimental uncertainties (0.5% in average) and, therefore, a fixed correction factor of 1.9% eliminated the energy dependence in our experimental conditions.« less

The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future.

PubMed

Denyer, John; Dyche, Tony

2010-04-01

Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

Dosimetric Comparison of Intensity-Modulated Stereotactic Radiotherapy With Other Stereotactic Techniques for Locally Recurrent Nasopharyngeal Carcinoma

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

Kung, Shiris Wai Sum; Wu, Vincent Wing Cheung; Kam, Michael Koon Ming, E-mail: kamkm@yahoo.co

2011-01-01

Purpose: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Methods and Materials: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrievedmore » from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. Results: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Conclusion: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.« less

SU-E-T-36: A GPU-Accelerated Monte-Carlo Dose Calculation Platform and Its Application Toward Validating a ViewRay Beam Model

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

Wang, Y; Mazur, T; Green, O

Purpose: To build a fast, accurate and easily-deployable research platform for Monte-Carlo dose calculations. We port the dose calculation engine PENELOPE to C++, and accelerate calculations using GPU acceleration. Simulations of a Co-60 beam model provided by ViewRay demonstrate the capabilities of the platform. Methods: We built software that incorporates a beam model interface, CT-phantom model, GPU-accelerated PENELOPE engine, and GUI front-end. We rewrote the PENELOPE kernel in C++ (from Fortran) and accelerated the code on a GPU. We seamlessly integrated a Co-60 beam model (obtained from ViewRay) into our platform. Simulations of various field sizes and SSDs using amore » homogeneous water phantom generated PDDs, dose profiles, and output factors that were compared to experiment data. Results: With GPU acceleration using a dated graphics card (Nvidia Tesla C2050), a highly accurate simulation – including 100*100*100 grid, 3×3×3 mm3 voxels, <1% uncertainty, and 4.2×4.2 cm2 field size – runs 24 times faster (20 minutes versus 8 hours) than when parallelizing on 8 threads across a new CPU (Intel i7-4770). Simulated PDDs, profiles and output ratios for the commercial system agree well with experiment data measured using radiographic film or ionization chamber. Based on our analysis, this beam model is precise enough for general applications. Conclusions: Using a beam model for a Co-60 system provided by ViewRay, we evaluate a dose calculation platform that we developed. Comparison to measurements demonstrates the promise of our software for use as a research platform for dose calculations, with applications including quality assurance and treatment plan verification.« less

Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

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

Jalali, Rakesh, E-mail: rjalali@tmc.gov.i; Mallick, Indranil; Dutta, Debnarayan

2010-07-15

Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated withmore » various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.« less

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

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

Malcolm, J; Mein, S; McNiven, A

2015-06-15

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

SU-E-T-433: Field-In-Field Irradiation for Breast Cancer with VERO-4DRT System: A Feasibility Study

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

Hayashi, N; Mizuno, T; Takada, Y

2015-06-15

Purpose: The Vero-4DRT system is a dedicated system for high precision radiation therapy. However, the field size is limited at 15 cm x 15 cm and shapes by using multi-leaf collimator (MLC) without X-Jaw and Y-Jaw. Therefore VERO-4DRT system is not available to simple wedged irradiation for breast cancer. In this study, we suppose FIF with ring and/or tilt/pan angles whole breast irradiation (FIFWBI). The purpose of this study is to verify the feasibility of FIFWBI with VERO-4DRT system. Methods: As fundamental evaluation, we performed commissioning test with phantom. The absorbed dose evaluation at several reference points and dose distributionmore » including split area were performed. We planned 10 demonstrative shapes in phantom for measuring these contents with i-plan workstation (BrainLAB). As clinical evaluation, the dose distribution and dose indexes were evaluated with actual patient data. Five patients with breast cancer were designed FIFWBI radiotherapy plan with split fields. Then, the dose distribution and dose indexes (including Dmax, Dmin, D95, D5 and Homogeneity index) were evaluated in these plans. Results: As the results of fundamental evaluation, all absorbed dose errors between calculated and measured doses were within 2%. The gamma passing rates with 2 mm/3% criteria in all cases were 96±2%. As the results of clinical evaluation, the values of Dmax, D95, D50, D5, and Homogeneity Index were 41.7±0.90 Gy, 49.4±0.34 Gy, 52.26±0.24 Gy, and 1.39±0.03, respectively. For Japanese breast cancer patients, this technique was feasible. However, the large split region was happened in FIFWBI in case of patient with large breast. Conclusion: We evaluated the FIFWBI technique with VERO-4DRT system. This technique is feasible for Japanese patients, but the patient with large breast should be disagreed with this technique.« less

Assessment of the unattached fraction of indoor radon progeny and its contribution to dose: a pilot study in China.

PubMed

Guo, Qiuju; Zhang, Lei; Guo, Lu

2012-12-01

The unattached fraction of radon progeny (f(p)) is one of the most important factors for accurate evaluation of the effective dose from a unit of radon exposure, and it may vary greatly in different environments. For precise evaluation of the indoor radon exposure dose and the influence of unattached radon progeny, a pilot survey of f(p) in different environments was carried out in China with a portable and integrating monitor. The dose conversion factors for radon progeny are calculated with LUDEP(®) code, and the dose contributions from the unattached and the attached radon progenies were simultaneously evaluated based on the results of field measurements. The results show that even though the concentrations of radon progeny vary significantly among different indoor environments, the variations of f(p) seem relatively small (9.3-16.9%). The dose contribution from unattached radon progeny is generally larger (30.2-46.2%) in an indoor environment.

A Clinical Concept for Interfractional Adaptive Radiation Therapy in the Treatment of Head and Neck Cancer

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

Jensen, Alexandra D., E-mail: Alexandra.Jensen@med.uni-heidelberg.de; Nill, Simeon; Huber, Peter E.

Purpose: To present an approach to fast, interfractional adaptive RT in intensity-modulated radiation therapy (IMRT) of head and neck tumors in clinical routine. Ensuring adequate patient position throughout treatment proves challenging in high-precision RT despite elaborate immobilization. Because of weight loss, treatment plans must be adapted to account for requiring supportive therapy incl. feeding tube or parenteral nutrition without treatment breaks. Methods and Materials: In-room CT position checks are used to create adapted IMRT treatment plans by stereotactic correlation to the initial setup, and volumes are adapted to the new geometry. New IMRT treatment plans are prospectively created on themore » basis of position control scans using the initial optimization parameters in KonRad without requiring complete reoptimization and thus facilitating quick replanning in daily routine. Patients treated for squamous cell head and neck cancer (SCCHN) in 2006-2007 were evaluated as to necessity/number of replannings, weight loss, dose, and plan parameters. Results: Seventy-two patients with SCCHN received IMRT to the primary site and lymph nodes (median dose 70.4 Gy). All patients received concomitant chemotherapy requiring supportive therapy by feeding tube or parenteral nutrition. Median weight loss was 7.8 kg, median volume loss was approximately 7%. Fifteen of 72 patients required adaptation of their treatment plans at least once. Target coverage was improved by up to 10.7% (median dose). The increase of dose to spared parotid without replanning was 11.7%. Replanning including outlining and optimization was feasible within 2 hours for each patient, and treatment could be continued without any interruptions. Conclusion: To preserve high-quality dose application, treatment plans must be adapted to anatomical changes. Replanning based on position control scans therefore presents a practical approach in clinical routine. In the absence of clinically usable online correction methods, this approach allows significant improvement of target volume coverage and continuous parotid sparing without treatment delays.« less

A clinical concept for interfractional adaptive radiation therapy in the treatment of head and neck cancer.

PubMed

Jensen, Alexandra D; Nill, Simeon; Huber, Peter E; Bendl, Rolf; Debus, Jürgen; Münter, Marc W

2012-02-01

To present an approach to fast, interfractional adaptive RT in intensity-modulated radiation therapy (IMRT) of head and neck tumors in clinical routine. Ensuring adequate patient position throughout treatment proves challenging in high-precision RT despite elaborate immobilization. Because of weight loss, treatment plans must be adapted to account for requiring supportive therapy incl. feeding tube or parenteral nutrition without treatment breaks. In-room CT position checks are used to create adapted IMRT treatment plans by stereotactic correlation to the initial setup, and volumes are adapted to the new geometry. New IMRT treatment plans are prospectively created on the basis of position control scans using the initial optimization parameters in KonRad without requiring complete reoptimization and thus facilitating quick replanning in daily routine. Patients treated for squamous cell head and neck cancer (SCCHN) in 2006-2007 were evaluated as to necessity/number of replannings, weight loss, dose, and plan parameters. Seventy-two patients with SCCHN received IMRT to the primary site and lymph nodes (median dose 70.4 Gy). All patients received concomitant chemotherapy requiring supportive therapy by feeding tube or parenteral nutrition. Median weight loss was 7.8 kg, median volume loss was approximately 7%. Fifteen of 72 patients required adaptation of their treatment plans at least once. Target coverage was improved by up to 10.7% (median dose). The increase of dose to spared parotid without replanning was 11.7%. Replanning including outlining and optimization was feasible within 2 hours for each patient, and treatment could be continued without any interruptions. To preserve high-quality dose application, treatment plans must be adapted to anatomical changes. Replanning based on position control scans therefore presents a practical approach in clinical routine. In the absence of clinically usable online correction methods, this approach allows significant improvement of target volume coverage and continuous parotid sparing without treatment delays. Copyright © 2012 Elsevier Inc. All rights reserved.

Precision-Cut Liver Slices of Salmo salar as a tool to investigate the oxidative impact of CYP1A-mediated PCB 126 and 3-methylcholanthrene metabolism.

PubMed

Lemaire, Benjamin; Beck, Michaël; Jaspart, Mélanie; Debier, Cathy; Calderon, Pedro Buc; Thomé, Jean-Pierre; Rees, Jean-François

2011-02-01

Fish isolated cell systems have long been used to predict in vivo toxicity of man-made chemicals. In present study, we tested the suitability of Precision-Cut Liver Slices (PCLS) as an alternative to these models that allows the evaluation of a global tissue response to toxicants, to investigate oxidative stress response to cytochrome P450 1A (CYP1A) induction in fish liver. PCLS of Salmo salar were exposed for 21 h to increasing doses of 3-methylcholanthrene (3-MC) and Polychlorobiphenyl 126 (PCB 126). 3-MC (25 μM) strongly induced CYP1A transcription. In dose-response analysis (25-100 μM), EROD activity was strongly increased at intermediate 3-MC concentrations. We found the counter-intuitive decline of EROD at the highest 3-MC doses to result from reversible competition with ethoxyresorufin. No increases of H(2)O(2) production, antioxidant enzymes activities or oxidative damage to lipids were found with 3-MC treatments. PCLS subjected to PCB 126 (2-200 nM) showed increased contamination levels and a parallel increased CYP1A mRNA synthesis and EROD activity. H(2)O(2) production tended to increase but no oxidative damage to lipids was found. As antioxidant enzymes activities declined at the highest PCB 126 dose, it is suggested that longer incubation periods could be required to generate oxidative stress in PCLS. Copyright © 2010 Elsevier Ltd. All rights reserved.

QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. © 2016 Society for Risk Analysis.

Conformal image-guided microbeam radiation therapy at the ESRF biomedical beamline ID17

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

Donzelli, Mattia, E-mail: donzelli@esrf.fr; Bräuer-Krisch, Elke; Nemoz, Christian

Purpose: Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target. Methods: This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles. Results: Usingmore » four external fiducial markers of 1.7  mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2  mm can be achieved with an angular deviation of less than 2{sup ∘}. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1  mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam. Conclusions: The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials.« less

Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.

PubMed

Anandi, Prathima; Tian, Xin; Ito, Sawa; Muranski, Pawel; Chokshi, Puja D; Watters, Noelle; Chawla, Upneet; Hensel, Nancy; Stroncek, David F; Battiwalla, Minoo; Barrett, A John

2017-06-01

T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10 4 /kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10 7 /kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT. Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy). Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse. Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients. Published by Elsevier Inc.

Oncentra brachytherapy planning system.

PubMed

Yang, Jack

2018-03-27

In modern cancer management, treatment planning has progressed as a contemporary tool with all the advances in computing power in recent years. One of the advanced planning tools uses 3-dimensional (3D) data sets for accurate dose distributions in patient prescription. Among these planning processes, brachytherapy has been a very important part of a successful cancer management program, offering clinical benefits with specific or combined treatments with external beam therapy. In this chapter, we mainly discussed the Elekta Oncentra planning system, which is the main treatment planning tool for high-dose rate (HDR) modality in our facility and in many other facilities in the United States. HDR is a technically advanced form of brachytherapy; a high-intensity radiation source (3.6 mm in length) is delivered with step motor in submillimeter precision under computer guidance directly into the tumor areas while minimizing injury to surrounding normal healthy tissue. Oncentra planning is the key component to generate a deliverable brachytherapy procedure, which is executed on the microSelectron V3 remote afterloader treatment system. Creating a highly conformal plan can be a time-consuming task. The development of Oncentra software (version 4.5.3) offers a variety of useful tools that facilitate many of the clinical challenging tasks for planning, such as contouring and image reconstruction, as well as rapid planning calculations with dose and dose volume histogram analysis. Oncentra Brachy module creates workflow and optimizes the planning accuracy for wide varieties of clinical HDR treatments, such as skin, gynecologic (GYN), breast, prostate, and many other applications. The treatment file can also be transferred to the afterloader control station for speedy delivery. The design concept, calculation algorithms, and optimization modules presented some key characteristics to plan and treat the patients effectively and accurately. The dose distribution and accuracy of several clinical sample cases were discussed to illustrate the effectiveness and clinical efficacy. The American Association of Physicists in Medicine brachytherapy reports of TG-43 and TG-186 were also described and compared in evaluations of fundamental calculation methodologies. Copyright © 2018 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PubMed

Mazeron, Renaud; Castelnau-Marchand, Pauline; Escande, Alexandre; Rivin Del Campo, Eleonor; Maroun, Pierre; Lefkopoulos, Dimitri; Chargari, Cyrus; Haie-Meder, Christine

2016-01-01

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Dynamic modulated brachytherapy (DMBT) and intensity modulated brachytherapy (IMBT) for the treatment of rectal and breast carcinomas

NASA Astrophysics Data System (ADS)

Webster, Matthew Julian

The ultimate goal of any treatment of cancer is to maximize the likelihood of killing the tumor while minimizing the chance of damaging healthy tissues. One of the most effective ways to accomplish this is through radiation therapy, which must be able to target the tumor volume with a high accuracy while minimizing the dose delivered to healthy tissues. A successful method of accomplishing this is brachytherapy which works by placing the radiation source in very close proximity to the tumor. However, most current applications of brachytherapy rely mostly on the geometric manipulation of isotropic sources, which limits the ability to specifically target the tumor. The purpose of this work is to introduce several types of shielded brachytherapy applicators which are capable of targeting tumors with much greater accuracy than existing technologies. These applicators rely on the modulation of the dose profile through a high-density tungsten alloy shields to create anisotropic dose distributions. Two classes of applicators have been developed in this work. The first relies on the active motion of the shield, to aim a highly directional radiation profile. This allows for very precise control of the dose distribution for treatment, achieving unparalleled dose coverage to the tumor while sparing healthy tissues. This technique has been given the moniker of Dynamic Modulated Brachytherapy (DMBT). The second class of applicators, designed to reduce treatment complexity uses static applicators. These applicators retain the use of the tungsten shield, but the shield is motionless during treatment. By intelligently designing the shield, significant improvements over current methods have been demonstrated. Although these static applicators fail to match the dosimetric quality of DMBT applicators the simplified setup and treatment procedure gives them significant appeal. The focus of this work has been to optimize these shield designs, specifically for the treatment of rectal and breast carcinomas. The use of Monte Carlo methods and development of optimization algorithms have played a prominent role in accomplishing this. The use of shielded applicators, such as the ones described here, is the next logical step in the rapidly evolving field of brachytherapy.

Pencil-beam redefinition algorithm dose calculations for electron therapy treatment planning

NASA Astrophysics Data System (ADS)

Boyd, Robert Arthur

2001-08-01

The electron pencil-beam redefinition algorithm (PBRA) of Shiu and Hogstrom has been developed for use in radiotherapy treatment planning (RTP). Earlier studies of Boyd and Hogstrom showed that the PBRA lacked an adequate incident beam model, that PBRA might require improved electron physics, and that no data existed which allowed adequate assessment of the PBRA-calculated dose accuracy in a heterogeneous medium such as one presented by patient anatomy. The hypothesis of this research was that by addressing the above issues the PBRA-calculated dose would be accurate to within 4% or 2 mm in regions of high dose gradients. A secondary electron source was added to the PBRA to account for collimation-scattered electrons in the incident beam. Parameters of the dual-source model were determined from a minimal data set to allow ease of beam commissioning. Comparisons with measured data showed 3% or better dose accuracy in water within the field for cases where 4% accuracy was not previously achievable. A measured data set was developed that allowed an evaluation of PBRA in regions distal to localized heterogeneities. Geometries in the data set included irregular surfaces and high- and low-density internal heterogeneities. The data was estimated to have 1% precision and 2% agreement with accurate, benchmarked Monte Carlo (MC) code. PBRA electron transport was enhanced by modeling local pencil beam divergence. This required fundamental changes to the mathematics of electron transport (divPBRA). Evaluation of divPBRA with the measured data set showed marginal improvement in dose accuracy when compared to PBRA; however, 4% or 2mm accuracy was not achieved by either PBRA version for all data points. Finally, PBRA was evaluated clinically by comparing PBRA- and MC-calculated dose distributions using site-specific patient RTP data. Results show PBRA did not agree with MC to within 4% or 2mm in a small fraction (<3%) of the irradiated volume. Although the hypothesis of the research was shown to be false, the minor dose inaccuracies should have little or no impact on RTP decisions or patient outcome. Therefore, given ease of beam commissioning, documentation of accuracy, and calculational speed, the PBRA should be considered a practical tool for clinical use.

Creating Ruddlesden-Popper phases by hybrid molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Haislmaier, Ryan C.; Stone, Greg; Alem, Nasim; Engel-Herbert, Roman

2016-07-01

The synthesis of a 50 unit cell thick n = 4 Srn+1TinO3n+1 (Sr5Ti4O13) Ruddlesden-Popper (RP) phase film is demonstrated by sequentially depositing SrO and TiO2 layers in an alternating fashion using hybrid molecular beam epitaxy (MBE), where Ti was supplied using titanium tetraisopropoxide (TTIP). A detailed calibration procedure is outlined for determining the shuttering times to deposit SrO and TiO2 layers with precise monolayer doses using in-situ reflection high energy electron diffraction (RHEED) as feedback. Using optimized Sr and TTIP shuttering times, a fully automated growth of the n = 4 RP phase was carried out over a period of >4.5 h. Very stable RHEED intensity oscillations were observed over the entire growth period. The structural characterization by X-ray diffraction and high resolution transmission electron microscopy revealed that a constant periodicity of four SrTiO3 perovskite unit cell blocks separating the double SrO rocksalt layer was maintained throughout the entire film thickness with a very little amount of planar faults oriented perpendicular to the growth front direction. These results illustrate that hybrid MBE is capable of layer-by-layer growth with atomic level precision and excellent flux stability.

Electromagnetic tracking (EMT) technology for improved treatment quality assurance in interstitial brachytherapy.

PubMed

Kellermeier, Markus; Herbolzheimer, Jens; Kreppner, Stephan; Lotter, Michael; Strnad, Vratislav; Bert, Christoph

2017-01-01

Electromagnetic Tracking (EMT) is a novel technique for error detection and quality assurance (QA) in interstitial high dose rate brachytherapy (HDR-iBT). The purpose of this study is to provide a concept for data acquisition developed as part of a clinical evaluation study on the use of EMT during interstitial treatment of breast cancer patients. The stability, accuracy, and precision of EMT-determined dwell positions were quantified. Dwell position reconstruction based on EMT was investigated on CT table, HDR table and PDR bed to examine the influence on precision and accuracy in a typical clinical workflow. All investigations were performed using a precise PMMA phantom. The track of catheters inserted in that phantom was measured by manually inserting a 5 degree of freedom (DoF) sensor while recording the position of three 6DoF fiducial sensors on the phantom surface to correct motion influences. From the corrected data, dwell positions were reconstructed along the catheter's track. The accuracy of the EMT-determined dwell positions was quantified by the residual distances to reference dwell positions after using a rigid registration. Precision and accuracy were investigated for different phantom-table and sensor-field generator (FG) distances. The measured precision of the EMT-determined dwell positions was ≤ 0.28 mm (95th percentile). Stability tests showed a drift of 0.03 mm in the first 20 min of use. Sudden shaking of the FG or (large) metallic objects close to the FG degrade the precision. The accuracy with respect to the reference dwell positions was on all clinical tables < 1 mm at 200 mm FG distance and 120 mm phantom-table distance. Phantom measurements showed that EMT-determined localization of dwell positions in HDR-iBT is stable, precise, and sufficiently accurate for clinical assessment. The presented method may be viable for clinical applications in HDR-iBT, like implant definition, error detection or quantification of uncertainties. Further clinical investigations are needed. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Dosimetric and clinical experience in eye proton treatment at INFN-LNS

NASA Astrophysics Data System (ADS)

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Lojacono, P.; Mongelli, V.; Lo Nigro, S.; Ott, J.; Patti, I. V.; Pittera, S.; Privitera, G.; Raffaele, L.; Reibaldi, A.; Russo, G.; Salamone, V.; Sabini, M. G.; Spatola, C.; Valastro, L. M.

2009-05-01

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged us in our activity in the battle against cancer

A Simple Approach to the Technical Aspects of Radiosurgery Treatments

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

Prasad, S.C.; Bassano, D.A.; King, G.A.

2015-01-15

An approach to radiosurgery treatment that can be readily adopted in most radiotherapy centers with linear accelerators is presented. In our institution, a Leksell-type of neurosurgical frame, a computed tomography scanner, locally fabricated cones, and 6 MV X-ray beams are used to perform radiosurgery treatments. Collimated arcs with dose distributions that conform to the shape of the lesion in the transverse and the sagittal planes are used. It is argued that the uncertainties in the localization of the isocenter within a lesion and the specifications of the size of the target volume do not justify high precision mechanical devices formore » most radiosurgery treatments.« less

Two complementary fluorimetric assays for the determination of aminoquinoline binding and uptake by human erythrocytes in vitro.

PubMed

Basilico, Nicoletta; Cortelezzi, Lucia; Serpellini, Chiara; Taramelli, Donatella; Omodeo-Salè, Fausta; Salè, Fausta

2009-02-15

We provide two simple low-cost and low-tech procedures to measure with good precision and accuracy the binding and internalization into human erythrocytes of chloroquine and other aminoquinolines. The methods are based on the high fluorescence of the quinoline ring and are complementary. Method A evaluates residual drugs in the supernatants of treated erythrocytes, whereas method B quantifies the total uptake by whole cells and the fraction bound to the membranes. Drug uptake is dose dependent and related to the number of erythrocytes. These assays could be useful when studying the cell interaction of quinoline-type compounds not available in the radioactive form.

Present challenges in hadrontherapy techniques

NASA Astrophysics Data System (ADS)

Amaldi, U.; Braccini, S.

2011-07-01

Hadrontherapy is a high-precision technique in cancer radiation therapy, which allows obtaining a superior conformal treatment with respect to photons used in conventional radiation therapy. To reach this ambitious goal without reducing the patient throughput needed in a hospital-based environment, the physical and radiobiological properties of charged hadrons, protons and carbon ions in particular, have to be exploited at best, making use of the most modern technologies issued from research in nuclear and particle physics. In the present days, we are assisting to a continuous technological challenge, leading to the conception and to the development of innovative methods and instruments. In this paper, the most relevant challenges in dose delivery systems, gantries, imaging, quality assurance and particle accelerators are reviewed.

Clinical application of pharmacogenetics: focusing on practical issues.

PubMed

Chang, Matthew T; McCarthy, Jeanette J; Shin, Jaekyu

2015-01-01

Recent large-scale genetic-based studies have transformed the field of pharmacogenetics to identify, characterize and leverage genetic information to inform patient care. Genetic testing can be used to alter drug selection, optimize drug dosing and prevent unnecessary adverse events. As precision medicine becomes the mainstay in the clinic, it becomes critical for clinicians to utilize pharmacogenetics to guide patient care. One primary challenge is identifying patients where genetic tests that can potentially impact patient care. To address this challenge, our review highlights many practical issues clinicians may encounter: identifying candidate patients and clinical laboratories for pharmacogenetic testing, selecting highly curated resources to help asses test validity, reimbursing costs of pharmacogenetic tests, and interpreting of pharmacogenetic test results.

The Challenges of Precision Medicine in COPD.

PubMed

Cazzola, Mario; Calzetta, Luigino; Rogliani, Paola; Matera, Maria Gabriella

2017-08-01

Pheno-/endotyping chronic obstructive pulmonary disease (COPD) is really important because it provides patients with precise and personalized medicine. The central concept of precision medicine is to take individual variability into account when making management decisions. Precision medicine should ensure that patients get the right treatment at the right dose at the right time, with minimum harmful consequences and maximum efficacy. Ideally, we should search for genetic and molecular biomarker-based profiles. Given the clinical complexity of COPD, it seems likely that a panel of several biomarkers will be required to characterize pathogenetic factors and their course over time. The need for biomarkers to guide the clinical care of individuals with COPD and to enhance the possibilities of success in drug development is clear and urgent, but biomarker development is tremendously challenging and expensive, and translation of research efforts to date has been largely ineffective. Furthermore, the development of personalized treatments will require a much more detailed understanding of the clinical and biological heterogeneity of COPD. Therefore, we are still far from being able to apply precision medicine in COPD and the treatable traits and FEV 1 -free approaches are attempts to precision medicine in COPD that must be considered still quite unsophisticated.

Fully automated lobe-based airway taper index calculation in a low dose MDCT CF study over 4 time-points

NASA Astrophysics Data System (ADS)

Weinheimer, Oliver; Wielpütz, Mark O.; Konietzke, Philip; Heussel, Claus P.; Kauczor, Hans-Ulrich; Brochhausen, Christoph; Hollemann, David; Savage, Dasha; Galbán, Craig J.; Robinson, Terry E.

2017-02-01

Cystic Fibrosis (CF) results in severe bronchiectasis in nearly all cases. Bronchiectasis is a disease where parts of the airways are permanently dilated. The development and the progression of bronchiectasis is not evenly distributed over the entire lungs - rather, individual functional units are affected differently. We developed a fully automated method for the precise calculation of lobe-based airway taper indices. To calculate taper indices, some preparatory algorithms are needed. The airway tree is segmented, skeletonized and transformed to a rooted acyclic graph. This graph is used to label the airways. Then a modified version of the previously validated integral based method (IBM) for airway geometry determination is utilized. The rooted graph, the airway lumen and wall information are then used to calculate the airway taper indices. Using a computer-generated phantom simulating 10 cross sections of airways we present results showing a high accuracy of the modified IBM. The new taper index calculation method was applied to 144 volumetric inspiratory low-dose MDCT scans. The scans were acquired from 36 children with mild CF at 4 time-points (baseline, 3 month, 1 year, 2 years). We found a moderate correlation with the visual lobar Brody bronchiectasis scores by three raters (r2 = 0.36, p < .0001). The taper index has the potential to be a precise imaging biomarker but further improvements are needed. In combination with other imaging biomarkers, taper index calculation can be an important tool for monitoring the progression and the individual treatment of patients with bronchiectasis.

Radiologic methods of evaluating generalized osteopenia

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

Schneider, R.

1984-10-01

Noninvasive methods of evaluating generalized osteopenia include radiography, radionuclide studies, and various quantitative studies. These methods differ in availability, cost, accuracy, precision, radiation dose, and information supplied about bony change. A combination of methods is necessary to detect and follow the course and treatment of osteopenia.

MONDO: A tracker for the characterization of secondary fast and ultrafast neutrons emitted in particle therapy

NASA Astrophysics Data System (ADS)

Mirabelli, R.; Battistoni, G.; Giacometti, V.; Patera, V.; Pinci, D.; Sarti, A.; Sciubba, A.; Traini, G.; Marafini, M.

2018-01-01

In Particle Therapy (PT) accelerated charged particles and light ions are used for treating tumors. One of the main limitation to the precision of PT is the emission of secondary particles due to the beam interaction with the patient: secondary emitted neutrons can release a significant dose far from the tumor. Therefore, a precise characterization of their flux, production energy and angle distribution is eagerly needed in order to improve the Treatment Planning Systems (TPS) codes. The principal aim of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is the development of a tracking device optimized for the detection of fast and ultra-fast secondary neutrons emitted in PT. The detector consists of a matrix of scintillating square fibres coupled with a CMOS-based readout. Here, we present the characterization of the detector tracker prototype and CMOS-based digital SPAD (Single Photon Avalanche Diode) array sensor tested with protons at the Beam Test Facility (Frascati, Italy) and at the Proton Therapy Centre (Trento, Italy), respectively.

In situ ion-beam-induced luminescence analysis for evaluating a micrometer-scale radio-photoluminescence glass dosimeter

NASA Astrophysics Data System (ADS)

Kawabata, Shunsuke; Kada, Wataru; Parajuli, Raj Kumar; Matsubara, Yoshinori; Sakai, Makoto; Miura, Kenta; Satoh, Takahiro; Koka, Masashi; Yamada, Naoto; Kamiya, Tomihiro; Hanaizumi, Osamu

2016-06-01

Micrometer-scale responses of radio-photoluminescence (RPL) glass dosimeters to focused ionized particle radiation were evaluated by combining ion-beam-induced luminescence (IBIL) and proton beam writing (PBW) using a 3 MeV focused proton microbeam. RPL phosphate glass dosimeters doped with ionic Ag or Cu activators at concentrations of 0.2 and 0.1% were fabricated, and their scintillation intensities were evaluated by IBIL spectroscopy under a PBW micropatterning condition. Compared with the Ag-doped dosimeter, the Cu-doped dosimeter was more tolerant of the radiation, while the peak intensity of its luminescence was lower, under the precise dose control of the proton microprobe. Proton-irradiated areas were successfully recorded using these dosimeters and their RPL centers were visualized under 375 nm ultraviolet light. The reproduction of the irradiated region by post-RPL imaging suggests that precise estimation of irradiation dose using microdosimeters can be accomplished by optimizing RPL glass dosimeters for various proton microprobe applications in organic material analysis and in micrometer-scale material modifications.

Are Evidence Standards Different for Genomic- vs. Clinical-Based Precision Medicine? A Quantitative Analysis of Individualized Warfarin Therapy.

PubMed

Dhanda, D S; Guzauskas, G F; Carlson, J J; Basu, A; Veenstra, D L

2017-11-01

Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics: value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic vs. amiodarone-warfarin drug-drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research. Over the past decade, the EVPI for the pharmacogenomic strategy decreased from $1,550 to $140 vs. $1,220 to $280 per patient for the drug-interaction strategy. Evidence levels thus appear to be higher for pharmacogenomic-guided vs. drug-interaction-guided warfarin dosing. Clinical guidelines and reimbursement policies for warfarin PM could be informed by these findings. © 2017 American Society for Clinical Pharmacology and Therapeutics.

High-performance liquid chromatography post-column derivatization with fluorescence detection to study the influence of ambroxol on dipalmitoylphosphatidylcholine levels in rabbit eustachian tube washings.

PubMed

Kitsos, M; Gandini, C; Massolini, G; De Lorenzi, E; Caccialanza, G

1991-08-16

In this work an appropriate high-performance liquid chromatography method was set up to guarantee specificity, sensitivity, precision and accuracy in analyzing dipalmitoylphosphatidylcholine (DPPC) in rabbit eustachian tube washings, as well as to determine its varying levels after administration of ambroxol chloride. The procedure is based on a post-column derivatization with fluorescence detection using 1,6-diphenyl-1,3,5-hexatriene which exhibits increased fluorescence in a lipid environment. DPPC was chromatographed on a Hypersil C18. The mobile phase for the isocratic elution consisted of 40 mmol/l choline chloride in methanol-tetrahydrofuran (97:3). Ambroxol was given to a group of New Zealand white rabbits at a dose of 30 mg/kg. A second group receiving vehicle only acted as controls.

Influence of functionalized silicones on hair fiber-fiber interactions and on the relationship with the macroscopic behavior of hair assembly.

PubMed

Dussaud, Anne; Fieschi-Corso, Lara

2009-01-01

It is well established that silicones alter hair surface properties and that silicones have a significant impact on the macroscopic behavior of hair assembly, such as visual appearance, combing performance and manageability of the hair. In order to fine-tune the chemistry of functionlized silicones for specific consumer benefits and hair types, we investigated the influence of silicones on hair fiber-fiber interactions and their correlation to hair volume. The incline plane fiber loop method, implemented with a high-precision motorized rotary stage, was used to quantify the fiber-fiber interactions. Low load static friction was studied as a function of polymer molecular weight, dose and chemical architecture. This information was related to the macroscopic behavior of hair assembly, using virgin curly hair in high humidity.

N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

PubMed

Norwood, Daniel L; Mullis, James O; Feinberg, Thomas N; Davis, Letha K

2009-01-01

N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform

PubMed Central

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2011-01-01

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP’s treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min−1 at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth–dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5–7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important. PMID:19687532

Extraction of depth-dependent perturbation factors for silicon diodes using a plastic scintillation detector.

PubMed

Lacroix, Frederic; Guillot, Mathieu; McEwen, Malcolm; Gingras, Luc; Beaulieu, Luc

2011-10-01

This work presents the experimental extraction of the perturbation factor in megavoltage electron beams for three models of silicon diodes (IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded) using a plastic scintillation detector (PSD). The authors used a single scanning PSD mounted on a high-precision scanning tank to measure depth-dose curves in 6-, 12-, and 18-MeV clinical electron beams. They also measured depth-dose curves using the IBA Dosimetry, EFD and SFD, and the PTW 60012 unshielded diodes. The authors used the depth-dose curves measured with the PSD as a perturbation-free reference to extract the perturbation factors of the diodes. The authors found that the perturbation factors for the diodes increased substantially with depth, especially for low-energy electron beams. The experimental results show the same trend as published Monte Carlo simulation results for the EFD diode; however, the perturbations measured experimentally were greater. They found that using an effective point of measurement (EPOM) placed slightly away from the source reduced the variation of perturbation factors with depth and that the optimal EPOM appears to be energy dependent. The manufacturer recommended EPOM appears to be incorrect at low electron energy (6 MeV). In addition, the perturbation factors for diodes may be greater than predicted by Monte Carlo simulations.

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform.

PubMed

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2009-09-07

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min(-1) at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth-dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5-7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important.

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

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans.

PubMed

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q; Otrakji, Alexi; Kalra, Mannudeep K; Xu, X George; Liu, Bob

2014-09-01

To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8%-25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2±3.3 and 16.5±2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.

Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields

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

Livingstone, Jayde, E-mail: Jayde.Livingstone@sync

Purpose: Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. Methods: Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence ofmore » the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30–120 keV. The dose-rate dependence was measured in the range 1–700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. Results: The detector exhibits an energy dependence; however, beam quality correction factors (k{sub Q}) have been measured for energies in the range 30–120 keV. The k{sub Q} factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1–700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. Conclusions: The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.« less

Defining Action Levels for In Vivo Dosimetry in Intraoperative Electron Radiotherapy.

PubMed

López-Tarjuelo, Juan; Morillo-Macías, Virginia; Bouché-Babiloni, Ana; Ferrer-Albiach, Carlos; Santos-Serra, Agustín

2016-06-01

In vivo dosimetry is recommended in intraoperative electron radiotherapy (IOERT). To perform real-time treatment monitoring, action levels (ALs) have to be calculated. Empirical approaches based on observation of samples have been reported previously, however, our aim is to present a predictive model for calculating ALs and to verify their validity with our experimental data. We considered the range of absorbed doses delivered to our detector by means of the percentage depth dose for the electron beams used. Then, we calculated the absorbed dose histograms and convoluted them with detector responses to obtain probability density functions in order to find ALs as certain probability levels. Our in vivo dosimeters were reinforced TN-502RDM-H mobile metal-oxide-semiconductor field-effect transistors (MOSFETs). Our experimental data came from 30 measurements carried out in patients undergoing IOERT for rectal, breast, sarcoma, and pancreas cancers, among others. The prescribed dose to the tumor bed was 90%, and the maximum absorbed dose was 100%. The theoretical mean absorbed dose was 90.3% and the measured mean was 93.9%. Associated confidence intervals at P = .05 were 89.2% and 91.4% and 91.6% and 96.4%, respectively. With regard to individual comparisons between the model and the experiment, 37% of MOSFET measurements lay outside particular ranges defined by the derived ALs. Calculated confidence intervals at P = .05 ranged from 8.6% to 14.7%. The model can describe global results successfully but cannot match all the experimental data reported. In terms of accuracy, this suggests an eventual underestimation of tumor bed bleeding or detector alignment. In terms of precision, it will be necessary to reduce positioning uncertainties for a wide set of location and treatment postures, and more precise detectors will be required. Planning and imaging tools currently under development will play a fundamental role. © The Author(s) 2015.

Monitor unit settings for intensity modulated beams delivered using a step-and-shoot approach.

PubMed

Sharpe, M B; Miller, B M; Yan, D; Wong, J W

2000-12-01

Two linear accelerators have been commissioned for delivering IMRT treatments using a step-and-shoot approach. To assess beam startup stability for 6 and 18 MV x-ray beams, dose delivered per monitor unit (MU), beam flatness, and beam symmetry were measured as a function of the total number of MU delivered at a clinical dose rate of 400 MU per minute. Relative to a 100 MU exposure, the dose delivered per MU by both linear accelerators was found to be within +/-2% for exposures larger than 4 MU. Beam flatness and symmetry also met accepted quality assurance standards for a minimum exposure of 4 MU. We have found that the performance of the two machines under study is well suited to the delivery of step-and-shoot IMRT. A system of dose calculation has also been commissioned for applying head scatter corrections to fields as small as 1x1 cm2. The accuracy and precision of the relative output calculations in water was validated for small fields and fields offset from the axis of collimator rotation. For both 6 and 18 MV x-ray beams, the dose per MU calculated in a water phantom agrees with measured data to within 1% on average, with a maximum deviation of 2.5%. The largest output factor discrepancies were seen when the actual radiation field size deviated from the set field size. The measured output in water can vary by as much 16% for 1x1 cm2 fields, when the measured field size deviates from the set field size by 2 mm. For a 1 mm deviation, this discrepancy was reduced to 8%. Steps should be taken to ensure collimator precision is tightly controlled when using such small fields. If this is not possible, very small fields should not contribute to a significant portion of the treatment, or uncertainties in the collimator position may effect the accuracy of the dose delivered.

Surface and buildup dose characteristics for 6, 10, and 18 MV photons from an Elekta Precise linear accelerator.

PubMed

Klein, Eric E; Esthappan, Jacqueline; Li, Zuofeng

2003-01-01

Understanding head scatter characteristics of photon beams is vital to properly commission treatment planning (TP) algorithms. Simultaneously, having definitive surface and buildup region dosimetry is important to optimize bolus. The Elekta Precise linacs have unique beam flattening filter configurations for each photon beam (6, 10, and 18 MV) in terms of material and location. We performed a comprehensive set of surface and buildup dose measurements with a thin window parallel-plate (PP) chamber to examine effects of field size (FS), source-to-skin distance (SSD), and attenuating media. Relative ionization data were converted to fractional depth dose (FDD) after correcting for bias effects and using the Gerbi method to account for chamber characteristics. Data were compared with a similar vintage Varian linac. At short SSDs the surface and buildup dose characteristics were similar to published data for Varian and Elekta accelerators. The FDD at surface (FDD(0)) for 6, 10, and 18 MV photons was 0.171, 0.159, and 0.199, respectively, for a 15x15 cm2, 100 cm SSD field. A blocking tray increased FDD(0) to 0.200, 0.200, and 0.256, while the universal wedge decreased FDD(0) to 0.107, 0.124, and 0.176. FDD(0) increased linearly with FS (approximately 1.16%/cm). FDD(0) decreased exponentially for 10 and 18 MV with increasing SSD. However, the 6 MV FDD(0) actually increased slightly with increasing SSD. This is likely due to the unique distal flattening filter for 6 MV. The measured buildup curves have been used to optimize TP calculations and guide bolus decisions. Overall the FDD(0) and buildup doses were very similar to published data. Of interest were the relatively low 10 MV surface doses, and the 6 MV FDD(0)'s dependence on SSD.

Disruptions in effort-based decision-making and consummatory behavior following antagonism of the dopamine D2 receptor.

PubMed

Robles, Cindee F; Johnson, Alexander W

2017-03-01

Dopamine is known to influence motivational processes, however the precise role of this neurotransmitter remains a contentious issue. In the current study we sought to further characterize dopamine signaling in reward-based decision-making and consummatory behavior in mice, via lateral ventricle infusion of the dopamine D2 receptor antagonist eticlopride. In Experiment 1, we examined effort-based decision-making, in which mice had a choice between one lever, where a single response led to the delivery of a low value reward (2% sucrose); and a second lever, which led to a higher value reward (20% sucrose) that gradually required more effort to obtain. As the response schedule for the high value reward became more strict, low dose (4μg in 0.5μl) central infusions of eticlopride biased preference away from the high value reward, and toward the lever that led to the low value reward. Similarly, a higher dose of eticlopride (8μg in 0.5μl) also disrupted choice responding for the high value reward, however it did so by increasing omissions. In Experiment 2, we assessed the effects of eticlopride on consumption of 20% sucrose. The antagonist led to a dose-dependent reduction in intake, and through an analysis of licking microstructure, it was revealed that this in part reflected a reduction in the motivation to engage in consummatory behavior, rather than alterations in the evaluation of the reward. These results suggest that disruptions in D2 receptor signaling reduce the willingness to engage in effortful operant responding and consumption of a desirable outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

MO-C-BRB-00: President’s Symposium: Revitalizing Scientific Excellence: Turning Research Into Clinical Reality Through Translational Research

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

NONE

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-06: Translating NIH / NIBIB funding to clinical reality in quantitative diagnostic imaging

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

Jackson, E.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

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

Yu, C.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-04: The role of the NIH in funding innovations in science and medicine

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

Pettigrew, R.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-03: RSNA President [Diagnostic radiology and radiation oncology

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

Arenson, R.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-01: Introduction [Diagnostic radiology and radiation oncology

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

Boone, J.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

MO-C-BRB-02: ASTRO President [Diagnostic radiology and radiation oncology

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

Minsky, B.

Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, andmore » the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration between medical physicists, radiologists, oncologists, industry representatives, and other stakeholders. The mission of QIBA is to improve the accuracy and practicality of quantitative image-based biomarkers by increasing precision across devices, patients, and time, an essential step in incorporating quantitative imaging biomarkers into radiology practice. Validated quantitative imaging biomarkers are necessary to support precision medicine initiatives, multimodality / multiparametric applications in medicine, treatment planning and response assessment, and radiogenomics applications. Current applications in the QIBA portfolio extend to cancer diagnosis and treatment, pulmonary diseases, and neurological disorders. The overall goal of this symposium is to illustrate the bidirectional exchange between medical research and clinical practice. Revitalizing scientific excellence in clinical medical physics challenges practitioners to identify clinical limitations, which then drive research innovation; research funded by the NIH and other agencies develops technological solutions to these limitations, which are translated to the care environment to ultimately improve clinical practice in radiology and radiation oncology.« less

Tumor detection in mice by measurement of fluorescence decay time matrices

NASA Astrophysics Data System (ADS)

Cubeddu, R.; Pifferi, A.; Taroni, P.; Valentini, G.; Canti, G.

1995-12-01

An intensified CCD video camera has been used to measure the spatial distribution of the fluorescence decay time in tumor-bearing mice sensitized with hematoporphyrin derivative. Mice were injected with five doses of sensitizer, ranging from 0.1 to 10 mg / kg body weight. For any drug dose the decay time of the exogenous fluorescence in the tumor is always significantly longer than in normal tissues. The image created by associating a gray-shade scale to the decay time matrix of each mouse permits a reliable and precise detection of the neoplasia.

Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn.

PubMed

Giaccone, Annie; Zuppa, Athena F; Sood, Beena; Cohen, Meryl S; O'Byrne, Michael L; Moorthy, Ganesh; Mathur, Amit; Kirpalani, Haresh

2017-07-01

Objective  To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design  Randomized, open label pilot study. Setting  Multicenter; level 3 and level 4 neonatal intensive care units. Patients  Six infants ≥34 weeks' gestational age and < 10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention  Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0.2 mcg/kg/minute, and (2) standard dose, 50 mcg/kg bolus followed by 0.5 mcg/kg/minute. Measurements and Main Results  The final structural model was a two-compartment disposition model with interindividual variability estimated on clearance (CL). The estimated value of CL is 7.65 mL/minute/3.4 kg (3.05 mL/minute/kg). The addition of age improved the precision of the CL estimate, and CL increased with chronological age in days. The oxygenation index was highly variable within each participant and improved with time. There were no observed safety concerns in either dosing group. Conclusion  The CL of milrinone in newborns with PPHN is reduced and increases with age. In this pilot study, we did not see significant pharmacodynamic or safety effects associated with drug exposure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Total body calcium analysis using the Ca-12(n, alpha) Ar-37 reaction

NASA Technical Reports Server (NTRS)

Lewellen, T. K.; Nelp, W. B.

1977-01-01

A low dose neutron activation technique was developed to measure total body calcium in vivo. The effort had included development of irradiation and processing facilities and conduction of human studies to determine the accuracy and precision of measurement attainable with the systems.

SU-D-202-01: Functional Lung Avoidance and Response-Adaptive Escalation (FLARE) RT: Feasibility of a Precision Radiation Oncology Strategy

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

Bowen, S; Lee, E; Miyaoka, R

Purpose: NSCLC patient RT is planned without consideration of spatial heterogeneity in lung function or tumor response, which may have contributed to failed uniform dose escalation in a randomized trial. The feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [{sup 99m}Tc]MAA-SPECT/CT perfused lung while redistributing 74Gy within [{sup 18}F]FDG-PET/CT biological target volumes was assessed. Methods: Eight Stage IIB–IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain <20Gy mean lung dose (MLD). Prescriptions included 60Gy to PTV and concomitantmore » boost of 74Gy mean to biological target volumes (BTV=GTV+PET margin) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial TPS via previously reported ROI discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with VMAT, proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination PBS (avoidance) plus VMAT (escalation). Dosimetric differences were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results: PTV and normal tissue objectives were not violated in 24 FLARE RT plans. Population median of mean BTV dose was 73.7Gy (68.5–75.5Gy), mean FDG-PET peak dose was 89.7Gy (73.5–103Gy), MLD was 12.3Gy (7.5–19.6Gy), and perfused MLD was 4.8Gy (0.9–12.1Gy). VMAT achieved higher dose to the FDG-PET peak subvolume (p=0.01), while PBS delivered lower dose to lung (p<0.001). Voxelwise linear correlation between BTV dose and FDG-PET uptake was higher for VMAT (R=0.93) and PBS+VMAT (R=0.94) compared to PBS alone (R=0.89). Conclusion: FLARE RT is feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG-PET dose escalation balances target/normal tissue objective tradeoffs. These results support future testing of FLARE RT safety and efficacy within a precision radiation oncology trial. This work was supported by a Research Scholar grant from the Radiological Society of North American Research & Education Foundation.« less

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

Shiraishi, Satomi; Moore, Kevin L., E-mail: kevinmoore@ucsd.edu

Purpose: To demonstrate knowledge-based 3D dose prediction for external beam radiotherapy. Methods: Using previously treated plans as training data, an artificial neural network (ANN) was trained to predict a dose matrix based on patient-specific geometric and planning parameters, such as the closest distance (r) to planning target volume (PTV) and organ-at-risks (OARs). Twenty-three prostate and 43 stereotactic radiosurgery/radiotherapy (SRS/SRT) cases with at least one nearby OAR were studied. All were planned with volumetric-modulated arc therapy to prescription doses of 81 Gy for prostate and 12–30 Gy for SRS. Using these clinically approved plans, ANNs were trained to predict dose matrixmore » and the predictive accuracy was evaluated using the dose difference between the clinical plan and prediction, δD = D{sub clin} − D{sub pred}. The mean (〈δD{sub r}〉), standard deviation (σ{sub δD{sub r}}), and their interquartile range (IQR) for the training plans were evaluated at a 2–3 mm interval from the PTV boundary (r{sub PTV}) to assess prediction bias and precision. Initially, unfiltered models which were trained using all plans in the cohorts were created for each treatment site. The models predict approximately the average quality of OAR sparing. Emphasizing a subset of plans that exhibited superior to the average OAR sparing during training, refined models were created to predict high-quality rectum sparing for prostate and brainstem sparing for SRS. Using the refined model, potentially suboptimal plans were identified where the model predicted further sparing of the OARs was achievable. Replans were performed to test if the OAR sparing could be improved as predicted by the model. Results: The refined models demonstrated highly accurate dose distribution prediction. For prostate cases, the average prediction bias for all voxels irrespective of organ delineation ranged from −1% to 0% with maximum IQR of 3% over r{sub PTV} ∈ [ − 6, 30] mm. The average prediction error was less than 10% for the same r{sub PTV} range. For SRS cases, the average prediction bias ranged from −0.7% to 1.5% with maximum IQR of 5% over r{sub PTV} ∈ [ − 4, 32] mm. The average prediction error was less than 8%. Four potentially suboptimal plans were identified for each site and subsequent replanning demonstrated improved sparing of rectum and brainstem. Conclusions: The study demonstrates highly accurate knowledge-based 3D dose predictions for radiotherapy plans.« less

Technical Note: Precision and accuracy of a commercially available CT optically stimulated luminescent dosimetry system for the measurement of CT dose index

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

Vrieze, Thomas J.; Sturchio, Glenn M.; McCollough, Cynthia H.

Purpose: To determine the precision and accuracy of CTDI{sub 100} measurements made using commercially available optically stimulated luminescent (OSL) dosimeters (Landaur, Inc.) as beam width, tube potential, and attenuating material were varied. Methods: One hundred forty OSL dosimeters were individually exposed to a single axial CT scan, either in air, a 16-cm (head), or 32-cm (body) CTDI phantom at both center and peripheral positions. Scans were performed using nominal total beam widths of 3.6, 6, 19.2, and 28.8 mm at 120 kV and 28.8 mm at 80 kV. Five measurements were made for each of 28 parameter combinations. Measurements weremore » made under the same conditions using a 100-mm long CTDI ion chamber. Exposed OSL dosimeters were returned to the manufacturer, who reported dose to air (in mGy) as a function of distance along the probe, integrated dose, and CTDI{sub 100}. Results: The mean precision averaged over 28 datasets containing five measurements each was 1.4%{+-} 0.6%, range = 0.6%-2.7% for OSL and 0.08%{+-} 0.06%, range = 0.02%-0.3% for ion chamber. The root mean square (RMS) percent differences between OSL and ion chamber CTDI{sub 100} values were 13.8%, 6.4%, and 8.7% for in-air, head, and body measurements, respectively, with an overall RMS percent difference of 10.1%. OSL underestimated CTDI{sub 100} relative to the ion chamber 21/28 times (75%). After manual correction of the 80 kV measurements, the RMS percent differences between OSL and ion chamber measurements were 9.9% and 10.0% for 80 and 120 kV, respectively. Conclusions: Measurements of CTDI{sub 100} with commercially available CT OSL dosimeters had a percent standard deviation of 1.4%. After energy-dependent correction factors were applied, the RMS percent difference in the measured CTDI{sub 100} values was about 10%, with a tendency of OSL to underestimate CTDI relative to the ion chamber. Unlike ion chamber methods, however, OSL dosimeters allow measurement of the radiation dose profile.« less

Technical Note: Precision and accuracy of a commercially available CT optically stimulated luminescent dosimetry system for the measurement of CT dose index

PubMed Central

Vrieze, Thomas J.; Sturchio, Glenn M.; McCollough, Cynthia H.

2012-01-01

Purpose: To determine the precision and accuracy of CTDI100 measurements made using commercially available optically stimulated luminescent (OSL) dosimeters (Landaur, Inc.) as beam width, tube potential, and attenuating material were varied. Methods: One hundred forty OSL dosimeters were individually exposed to a single axial CT scan, either in air, a 16-cm (head), or 32-cm (body) CTDI phantom at both center and peripheral positions. Scans were performed using nominal total beam widths of 3.6, 6, 19.2, and 28.8 mm at 120 kV and 28.8 mm at 80 kV. Five measurements were made for each of 28 parameter combinations. Measurements were made under the same conditions using a 100-mm long CTDI ion chamber. Exposed OSL dosimeters were returned to the manufacturer, who reported dose to air (in mGy) as a function of distance along the probe, integrated dose, and CTDI100. Results: The mean precision averaged over 28 datasets containing five measurements each was 1.4% ± 0.6%, range = 0.6%–2.7% for OSL and 0.08% ± 0.06%, range = 0.02%–0.3% for ion chamber. The root mean square (RMS) percent differences between OSL and ion chamber CTDI100 values were 13.8%, 6.4%, and 8.7% for in-air, head, and body measurements, respectively, with an overall RMS percent difference of 10.1%. OSL underestimated CTDI100 relative to the ion chamber 21/28 times (75%). After manual correction of the 80 kV measurements, the RMS percent differences between OSL and ion chamber measurements were 9.9% and 10.0% for 80 and 120 kV, respectively. Conclusions: Measurements of CTDI100 with commercially available CT OSL dosimeters had a percent standard deviation of 1.4%. After energy-dependent correction factors were applied, the RMS percent difference in the measured CTDI100 values was about 10%, with a tendency of OSL to underestimate CTDI relative to the ion chamber. Unlike ion chamber methods, however, OSL dosimeters allow measurement of the radiation dose profile. PMID:23127052

Technical note: precision and accuracy of a commercially available CT optically stimulated luminescent dosimetry system for the measurement of CT dose index.

PubMed

Vrieze, Thomas J; Sturchio, Glenn M; McCollough, Cynthia H

2012-11-01

To determine the precision and accuracy of CTDI(100) measurements made using commercially available optically stimulated luminescent (OSL) dosimeters (Landaur, Inc.) as beam width, tube potential, and attenuating material were varied. One hundred forty OSL dosimeters were individually exposed to a single axial CT scan, either in air, a 16-cm (head), or 32-cm (body) CTDI phantom at both center and peripheral positions. Scans were performed using nominal total beam widths of 3.6, 6, 19.2, and 28.8 mm at 120 kV and 28.8 mm at 80 kV. Five measurements were made for each of 28 parameter combinations. Measurements were made under the same conditions using a 100-mm long CTDI ion chamber. Exposed OSL dosimeters were returned to the manufacturer, who reported dose to air (in mGy) as a function of distance along the probe, integrated dose, and CTDI(100). The mean precision averaged over 28 datasets containing five measurements each was 1.4% ± 0.6%, range = 0.6%-2.7% for OSL and 0.08% ± 0.06%, range = 0.02%-0.3% for ion chamber. The root mean square (RMS) percent differences between OSL and ion chamber CTDI(100) values were 13.8%, 6.4%, and 8.7% for in-air, head, and body measurements, respectively, with an overall RMS percent difference of 10.1%. OSL underestimated CTDI(100) relative to the ion chamber 21∕28 times (75%). After manual correction of the 80 kV measurements, the RMS percent differences between OSL and ion chamber measurements were 9.9% and 10.0% for 80 and 120 kV, respectively. Measurements of CTDI(100) with commercially available CT OSL dosimeters had a percent standard deviation of 1.4%. After energy-dependent correction factors were applied, the RMS percent difference in the measured CTDI(100) values was about 10%, with a tendency of OSL to underestimate CTDI relative to the ion chamber. Unlike ion chamber methods, however, OSL dosimeters allow measurement of the radiation dose profile.

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

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

Patwe, P; Mhatre, V; Dandekar, P

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

Biological dosimetry of ionizing radiation: Evaluation of the dose with cytogenetic methodologies by the construction of calibration curves

NASA Astrophysics Data System (ADS)

Zafiropoulos, Demetre; Facco, E.; Sarchiapone, Lucia

2016-09-01

In case of a radiation accident, it is well known that in the absence of physical dosimetry biological dosimetry based on cytogenetic methods is a unique tool to estimate individual absorbed dose. Moreover, even when physical dosimetry indicates an overexposure, scoring chromosome aberrations (dicentrics and rings) in human peripheral blood lymphocytes (PBLs) at metaphase is presently the most widely used method to confirm dose assessment. The analysis of dicentrics and rings in PBLs after Giemsa staining of metaphase cells is considered the most valid assay for radiation injury. This work shows that applying the fluorescence in situ hybridization (FISH) technique, using telomeric/centromeric peptide nucleic acid (PNA) probes in metaphase chromosomes for radiation dosimetry, could become a fast scoring, reliable and precise method for biological dosimetry after accidental radiation exposures. In both in vitro methods described above, lymphocyte stimulation is needed, and this limits the application in radiation emergency medicine where speed is considered to be a high priority. Using premature chromosome condensation (PCC), irradiated human PBLs (non-stimulated) were fused with mitotic CHO cells, and the yield of excess PCC fragments in Giemsa stained cells was scored. To score dicentrics and rings under PCC conditions, the necessary centromere and telomere detection of the chromosomes was obtained using FISH and specific PNA probes. Of course, a prerequisite for dose assessment in all cases is a dose-effect calibration curve. This work illustrates the various methods used; dose response calibration curves, with 95% confidence limits used to estimate dose uncertainties, have been constructed for conventional metaphase analysis and FISH. We also compare the dose-response curve constructed after scoring of dicentrics and rings using PCC combined with FISH and PNA probes. Also reported are dose response curves showing scored dicentrics and rings per cell, combining PCC of lymphocytes and CHO cells with FISH using PNA probes after 10 h and 24 h after irradiation, and, finally, calibration data of excess PCC fragments (Giemsa) to be used if human blood is available immediately after irradiation or within 24 h.

New Directions in Nicotine Vaccine Design and Use

PubMed Central

Pentel, Paul R.; LeSage, Mark G.

2014-01-01

Clinical trials of nicotine vaccines suggest that they can enhance smoking cessation rates but do not reliably produce the consistently high serum antibody concentrations required. A wide array of next-generation strategies are being evaluated to enhance vaccine efficacy or provide antibody through other mechanisms. Protein conjugate vaccines may be improved by modifications of hapten or linker design or by optimizing hapten density. Conjugating hapten to viruslike particles or disrupted virus may allow exploitation of naturally occurring viral features associated with high immunogenicity. Conjugates that utilize different linker positions on nicotine can function as independent immunogens, so that using them in combination generates higher antibody concentrations than can be produced by a single immunogen. Nanoparticle vaccines, consisting of hapten, T cell help peptides, and adjuvants attached to a liposome or synthetic scaffold, are in the early stages of development. Nanoparticle vaccines offer the possibility of obtaining precise and consistent control of vaccine component stoichiometry and spacing and immunogen size and shape. Passive transfer of nicotine-specific monoclonal antibodies offers a greater control of antibody dose, the ability to give very high doses, and an immediate onset of action but is expensive and has a shorter duration of action than vaccines. Viral vector-mediated transfer of genes for antibody production can elicit high levels of antibody expression in animals and may present an alternative to vaccination or passive immunization if the long-term safety of this approach is confirmed. Next-generation immunotherapies are likely to be substantially more effective than first-generation vaccines. PMID:24484987

A method to quantify infectious airborne pathogens at concentrations below the threshold of quantification by culture

PubMed Central

Cutler, Timothy D.; Wang, Chong; Hoff, Steven J.; Zimmerman, Jeffrey J.

2013-01-01

In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT). PMID:24082399

Dose controlled low energy electron irradiator for biomolecular films

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

Kumar, S. V. K., E-mail: svkk@tifr.res.in; Tare, Satej T.; Upalekar, Yogesh V.

2016-03-15

We have developed a multi target, Low Energy Electron (LEE), precise dose controlled irradiator for biomolecular films. Up to seven samples can be irradiated one after another at any preset electron energy and dose under UHV conditions without venting the chamber. In addition, one more sample goes through all the steps except irradiation, which can be used as control for comparison with the irradiated samples. All the samples are protected against stray electron irradiation by biasing them at −20 V during the entire period, except during irradiation. Ethernet based communication electronics hardware, LEE beam control electronics and computer interface weremore » developed in house. The user Graphical User Interface to control the irradiation and dose measurement was developed using National Instruments Lab Windows CVI. The working and reliability of the dose controlled irradiator has been fully tested over the electron energy range of 0.5 to 500 eV by studying LEE induced single strand breaks to ΦX174 RF1 dsDNA.« less

Analyzing U.S. prescription lists with RxNorm and the ATC/DDD Index.

PubMed

Bodenreider, Olivier; Rodriguez, Laritza M

2014-01-01

To evaluate the suitability of the ATC/DDD Index (Anatomical Therapeutic Chemical (ATC) Classification System/Defined Daily Dose) for analyzing prescription lists in the U.S. We mapped RxNorm clinical drugs to ATC. We used this mapping to classify a large set of prescription drugs with ATC and compared the prescribed daily dose to the defined daily dose (DDD) in ATC. 64% of the 11,422 clinical drugs could be precisely mapped to ATC. 97% of the 87,001 RxNorm codes from the prescription dataset could be classified with ATC, and 97% of the prescribed daily doses could be assessed. Although the mapping of RxNorm ingredients to ATC appears to be largely incomplete, the most frequently prescribed drugs in the prescription dataset we analyzed were covered. This study demonstrates the feasibility of using ATC in conjunction with RxNorm for analyzing U.S. prescription datasets for drug classification and assessment of the prescribed daily doses.

Method for preparing dosimeter for measuring skin dose

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1982-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with neutron-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Dosimeter for measuring skin dose and more deeply penetrating radiation

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1981-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Feasibility study of proton-based quality assurance of proton range compensator

NASA Astrophysics Data System (ADS)

Park, S.; Jeong, C.; Min, B. J.; Kwak, J.; Lee, J.; Cho, S.; Shin, D.; Lim, Y. K.; Park, S. Y.; Lee, S. B.

2013-06-01

All patient specific range compensators (RCs) are customized for achieving distal dose conformity of target volume in passively scattered proton therapy. Compensators are milled precisely using a computerized machine. In proton therapy, precision of the compensator is critical and quality assurance (QA) is required to protect normal tissues and organs from radiation damage. This study aims to evaluate the precision of proton-based quality assurance of range compensator. First, the geometry information of two compensators was extracted from the DICOM Radiotherapy (RT) plan. Next, RCs were irradiated on the EBT film individually by proton beam which is modulated to have a photon-like percent depth dose (PDD). Step phantoms were also irradiated on the EBT film to generate calibration curve which indicates relationship between optical density of irradiated film and perpendicular depth of compensator. Comparisons were made using the mean absolute difference (MAD) between coordinate information from DICOM RT and converted depth information from the EBT film. MAD over the whole region was 1.7, and 2.0 mm. However, MAD over the relatively flat regions on each compensator selected for comparison was within 1 mm. These results shows that proton-based quality assurance of range compensator is feasible and it is expected to achieve MAD over the whole region less than 1 mm with further correction about scattering effect of proton imaging.

Determination of the structural phase and octahedral rotation angle in halide perovskites

DOE PAGES

dos Reis, Roberto; Yang, Hao; Ophus, Colin; ...

2018-02-12

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr 3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr 3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurementmore » of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). Finally, the approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.« less

Mobile-Dose: A Dose-Meter Designed for Use in Automatic Machineries for Dose Manipulation in Nuclear Medicine

NASA Astrophysics Data System (ADS)

de Asmundis, Riccardo; Boiano, Alfonso; Ramaglia, Antonio

2008-06-01

Mobile-Dose has been designed for a very innovative use: the integration in a robotic machinery for automatic preparation of radioactive doses, to be injected to patients in Nuclear Medicine Departments, with real time measurement of the activity under preparation. Mobile-Dose gives a constant measurement of the dose during the filling of vials or syringes, triggering the end of the filling process based on a predefined dose limit. Several applications of Mobile-Dose have been delivered worldwide, from Italian hospitals and clinics to European and Japanese ones. The design of such an instrument and its integration in robotic machineries, was required by an Italian company specialised in radiation protection tools for nuclear applications, in the period 2001-2003. At the time of its design, apparently no commercial instruments with a suitable interfacing capability to the external world existed: we designed it in order to satisfy all the strict requirements coming from the medical aspects (precision within 10%, repeatability, stability, time response) and from the industrial conceiving principles that are mandatory to ensure a good reliability in such a complicated environment. The instrument is suitable to be used in standalone mode too, thanks to its portability and compactness and to the intelligent operator panel programmed for this purpose.

The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors.

PubMed

Rock, Jack P; Ryu, Samuel; Yin, Fang-Fang; Schreiber, Faye; Abdulhak, Muwaffak

2004-01-01

Traditional management strategies for patients with spinal tumors have undergone considerable changes during the last 15 years. Significant improvements in digital imaging, computer processing, and treatment planning have provided the basis for the application of stereotactic techniques, now the standard of care for intracranial pathology, to spinal pathology. In addition, certain of these improvements have also allowed us to progress from frame-based to frameless systems which now act to accurately assure the delivery of high doses of radiation to a precisely defined target volume while sparing injury to adjacent normal tissues. In this article we will describe the evolution from yesterday's standards for radiation therapy to the current state of the art for the treatment of patients with spinal tumors. This presentation will include a discussion of radiation dosing and toxicity, the overall process of extracranial radiation delivery, and the current state of the art regarding Cyberknife, Novalis, and tomotherapy. Additional discussion relating current research protocols and future directions for the management of benign tumors of the spine will also be presented.

Precise let-7 expression levels balance organ regeneration against tumor suppression

PubMed Central

Wu, Linwei; Nguyen, Liem H; Zhou, Kejin; de Soysa, T Yvanka; Li, Lin; Miller, Jason B; Tian, Jianmin; Locker, Joseph; Zhang, Shuyuan; Shinoda, Gen; Seligson, Marc T; Zeitels, Lauren R; Acharya, Asha; Wang, Sam C; Mendell, Joshua T; He, Xiaoshun; Nishino, Jinsuke; Morrison, Sean J; Siegwart, Daniel J; Daley, George Q; Shyh-Chang, Ng; Zhu, Hao

2015-01-01

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09431.001 PMID:26445246

The new frontiers of the targeted interventions in the pulmonary vasculature: precision and safety (2017 Grover Conference Series).

PubMed

Brenner, Jacob S; Kiseleva, Raisa Yu; Glassman, Patrick M; Parhiz, Hamideh; Greineder, Colin F; Hood, Elizabeth D; Shuvaev, Vladimir V; Muzykantov, Vladimir R

2018-01-01

The pulmonary vasculature plays an important role in many lung pathologies, such as pulmonary arterial hypertension, primary graft dysfunction of lung transplant, and acute respiratory distress syndrome. Therapy for these diseases is quite limited, largely due to dose-limiting side effects of numerous drugs that have been trialed or approved. High doses of drugs targeting the pulmonary vasculature are needed due to the lack of specific affinity of therapeutic compounds to the vasculature. To overcome this problem, the field of targeted drug delivery aims to target drugs to the pulmonary endothelial cells, especially those in pathological regions. The field uses a variety of drug delivery systems (DDSs), ranging from nano-scale drug carriers, such as liposomes, to methods of conjugating drugs to affinity moieites, such as antibodies. These DDSs can deliver small molecule drugs, protein therapeutics, and imaging agents. Here we review targeted drug delivery to the pulmonary endothelium for the treatment of pulmonary diseases. Cautionary notes are made of the risk-benefit ratio and safety-parameters one should keep in mind when developing a translational therapeutic.

Optimization of fertirrigation efficiency in strawberry crops by application of fuzzy logic techniques.

PubMed

de la Torre, M L; Grande, J A; Aroba, J; Andujar, J M

2005-11-01

A high level of price support has favoured intensive agriculture and an increasing use of fertilisers and pesticides. This has resulted in the pollution of water and soils and damage to certain eco-systems. The target relationship that must be established between agriculture and environment can be called "sustainable agriculture". In this work we aim at relating strawberry total yield with nitrate concentration in water at different soil depths. To achieve this objective, we have used the Predictive Fuzzy Rules Generator (PreFuRGe) tool, based on fuzzy logic and data mining, by means of which the dose that allows a balance between yield and environmental damage minimization can be determined. This determination is quite simple and is done directly from the obtained charts. This technique can be used in other types of crops permitting one to determine in a precise way at which depth the appropriate dose of nitrate fertilizer must be correctly applied, on the one hand providing the maximum yield but, on the other hand, with the minimum loss of nitrates that leachate through the saturated zone polluting aquifers.

Feasibility of using interstitial ultrasound for intradiscal thermal therapy: a study in human cadaver lumbar discs

NASA Astrophysics Data System (ADS)

Nau, William H.; Diederich, Chris J.; Shu, Richard

2005-06-01

Application of heat in the spine using resistive wire heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. In this study, interstitial ultrasound was evaluated for the potential to heat intradiscal tissue more precisely by directing energy towards the posterior annular wall while avoiding vertebral bodies. Two single-element directional applicator design configurations were tested: a 1.5 mm OD direct-coupled (DC) applicator which can be implanted directly within the disc, and a catheter-cooled (CC) applicator which is inserted in a 2.4 mm OD catheter with integrated water cooling and implanted within the disc. The transducers were sectored to produce 90° spatial heating patterns for directional control. Both applicator configurations were evaluated in four human cadaver lumbar disc motion segments. Two heating protocols were employed in this study in which the temperature measured 5 mm away from the applicator was controlled to either T = 52 °C, or T > 70 °C for the treatment period. These temperatures (thermal doses) are representative of those required for thermal necrosis of in-growing nociceptor nerve fibres and disc cellularity alone, or with coagulation and restructuring of annular collagen in the high-temperature case. Steady-state temperature maps, and thermal doses (t43) were used to assess the thermal treatments. Results from these studies demonstrated the capability of controlling temperature distributions within selected regions of the disc and annular wall using interstitial ultrasound, with minimal vertebral end-plate heating. While directional heating was demonstrated with both applicator designs, the CC configuration had greater directional heating capabilities and offered better temperature control than the DC configuration, particularly during the high-temperature protocol. Further, ultrasound energy was capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain.

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.

Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC.

PubMed

Shende, Ravindra; Patel, Ganesh

2017-01-01

Objective of present study is to determine optimum value of DLG and its validation prior to being incorporated in TPS for Varian TrueBeam™ millennium 120 leaves MLC. Partial transmission through the rounded leaf ends of the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light field and radiation field. Parameter account for this partial transmission is called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose calculation. Distinct synchronized uniformed extension of sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were use to determine DLG. DLG measurements performed with both 0.13 cc semi-flex ionization chamber and 2D-Array I-Matrix were used to validate the DLG; similarly, values of DLG from TPS were estimated from predicted dose. Similar mathematical approaches were employed to determine DLG from delivered and TPS predicted dose. DLG determined from delivered dose measured with both ionization chamber (DLG Ion ) and I-Matrix (DLG I-Matrix ) compared with DLG estimate from TPS predicted dose (DLG TPS ). Measurements were carried out for all available 6MV, 10MV, 15MV, 6MVFFF and 10MVFFF beam energies. Maximum and minimum DLG deviation between measured and TPS calculated DLG was found to be 0.2 mm and 0.1 mm, respectively. Both of the measured DLGs (DLG Ion and DLG I-Matrix ) were found to be in a very good agreement with estimated DLG from TPS (DLG TPS ). Proposed method proved to be helpful in verifying and validating the DLG value prior to its clinical implementation in TPS.

Comparison of parameters affecting GNP-loaded choroidal melanoma dosimetry; Monte Carlo study

NASA Astrophysics Data System (ADS)

Sharabiani, Marjan; Asadi, Somayeh; Barghi, Amir Rahnamai; Vaezzadeh, Mehdi

2018-04-01

The current study reports the results of tumor dosimetry in the presence of gold nanoparticles (GNPs) with different sizes and concentrations. Due to limited number of works carried out on the brachytherapy of choroidal melanoma in combination with GNPs, this study was performed to determine the optimum size and concentration for GNPs which contributes the highest dose deposition in tumor region, using two phantom test cases namely water phantom and a full Monte Carlo model of human eye. Both water and human eye phantoms were simulated with MCNP5 code. Tumor dosimetry was performed for a typical point photon source with an energy of 0.38 MeV as a high energy source and 103Pd brachytherapy source with an average energy of 0.021 MeV as a low energy source in water phantom and eye phantom respectively. Such a dosimetry was done for different sizes and concentrations of GNPs. For all of the diameters, increase in concentration of GNPs resulted in an increase in dose deposited in the region of interest. In a certain concentration, GNPs with larger diameters contributed more dose to the tumor region, which was more pronounced using eye phantom. 100 nm was reported as the optimum size in order to achieve the highest energy deposition within the target. This work investigated the optimum parameters affecting macroscopic dose enhancement in GNP-aided brachytherapy of choroidal melanoma. The current work also had implications on using low energy photon sources in the presence of GNPs to acquire the highest dose enhancement. This study is conducted through four different sizes and concentrations of GNPs. Considering the sensitivity of human eye tissue, in order to report the precise optimum parameters affecting radiosensitivity, a comprehensive study on a wide range of sizes and concentrations are required.

Laser-based irradiation apparatus and methods for monitoring the dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2006-03-28

A scanned, pulsed, focused laser irradiation apparatus can measure and image the photocurrent collection resulting from a dose-rate equivalent exposure to infrared laser light across an entire silicon die. Comparisons of dose-rate response images or time-delay images from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems allows precise identification of those specific age-affected circuit structures within a device that merit further quantitative analysis with targeted materials or electrical testing techniques. Another embodiment of the invention comprises a broad-beam, dose rate-equivalent exposure apparatus. The broad-beam laser irradiation apparatus can determine if aging has affected the device's overall functionality. This embodiment can be combined with the synchronized introduction of external electrical transients into a device under test to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure.

Comparison of the dose distribution obtained from dosimetric systems with intensity modulated radiotherapy planning system in the treatment of prostate cancer

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

Gökçe, M., E-mail: mgokce@adu.edu.tr; Uslu, D. Koçyiğit; Ertunç, C.

The aim of this study is to compare Intensity Modulated Radiation Therapy (IMRT) plan of prostate cancer patients with different dose verification systems in dosimetric aspects and to compare these systems with each other in terms of reliability, applicability and application time. Dosimetric control processes of IMRT plan of three prostate cancer patients were carried out using thermoluminescent dosimeter (TLD), ion chamber (IC) and 2D Array detector systems. The difference between the dose values obtained from the dosimetric systems and treatment planning system (TPS) were found to be about % 5. For the measured (TLD) and calculated (TPS) doses %3more » percentage differences were obtained for the points close to center while percentage differences increased at the field edges. It was found that TLD and IC measurements will increase the precision and reliability of the results of 2D Array.« less

Action of acetylstrophanthidin on experimental myocardial infarction.

NASA Technical Reports Server (NTRS)

Nola, G. T.; Pope, S. E.; Harrison, D. C.

1972-01-01

An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

Nanocrystalline materials for the dosimetry of heavy charged particles: A review

NASA Astrophysics Data System (ADS)

Salah, Numan

2011-01-01

Thermally stimulated luminescence or better known as thermoluminescence (TL) is a powerful technique extensively used for dosimetry of ionizing radiations. TL dosimeter (TLD) materials presently in use are inorganic crystalline materials. They are in the form of chips, single crystals or microcrystalline size powder. The most popular are LiF:Mg,Ti, LiF:Mg,Cu,P, CaSO 4:Dy, CaF 2:Dy and Al 2O 3:C. However, these TLD materials are not capable of precisely detecting heavy charged particles (HCP) irradiations in their present forms. The saturation effect is the major problem, which occurs at relatively low fluences (doses). Moreover, there is a significant variation in the TL glow curves structure with increase in doses, which is undesirable for the use in dosimetry. However, with the use of very tiny particles such as nanoscale TLD materials, this problem is overcome to a major extent. The TL results of the recently reported nanomaterials have revealed very imperative characteristics such as high sensitivity and saturation at very high doses. Recent studies on different luminescent nanomaterials showed that they have a potential application in dosimetry of heavy charged particles using TL technique, where the conventional microcrystalline phosphors saturate. This paper is a review on the prepared TLD nanomaterials, studied for their TL response to HCP. These are CaSO 4:Dy, LiF:Mg,Cu,P, K 2Ca 2(SO 4) 3:Eu and Ba 0.97Ca 0.03SO 4:Eu nanomaterials. The important results obtained in these nanomaterials and the possibility of using them as HCP dosimeters are discussed.

[Determination of morroniside concentration in beagle plasma and its pharmacokinetics by high performance liquid chromatography-tandem mass spectrometry].

PubMed

Xiong, Shan; Li, Jinglai; Zhu, Xiuqing; Wang, Xiaoying; Lü, Guiyuan; Zhang, Zhenqing

2014-03-01

A sensitive, simple and specific high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) method was developed for the determination of morroniside in the plasma of beagles administered via intragastric (ig) doses of morroniside. The method employed paeoniflorin as the internal standard and extracted by simple protein precipitation. The separation was achieved using an Inertsil ODS-SP column (50 mm x 2.1 mm, 5 microm) with mobile phases of 1 mmol/L sodium formate aqueous solution and acetonitrile (gradient elution) at a flow rate of 0.4 mL/min. The detection was accomplished by a mass spectrometer using multiple reaction monitoring (MRM) in positive mode. Pharmacokinetic parameters were fitted by software DAS 2.0. The methodological study showed a good linear relationship of 2-5 000 microg/L (r = 0.996 6) with a sensitivity of 2 microg/L as the limit of quantification. The precision, accuracy, mean recoveries and the matrix effects were satisfied with the requirements of biological sample measurement. The method described above was successfully applied to the pharmacokinetic study of morroniside in the beagle plasma samples. The area under the plasma concentration-time curves (AUC(0-infinity)) of morroniside after single ig administration doses of 5, 15 and 45 mg/kg were (1 631.20 +/- 238.50), (3 984.05 +/- 750.38) and (10 397.64 +/- 3 156.34) microg/L x h. The relationship between dose and AUC showed a good linearity. The pharmacokinetic property of morroniside was proposed to be linear pharmacokinetics.

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

Cojocaru, Claudiu; Mui, Bryan; McEwen, Malcolm

Purpose: To investigate the stability of a water calorimetry system as a primary standard for absorbed dose to water using measurements performed in cobalt-60 and high-energy linac photon beams over a span of more than a decade. Methods: Calorimetry measures adsorbed dose directly by recording the amount of heat created when ionizing radiation passes through matter. The radiation-induced temperature rise was measured using two thermistors calibrated against the NRC temperature primary standard, using an AC bridge with lock-in amplifier for precise measurement. The calorimeter system was operated under thermal equilibrium at 4 °C (to eliminate convection) with drifts in watermore » temperature less than 0.1 mK/min. Seven water vessels of various designs were used to make repeated measurements over the course of 17 years. Results: The standard uncertainty achieved for a set of ten calorimeter measurements (4 Gy delivered) was generally well below 0.15 % while the variation between multiple sets for a given vessel was consistent with this value. The long-term stability of the system combined with inter-vessel variations indicated that there was good control of the radiochemistry (chemical heat defect). Conclusions: The measurements performed over a period of several years showed that the combined water calorimeters showed stability at +/− 0.25 % level. Thus, rather than relying on a particular vessel as an artifact one can realize the Gray through the more generalized method of combining a glass vessel, high-purity water and thermistor probes. This provides increased robustness in the dissemination of absorbed dose to Canadian users.« less

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

PubMed Central

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

2014-01-01

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

Timing considerations for preclinical MRgRT: effects of ion diffusion, SNR and imaging times on FXG gel calibration

NASA Astrophysics Data System (ADS)

Welch, M.; Foltz, W. D.; Jaffray, D. A.

2015-01-01

Sub-millimeter resolution images are required for gel dosimeters to be used in preclinical research, which is challenging for MR probed ferrous xylenol-orange (FXG) dosimeters due to ion diffusion and inadequate SNR. A preclinical 7 T MR, small animal irradiator and FXG dosimeters were used in all experiments. Ion diffusion was analyzed using high resolution (0.2 mm/pixel) T1 MR images collected every 5 minutes, post-irradiation, for an hour. Using Fick's second law, ion diffusion was approximated for the first hour post-irradiation. SNR, T1 map precision and calibration fit were determined for two MR protocols: (1) 10 minute acquisition, 0.35mm/pixel and 3mm slices, (2) 45 minute acquisition, 0. 25 mm/pixel and 2 mm slices. SNR and T1 map precision were calculated using a Monte Carlo simulation. Calibration curves were determined by plotting R1 relaxation rates versus depth dose data, and fitting a linear trend line. Ion diffusion was estimated as 0.003mm2 in the first hour post-irradiation. For protocols (1) and (2) respectively, Monte Carlo simulation predicted T1 precisions of 3% and 5% within individual voxels using experimental SNRs; the corresponding measured T1 precisions were 8% and 12%. The linear trend lines reported slopes of 27 ± 3 Gy*s (R2: 0.80 ± 0.04) and 27 ± 4 Gy*s (R2: 0.90 ± 0.04). Ion diffusion is negligible within the first hour post-irradiation, and an accurate and reproducible calibration can be achieved in a preclinical setting with sub-millimeter resolution.

Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

PubMed

Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

2013-05-01

Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Computer controlled titration with piston burette or peristaltic pump - a comparison.

PubMed

Hoffmann, W

1996-09-01

The advantages and problems of the use of piston burettes and peristaltic pumps for dosage of titrant solutions in automatic titrations are shown. For comparison, only the dosing devices were exchanged and all other components and conditions remained unchanged. The results of continuous acid base titration show good agreement and comparable reproducibility. Potentiometric sensors (glass electrodes) with different equilibration behaviour influence the results. The capability of such electrodes was tested. Conductometric measurements allow a much faster detection because there is no equilibration of electrodes. Piston burettes should be used for titration with very high precision, titration with organic solvents and slow titrations. Peristaltic pumps seem to be more suitable for continuous titrations and long time operation without service.

Practical aspects and applications of the biological effective dose three-dimensional calculation for multi-phase radiotherapy treatment plans

NASA Astrophysics Data System (ADS)

Kauweloa, Kevin Ikaika

The approximate BED (BEDA) is calculated for multi-phase cases due to current treatment planning systems (TPSs) being incapable of performing BED calculations. There has been no study on the mathematical accuracy and precision of BEDA relative to the true BED (BEDT), and how that might negatively impact patient care. The purpose of the first aim was to study the mathematical accuracy and precision in both hypothetical and clinical situations, while the next two aims were to create multi-phase BED optimization ideas for both multi-target liver stereotactic body radiation therapy (SBRT) cases, and gynecological cases where patients are treated with high-dose rate (HDR) brachytherapy along with external beam radiotherapy (EBRT). MATLAB algorithms created for this work were used to mathematically analyze the accuracy and precision of BEDA relative to BEDT in both hypothetical and clinical situations on a 3D basis. The organs-at-risk (OARs) of ten head & neck and ten prostate cancer patients were studied for the clinical situations. The accuracy of BEDA was shown to vary between OARs as well as between patients. The percentage of patients with an overall BEDA percent error less than 1% were, 50% for the Optic Chiasm and Brainstem, 70% for the Left and Right Optic Nerves, as well as the Rectum and Bladder, and 80% for the Normal Brain and Spinal Cord. As seen for each OAR among different patients, there were always cases where the percent error was greater than 1%. This is a cause for concern since the goal of radiation therapy is to reduce the overall uncertainty of treatment, and calculating BEDA distributions increases the treatment uncertainty with percent errors greater than 1%. The revealed inaccuracy and imprecision of BEDA supports the argument to use BEDT. The multi-target liver study involved applying BEDT in order to reduce the number of dose limits to one rather than have one for each fractionation scheme in multi-target liver SBRT treatments. A BEDT limit was found using the current, clinically accepted dose limits, allowing the BEDT distributions to be calculated, which could be used to determine whether at least 700 cc of the healthy liver did not receive the BEDT limit. Three previously multi-target liver cancer patients were studied. For each case, it was shown that the conventional treatment plans were relatively conservative and that more than 700 cc of the healthy liver received less than the BED T limit. These results show that greater doses can be delivered to the targets without exceeding the BEDT limit to the healthy tissue, which typically causes radiation toxicity. When applying BEDT to gynecological cases, the BEDT can reveal the relative effect each treatment would have individually hence the cumulative BEDT would better inform the physician of the potential results with the patient's treatment. The problem presented for these cases, however, is the method in summing dose distributions together when there is significant motion between treatments and the presence of applicators for the HDR phase. One way to calculate the cumulative BEDT is to use structure guided deformable image registration (SG-DIR) that only focuses on the anatomical contours, to avoid errors introduced by the applicators. Eighteen gynecological patients were studied and VelocityAI was used to perform this SG- DIR. In addition, formalism was developed to assess and characterize the remnant dose-mapping error from this approach, from the shortest distance between contour points (SDBP). The results revealed that warping errors rendered relatively large normal tissue complication probability (NTCP) values which are certainly non negligible and does render this method not clinically viable. However, a more accurate SG-DIR algorithm could improve the accuracy of BEDT distributions in these multi-phase cases.

Fast method for in-flight estimation of total dose from protons and electrons using RADE Minstrument on JUICE

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

The primary concern of the ESA JUICE mission to Jupiter is the harsh particle radiation environment. Ionizing particles introduce radiation damage by total dose effects, displacement damages or single events effects. Therefore, both the total ionizing dose and the displacement damage equivalent fluence must be assessed to alert spacecraft and its payload as well as to quantify radiation levels for the entire mission lifetime. We present a concept and implementations steps for simplified method used to compute in flight a dose rate and total dose caused by protons. We also provide refinement of the method previously developed for electrons. The dose rates values are given for predefined active volumes located behind layers of materials with known thickness. Both methods are based on the electron and proton flux measurements provided by the Electron and Proton Detectors inside the Radiation Hard Electron Monitor (RADEM) located on-board of JUICE. The trade-off between method accuracy and programming limitations for in-flight computations are discussed. More comprehensive and precise dose rate computations based on detailed analysis of all stack detectors will be made during off-line data processing. It will utilize full spectral unfolding from all RADEM detector subsystems.

Quantification of rifampicin in human plasma and cerebrospinal fluid by a highly sensitive and rapid liquid chromatographic-tandem mass spectrometric method.

PubMed

Srivastava, Abhishek; Waterhouse, David; Ardrey, Alison; Ward, Stephen A

2012-11-01

A highly sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed to measure the levels of the antitubercular drug rifampicin (RIF) in human plasma and cerebrospinal fluid (CSF). The analyte and internal standard (IS) were isolated from plasma and CSF by a simple organic solvent based precipitation of proteins followed by centrifugation. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring (MRM) mode. The assay was linear in the concentration range 25-6400 ng/mL with intra- and inter-day precision of <7% and <8%, respectively. The validated method was applied to the study of RIF pharmacokinetics in human CSF and plasma over 25 h period after a 10 mg/kg oral dose. Copyright © 2012 Elsevier B.V. All rights reserved.

Sensitive high-performance liquid chromatography/mass spectrometry method for determination of steviol in rat plasma.

PubMed

Wang, L Z; Goh, B C; Fan, L; Lee, H S

2004-01-01

The main toxicological concern of stevioside, a highly potent sweetener from S. rebaudiana, is its main metabolite, steviol. To determine very low levels of steviol in in vivo experiments, a sensitive liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) method was developed for quantifying steviol in rat plasma after oral administration of a single dose of stevioside (0.5 g/kg). The sample preparation uses liquid-liquid extraction with tert-butyl methyl ether in an acidic environment. The retention time of steviol was 10.5 min. The assay was linear over the range 2-1000 ng/mL with a lower limit of detection of 1 ng/mL. The intra- and inter-day precision were <5 and <7%, respectively, and the accuracy was in the range 95-108%. The steviol concentration profile in rat plasma was determined. Copyright 2003 John Wiley & Sons, Ltd.

Measurements of carbon-14 with cavity ring-down spectroscopy

DOE PAGES

McCartt, A. D.; Ognibene, T.; Bench, G.; ...

2015-06-13

Accelerator Mass Spectrometry (AMS) is the most sensitive method for quantitation of 14C in biological samples. This technology has been used in a variety of low dose, human health related studies over the last 20 years when very high sensitivity was needed. AMS helped pioneer these scientific methods, but its expensive facilities and requirements for highly trained technical staff have limited their proliferation. Quantification of 14C by cavity ring-down spectroscopy (CRDS) offers an approach that eliminates many of the shortcomings of an accelerator-based system and would supplement the use of AMS in biomedical research. Our initial prototype, using a non-idealmore » wavelength laser and under suboptimal experimental conditions, has a 3.5-modern, 1-σ precision for detection of milligram-sized, carbon-14-elevated samples. Furthermore, these results demonstrate proof of principle and provided a starting point for the development of a spectrometer capable of biologically relevant sensitivities.« less

Development of a multi-knife-edge slit collimator for prompt gamma ray imaging during proton beam cancer therapy

NASA Astrophysics Data System (ADS)

Ready, John Francis, III

Proton beam usage to treat cancer has recently experienced rapid growth, as it offers the ability to target dose delivery in a patient more precisely than traditional x-ray treatment methods. Protons stop within the patient, delivering the maximum dose at the end of their track--a phenomenon described as the Bragg peak. However, because a large dose is delivered to a small volume, proton therapy is very sensitive to errors in patient setup and treatment planning calculations. Additionally, because all primary beam particles stop in the patient, there is no direct information available to verify dose delivery. These factors contribute to the range uncertainty in proton therapy, which ultimately hinders its clinical usefulness. A reliable method of proton range verification would allow the clinician to fully utilize the precise dose delivery of the Bragg peak. Several methods to verify proton range detect secondary emissions, especially prompt gamma ray (PG) emissions. However, detection of PGs is challenging due to their high energy (2-10 MeV) and low attenuation coefficients, which limit PG interactions in materials. Therefore, detection and collimation methods must be specifically designed for prompt gamma ray imaging (PGI) applications. In addition, production of PGs relies on delivering a dose of radiation to the patient. Ideally, verification of the Bragg peak location exposes patients to a minimal dose, thus limiting the PG counts available to the imaging system. An additional challenge for PGI is the lack of accurate simulation models, which limit the study of PG production characteristics and the relationship between PG distribution and dose delivery. Specific limitations include incorrect modeling of the reaction cross sections, gamma emission yields, and angular distribution of emission for specific photon energies. While simulations can still be valuable assets in designing a system to detect and image PGs, until new models are developed and incorporated into Monte Carlo simulation packages, simulations cannot be used to study the production and location of PG emissions during proton therapy. This work presents a novel system to image PGs emitted during proton therapy to verify proton beam range. The imaging system consists of a multi-slit collimator paired with a position-sensitive LSO scintillation detector. This innovative design is the first collimated imaging system to implement two-dimensional (2-D) imaging for PG proton beam range verification, while also providing a larger field of view than compared to single-slit collimator systems. Other, uncollimated imaging systems have been explored for PGI applications, such as Compton cameras. However, Compton camera designs are severely limited by counting rate capabilities. A recent Compton camera study reported count rate capability of about 5 kHz. However, at a typical clinical beam current of 1.0 nA, the estimated PG emission rate would be 6 x 108 per second. After accounting for distance to the detector and interaction efficiencies, the detection system will still be overwhelmed with counts in the MHz range, causing false coincidences and hindering the operation of the imaging system. Initial measurements using 50 MeV protons demonstrated the ability of our system to reconstruct 2-D PG distributions at clinical beam currents. A Bragg peak localization precision of 1 mm (2sigma) was achieved with delivery of (1.7 +/- 0.8) x 108 protons into a PMMA target, suggesting the ability of the system to detect relative shifts in proton range while delivering fewer protons than used in a typical treatment fraction. This is key, as the ideal system allows the clinician to verify proton range when delivering only a small portion of the prescribed dose, preventing the mistreatment of the patient. Additionally, the absolute position of the Bragg peak was identified to within 1.6 mm (2sigma) with 5.6 x 1010 protons delivered. These promising results warrant further investigation and system optimization for clinical implementation. While further measurements at clinical beam energy levels will be required to verify system performance, these preliminary results provide evidence that 2-D image reconstruction, with 1-2 mm accuracy, is possible with this design. Implementing such a system in the clinical setting would greatly improve proton therapy cancer treatment outcomes.

High resolution X-ray fluorescence imaging for a microbeam radiation therapy treatment planning system

NASA Astrophysics Data System (ADS)

Chtcheprov, Pavel; Inscoe, Christina; Burk, Laurel; Ger, Rachel; Yuan, Hong; Lu, Jianping; Chang, Sha; Zhou, Otto

2014-03-01

Microbeam radiation therapy (MRT) uses an array of high-dose, narrow (~100 μm) beams separated by a fraction of a millimeter to treat various radio-resistant, deep-seated tumors. MRT has been shown to spare normal tissue up to 1000 Gy of entrance dose while still being highly tumoricidal. Current methods of tumor localization for our MRT treatments require MRI and X-ray imaging with subject motion and image registration that contribute to the measurement error. The purpose of this study is to develop a novel form of imaging to quickly and accurately assist in high resolution target positioning for MRT treatments using X-ray fluorescence (XRF). The key to this method is using the microbeam to both treat and image. High Z contrast media is injected into the phantom or blood pool of the subject prior to imaging. Using a collimated spectrum analyzer, the region of interest is scanned through the MRT beam and the fluorescence signal is recorded for each slice. The signal can be processed to show vascular differences in the tissue and isolate tumor regions. Using the radiation therapy source as the imaging source, repositioning and registration errors are eliminated. A phantom study showed that a spatial resolution of a fraction of microbeam width can be achieved by precision translation of the mouse stage. Preliminary results from an animal study showed accurate iodine profusion, confirmed by CT. The proposed image guidance method, using XRF to locate and ablate tumors, can be used as a fast and accurate MRT treatment planning system.

Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

PubMed

Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

2012-01-01

Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

Research on the tool holder mode in high speed machining

NASA Astrophysics Data System (ADS)

Zhenyu, Zhao; Yongquan, Zhou; Houming, Zhou; Xiaomei, Xu; Haibin, Xiao

2018-03-01

High speed machining technology can improve the processing efficiency and precision, but also reduce the processing cost. Therefore, the technology is widely regarded in the industry. With the extensive application of high-speed machining technology, high-speed tool system has higher and higher requirements on the tool chuck. At present, in high speed precision machining, several new kinds of clip heads are as long as there are heat shrinkage tool-holder, high-precision spring chuck, hydraulic tool-holder, and the three-rib deformation chuck. Among them, the heat shrinkage tool-holder has the advantages of high precision, high clamping force, high bending rigidity and dynamic balance, etc., which are widely used. Therefore, it is of great significance to research the new requirements of the machining tool system. In order to adapt to the requirement of high speed machining precision machining technology, this paper expounds the common tool holder technology of high precision machining, and proposes how to select correctly tool clamping system in practice. The characteristics and existing problems are analyzed in the tool clamping system.

Clinical evaluation of a simultaneous closed-loop anaesthesia control system for depth of anaesthesia and neuromuscular blockade*.

PubMed

Janda, M; Simanski, O; Bajorat, J; Pohl, B; Noeldge-Schomburg, G F E; Hofmockel, R

2011-12-01

We developed a closed-loop system to control the depth of anaesthesia and neuromuscular blockade using the bispectral index and the electromyogram simultaneously and evaluated the clinical performance of this combined system for general anaesthesia. Twenty-two adult patients were included in this study. Anaesthesia was induced by a continuous infusion of remifentanil at 0.4 μg.kg(-1) .min(-1) (induction dose) and then 0.25 μg.kg(-1) .min(-1) (maintenance dose) and propofol at 2 mg.kg(-1) 3 min later. The combined automatic control was started 2 min after tracheal intubation. The depth of anaesthesia was recorded using bispectral index monitoring using a target value of 40. The target value of neuromuscular blockade, using mivacurium, was a T1/T1(0) twitch height of 10%. The precision of the system was calculated using internationally defined performance parameters. Twenty patients were included in the data analysis. The mean (SD) duration of simultaneous control was 129 (69) min. No human intervention was necessary during the computer-controlled administration of propofol and mivacurium. All patients assessed the quality of anaesthesia as 'good' to 'very good'; there were no episodes of awareness. The mean (SD) median performance error, median absolute performance error and wobble for the control of depth of anaesthesia and for neuromuscular blockade were -0.31 (1.78), 6.76 (3.45), 6.32 (2.93) and -0.38 (1.68), 3.75 (4.83), 3.63 (4.69), respectively. The simultaneous closed-loop system using propofol and mivacurium was able to maintain the target values with a high level of precision in a clinical setting. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans

PubMed Central

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q.; Otrakji, Alexi; Kalra, Mannudeep K.; Xu, X. George; Liu, Bob

2014-01-01

Purpose: To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Methods: Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. Results: The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8% − 25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2 ± 3.3 and 16.5 ± 2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. Conclusions: This study revealed the complexity of CT dose fluctuation and variation with a human cadaver. PMID:25186398

Reduced Variance using ADVANTG in Monte Carlo Calculations of Dose Coefficients to Stylized Phantoms

NASA Astrophysics Data System (ADS)

Hiller, Mauritius; Bellamy, Michael; Eckerman, Keith; Hertel, Nolan

2017-09-01

The estimation of dose coefficients of external radiation sources to the organs in phantoms becomes increasingly difficult for lower photon source energies. This study focus on the estimation of photon emitters around the phantom. The computer time needed to calculate a result within a certain precision can be lowered by several orders of magnitude using ADVANTG compared to a standard run. Using ADVANTG which employs the DENOVO adjoint calculation package enables the user to create a fully populated set of weight windows and source biasing instructions for an MCNP calculation.

Preliminary On-Orbit Neutron Dose Equivalent and Energy Spectrum Results from the ISS-RAD Fast Neutron Detector (FND)

NASA Technical Reports Server (NTRS)

Semones, Edward; Leitgab, Martin

2016-01-01

The ISS-RAD instrument was activated on ISS on February 1st, 2016. Integrated in ISS-RAD, the Fast Neutron Detector (FND) performs, for the first time on ISS, routine and precise direct neutron measurements between 0.5 and 8 MeV. Preliminary results for neutron dose equivalent and neutron flux energy distributions from online/on-board algorithms and offline ground analyses will be shown, along with comparisons to simulated data and previously measured neutron spectral data. On-orbit data quality and pre-launch analysis validation results will be discussed as well.

Real-time, ray casting-based scatter dose estimation for c-arm x-ray system.

PubMed

Alnewaini, Zaid; Langer, Eric; Schaber, Philipp; David, Matthias; Kretz, Dominik; Steil, Volker; Hesser, Jürgen

2017-03-01

Dosimetric control of staff exposure during interventional procedures under fluoroscopy is of high relevance. In this paper, a novel ray casting approximation of radiation transport is presented and the potential and limitation vs. a full Monte Carlo transport and dose measurements are discussed. The x-ray source of a Siemens Axiom Artix C-arm is modeled by a virtual source model using single Gaussian-shaped source. A Geant4-based Monte Carlo simulation determines the radiation transport from the source to compute scatter from the patient, the table, the ceiling and the floor. A phase space around these scatterers stores all photon information. Only those photons are traced that hit a surface of phantom that represents medical staff in the treatment room, no indirect scattering is considered; and a complete dose deposition on the surface is calculated. To evaluate the accuracy of the approximation, both experimental measurements using Thermoluminescent dosimeters (TLDs) and a Geant4-based Monte Carlo simulation of dose depositing for different tube angulations of the C-arm from cranial-caudal angle 0° and from LAO (Left Anterior Oblique) 0°-90° are realized. Since the measurements were performed on both sides of the table, using the symmetry of the setup, RAO (Right Anterior Oblique) measurements were not necessary. The Geant4-Monte Carlo simulation agreed within 3% with the measured data, which is within the accuracy of measurement and simulation. The ray casting approximation has been compared to TLD measurements and the achieved percentage difference was -7% for data from tube angulations 45°-90° and -29% from tube angulations 0°-45° on the side of the x-ray source, whereas on the opposite side of the x-ray source, the difference was -83.8% and -75%, respectively. Ray casting approximation for only LAO 90° was compared to a Monte Carlo simulation, where the percentage differences were between 0.5-3% on the side of the x-ray source where the highest dose usually detected was mainly from primary scattering (photons), whereas percentage differences between 2.8-20% are found on the side opposite to the x-ray source, where the lowest doses were detected. Dose calculation time of our approach was 0.85 seconds. The proposed approach yields a fast scatter dose estimation where we could run the Monte Carlo simulation only once for each x-ray tube angulation to get the Phase Space Files (PSF) for being used later by our ray casting approach to calculate the dose from only photons which will hit an movable elliptical cylinder shaped phantom and getting an output file for the positions of those hits to be used for visualizing the scatter dose propagation on the phantom surface. With dose calculation times of less than one second, we are saving much time compared to using a Monte Carlo simulation instead. With our approach, larger deviations occur only in regions with very low doses, whereas it provides a high precision in high-dose regions. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Creating Ruddlesden-Popper phases by hybrid molecular beam epitaxy

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

Haislmaier, Ryan C.; Stone, Greg; Alem, Nasim

2016-07-25

The synthesis of a 50 unit cell thick n = 4 Sr{sub n+1}Ti{sub n}O{sub 3n+1} (Sr{sub 5}Ti{sub 4}O{sub 13}) Ruddlesden-Popper (RP) phase film is demonstrated by sequentially depositing SrO and TiO{sub 2} layers in an alternating fashion using hybrid molecular beam epitaxy (MBE), where Ti was supplied using titanium tetraisopropoxide (TTIP). A detailed calibration procedure is outlined for determining the shuttering times to deposit SrO and TiO{sub 2} layers with precise monolayer doses using in-situ reflection high energy electron diffraction (RHEED) as feedback. Using optimized Sr and TTIP shuttering times, a fully automated growth of the n = 4 RP phase was carried outmore » over a period of >4.5 h. Very stable RHEED intensity oscillations were observed over the entire growth period. The structural characterization by X-ray diffraction and high resolution transmission electron microscopy revealed that a constant periodicity of four SrTiO{sub 3} perovskite unit cell blocks separating the double SrO rocksalt layer was maintained throughout the entire film thickness with a very little amount of planar faults oriented perpendicular to the growth front direction. These results illustrate that hybrid MBE is capable of layer-by-layer growth with atomic level precision and excellent flux stability.« less

Effects of low doses and low dose rates of external ionizing radiation: Cancer mortality among nuclear industry workers in three countries

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

Cardis, E.; Kato, I.; Lave, C.

Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly {gamma}, radiation. The combination of the data from the various studies increases themore » power to study associations between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)-the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates-was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI):-0.4,0.3] and 2.18 per Sv (90% CI:0.1,5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to O mSv. 53 refs., 1 fig., 8 tabs.« less

Optimal design of clinical trials with biologics using dose-time-response models.

PubMed

Lange, Markus R; Schmidli, Heinz

2014-12-30

Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. Copyright © 2014 John Wiley & Sons, Ltd.

Linked Orders Improve Safety in Scheduling and Administration of Chemotherapeutic Agents

PubMed Central

Whipple, Nancy; Boulware, Joy; Danca, Kala; Boyarin, Kirill; Ginsberg, Eliot; Poon, Eric; Sweet, Micheal; Schade, Sue; Rogala, Jennifer

2010-01-01

The pharmacologic treatment for cancer must adhere to complex, finely orchestrated treatment plans, including not only chemotherapy medications, but pre/post-hydration, anti-emetics, anti-anxiety, and other medications that are given before, during and after chemotherapy doses. The treatment plans specify the medications and dictate precise dosing, frequency, and timing. This is a challenge to most Computerized Physician Order Entry (CPOE), Pharmacy and Electronic Medication Administration record (eMAR) Systems. Medications are scheduled on specific dates, referred to as chemo days, from the onset of the treatment, and precisely timed on the designated chemo day. For patients enrolled in research protocols, the adherence to the defined schedule takes on additional import, since variation is a violation of the protocol. If the oncologist determines that medications must be administered outside the defined constraints, the patient must be un-enrolled from the protocol and the course of therapy is re-written. Pharmacy and eMAR systems utilized in processing chemotherapy medications must be able to support the intricate relationships between each drug defined in the treatment plans. PMID:21347104

Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

PubMed

Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

2017-01-01

Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparative study on skin dose measurement using MOSFET and TLD for pediatric patients with acute lymphatic leukemia.

PubMed

Al-Mohammed, Huda I; Mahyoub, Fareed H; Moftah, Belal A

2010-07-01

The object of this study was to compare the difference of skin dose measured in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using metal oxide semiconductor field-effect transistors (mobile MOSFET dose verification system (TN-RD-70-W) and thermoluminescent dosimeters (TLD-100 chips, Harshaw/ Bicron, OH, USA). Because TLD has been the most-commonly used technique in the skin dose measurement of TBI, the aim of the present study is to prove the benefit of using the mobile MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements during the total body irradiation (TBI) over thermoluminescent dosimeters (TLD). The measurements involved 10 pediatric patients ages between 3 and 14 years. Thermoluminescent dosimeters and MOSFET dosimetry were performed at 9 different anatomic sites on each patient. The present results show there is a variation between skin dose measured with MOSFET and TLD in all patients, and for every anatomic site selected, there is no significant difference in the dose delivered using MOSFET as compared to the prescribed dose. However, there is a significant difference for every anatomic site using TLD compared with either the prescribed dose or MOSFET. The results indicate that the dosimeter measurements using the MOSFET gave precise measurements of prescribed dose. However, TLD measurement showed significant increased skin dose of cGy as compared to either prescribed dose or MOSFET group. MOSFET dosimeters provide superior dose accuracy for skin dose measurement in TBI as compared with TLD.

NTP Carcinogenesis Bioassay of Diallyl Phthalate (CAS No. 131-17-9) in B6C3F1 Mice (Gavage Study).

PubMed

1983-04-01

Diallyl phthalate is a widely used crosslinking agent for unsaturated polyesters. Diallyl phthalate or diallyl phthalate polyester blends are used primarily as plasticizers and carriers for adding catalysts and pigments to polyesters and in molding, electrical parts, laminating compounds, and impregnation of metal castings. Rubber compounds, epoxy formulations, and polyurethane foams may also contain diallyl phthalate. Annual production of diallyl phthalate in the United States exceeds 5,000 pounds; precise figures are not available. A NTP Carcinogenesis bioassay of diallyl phthalate (99% pure) was conducted by administering 0 (vehicle control), 150, or 300 mg/kg diallyl phthalate in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 male and 50 female B6C3F1 mice. Survival rates and mean body weights of dosed mice were not different from those of the controls, and pathological lesions unrelated to proliferative changes were not observed. Therefore, a maximally tolerated dose for the purposes of carcinogenicity testing may not have been achieved. The incidences of lymphoma and either lymphoma or leukemia in dosed male mice were no significantly greater than those in the controls according to pairwise comparisons (P=0.051 to P=0.096), but the trend tests were statistically significant by either life table or incidental tumor analysis (P=0.031 to P=0.045). The incidence of lymphomas in the high-dose male mice was 12/50 (24%) in comparison with 6/50 (12%) in the controls. Recent historical incidences at the performing laboratory and in the NTP Bioassay Program were 18/120 (15%) and 71/661 (11%), respectively. Since the incidence of high-dose male mice with leukemia was not significantly greater than that of concurrent or historical controls at the performing laboratory by pairwise comparisons, this marginal increase was considered only to be equivocally related to diallyl phthalate administration. Increased incidences of squamous cell papillomas, hyperplasia, and inflammatory lesions of the forestomach were observed in diallyl phthalate-dosed mice of both sexes in a dose-related manner. Papillomas of the forestomach were observed in 0%, 2%, and 4% of the control, low-dose, and high-dose mice of both sexes. The recent historical incidence of this tumor in gavage control mice from both the performing laboratory and other laboratories within the Bioassay Program was less than 1%. Forestomach hyperplasia was diagnosed in 0%, 15%, and 18%, and in 8%, 2%, and 29% of the control, low-dose, and high-dose male and female mice, respectively; chronic inflammation of the forestomach was diagnosed in 0%, 9%, and 16% and in 4%, 2%, and 18% of the control, low-dose, and high-dose male and female mice, respectively. Because of the numerical elevation of the forestomach papillomas in the high-dose mice of both sexes, the concomitant observation of dose related forestomach hyperplasia, and the rarity of this tumor in corn oil (gavage) control B6C3F1 mice, the development of squamous cell papillomas of the forestomach may have been related to diallyl phthalate administration. Under the conditions of this bioassay, the development of chronic inflammation and hyperplasia of the forestomach in both male and female B6C3F1 mice was considered to be related to the administration of diallyl phthalate. The development of squamous cell papillomas of the forestomach may also have been related to chemical administration, but the available data are insufficient to indicate a clear cause and effect relationship. An increase in the incidence of male mice with lymphomas was observed, but this increase was considered only to be equivocally related to diallyl phthalate administration. The results of this bioassay, therefore, do not indicate that diallyl phthalate is carcinogenic in B6C3F1 mice, although a maximum tolerated dose may not have been achieved. A carcinogenicity study by the National Toxicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg boicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg body weight is currently being evaluated. Levels of Evidence of Carcinogenicity: Male Mice: Equivocal Female Mice: Equivocal

Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

DOE PAGES

Herklotz, A.; Dörr, Kathrin; Ward, T. Z.; ...

2015-04-03

In this paper, to have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can bemore » utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr n +1Ti n O 3 n +1 Ruddlesden-Popper phases are grown with good long-range order. Finally, this method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.« less

Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

DOE PAGES

Herklotz, Andreas; Dorr, Kathrin; Ward, Thomas Zac; ...

2015-04-03

To have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can be utilized to determinemore » the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr n+1Ti nO 3 n+1 Ruddlesden-Popper phases are grown with good long-range order. Furthermore, this method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.« less

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

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

Widder, Joachim, E-mail: j.widder@umcg.nl; Schaaf, Arjen van der; Lambin, Philippe

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be testedmore » in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.« less

Adaptive radiotherapy for head and neck cancers: Fact or fallacy to improve therapeutic ratio?

PubMed

Li, Y Q; Tan, J S H; Wee, J T S; Chua, M L K

2018-04-23

Modern standards of precision radiotherapy, primarily driven by the technological advances of intensity modulation and image guidance, have led to increased versatility in radiotherapy planning and delivery. The ability to shape doses around critical normal organs, while simultaneously "painting" boost doses to the tumor have translated to substantial therapeutic gains in head and neck cancer patients. Recently, dose adaptation (or adaptive radiotherapy) has been proposed as a novel concept to enhance the therapeutic ratio of head and neck radiotherapy, facilitated in part by the onset of molecular and functional imaging. These contemporary imaging techniques have enabled visualisation of the spatial molecular architecture of the tumor. Daily cone-beam imaging, besides improving treatment accuracy, offers another unique angle to explore radiomics - a novel high throughput feature extraction and selection workflow, for adapting radiotherapy based on real-time tumor changes. Here, we review the existing evidence of molecular and functional imaging in head and neck cancers, as well as the current application of adaptive radiotherapy in the treatment of this tumor type. We propose that adaptive radiotherapy can be further exploited through a systematic application of molecular and functional imaging, including radiomics, at the different phases of planning and treatment. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.

PubMed

López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

2015-01-01

To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer patients. Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. We carried out a retrospective study in order to analyse RT planning modification based on (11)C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy. In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. In our experience, concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites.

Optimisation of the imaging and dosimetric characteristics of an electronic portal imaging device employing plastic scintillating fibres using Monte Carlo simulations.

PubMed

Blake, S J; McNamara, A L; Vial, P; Holloway, L; Kuncic, Z

2014-11-21

A Monte Carlo model of a novel electronic portal imaging device (EPID) has been developed using Geant4 and its performance for imaging and dosimetry applications in radiotherapy has been characterised. The EPID geometry is based on a physical prototype under ongoing investigation and comprises an array of plastic scintillating fibres in place of the metal plate/phosphor screen in standard EPIDs. Geometrical and optical transport parameters were varied to investigate their impact on imaging and dosimetry performance. Detection efficiency was most sensitive to variations in fibre length, achieving a peak value of 36% at 50 mm using 400 keV x-rays for the lengths considered. Increases in efficiency for longer fibres were partially offset by reductions in sensitivity. Removing the extra-mural absorber surrounding individual fibres severely decreased the modulation transfer function (MTF), highlighting its importance in maximising spatial resolution. Field size response and relative dose profile simulations demonstrated a water-equivalent dose response and thus the prototype's suitability for dosimetry applications. Element-to-element mismatch between scintillating fibres and underlying photodiode pixels resulted in a reduced MTF for high spatial frequencies and quasi-periodic variations in dose profile response. This effect is eliminated when fibres are precisely matched to underlying pixels. Simulations strongly suggest that with further optimisation, this prototype EPID may be capable of simultaneous imaging and dosimetry in radiotherapy.

The thermoluminescence response of doped SiO2 optical fibres subjected to photon and electron irradiations.

PubMed

Hashim, S; Al-Ahbabi, S; Bradley, D A; Webb, M; Jeynes, C; Ramli, A T; Wagiran, H

2009-03-01

Modern linear accelerators, the predominant teletherapy machine in major radiotherapy centres worldwide, provide multiple electron and photon beam energies. To obtain reasonable treatment times, intense electron beam currents are achievable. In association with this capability, there is considerable demand to validate patient dose using systems of dosimetry offering characteristics that include good spatial resolution, high precision and accuracy. Present interest is in the thermoluminescence response and dosimetric utility of commercially available doped optical fibres. The important parameter for obtaining the highest TL yield during this study is to know the dopant concentration of the SiO2 fibre because during the production of the optical fibres, the dopants tend to diffuse. To achieve this aim, proton-induced X-ray emission (PIXE), which has no depth resolution but can unambiguously identify elements and analyse for trace elements with detection limits approaching microg/g, was used. For Al-doped fibres, the dopant concentration in the range 0.98-2.93 mol% have been estimated, with equivalent range for Ge-doped fibres being 0.53-0.71 mol%. In making central-axis irradiation measurements a solid water phantom was used. For 6-MV photons and electron energies in the range 6, 9 and 12 MeV, a source to surface distance of 100 cm was used, with a dose rate of 400 cGy/min for photons and electrons. The TL measurements show a linear dose-response over the delivered range of absorbed dose from 1 to 4 Gy. Fading was found to be minimal, less than 10% over five days subsequent to irradiation. The minimum detectable dose for 6-MV photons was found to be 4, 30 and 900 microGy for TLD-100 chips, Ge- and Al-doped fibres, respectively. For 6-, 9- and 12-MeV electron energies, the minimum detectable dose were in the range 3-5, 30-50 and 800-1400 microGy for TLD-100 chip, Ge-doped and Al-doped fibres, respectively.

Dosimetric characterization of optically stimulated luminescence dosimeter with therapeutic photon beams for use in clinical radiotherapy measurements.

PubMed

Ponmalar, Retna; Manickam, Ravikumar; Ganesh, K M; Saminathan, Sathiyan; Raman, Arun; Godson, Henry Finlay

2017-01-01

The modern radiotherapy techniques impose new challenges for dosimetry systems with high precision and accuracy in in vivo and in phantom dosimetric measurements. The knowledge of the basic characterization of a dosimetric system before patient dose verification is crucial. This incites the investigation of the potential use of nanoDot optically stimulated luminescence dosimeter (OSLD) for application in radiotherapy with therapeutic photon beams. Measurements were carried out with nanoDot OSLDs to evaluate the dosimetric characteristics such as dose linearity, dependency on field size, dose rate, energy and source-to-surface distance (SSD), reproducibility, fading effect, reader stability, and signal depletion per read out with cobalt-60 (60 Co) beam, 6 and 18 MV therapeutic photon beams. The data acquired with OSLDs were validated with ionization chamber data where applicable. Good dose linearity was observed for doses up to 300 cGy and above which supralinear behavior. The standard uncertainty with field size observed was 1.10% ± 0.4%, 1.09% ± 0.34%, and 1.2% ± 0.26% for 6 MV, 18 MV, and 60 Co beam, respectively. The maximum difference with dose rate was 1.3% ± 0.4% for 6 MV and 1.4% ± 0.4% for 18 MV photon beams. The largest variation in SSD was 1.5% ± 1.2% for 60 Co, 1.5% ± 0.9% for 6 MV, and 1.5% ± 1.3% for 18 MV photon beams. The energy dependence of OSL response at 18 MV and 60 Co with 6 MV beam was 1.5% ± 0.7% and 1.7% ± 0.6%, respectively. In addition, good reproducibility, stability after the decay of transient signal, and predictable fading were observed. The results obtained in this study indicate the efficacy and suitability of nanoDot OSLD for dosimetric measurements in clinical radiotherapy.

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

PubMed Central

Suetens, Annelies; Konings, Katrien; Moreels, Marjan; Quintens, Roel; Verslegers, Mieke; Soors, Els; Tabury, Kevin; Grégoire, Vincent; Baatout, Sarah

2016-01-01

The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy). PMID:27148479

Exposure Risks Among Children Undergoing Radiation Therapy: Considerations in the Era of Image Guided Radiation Therapy

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

Hess, Clayton B.; Thompson, Holly M.; Benedict, Stanley H.

Recent improvements in toxicity profiles of pediatric oncology patients are attributable, in part, to advances in the field of radiation oncology such as intensity modulated radiation (IMRT) and proton therapy (IMPT). While IMRT and IMPT deliver highly conformal dose to targeted volumes, they commonly demand the addition of 2- or 3-dimensional imaging for precise positioning—a technique known as image guided radiation therapy (IGRT). In this manuscript we address strategies to further minimize exposure risk in children by reducing effective IGRT dose. Portal X rays and cone beam computed tomography (CBCT) are commonly used to verify patient position during IGRT and,more » because their relative radiation exposure is far less than the radiation absorbed from therapeutic treatment beams, their sometimes significant contribution to cumulative risk can be easily overlooked. Optimizing the conformality of IMRT/IMPT while simultaneously ignoring IGRT dose may result in organs at risk being exposed to a greater proportion of radiation from IGRT than from therapeutic beams. Over a treatment course, cumulative central-axis CBCT effective dose can approach or supersede the amount of radiation absorbed from a single treatment fraction, a theoretical increase of 3% to 5% in mutagenic risk. In select scenarios, this may result in the underprediction of acute and late toxicity risk (such as azoospermia, ovarian dysfunction, or increased lifetime mutagenic risk) in radiation-sensitive organs and patients. Although dependent on variables such as patient age, gender, weight, body habitus, anatomic location, and dose-toxicity thresholds, modifying IGRT use and acquisition parameters such as frequency, imaging modality, beam energy, current, voltage, rotational degree, collimation, field size, reconstruction algorithm, and documentation can reduce exposure, avoid unnecessary toxicity, and achieve doses as low as reasonably achievable, promoting a culture and practice of “gentle IGRT.”.« less

Sci—Fri PM: Topics — 07: Monte Carlo Simulation of Primary Dose and PET Isotope Production for the TRIUMF Proton Therapy Facility

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

Lindsay, C; Jirasek, A; Blackmore, E

Uveal melanoma is a rare and deadly tumour of the eye with primary metastases in the liver resulting in an 8% 2-year survival rate upon detection. Large growths, or those in close proximity to the optic nerve, pose a particular challenge to the commonly employed eye-sparing technique of eye-plaque brachytherapy. In these cases external beam charged particle therapy offers improved odds in avoiding catastrophic side effects such as neuropathy or blindness. Since 1995, the British Columbia Cancer Agency in partnership with the TRIUMF national laboratory have offered proton therapy in the treatment of difficult ocular tumors. Having seen 175 patients,more » yielding 80% globe preservation and 82% metastasis free survival as of 2010, this modality has proven to be highly effective. Despite this success, there have been few studies into the use of the world's largest cyclotron in patient care. Here we describe first efforts of modeling the TRIUMF dose delivery system using the FLUKA Monte Carlo package. Details on geometry, estimating beam parameters, measurement of primary dose and simulation of PET isotope production are discussed. Proton depth dose in both modulated and pristine beams is successfully simulated to sub-millimeter precision in range (within limits of measurement) and 2% agreement to measurement within in a treatment volume. With the goal of using PET signals for in vivo dosimetry (alignment), a first look at PET isotope depth distribution is presented — comparing favourably to a naive method of approximating simulated PET slice activity in a Lucite phantom.« less

Comparison of electromagnetic and hadronic models generated using Geant 4 with antiproton dose measured in CERN.

PubMed

Tavakoli, Mohammad Bagher; Reiazi, Reza; Mohammadi, Mohammad Mehdi; Jabbari, Keyvan

2015-01-01

After proposing the idea of antiproton cancer treatment in 1984 many experiments were launched to investigate different aspects of physical and radiobiological properties of antiproton, which came from its annihilation reactions. One of these experiments has been done at the European Organization for Nuclear Research known as CERN using the antiproton decelerator. The ultimate goal of this experiment was to assess the dosimetric and radiobiological properties of beams of antiprotons in order to estimate the suitability of antiprotons for radiotherapy. One difficulty on this way was the unavailability of antiproton beam in CERN for a long time, so the verification of Monte Carlo codes to simulate antiproton depth dose could be useful. Among available simulation codes, Geant4 provides acceptable flexibility and extensibility, which progressively lead to the development of novel Geant4 applications in research domains, especially modeling the biological effects of ionizing radiation at the sub-cellular scale. In this study, the depth dose corresponding to CERN antiproton beam energy by Geant4 recruiting all the standard physics lists currently available and benchmarked for other use cases were calculated. Overall, none of the standard physics lists was able to draw the antiproton percentage depth dose. Although, with some models our results were promising, the Bragg peak level remained as the point of concern for our study. It is concluded that the Bertini model with high precision neutron tracking (QGSP_BERT_HP) is the best to match the experimental data though it is also the slowest model to simulate events among the physics lists.

High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate.

PubMed

Mercier, Thomas; Tissot, Fréderic; Gardiol, Céline; Corti, Natascia; Wehrli, Stéphane; Guidi, Monia; Csajka, Chantal; Buclin, Thierry; Couet, William; Marchetti, Oscar; Decosterd, Laurent A

2014-11-21

Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid--BEH--Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006 μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20 μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48 h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15 min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4 h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Poster — Thur Eve — 10: Partial kV CBCT, complete kV CBCT and EPID in breast treatment: a dose comparison study for skin, breasts, heart and lungs

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

Roussin, E; Archambault, L K; Wierzbicki, W

The advantages of kilovoltage cone beam CT (kV CBCT) imaging over electronic portal imaging device (EPID) such as accurate 3D anatomy, soft tissue visualization, fast rigid registration and enhanced precision on patient positioning has lead to its increasing use in clinics. The benefits of this imaging technique are at the cost of increasing the dose to healthy surrounding organs. Our center has moved toward the use of daily partial rotation kV CBCT to restrict the dose to healthy tissues. This study aims to better quantify radiation doses from different image-guidance techniques such as tangential EPID, complete and partial kV CBCTmore » for breast treatments. Cross-calibrated ionization chambers and kV calibrated Gafchromic films were used to measure the dose to the heart, lungs, breasts and skin. It was found that performing partial kV CBCT decreases the heart dose by about 36%, the lungs dose by 31%, the contralateral breast dose by 41% and the ipsilateral breast dose by 43% when compared to a full rotation CBCT. The skin dose measured for a full rotation CBCT was about 0.8 cGy for the contralateral breast and about 0.3 cGy for the ipsilateral breast. The study is still ongoing and results on skin doses for partial rotation kV CBCT as well as for tangential EPID images are upcoming.« less

Effects of the dose and viability of Saccharomyces cerevisiae. 1. Diversity of ruminal microbes as analyzed by Illumina MiSeq sequencing and quantitative PCR.

PubMed

Jiang, Y; Ogunade, I M; Qi, S; Hackmann, T J; Staples, C R; Adesogan, A T

2017-01-01

This study was conducted to examine effects of the dose and viability of supplemental Saccharomyces cerevisiae on the ruminal fermentation and bacteria population and the performance of lactating dairy cows. Four ruminally cannulated lactating cows averaging 284±18d in milk were assigned to 4 treatments arranged in a 4×4 Latin square design with four 21-d periods. Cows were fed a total mixed ration containing 41.7% corn silage, 12.1% brewer's grains, and 46.2% concentrate on a dry matter basis. The diet was supplemented with no yeast (control) or with a low dose of live yeast (5.7×10 7 cfu/cow per day; LLY), a high dose of live yeast (6.0×10 8 cfu/cow per day; HLY), or a high dose of killed yeast (6.0×10 8 cfu/cow per day; HDY). Microbial diversity was examined by high-throughput Illumina MiSeq sequencing (Illumina Inc., San Diego, CA) of the V4 region of the 16S rRNA gene. The relative abundance of select ruminal bacteria was also quantified by quantitative PCR (qPCR). Adding LLY to the diet increased the relative abundance of some ruminal cellulolytic bacteria (Ruminococcus and Fibrobacter succinogenes) and amylolytic bacteria (Ruminobacter, Bifidobacterium, and Selenomonas ruminantium). Adding live instead of killed yeast increased the relative abundance of Ruminococcus and F. succinogenes; adding HDY increased the relative abundance of Ruminobacter, Bifidobacterium, Streptococcus bovis, and Selenomonas ruminantium. The most dominant (≥1% of total sequences) bacteria that responded to LLY addition whose functions are among the least understood in relation to the mode of action of yeast include Paraprevotellaceae, CF231, Treponema, and Lachnospiraceae. Future studies should aim to speciate, culture, and examine the function of these bacteria to better understand their roles in the mode of action of yeast. A relatively precise relationship was detected between the relative abundance of F. succinogenes (R 2 =0.67) from qPCR and MiSeq sequencing, but weak relationships were detected for Megasphaera elsdenii, Ruminococcus flavefaciens, and S. ruminantium (R 2 ≤0.19). Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Prostate tissue ablation with MRI guided transurethral therapeutic ultrasound and intraoperative assessment of the integrity of the neurovascular bundle

NASA Astrophysics Data System (ADS)

Sammet, Steffen; Partanen, Ari; Yousuf, Ambereen; Wardrip, Craig; Niekrasz, Marek; Antic, Tatjana; Razmaria, Aria; Sokka, Sham; Karczmar, Gregory; Oto, Aytekin

2017-03-01

OBJECTIVES: Evaluation of the precision of prostate tissue ablation with MRI guided therapeuticultrasound by intraoperative objective assessment of the neurovascular bundle in canines in-vivo. METHODS: In this ongoing IACUC approved study, eight male canines were scanned in a clinical 3T Achieva MRI scanner (Philips) before, during, and after ultrasound therapy with a prototype MR-guided ultrasound therapy system (Philips). The system includes a therapy console to plan treatment, to calculate real-time temperature maps, and to control ultrasound exposures with temperature feedback. Atransurethral ultrasound applicator with eight transducer elements was used to ablate canine prostate tissue in-vivo. Ablated prostate tissue volumes were compared to the prescribed target volumes to evaluate technical effectiveness. The ablated volumes determined by MRI (T1, T2, diffusion, dynamic contrast enhanced and 240 CEM43 thermal dose maps) were compared to H&E stained histological slides afterprostatectomy. Potential nerve damage of the neurovascular bundle was objectively assessed intraoperativelyduring prostatectomy with a CaverMap Surgical Aid nerve stimulator (Blue Torch Medical Technologies). RESULTS: Transurethral MRI -guided ultrasound therapy can effectively ablate canine prostate tissue invivo. Coronal MR-imaging confirmed the correct placement of the HIFU transducer. MRI temperature maps were acquired during HIFU treatment, and subsequently used for calculating thermal dose. Prescribed target volumes corresponded to the 240 CEM43 thermal dose maps during HIFU treatment in all canines. Ablated volumes on high resolution anatomical, diffusion weighted, and contrast enhanced MR images matched corresponding histological slides after prostatectomy. MRI guidance with realtime temperature monitoring showed no damage to surrounding tissues, especially to the neurovascular bundle (assessed intra-operatively with a nerve stimulator) or to the rectum wall. CONCLUSIONS: Our study demonstrates the effectiveness and precision of transurethral ultrasound ablation of prostatic tissue in canines with MRI monitoring and guidance. The canine prostate is an excellent model for the human prostate with similar anatomical characteristics and diseases. MRI guidance with real-time, intraoperative temperature monitoring reduces the risk of damaging critical surrounding anatomical structures in ultrasound therapy of the prostate.

Feasibility of real-time MR thermal dose mapping for predicting radiofrequency ablation outcome in the myocardium in vivo.

PubMed

Toupin, Solenn; Bour, Pierre; Lepetit-Coiffé, Matthieu; Ozenne, Valéry; Denis de Senneville, Baudouin; Schneider, Rainer; Vaussy, Alexis; Chaumeil, Arnaud; Cochet, Hubert; Sacher, Frédéric; Jaïs, Pierre; Quesson, Bruno

2017-01-25

Clinical treatment of cardiac arrhythmia by radiofrequency ablation (RFA) currently lacks quantitative and precise visualization of lesion formation in the myocardium during the procedure. This study aims at evaluating thermal dose (TD) imaging obtained from real-time magnetic resonance (MR) thermometry on the heart as a relevant indicator of the thermal lesion extent. MR temperature mapping based on the Proton Resonance Frequency Shift (PRFS) method was performed at 1.5 T on the heart, with 4 to 5 slices acquired per heartbeat. Respiratory motion was compensated using navigator-based slice tracking. Residual in-plane motion and related magnetic susceptibility artifacts were corrected online. The standard deviation of temperature was measured on healthy volunteers (N = 5) in both ventricles. On animals, the MR-compatible catheter was positioned and visualized in the left ventricle (LV) using a bSSFP pulse sequence with active catheter tracking. Twelve MR-guided RFA were performed on three sheep in vivo at various locations in left ventricle (LV). The dimensions of the thermal lesions measured on thermal dose images, on 3D T1-weighted (T1-w) images acquired immediately after the ablation and at gross pathology were correlated. MR thermometry uncertainty was 1.5 °C on average over more than 96% of the pixels covering the left and right ventricles, on each volunteer. On animals, catheter repositioning in the LV with active slice tracking was successfully performed and each ablation could be monitored in real-time by MR thermometry and thermal dosimetry. Thermal lesion dimensions on TD maps were found to be highly correlated with those observed on post-ablation T1-w images (R = 0.87) that also correlated (R = 0.89) with measurements at gross pathology. Quantitative TD mapping from real-time rapid CMR thermometry during catheter-based RFA is feasible. It provides a direct assessment of the lesion extent in the myocardium with precision in the range of one millimeter. Real-time MR thermometry and thermal dosimetry may improve safety and efficacy of the RFA procedure by offering a reliable indicator of therapy outcome during the procedure.

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

2017-01-01

Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans

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

Zhang, Da; Padole, Atul; Li, Xinhua

2014-09-15

Purpose: To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Methods: Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin dosesmore » were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. Results: The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8% − 25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2 ± 3.3 and 16.5 ± 2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. Conclusions: This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.« less

Assessing the dosimetric and geometric accuracy of stereotactic radiosurgery

NASA Astrophysics Data System (ADS)

Dimitriadis, Alexis

Stereotactic radiosurgery (SRS) is a non-invasive treatment predominantly used for the management of malignant and benign brain tumours. The treatment can be delivered by various platforms in a single fraction where a high dose of radiation is delivered to the target whilst the surrounding healthy tissue is spared. This requires a high degree of accuracy in terms of the dose level delivered but also in terms of geometric precision. The purpose of this work was to identify the variations of SRS practice in the UK and develop a novel method compatible with all practices, capable of assessing the accuracy of delivery. The motivation behind this effort was to contribute to safety in SRS delivery, provide confidence through a quality assurance audit and form a basis to support standardisation in SRS. A national survey was performed to investigate SRS practices in the UK and to help guide the methodology of this thesis. This resulted to the development of a method for an end-to-end audit of SRS. This was based on an anthropomorphic head phantom with a medium sized target located centrally in the brain, in close proximity to the brainstem. This realistic patient scenario was presented to all 26 radiosurgery centres in the UK who were asked to treat it with SRS. The dose delivered was assessed using two novel commercially available radiation detectors, a plastic scintillator and radiochromic film. These detectors were characterised for measuring the dose delivered in SRS. Another established dosimetry system, alanine, was also used alongside these detectors to assess the accuracy of each delivery. The results allowed the assessment of SRS practices in the UK and the comparison of all centres that participated in the audit. The results were also used to evaluate the performance of the dosimeters used for the purposes of quality assurance measurements and audit.

Error analysis of high-rate GNSS precise point positioning for seismic wave measurement

NASA Astrophysics Data System (ADS)

Shu, Yuanming; Shi, Yun; Xu, Peiliang; Niu, Xiaoji; Liu, Jingnan

2017-06-01

High-rate GNSS precise point positioning (PPP) has been playing a more and more important role in providing precise positioning information in fast time-varying environments. Although kinematic PPP is commonly known to have a precision of a few centimeters, the precision of high-rate PPP within a short period of time has been reported recently with experiments to reach a few millimeters in the horizontal components and sub-centimeters in the vertical component to measure seismic motion, which is several times better than the conventional kinematic PPP practice. To fully understand the mechanism of mystified excellent performance of high-rate PPP within a short period of time, we have carried out a theoretical error analysis of PPP and conducted the corresponding simulations within a short period of time. The theoretical analysis has clearly indicated that the high-rate PPP errors consist of two types: the residual systematic errors at the starting epoch, which affect high-rate PPP through the change of satellite geometry, and the time-varying systematic errors between the starting epoch and the current epoch. Both the theoretical error analysis and simulated results are fully consistent with and thus have unambiguously confirmed the reported high precision of high-rate PPP, which has been further affirmed here by the real data experiments, indicating that high-rate PPP can indeed achieve the millimeter level of precision in the horizontal components and the sub-centimeter level of precision in the vertical component to measure motion within a short period of time. The simulation results have clearly shown that the random noise of carrier phases and higher order ionospheric errors are two major factors to affect the precision of high-rate PPP within a short period of time. The experiments with real data have also indicated that the precision of PPP solutions can degrade to the cm level in both the horizontal and vertical components, if the geometry of satellites is rather poor with a large DOP value.

Note: High precision measurements using high frequency gigahertz signals

NASA Astrophysics Data System (ADS)

Jin, Aohan; Fu, Siyuan; Sakurai, Atsunori; Liu, Liang; Edman, Fredrik; Pullerits, Tõnu; Öwall, Viktor; Karki, Khadga Jung

2014-12-01

Generalized lock-in amplifiers use digital cavities with Q-factors as high as 5 × 108 to measure signals with very high precision. In this Note, we show that generalized lock-in amplifiers can be used to analyze microwave (giga-hertz) signals with a precision of few tens of hertz. We propose that the physical changes in the medium of propagation can be measured precisely by the ultra-high precision measurement of the signal. We provide evidence to our proposition by verifying the Newton's law of cooling by measuring the effect of change in temperature on the phase and amplitude of the signals propagating through two calibrated cables. The technique could be used to precisely measure different physical properties of the propagation medium, for example, the change in length, resistance, etc. Real time implementation of the technique can open up new methodologies of in situ virtual metrology in material design.

Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced radiation pneumonitis.

PubMed

Su, QiaoLi; Wang, Duoning; Yuan, Bo; Liu, Feng; Lei, Yi; Li, Shuangqing

2014-11-01

The objective of this study was to explore the effects of proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy were retrospectively analyzed, and the patients were divided into PPI group and control group, according to whether or not PPIs were applied. The development and prognosis of patients and the effects of different doses of PPI on patient condition from two groups were compared. There were 57 PPI cases in PPI group and 27 cases in control group. Basic characteristics of patients were not statistically different between the two groups; however, white blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05), indicating that radiation pneumonitis tended to be more severe in PPI group. As regards effects of PPI on prognosis of two groups, remission rate of radiation pneumonia in PPI group was significantly less than that of the control group. Among 57 cases in PPI group, there were 31 patients applied with PPI ≤ 1DDD and 31 patients applied with PPI > 1DDD. In comparison of the various parameters of patients, 7 days after being applied with different doses of PPI, there were no significant differences between the parameters of radiation pneumonitis. PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.

A biotin-triggered genetic switch in mammalian cells and mice.

PubMed

Weber, Wilfried; Lienhart, Cédric; Baba, Marie Daoud-El; Fussenegger, Martin

2009-03-01

Adjustable and reversible transgene expression systems enabling precise control of metabolic pathways and tunable production of specific target proteins have been essential for conditional reprogramming of mammalian cells to achieve progress in basic and applied bioengineering disciplines. Most of the currently available transgene control modalities have been designed to be responsive to clinically licensed pharmacologically active drugs which were expected to prevail in future clinical trials yet raised concerns about side effects when administered long term at subclinical doses. We have chosen vitamin H, also known as biotin, to control target gene transcription in mammalian cells in a potentially side effect-free manner. BirA, the Escherichia coli repressor of the biotin biosynthesis operon, was fused to the Herpes simplex transactivation domain to generate a biotin-dependent transactivator(BIT), which, in the presence of biotin, binds and activates chimeric target promoters (P(BIT)) harboring BirA-specific operator sites 5' of a minimal promoter. Biotin-inducible transgene expression was functional in a variety of rodent, monkey and human cell lines, showed excellent adjustability and reversibility in transgenic Chinese hamster ovary cell lines, provided precise product gene control in standard bioreactor cultures and enabled dose-dependent vitamin H control of a human glycoprotein in mice. The combination of a side effect-free inducer, precise and reversible transcription tunability and broad functionality in different cell types as well as in entire animals represents a unique asset for the use of biotin-inducible transgene control in future gene therapy, tissue engineering and biopharmaceutical manufacturing scenarios.

Radiobiological basis of SBRT and SRS.

PubMed

Song, Chang W; Kim, Mi-Sook; Cho, L Chinsoo; Dusenbery, Kathryn; Sperduto, Paul W

2014-08-01

Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) have been demonstrated to be highly effective for a variety of tumors. However, the radiobiological principles of SBRT and SRS have not yet been clearly defined. It is well known that newly formed tumor blood vessels are fragile and extremely sensitive to ionizing radiation. Various lines of evidence indicate that irradiation of tumors with high dose per fraction, i.e. >10 Gy per fraction, not only kills tumor cells but also causes significant damage in tumor vasculatures. Such vascular damage and ensuing deterioration of the intratumor environment then cause ischemic or indirect/secondary tumor cell death within a few days after radiation exposure, indicating that vascular damage plays an important role in the response of tumors to SBRT and SRS. Indications are that the extensive tumor cell death due to the direct effect of radiation on tumor cells and the secondary effect through vascular damage may lead to massive release of tumor-associated antigens and various pro-inflammatory cytokines, thereby triggering an anti-tumor immune response. However, the precise role of immune assault on tumor cells in SBRT and SRS has not yet been clearly defined. The "4 Rs" for conventional fractionated radiotherapy do not include indirect cell death and thus 4 Rs cannot account for the effective tumor control by SBRT and SRS. The linear-quadratic model is for cell death caused by DNA breaks and thus the usefulness of this model for ablative high-dose SBRT and SRS is limited.

Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability.

PubMed

Clarke, John D; Cherrington, Nathan J

2015-07-01

There are numerous factors in individual variability that make the development and implementation of precision medicine a challenge in the clinic. One of the main goals of precision medicine is to identify the correct dose for each individual in order to maximize therapeutic effect and minimize the occurrence of adverse drug reactions. Many promising advances have been made in identifying and understanding how factors such as genetic polymorphisms can influence drug pharmacokinetics (PK) and contribute to variable drug response (VDR), but it is clear that there remain many unidentified variables. Underlying liver diseases such as nonalcoholic steatohepatitis (NASH) alter absorption, distribution, metabolism, and excretion (ADME) processes and must be considered in the implementation of precision medicine. There is still a profound need for clinical investigation into how NASH-associated changes in ADME mediators, such as metabolism enzymes and transporters, affect the pharmacokinetics of individual drugs known to rely on these pathways for elimination. This review summarizes the key PK factors in individual variability and VDR and highlights NASH as an essential underlying factor that must be considered as the development of precision medicine advances. A multifactorial approach to precision medicine that considers the combination of two or more risk factors (e.g. genetics and NASH) will be required in our effort to provide a new era of benefit for patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Numerical Simulation Analysis of High-precision Dispensing Needles for Solid-liquid Two-phase Grinding

NASA Astrophysics Data System (ADS)

Li, Junye; Hu, Jinglei; Wang, Binyu; Sheng, Liang; Zhang, Xinming

2018-03-01

In order to investigate the effect of abrasive flow polishing surface variable diameter pipe parts, with high precision dispensing needles as the research object, the numerical simulation of the process of polishing high precision dispensing needle was carried out. Analysis of different volume fraction conditions, the distribution of the dynamic pressure and the turbulence viscosity of the abrasive flow field in the high precision dispensing needle, through comparative analysis, the effectiveness of the abrasive grain polishing high precision dispensing needle was studied, controlling the volume fraction of silicon carbide can change the viscosity characteristics of the abrasive flow during the polishing process, so that the polishing quality of the abrasive grains can be controlled.

Errors in the absorbed and the administered 131I therapeutic dose in patients with Graves' disease. A suggested more precise technique.

PubMed

Chen, Yangchun; Huang, Jincheng; Wang, Yuehui; Xie, Sipei; He, Fang

2017-01-01

The aim of this study was to evaluate the relative error (RE) in the thyroid absorbed dose (TD) of iodine-131 ( 131 I) in patients with Graves' disease comparing the simplified Quimby-Marinelli-Hine formula method (sQMHF) and the Standard Operational Procedures for dosimetry (SOPD) recommended by the European Association of Nuclear Medicine. This study included 45 patients with Graves' disease 12 men and 33 women; age 44.1±12.8 years. Thyroid mass (TM) was measured using ultrasound. Uptake of 131 I (RAIU) was tested at 2, 4-6, 24, 48-72, and 96-168h after its administration and the half-life (T 1/2eff ) and resident time (RT) of 131 I were computed. According to the sQMHF, a prescribed TD of 75Gy required 3.7MBq/g of 131 I, correction based on the RAIU 24h and T 1/2eff . Subsequently, the therapeutic TD was computed according to the SOPD and the RE was recorded. The data were analyzed using t-tests. The TM, RAIU 24h , therapeutic TD, and RE were 36.5±23.9g, 0.54±0.14, 89.4±9.4Gy, and -0.01±0.02, respectively. There was a significant difference (t-value 9.84, P<0.01) between the prescribed and therapeutic TD because the sQMHF ignores the absorbed dose deposited in the thyroid during the first 24h, which is included in the SOPD. In addition, the RE was significantly smaller than the variable coefficient (VC) of the therapeutic TD (t=-39.6, P<0.01). When the activity of 131 I was calculated using the simplified Q-M-H formula, the therapeutic absorbed thyroid dose was significantly higher than what was expected for the prescribed dose. Precision of the individualized therapeutic absorbed dose could be improved by computing the activity of 131 I using the standard operational procedures for dosimetry of the EANM.

The DosiMap, a new 2D scintillating dosimeter for IMRT quality assurance: characterization of two Cerenkov discrimination methods.

PubMed

Frelin, A M; Fontbonne, J M; Ban, G; Colin, J; Labalme, M; Batalla, A; Vela, A; Boher, P; Braud, M; Leroux, T

2008-05-01

New radiation therapy techniques such as IMRT present significant efficiency due to their highly conformal dose distributions. A consequence of the complexity of their dose distributions (high gradients, small irradiation fields, low dose distribution, ...) is the requirement for better precision quality assurance than in classical radiotherapy in order to compare the conformation of the delivered dose with the planned dose distribution and to guarantee the quality of the treatment. Currently this control is mostly performed by matrices of ionization chambers, diode detectors, dosimetric films, portal imaging, or dosimetric gels. Another approach is scintillation dosimetry, which has been developed in the last 15 years mainly through scintillating fiber devices. Despite having many advantages over other methods it is still at an experimental level for routine dosimetry because the Cerenkov radiation produced under irradiation represents an important stem effect. A new 2D water equivalent scintillating dosimeter, the DosiMap, and two different Cerenkov discrimination methods were developed with the collaboration of the Laboratoire de Physique Corpusculaire of Caen, the Comprehensive Cancer Center François Baclesse, and the ELDIM Co., in the frame of the MAESTRO European project. The DosiMap consists of a plastic scintillating sheet placed inside a transparent polystyrene phantom. The light distribution produced under irradiation is recorded by a CCD camera. Our first Cerenkov discrimination technique is subtractive. It uses a chessboard pattern placed in front of the scintillator, which provides a background signal containing only Cerenkov light. Our second discrimination technique is colorimetric. It performs a spectral analysis of the light signal, which allows the unfolding of the Cerenkov radiation and the scintillation. Tests were carried out with our DosiMap prototype and the performances of the two discrimination methods were assessed. The comparison of the dose measurements performed with the DosiMap and with dosimetric films for three different irradiation configurations showed discrepancies smaller than 3.5% for a 2 mm spatial resolution. Two innovative discrimination solutions were demonstrated to separate the scintillation from the Cerenkov radiation. It was also shown that the DosiMap, which is water equivalent, fast, and user friendly, is a very promising tool for radiotherapy quality assurance.

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.