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At least 541 records · Page 30

Loss of Nrf2 promotes rapid progression to heart failure following myocardial infarction

Nrf2 gene encodes a transcription factor regulating the expression of antioxidant and detoxification genes. We test here whether Nrf2 plays a role for cardiac protection during ischemic injury in an effort to establish Nrf2 as a target for cardiac protection therapies. Cardiac ischemia induced by the left anterior descending (LAD) coronary artery ligation results in myocardial infarction (MI). Young mice surviving MI show minimal signs of heart failure. Mice lacking Nrf2 experience an accelerated progression to heart failure that occurs within 10 days following induction of MI. Nrf2 knockout (Nrf2 KO) mice have a survival rate similar to wild type (WT) mice at 24 h after MI, but a significantly higher mortality rate within 10 days after MI (50% vs 86%). Morphological examination revealed maladaptive remodeling, including cardiac hypertrophy and dilated left ventricle in Nrf2 KO mice, which were absent in WT mice. Measurements of cardiac function revealed increased left ventricular mass and decreases in cardiac output in Nrf2 KO mice. In addition, Nrf2 KO mice show biomarkers of heart failure, such as elevated levels of β-MHC, ANF, and BNP mRNA in the myocardium. These data support that Nrf2 plays an important role in protecting the myocardium from ischemic injury. Lack of Nrf2 leads to rapid development of heart failure. - Highlights: • We test whether Nrf2 serves to protect the heart from ischemic injury. • Nrf2 knockout mice have increased mortality following myocardial ischemia. • Heart failure develops in 10 days following myocardial ischemia due to Nrf2 knockout.

60 APPLIED LIFE SCIENCES↗

Model 9975 O-Ring Fixture Long-Term Leak Performance (FY2020 Status Report)

Leak testing experiments to monitor the aging performance of Viton GLT and GLT-S O-rings used in the model 9975 shipping package has been ongoing since 2004 at Savannah River National Laboratory. Seventy tests using mock-up 9975 primary containment vessels (PCVs) with GLT O-rings were assembled and heated to temperatures ranging from 200 to 450 °F. In addition, fourteen tests with GLT-S O-rings were initiated in 2008 and heated to temperatures ranging from 200 to 400 °F. The conditioning temperatures are elevated compared to the calculated maximum O-ring temperature in a 9975 package in storage, 158 °F, to accelerate aging and enable observations of O-ring failures in a reasonable time frame. The fixtures are leak tested periodically and all GLT O-ring fixtures aging at 350 °F or above have failed to maintain a leak-tight seal. Eight GLT O-ring fixtures aging at 300 °F have failed after 2.8 to 5.7 years at temperature while the remaining fixtures at 300 °F were retired from testing following more than five years without failure. No failures have yet been observed in GLT O-ring fixtures aging at 200 °F for 12 to 14 years or aging at 270 °F for 8.5 years. All GLT-S O-ring fixtures aging at 300 °F or above have failed their leak test. No failures have yet been observed in GLT-S O-ring fixtures aging at 200 and 250 °F for 10 to 10.5 years. Data from the O-ring fixtures are generally consistent with results from compression stress-relaxation testing, and provide confidence in the predictive models based on those results. However, uncertainty exists in extrapolating these elevated temperature results to the lower temperatures of interest for normal storage in K-Area Complex (KAC). Oxygen consumption testing, which includes results from temperatures near KAC normal storage temperatures, is ongoing to provide further confidence and corroborate these extrapolations. The collective data from these test efforts suggest the minimum O-ring service life at KAC normal storage conditions should be at least 34 years for GLT and GLT-S O-rings. Measurement of compression set in O-rings removed from failed fixtures, compared to that from KAC surveillance O-rings, indicates margin remains for O-rings still in service. Aging and periodic leak testing will continue for the remaining PCV fixtures.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

SU-E-T-195: Gantry Angle Dependency of MLC Leaf Position Error

Purpose: The aim of this study was to investigate the gantry angle dependency of the multileaf collimator (MLC) leaf position error. Methods: An automatic MLC quality assurance system (AutoMLCQA) was developed to evaluate the gantry angle dependency of the MLC leaf position error using an electronic portal imaging device (EPID). To eliminate the EPID position error due to gantry rotation, we designed a reference maker (RM) that could be inserted into the wedge mount. After setting up the EPID, a reference image was taken of the RM using an open field. Next, an EPID-based picket-fence test (PFT) was performed without the RM. These procedures were repeated at every 45° intervals of the gantry angle. A total of eight reference images and PFT image sets were analyzed using in-house software. The average MLC leaf position error was calculated at five pickets (-10, -5, 0, 5, and 10 cm) in accordance with general PFT guidelines using in-house software. This test was carried out for four linear accelerators. Results: The average MLC leaf position errors were within the set criterion of <1 mm (actual errors ranged from -0.7 to 0.8 mm) for all gantry angles, but significant gantry angle dependency was observed in all machines. The error was smaller at a gantry angle of 0° but increased toward the positive direction with gantry angle increments in the clockwise direction. The error reached a maximum value at a gantry angle of 90° and then gradually decreased until 180°. In the counter-clockwise rotation of the gantry, the same pattern of error was observed but the error increased in the negative direction. Conclusion: The AutoMLCQA system was useful to evaluate the MLC leaf position error for various gantry angles without the EPID position error. The Gantry angle dependency should be considered during MLC leaf position error analysis.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-T-532: Validation and Implementation of Model-Based Patient Specific Quality Assurance Using Mobius3D and MobiusFX in a Clinical Setting

Purpose: This work carries out the commissioning and validation of the Mobius3D and MobiusFX software tools, which can replace the time-consuming measurement-based patient specific quality assurance (PSQA). Methods: The beam model supplied by Mobius3D was validated against a 21EX linac's beam measured data. Complex patient (VMAT) plans using Eclipse treatment planning system (TPS) was used to test the consistency between Mobius3D (calculates dose using patient image and field data) and MobiusFx (calculates dose using treatment dynalog files). Dose difference and gamma analysis (3%/3mm) between Mobius3D and MobiusFx were used to assess treatment plan and treatment delivery consistency. An end-to-end test was performed to validate Mobius3D and MobiusFx against ion chamber measurements. Effect of the dosimetric leaf gap (DLG) on Mobius3D dose calculation was additionally investigated. Results: Mobius3D beam model parameters matched within 1%-3% with our beam measured data. A comparison of Mobius3D and MobiusFx dose matrices for VMAT planned prostate cases showed (0.33±0.07)% mean dose difference with gamma values above 95%. The end-to-end test showed dose differences of 1% between Mobius3D and MobiusFx. Dependence of Mobius3D dose calculation upon DLG was explored by introducing a ±0.5 mm change in the default value for DLG. This change resulted in agreement differences above 2% Conclusion: Use of reference beam data would appear to speed up commissioning process for the clinical implementation of Mobius3D. However, careful consideration is required when comparing the information provided by the software, since large dose variations can be seen when the proper parameters are not optimized. The plan and delivered dose were in good agreement; hence MobiusFx has the potential to significantly speed up the PSQA process and at the same time helps to verify treatment parameters that are not possible with measurement-based PSQA.

60 APPLIED LIFE SCIENCES↗

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. We report our studies have identified several compounds with inhibitory activity (IC 50 ) and binding affinity (K D ) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a $K_i$ value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

59 BASIC BIOLOGICAL SCIENCES↗

SU-E-T-506: Dosimetric Verification of Photon MLC Delivered Electron Fields for Implementing MERT On An Artiste Linac

Purpose: To verify the dose accuracy of photon MLC delivered electron fields for implementing energy-intensity modulated electron radiotherapy (MERT) on an Artiste linac. Methods: It was proposed to deliver MERT on an Artiste linac at a short SSD (60 cm) to reduce beam penumbra caused by electron scatters. An in-house developed Monte Carlo (MC)-based dose calculation/optimization planning code was used for treatment planning. Our previous study showed that the measured dose distribution of a breast plan showed good agreement with the calculations in low-medium dose regions while the differences in high dose regions were outstanding. A continuous work found that the discrepancy is mainly caused by improper modeling in MC for the single focused MLC in the Artiste which was simplified as double focused in the previous MC simulations. With this remodeled MLC in the calculations, an energy-intensity modulated electron plan using 6, 9, 12 and 15 MeV was generated for a breast treatment on a breast phantom at a 60 cm SSD and recalculated regarding a solid water phantom. For a test study, four of MLC segments (each with a different energy) generated in the plan were delivered to the phantom and a film measurement was performed at the depth of 2 cm. The measured 2D dose distribution was then compared with calculations. Results: For composite doses of the four segments, measured 2D dose distributions overall agree well with the calculations (3mm/3%) in most area. The separate measurement for a single MLC segment for each of energies also showed the consistence with the calculations. Conclusion: After remodeling MLC in the MC calculations, the measured dose distribution for a subset of MLC segments from a MERT plan showed good agreement. Further detailed verification for the full plan will be the work in the next step.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-E-15: Design of a Water Calorimeter for Dual Use in An Integrated MRI-Linac and Gamma-Knife

Purpose: To design a water calorimeter for dual use in an integrated MRI-linac and Gamma-Knife. In calorimetry, dose to water is measured based on the assumption that energy absorbed in a sensitive volume is completely converted to temperature rise {sub (}ΔΤ{sub )} according to the specific heat capacity of the medium c: D=c*ΔT*k, where k is heat transfer correction factor and compensates for heat gain or loss at point of measurement due to conductive effects. Methods: A commercial finite element method software package was used to model four different water calorimeter designs. The long term (48 h) thermal stability of each design was accurately modeled, and the optimization of the final design was based on evaluation of the standard deviation of k for ten consecutive irradiation runs (lower standard deviation translates to greater thermal stability). Several insulator materials of varying thicknesses were investigated, and a sensitivity study of thermal stability to variations in ambient temperature fluctuations was undertaken. Specifically, we evaluated the effect of possible variations in coolant temperature circulating around the calorimeter tank in several scenarios (constant, slowly increasing, or fluctuating). Results: Due to MRI-compatibility requirements, the calorimeter is to be built entirely out of plastic. Among all insulation materials tested, solid state aerogel-based insulation resulted in least heat loss and thermal stability. The final design is cylindrical on top (to be used upright in MRI-linac) and semi-spherical at bottom (for use in GammaKnife). The range of k was found to be 1.002 ± 0.013 (k = 1), comparable with a k of 1.002 ± 0.014 for typical water calorimeters used in high energy beams. A long term stability of 0.36 µK/hr was evaluated. Conclusion: Optimization of a water calorimeter design for dual use in MRI-linac and Gamma-Knife has been completed and the device is currently in production. Supported by NSERC RGPIN 435608.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-J-200: Operation of An Electron Accelerator On An Integrated MR-Linac System

Purpose: An integrated MRI guided radiotherapy system poses a challenge of operating a linear accelerator in the presence of a magnetic field as the magnetic force acting on the electrons could Result in radiation source displacement and subsequent reduction of dose output. It was the purpose of this work to test the performance of a linac in the presence of a 1.5T MRI system. Methods: The first experimental MRI guided radiotherapy system at UMC-Utrecht consisting of an Elekta linac rotating around a 1.5T Magnex magnet was examined. A passive magnetic shield was simulated, designed and installed to reduce the influence of the MRI magnet stray field on the electron beamline. The B field inside the shield was measured as a function of gantry angle and measurements of dose rate constancy upon gantry rotation were performed. Results: The magnitude of the magnetic field on the electron beam path without the shield was as high as 70G. It varied by up to 15G with gantry rotation due to the presence of metal beams in the bunker floor which resulted in dose output drop of up to 70% at certain gantry angles. With the prototype shield, field magnitude was reduced to well below 0.5G everywhere along the electron beam path. Field variation with gantry rotation was decreased to below 0.2G and enabled dose output of the linac to be recovered at all gantry angles. The homogeneity of the field inside the MRI magnet has not been compromised. Conclusion: It was demonstrated that the influence of the 1.5T magnet and the bunker design on the linac operation has been minimised. The performance will be further improved on the Elekta Atlantic system which incorporates a newly developed and optimised Philips magnet design and bunker construction. J Harasimowicz, D Roberts, I Shinton and S Sund are employed by Elekta Limited Crawley, H Wang and M Zhong are employed by Elekta Beijing Medical Systems Co. Ltd., J Overweg is employed by Philips Technologie GmbH Forschungslaboratorien.

60 APPLIED LIFE SCIENCES↗

An efficient protocol for radiochromic film dosimetry combining calibration and measurement in a single scan

Purpose: Radiochromic film provides dose measurement at high spatial resolution, but often is not preferred for routine evaluation of patient-specific intensity modulated radiation therapy (IMRT) plans owing to ease-of-use factors. The authors have established an efficient protocol that combines calibration and measurement in a single scan and enables measurement results to be obtained in less than 30 min. This avoids complications due to postexposure changes in radiochromic film that delay the completion of a measurement, often for up to 24 h, in commonly used methods. In addition, the protocol addresses the accuracy and integrity of the measurement by eliminating environmental and interscan variability issues. Methods: The authors collected dose-response data from six production lots of Gafchromic EBT3 film and three production lots of EBT2 film at doses up to 480 cGy. In this work, the authors used seven different scanners of two different models-Epson 10000XL and V700; postexposure times before scanning from 30 min to 9 days; ambient temperatures for scanning spanning 11 Degree-Sign C; and two film orientations. Scanning was in 48-bit RGB format at 72 dpi resolution. Dose evaluation was conducted using a triple-channel dosimetry method. To evaluate the measurement protocol, patient specific IMRT and volumetric modulated arc therapy (VMAT) plans were exposed onto EBT3 films on a Varian Trilogy Linac. Film scanning was done following the protocol under a number of different conditions and the dose maps were analyzed to demonstrate the equivalence of results. Results: The results indicated that the dose-response data could be fit by a set of related rational functions leading to the description of a generic calibration curve. A simplified dosimetry protocol was established where dose-response data for a specific film lot, scanner, and scanning conditions could be derived from two films exposed to known doses. In most cases only one calibrated exposure was required since the dose for one of the films could be zero. Using the Gamma test criterion of 2%/2 mm to evaluate the measurements, similar passing rates ranging between about 95% and 99% for the fields studied were obtained from application films digitized under a variety of conditions all of them different than the conditions under which the calibration films were scanned. Conclusions: The authors have developed a simplified and efficient protocol to measure doses delivered by an IMRT or VMAT plan using only the patient film, one calibration film, one unexposed film, and applying a single scan to acquire a digital image for calculation and analysis. The simplification and timesaving offer a potential practical solution for using radiochromic film for routine treatment plan quality assurance without sacrificing spatial resolution for convenience.

07 ISOTOPE AND RADIATION SOURCES↗

Measuring neutron spectra in radiotherapy using the nested neutron spectrometer

Purpose: Out-of-field neutron doses resulting from photonuclear interactions in the head of a linear accelerator pose an iatrogenic risk to patients and an occupational risk to personnel during radiotherapy. To quantify neutron production, in-room measurements have traditionally been carried out using Bonner sphere systems (BSS) with activation foils and TLDs. In this work, a recently developed active detector, the nested neutron spectrometer (NNS), was tested in radiotherapy bunkers. Methods: The NNS is designed for easy handling and is more practical than the traditional BSS. Operated in current-mode, the problem of pulse pileup due to high dose-rates is overcome by measuring current, similar to an ionization chamber. In a bunker housing a Varian Clinac 21EX, the performance of the NNS was evaluated in terms of reproducibility, linearity, and dose-rate effects. Using a custom maximum-likelihood expectation–maximization algorithm, measured neutron spectra at various locations inside the bunker were then compared to Monte Carlo simulations of an identical setup. In terms of dose, neutron ambient dose equivalents were calculated from the measured spectra and compared to bubble detector neutron dose equivalent measurements. Results: The NNS-measured spectra for neutrons at various locations in a treatment room were found to be consistent with expectations for both relative shape and absolute magnitude. Neutron fluence-rate decreased with distance from the source and the shape of the spectrum changed from a dominant fast neutron peak near the Linac head to a dominant thermal neutron peak in the moderating conditions of the maze. Monte Carlo data and NNS-measured spectra agreed within 30% at all locations except in the maze where the deviation was a maximum of 40%. Neutron ambient dose equivalents calculated from the authors’ measured spectra were consistent (one standard deviation) with bubble detector measurements in the treatment room. Conclusions: The NNS may be used to reliably measure the neutron spectrum of a radiotherapy beam in less than 1 h, including setup and data unfolding. This work thus represents a new, fast, and practical method for neutron spectral measurements in radiotherapy.

60 APPLIED LIFE SCIENCES↗

TH-EF-BRB-11: Volumetric Modulated Arc Therapy for Total Body Irradiation

Purpose: To develop a modern, patient-comfortable total body irradiation (TBI) technique suitable for standard-sized linac vaults. Methods: An indexed rotatable immobilization system (IRIS) was developed to make possible total-body CT imaging and radiation delivery on conventional couches. Treatment consists of multi-isocentric volumetric modulated arc therapy (VMAT) to the upper body and parallel-opposed fields to the lower body. Each isocenter is indexed to the couch and includes a 180° IRIS rotation between the upper and lower body fields. VMAT fields are optimized to satisfy lung dose objectives while achieving a uniform therapeutic dose to the torso. End-to-end tests with a rando phantom were used to verify dosimetric characteristics. Treatment plan robustness regarding setup uncertainty was assessed by simulating global and regional isocenter setup shifts on patient data sets. Dosimetric comparisons were made with conventional extended distance, standing TBI (cTBI) plans using a Monte Carlo-based calculation. Treatment efficiency was assessed for eight courses of patient treatment. Results: The IRIS system is level and orthogonal to the scanned CT image plane, with lateral shifts <2mm following rotation. End-to-end tests showed surface doses within ±10% of the prescription dose, field junction doses within ±15% of prescription dose. Plan robustness tests showed <15% changes in dose with global setup errors up to 5mm in each direction. Local 5mm relative setup errors in the chest resulted in < 5% dose changes. Local 5mm shift errors in the pelvic and upper leg junction resulted in <10% dose changes while a 10mm shift error causes dose changes up to 25%. Dosimetric comparison with cTBI showed VMAT-TBI has advantages in preserving chest wall dose with flexibility in leveraging the PTV-body and PTV-lung dose. Conclusion: VMAT-TBI with the IRIS system was shown clinically feasible as a cost-effective approach to TBI for standard-sized linac vaults.

60 APPLIED LIFE SCIENCES↗

Progress toward a universal biomedical data translator

Clinical, biomedical, and translational science has reached an inflection point in the breadth and diversity of available data and the potential impact of such data to improve human health and well-being. However, the data are often siloed, disorganized, and not broadly accessible due to discipline-specific differences in terminology and representation. To address these challenges, the Biomedical Data Translator Consortium has developed and tested a pilot knowledge graph-based “Translator” system capable of integrating existing biomedical data sets and “translating” those data into insights intended to augment human reasoning and accelerate translational science. Having demonstrated feasibility of the Translator system, the Translator program has since moved into development, and the Translator Consortium has made significant progress in the research, design, and implementation of an operational system. Herein, we describe the current system’s architecture, performance, and quality of results. We apply Translator to several real-world use cases developed in collaboration with subject-matter experts. Finally, we discuss the scientific and technical features of Translator and compare those features to other state-of-the-art, biomedical graph-based question-answering systems.

60 APPLIED LIFE SCIENCES↗

Multi-Speed Transmission For Commercial Delivery Medium Duty PEDVs

Successful completion of the proposed project will set a course for improving quality of life by overcoming key challenges in the gearbox for commercial-delivery, medium-duty, plug-in electric drive vehicles: It will reduce US dependency on foreign oil through the use of electric driven propulsion instead of fuel driven. It will reduce health risks by replacing tailpipe emissions in densely populated city centers. Finally, it will improve the performance-cost basis to meet or exceed the expectations of the targeted medium duty vehicle fleet owners and the independent customers. The proposed multi-speed transmission will narrow motor operation to the peak efficiency region, thereby increasing the electric powertrain efficiency to help close the range gap. Further, it will enhance customer satisfaction by improving vehicle acceleration, top speed and gradeability over the baseline. The project was conducted in three budget periods: In BP1: Technology Development, High-level vehicle powertrain models were used to optimize candidate transmission architectures and ratios along with a variety of traction motor characteristics for concept selection. The detailed driveline designs and component dynamics were investigated to meet medium-duty EV requirements; In BP2: Technology Development and Prototype Demonstration, The modeling and simulations with multi-speed transmissions were extended to other MD and HD EV platforms. Clean sheet design of a compact, lightweight, flexible, and modular, four-speed transmission was completed. Development of novel shifting and controls strategies were started and procurement of the prototype transmission and the controller hardware was begun; In BP3: Technology Integration, Testing, and Demonstration, Prototyping the four-speed automated mechanical transmission was completed. The transmission controls system and software development and preliminary gearbox dyno tests were done at Eaton. ORNL conducted integrated powertrain HIL tests. One of the prototype units was fully integrated into a Proterra BE35 demonstration electric bus. The shift control strategy was fine-tuned on the integrated vehicle at Eaton Marshall Proving Grounds. NREL tested the vehicle and validated the performance gains. Simulations predicted up to 20% increase in system energy efficiency depending on drive cycles, a top speed of greater than70 mph on flat road, 40% faster acceleration and a doubled gradeability with four-speed transmission as compared to the baseline EVs. Chassis Dyno Tests at NREL verified the simulation results of Eaton team and the HIL test results of ORNL team. The new four-speed EV transmission is efficient, reliable, modular, scalable, light weight, small size, and will be affordable. Furthermore, four-speed transmission enables downsizing of motor, battery and final drive, thereby reducing the total system cost.

33 ADVANCED PROPULSION SYSTEMS↗

SU-E-T-29: A Web Application for GPU-Based Monte Carlo IMRT/VMAT QA with Delivered Dose Verification

Purpose: To enable an existing web application for GPU-based Monte Carlo (MC) 3D dosimetry quality assurance (QA) to compute “delivered dose” from linac logfile data. Methods: We added significant features to an IMRT/VMAT QA web application which is based on existing technologies (HTML5, Python, and Django). This tool interfaces with python, c-code libraries, and command line-based GPU applications to perform a MC-based IMRT/VMAT QA. The web app automates many complicated aspects of interfacing clinical DICOM and logfile data with cutting-edge GPU software to run a MC dose calculation. The resultant web app is powerful, easy to use, and is able to re-compute both plan dose (from DICOM data) and delivered dose (from logfile data). Both dynalog and trajectorylog file formats are supported. Users upload zipped DICOM RP, CT, and RD data and set the expected statistic uncertainty for the MC dose calculation. A 3D gamma index map, 3D dose distribution, gamma histogram, dosimetric statistics, and DVH curves are displayed to the user. Additional the user may upload the delivery logfile data from the linac to compute a 'delivered dose' calculation and corresponding gamma tests. A comprehensive PDF QA report summarizing the results can also be downloaded. Results: We successfully improved a web app for a GPU-based QA tool that consists of logfile parcing, fluence map generation, CT image processing, GPU based MC dose calculation, gamma index calculation, and DVH calculation. The result is an IMRT and VMAT QA tool that conducts an independent dose calculation for a given treatment plan and delivery log file. The system takes both DICOM data and logfile data to compute plan dose and delivered dose respectively. Conclusion: We sucessfully improved a GPU-based MC QA tool to allow for logfile dose calculation. The high efficiency and accessibility will greatly facilitate IMRT and VMAT QA.

07 ISOTOPE AND RADIATION SOURCES↗

TH-C-19A-09: Quantification of Transmission and Backscatter Factors as a function of Distance to Inhomogeneity Interface for Three Types of Surgical Implant Plates

Purpose: Carbon fiber materials have been increasingly used clinically, mainly in orthopedics, as an alternative to metallic implants because of their minimal artifacts on CT and MRI images. This study characterizes the transmission and backscatter property of carbon fiber plates (CarboFix Orthopedics, Herzeliya, Israel) with measurements for radiation therapy applications, and compares them to traditional Stainless Steel (SS) and Titanium (Ti) metal materials. Methods: For the transmission measurements, 1-mm-thick test plate was placed upstream from a plane parallel Markus chamber, separated by various thicknesses of polystyrene plates in 0.5 cm increments between 0 and 5 cm. With this setup, we quantified the radiation transmission as a function of distance to the inhomogeneity interface. The LINAC source to detector distance was maintained at 100 cm and 200 MU was delivered for each measurement. Two 3-cm solid water phantoms were placed at the top and bottom to provide build up. All the measurements were performed for 6 MV and 18 MV photons. The backscatter measurements had the identical setup, except that the test plate was downstream of the chamber from radiation. Results: The carbon fiber plates did not introduce any measureable inhomogeneity effect on the transmission and backscatter factor because of its low atomic number. In contrast, traditional metal implant materials caused up to 15% dose difference at upstream and 25% backscatter at downstream from radiation. Such differences decrease as the distance to the inhomogeneity interface increases and become unmeasurable at distance of 3 cm and 1 cm for upstream and downstream, respectively. Conclusion: A new type of carbon fiber implant plate was evaluated and found to have minimal inhomogeneity effect in MV radiation beams. Patients would benefit from a carbon based implant over metal for radiation therapy due to their minimal backscatter and imaging artifacts.

60 APPLIED LIFE SCIENCES↗

SU-E-T-100: An Approach to Improving the Dynamic Delivery Accuracy for Breast IMRT

Purpose: A method is established to improve the accuracy of the IMRT dose delivery for the treatment of breast and chest wall tumors when the higher dose gradient is delivered at the end of the leaf sequence. Methods: Dynamic MLC deliveries on Varian Linacs are achieved through the motion of the leaves from X1 to X2 direction. If the higher dose gradient is at the end of the leaf motion sequence, this can Result in an increased error in the overall dose delivery. Such errors have been observed in Lateral beams for Left-sided and Medial beams for Right-sided treatments. To evaluate and resolve this issue we adopted an approach where the fluence for such beams was geometrically flipped (mirrored) to treat the higher end of the dose gradient first. Results: Using this method, it was possible to deliver the optimized dose map to the area of interest still using only the X1–X2 direction of the leaf motion. The accuracy of this method was tested on different beam as part of our pre-treatment QA program on both Varian delivery systems. With this approach we found that there was significant improvement in delivery accuracy on both 21EX and TrueBeam systems. Beams of initial Gamma index (3% and 3mm) 89–93% were increased to 98–99%. We also observed superior delivery accuracy with TB compared to the 21EX Conclusion: This work demonstrate the need for a delivery sequence option from X2–X1 in situations where the MLC sequence indicates higher dose gradient component is being delivered at the end of the sequence. Results from this work can be considered in the IMRT beam optimization in the treatment planning systems. Further work will be required to establish the application of this approach in clinical setting.

60 APPLIED LIFE SCIENCES↗

Angular independent silicon detector for dosimetry in external beam radiotherapy

Purpose: In this work, the “edgeless” silicon detector technology is investigated, in combination with an innovative packaging solution, to manufacture silicon detectors with negligible angular response. The new diode is also characterized as a dosimeter for radiotherapy with the aim to verify its suitability as a single detector for in vivo dosimetry as well as large area 2D array that does not require angular correction to their response. Methods: For the characterisation of the “edgeless-drop-in” detector technology, a set of samples have been manufactured with different sensitive areas (1 × 1 and 0.5 × 0.5 mm{sup 2}) and different thicknesses (0.1 and 0.5 mm) in four different combinations of top and peripheral p–n junction fabricated on p-type and n-type silicon substrates. The diode probes were tested in terms of percentage depth dose (PDD), dose rate, and linearity and compared to ion chambers. Measurements of the output factor have been compared to film. The angular response of the diodes probes has been tested in a cylindrical PMMA phantom, rotated with bidirectional accuracy of 0.25° under 10 × 10 cm{sup 2} 6 MV Linac photon beam. The radiation hardness has been investigated as well as the effect of radiation damage on the angular and dose rate response of the diode probes when irradiated with photons from a Co-60 gamma source up to dose of 40 kGy. Results: The PDDs measured by the edgeless detectors show an agreement with the data obtained using ion chambers within ±2%. The output factor measured with the smallest area edgeless diodes (0.5 × 0.5 mm{sup 2}—0.1 and 0.5 mm thick) matches EBT3 film to within 2% for square field size from 10 to 0.5 cm side equivalent distance. The dose rate dependence in a dose per pulse range of 0.9 × 10{sup −5}–2.7 × 10{sup −4} Gy/pulse was less than −7% and +300% for diodes fabricated on p-type and n-type substrates, respectively. The edgeless diodes fabricated on the p-type substrate demonstrated degradation of the response as a function of the irradiation dose within 5%–15%, while diodes on the n-type substrate show a variation of approximately 30% after 40 kGy. The angular response of all probes is minimal (within 2%) but the N on N and P on P configurations show the best performances with an angular dependence of ±1.0% between 0° and 180° in the transversal direction. In this configuration, the space charge region of the passive diode extends from the behind and sidewall toward the anode on the top providing beneficial electric field distribution in the peripheral area of the diode. Such performance has also been tested after irradiation by Co-60 up to 40 kGy with no measurable change in angular response. Conclusions: A new edgeless-drop-in silicon diode fabrication and packaging technology has been used to develop detectors that show no significant angular dependence in their response for dosimetry in radiation therapy. From the characterisation of the diodes, proposed in a wide range of different geometries and configurations, the authors recommend the P-on-P detectors in conjunction with “drop in” packaging technology as the candidate for further development as single diode probe or 2D diode array for dosimetry in radiotherapy.

60 APPLIED LIFE SCIENCES↗

SU-E-T-76: A Software System to Monitor VMAT Plan Complexity in a Large Radiotherapy Centre

Purpose: To develop a system that analyses and reports the complexity of Volumetric Modulated Arc Therapy (VMAT) plans to aid in the decision making for streamlining patient specific dosimetric quality assurance (QA) tests. Methods: A software system, Delcheck, was developed in-house to calculate VMAT plan and delivery complexity using the treatment delivery file. Delcheck has the functionality to calculate multiple plan complexity metrics including the Li-Xing Modulation Index (LI-MI), multiplicative combination of Leaf Travel and Modulation Complexity Score (LTMCSv), Monitor Units per prescribed dose (MU/D) and the delivery complexity index (MIt) that incorporates the modulation of dose rate, leaf speed and gantry speed. Delcheck includes database functionality to store and compare plan metrics for a specified treatment site. The overall plan and delivery complexity is assessed based on the 95% conformance limit of the complexity metrics as Similar, More or Less complex. The functionality of the software was tested using 42 prostate conventional, 10 prostate SBRT and 15 prostate bed VMAT plans generated for an Elekta linear accelerator. Results: The mean(σ) of LI-MI for conventional, SBRT and prostate bed plans were 1690(486), 3215.4(1294) and 3258(982) respectively. The LTMCSv of the studied categories were 0.334(0.05), 0.325(0.07) and 0.3112(0.09). The MU/D of the studied categories were 2.4(0.4), 2.7(0.7) and 2.5(0.5). The MIt of the studied categories were 21.6(3.4), 18.2(3.0) and 35.9(6.6). The values of the complexity metrics show that LI-MI appeared to resolve the plan complexity better than LTMCSv and MU/D. The MIt value increased as the delivery complexity increased. Conclusion: The developed software was shown to be working as expected. In studied treatment categories Prostate bed plans are more complex in both plan and delivery and SBRT is more complex in plan and less complex in delivery as demonstrated by LI-MI and MIt. This project was funded through a Cancer Council NSW Project Grant (RG14-11)

60 APPLIED LIFE SCIENCES↗