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DOE OSTI2016

SU-F-T-275: A Correlation Study On 3D Fluence-Based QA and 2D Dose Measurement-Based QA

Purpose: The aim of this paper was to demonstrate the feasibility and creditability of computing and verifying 3D fluencies to assure IMRT and VMAT treatment deliveries, by correlating the passing rates of the 3D fluence-based QA (P(ά)) to the passing rates of 2D dose measurementbased QA (P(Dm)). Methods: 3D volumetric primary fluencies are calculated by forward-projecting the beam apertures and modulated by beam MU values at all gantry angles. We first introduce simulated machine parameter errors (MU, MLC positions, jaw, gantry and collimator) to the plan. Using passing rates of voxel intensity differences (P(Ir)) and 3D gamma analysis (P(γ)), calculated 3D fluencies, calculated 3D delivered dose, and measured 2D planar dose in phantom from the original plan are then compared with those from corresponding plans with errors, respectively. The correlations of these three groups of resultant passing rates, i.e. 3D fluence-based QA (P(ά,Ir) and P(ά,γ)), calculated 3D dose (P(Dc,Ir) and P(Dc,γ)), and 2D dose measurement-based QA (P(Dm,Ir) and P(Dm,γ)), will be investigated. Results: 20 treatment plans with 5 different types of errors were tested. Spearman’s correlations were found between P(ά,Ir) and P(Dc,Ir), and also between P(ά,γ) and P(Dc,γ), with averaged p-value 0.037, 0.065, and averaged correlation coefficient ρ-value 0.942, 0.871 respectively. Using Matrixx QA for IMRT plans, Spearman’s correlations were also obtained between P(ά,Ir) and P(Dm,Ir) and also between P(ά,γ) and P(Dm,γ), with p-value being 0.048, 0.071 and ρ-value being 0.897, 0.779 respectively. Conclusion: The demonstrated correlations improve the creditability of using 3D fluence-based QA for assuring treatment deliveries for IMRT/VMAT plans. Together with advantages of high detection sensitivity and better visualization of machine parameter errors, this study further demonstrates the accuracy and feasibility of 3D fluence based-QA in pre-treatment QA and daily QA. Research reported in this study is supported by the Agency for Healthcare Research and Quality (AHRQ) under award 1R01HS0222888. The senior author received research grants from ViewRay Inc. and Varian Medical System.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-292: Imaging and Radiation Oncology Core (IROC) Houston QA Center’s Anthropomorphic Phantom Program

Purpose: To describe the results of IROC Houston’s international and domestic end-to-end QA phantom irradiations. Methods: IROC Houston has anthropomorphic lung, liver, head and neck, prostate, SRS and spine phantoms that are used for credentialing and quality assurance purposes. The phantoms include structures that closely mimic targets and organs at risk and are made from tissue equivalent materials: high impact polystyrene, solid water, cork and acrylic. Motion tables are used to mimic breathing motion for some lung and liver phantoms. Dose is measured with TLD and radiochromic film in various planes within the target of the phantoms. Results: The most common phantom requested is the head and neck followed by the lung phantom. The head and neck phantom was sent to 800 domestic and 148 international sites between 2011 and 2015, with average pass rates of 89% and 92%, respectively. During the past five years, a general upward trend exists regarding demand for the lung phantom for both international and domestic sites with international sites more than tripling from 5 (2011) to 16 (2015) and domestic sites doubling from 66 (2011) to 152 (2015). The pass rate for lung phantoms has been consistent from year to year despite this large increase in the number of phantoms irradiated with an average pass rate of 85% (domestic) and 95% (international) sites. The percentage of lung phantoms used in combination with motions tables increased from 38% to 79% over the 5 year time span. Conclusion: The number of domestic and international sites irradiating the head and neck and lung phantoms continues to increase and the pass rates remained constant. These end-to-end QA tests continue to be a crucial part of clinical trial credentialing and institution quality assurance. This investigation was supported by IROC grant CA180803 awarded by the NCI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-328: Real-Time in Vivo Dosimetry of Prostate SBRT Boost Treatments Using MOSkin Detectors

Purpose: To provide in vivo measurements of dose to the anterior rectal wall during prostate SBRT boost treatments using MOSFET detectors. Methods: Dual MOSkin detectors were attached to a Rectafix rectal sparing device and inserted into patients during SBRT boost treatments. Patients received two boost fractions, each of 9.5–10 Gy and delivered using 2 VMAT arcs. Measurements were acquired for 12 patients. MOSFET voltages were read out at 1 Hz during delivery and converted to dose. MV images were acquired at known frequency during treatment so that the position of the gantry at each point in time was known. The cumulative dose at the MOSFET location was extracted from the treatment planning system at in 5.2° increments (FF beams) or at 5 points during each delivered arc (FFF beams). The MOSFET dose and planning system dose throughout the entirety of each arc were then compared using root mean square error normalised to the final planned dose for each arc. Results: The average difference between MOSFET measured and planning system doses determined over the entire course of treatment was 9.7% with a standard deviation of 3.6%. MOSFETs measured below the planned dose in 66% of arcs measured. Uncertainty in the position of the MOSFET detector and verification point are major sources of discrepancy, as the detector is placed in a high dose gradient region during treatment. Conclusion: MOSkin detectors were able to provide real time in vivo measurements of anterior rectal wall dose during prostate SBRT boost treatments. This method could be used to verify Rectafix positioning and treatment delivery. Further developments could enable this method to be used during high dose treatments to monitor dose to the rectal wall to ensure it remains at safe levels. Funding has been provided by the University of Newcastle. Kimberley Legge is the recipient of an Australian Postgraduate Award.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-485: Independent Remote Audits for TG51 NonCompliant Photon Beams Performed by the IROC Houston QA Center

Purpose: IROC-H conducts external audits for output check verification of photon and electron beams. Many of these beams can meet the geometric requirements of the TG 51 calibration protocol. For those photon beams that are non TG 51 compliant like Elekta GammaKnife, Accuray CyberKnife and TomoTherapy, IROC-H has specific audit tools to monitor the reference calibration. Methods: IROC-H used its TLD and OSLD remote monitoring systems to verify the output of machines with TG 51 non compliant beams. Acrylic OSLD miniphantoms are used for the CyberKnife. Special TLD phantoms are used for TomoTherapy and GammaKnife machines to accommodate the specific geometry of each machine. These remote audit tools are sent to institutions to be irradiated and returned to IROC-H for analysis. Results: The average IROC-H/institution ratios for 480 GammaKnife, 660 CyberKnife and 907 rotational TomoTherapy beams are 1.000±0.021, 1.008±0.019, 0.974±0.023, respectively. In the particular case of TomoTherapy, the overall ratio is 0.977±0.022 for HD units. The standard deviations of all results are consistent with values determined for TG 51 compliant photon beams. These ratios have shown some changes compared to values presented in 2008. The GammaKnife results were corrected by an experimentally determined scatter factor of 1.025 in 2013. The TomoTherapy helical beam results are now from a rotational beam whereas in 2008 the results were from a static beam. The decision to change modality was based on recommendations from the users. Conclusion: External audits of beam outputs is a valuable tool to confirm the calibrations of photon beams regardless of whether the machine is TG 51 or TG 51 non compliant. The difference found for TomoTherapy units is under investigation. This investigation was supported by IROC grant CA180803 awarded by the NCI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-G-TeP2-12: IROCHouston and MDAPL SRS Anthropomorphic Phantom Results

Purpose: To report the results of SRS phantom irradiations Methods: Anthropomorphic SRS head phantoms were sent to institutions participating in NCI sponsored SRS clinical trials and institutions interested in verifying SRS treatment delivery. The phantom shell was purchased from Phantom Laboratory and altered to house dosimetry and imaging inserts. The imaging insert has 1.9 cm diameter spherical target. The dosimetry insert holds two TLD capsules and radiochromic film in the coronal and sagittal planes through the center of the target. Institutions were asked to image, plan and treat the phantom as they would an SRS patient. GammaKnife, CyberKnife and c-arm accelerator institutions were asked to cover the target with 15 Gy, 20 Gy and 25 Gy, respectively. Following these guidelines and typical planning protocols for these three types of machines gives roughly 30 Gy to the center of the target for all units. Submission of the DICOM digital data set was required for analysis. Criteria of 5% for TLD results and 85% of pixels passing 5%/3mm gamma analysis were applied beginning in 2013. Results: The phantom was analyzed 269 times between the beginning of 2013 to present. The pass rate is 81%. Nineteen of the irradiation results failed only the TLD criteria, 19 failed only the film criteria and 12 failed both. Irradiations included 32 CyberKnife 23 GammaKnife, 3 TomoTherapy and 211 c-arm units. Planning systems included Eclipse, Ergo, GammaPlan, Hi-Art, iPlan, Monaco, MultiPlan, Pinnacle, RayStation, XiO and XKnife. Irradiations that were not accompanied with DICOM data were not included in this analysis. Conclusion: The phantom is a valuable end-to-end test used to independently verify the accuracy of SRS treatment delivery. This investigation was supported by IROC grant CA180803 awarded by the NCI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-G-JeP4-10: Measurement of Prostate Motion Trajectories During Prostate SBRT Boost Treatments with a Rectafix

Purpose: To determine prostate motion during SBRT boost treatments with a Rectafix rectal sparing device in place using kV imaging during treatment. Methods: Patients each had three gold fiducial markers inserted into the prostate and received two VMAT boost fractions of 9.5–10 Gy under the PROMETHEUS clinical trial protocol with a Rectafix rectal retractor in place. Two-dimensional kilovoltage images of fiducial markers were acquired continuously during delivery. Three patients were treated on a Varian Clinac iX linear accelerator (6X, 600 MU/min), where kV images were acquired at 5 Hz during treatment. Seven patients were treated on a Varian Truebeam linear accelerator (10XFFF, 2400 MU/min) where kV images were acquired every 3 seconds. Images were processed off-line using the Kilovoltage Intrafraction Monitoring (KIM) software after treatment. KIM determines prostate position in three dimensions from 2D kV projections using a probability density model and a pre-treatment kV arc. The 3D displacement of the prostate was quantified as a function of time throughout each fraction. Results: From all fractions analyzed, it was found that the prostate had moved less than 1 mm in any direction from its initial position 84.6% of the time. The prostate was between 1 and 2 mm from its initial position 14.2% of the time, between 2 and 3 mm of its initial position 0.8% of the time and was greater than 3 mm from its initial position only 0.4% of the time. Conclusion: The amount of prostate motion observed during prostate SBRT boost treatments with a Rectafix device in place was minimal and lower than that observed in non-Rectafix studies. The Rectafix device reduces rectal dose as well as immobilizing the prostate. Kimberley Legge is the recipient of an Australian Postgraduate Award.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-DE-207A-06: ECG-Gated CT Reconstruction for a C-Arm Inverse Geometry X-Ray System

Purpose: To obtain ECG-gated CT images from truncated projection data acquired with a C-arm based inverse geometry fluoroscopy system, for the purpose of cardiac chamber mapping in interventional procedures. Methods: Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system with a scanned multisource x-ray tube and a photon-counting detector mounted to a C-arm. In the proposed method, SBDX short-scan rotational acquisition is performed followed by inverse geometry CT (IGCT) reconstruction and segmentation of contrast-enhanced objects. The prior image constrained compressed sensing (PICCS) framework was adapted for IGCT reconstruction to mitigate artifacts arising from data truncation and angular undersampling due to cardiac gating. The performance of the reconstruction algorithm was evaluated in numerical simulations of truncated and non-truncated thorax phantoms containing a dynamic ellipsoid to represent a moving cardiac chamber. The eccentricity of the ellipsoid was varied at frequencies from 1–1.5 Hz. Projection data were retrospectively sorted into 13 cardiac phases. Each phase was reconstructed using IGCT-PICCS, with a nongated gridded FBP (gFBP) prior image. Surface accuracy was determined using Dice similarity coefficient and a histogram of the point distances between the segmented surface and ground truth surface. Results: The gated IGCT-PICCS algorithm improved surface accuracy and reduced streaking and truncation artifacts when compared to nongated gFBP. For the non-truncated thorax with 1.25 Hz motion, 99% of segmented surface points were within 0.3 mm of the 15 mm diameter ground truth ellipse, versus 1.0 mm for gFBP. For the truncated thorax phantom with a 40 mm diameter ellipse, IGCT-PICCS surface accuracy measured 0.3 mm versus 7.8 mm for gFBP. Dice similarity coefficient was 0.99–1.00 (IGCT-PICCS) versus 0.63–0.75 (gFBP) for intensity-based segmentation thresholds ranging from 25–75% maximum contrast. Conclusions: The PICCS algorithm was successfully applied to reconstruct truncated IGCT projection data with angular undersampling resulting from simulated cardiac gating. Research supported by the National Heart, Lung, and Blood Institute of the NIH under award number R01HL084022. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-CAMPUS-JeP1-01: Prompt Gamma Imaging with a Multi-Knife-Edge Slit Collimator: Evaluation for Use in Proton Beam Range Verification

Purpose: To evaluate and characterize a multi-slit collimated imaging system for use in prompt gamma range verification of proton therapy. Methods: Acrylic (PMMA) targets were irradiated with a 50 MeV proton beam. With the collimator placed 13 cm from the beam axis, photons of energy from 2–7 MeV were measured. Image reconstruction provided 2-dimensional distribution of gamma rays. Estimated Bragg peak location was compared with 1-dimensional profiles of photon images. Shifts in Bragg peak were simulated by physically moving the targets in 1 mm increments. Results: The imaging system measured prompt gamma emissions resulting from a 50 MeV proton beam, at currents up to 2 nA, incident on a PMMA target. Overall system detection efficiency was approximately 2.6×10{sup −5} gamma/proton. With delivery of 1×10{sup 11} protons, shifts of 1 mm in the target location were detected in 2D prompt gamma images and 1D profiles. With delivery of 1×10{sup 8} protons, shifts of approximately 3 mm were detectable. Conclusion: This work has characterized the performance of a prototype multi-slit collimated imaging system. The system can produce 2D images of prompt gamma distributions and detect shifts in Bragg peak location down to 1 mm. These results encourage further development and optimization of the system for clinical proton beam applications. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number: DENA0000979 through the Nuclear Science and Security Consortium.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-CAMPUS-JeP2-01: 4D-MRI with 3D Radial Sampling and Self-Gating-Based K-Space Sorting: Image Quality Improvement by Slab-Selective Excitation

Purpose: A recent 4D MRI technique based on 3D radial sampling and self-gating-based K-space sorting has shown promising results in characterizing respiratory motion. However due to continuous acquisition and potentially drastic k-space undersampling resultant images could suffer from low blood-to-tissue contrast and streaking artifacts. In this study 3D radial sampling with slab-selective excitation (SS) was proposed in attempt to enhance blood-to-tissue contrast by exploiting the in-flow effect and to suppress the excess signal from the peripheral structures particularly in the superior-inferior direction. The feasibility of improving image quality by using this approach was investigated through a comparison with the previously developed non-selective excitation (NS) approach. Methods: Two excitation approaches SS and NS were compared in 5 cancer patients (1 lung 1 liver 2 pancreas and 1 esophagus) at 3Tesla. Image artifact was assessed in all patients on a 4-point scale (0: poor; 3: excellent). Signal-tonoise ratio (SNR) of the blood vessel (aorta) at the center of field-of-view and its nearby tissue were measured in 3 of the 5 patients (1 liver 2 pancreas) and blood-to-tissue contrast-to-noise ratio (CNR) were then determined. Results: Compared with NS the image quality of SS was visually improved with overall higher signal in all patients (2.6±0.55 vs. 3.4±0.55). SS showed an approximately 2-fold increase of SNR in the blood (aorta: 16.39±1.95 vs. 32.19±7.93) and slight increase in the surrounding tissue (liver/pancreas: 16.91±1.82 vs. 22.31±3.03). As a result the blood-totissue CNR was dramatically higher in the SS method (1.20±1.20 vs. 9.87±6.67). Conclusion: The proposed 3D radial sampling with slabselective excitation allows for reduced image artifact and improved blood SNR and blood-to-tissue CNR. The success of this technique could potentially benefit patients with cancerous tumors that have invaded the surrounding blood vessels where radiation therapy is needed to remove tumor from those regions prior to surgical resection. This work is partially supported by NIH R03CA173273; and CTSI core voucher award.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-AB-BRC-08: Egs-brachy, a Fast and Versatile Monte Carlo Code for Brachytherapy Applications

Purpose: To introduce egs-brachy, a new, fast, and versatile Monte Carlo code for brachytherapy applications. Methods: egs-brachy is an EGSnrc user-code based on the EGSnrc C++ class library (egs++). Complex phantom, applicator, and source model geometries are built using the egs++ geometry module. egs-brachy uses a tracklength estimator to score collision kerma in voxels. Interaction, spectrum, energy fluence, and phase space scoring are also implemented. Phase space sources and particle recycling may be used to improve simulation efficiency. HDR treatments (e.g. stepping source through dwell positions) can be simulated. Standard brachytherapy seeds, as well as electron and miniature x-ray tube sources are fully modelled. Variance reduction techniques for electron source simulations are implemented (Bremsstrahlung cross section enhancement, uniform Bremsstrahlung splitting, and Russian Roulette). TG-43 parameters of seeds are computed and compared to published values. Example simulations of various treatments are carried out on a single 2.5 GHz Intel Xeon E5-2680 v3 processor core. Results: TG-43 parameters calculated with egs-brachy show excellent agreement with published values. Using a phase space source, 2% average statistical uncertainty in the PTV ((2mm){sup 3} voxels) can be achieved in 10 s for 100 {sup 125}I or {sup 103}Pd seeds in a 36.2 cm{sup 3} prostate PTV, 31 s for 64 {sup 103}Pd seeds in a 64 cm{sup 3} breast PTV, and 56 s for a miniature x-ray tube in a 27 cm{sup 3} breast PTV. Comparable uncertainty is reached in 12 s in a (1 mm){sup 3} water voxel 5 mm away from a COMS 16mm eye plaque with 13 {sup 103}Pd seeds. Conclusion: The accuracy of egs-brachy has been demonstrated through benchmarking calculations. Calculation times are sufficiently fast to allow full MC simulations for routine treatment planning for diverse brachytherapy treatments (LDR, HDR, miniature x-ray tube). egs-brachy will be available as free and open-source software to the medical physics research community. This work is partially funded by the Canada Research Chairs program, the Natural Sciences and Engineering Research Council of Canada, and the Ontario Ministry of Research and Innovation (Ontario Early Researcher Award).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-C-HORIZONS-01: The Expanding Horizons Travel Grant Program: ePosters and Discussion

The Expanding Horizons travel grant program provides opportunity for students and trainees to broaden the scope of scientific meetings they attend and gain insight from research outside traditional domains of medical physics. Through participation in such conferences, early-career researchers are introduced to new topics with relevance to medical physics research as a means to expand the scientific horizons of our discipline. This year, 21 Expanding Horizons travel grants were awarded, granting travel to 17 conferences, including: Radiomics, the World Molecular Imaging Society (WMIS), the 3D Printing Conference and Expo, the GPU Technology Conference, the SIAM Imaging Science Conference, the Human Brain Mapping Conference, the OSA Conference on Clinical and Translational Biophotonics, the Society for Neuroscience, the AACR Conference on Tumor Microenvironment, and the Conference on Knowledge Discovery and Data Mining. The Expanding Horizons electronic poster session gives a venue for AAPM conference attendees to meet and discuss with awardees, learn the hot topics and emerging research areas presented at these conferences, and understand the relevance to future medical physics research.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

TU-FG-201-03: Automatic Pre-Delivery Verification Using Statistical Analysis of Consistencies in Treatment Plan Parameters by the Treatment Site and Modality

Purpose: A novel computer software system, namely APDV (Automatic Pre-Delivery Verification), has been developed for verifying patient treatment plan parameters right prior to treatment deliveries in order to automatically detect and prevent catastrophic errors. Methods: APDV is designed to continuously monitor new DICOM plan files on the TMS computer at the treatment console. When new plans to be delivered are detected, APDV checks the consistencies of plan parameters and high-level plan statistics using underlying rules and statistical properties based on given treatment site, technique and modality. These rules were quantitatively derived by retrospectively analyzing all the EBRT treatment plans of the past 8 years at authors’ institution. Therapists and physicists will be notified with a warning message displayed on the TMS computer if any critical errors are detected, and check results, confirmation, together with dismissal actions will be saved into database for further review. Results: APDV was implemented as a stand-alone program using C# to ensure required real time performance. Mean values and standard deviations were quantitatively derived for various plan parameters including MLC usage, MU/cGy radio, beam SSD, beam weighting, and the beam gantry angles (only for lateral targets) per treatment site, technique and modality. 2D-based rules of combined MU/cGy ratio and averaged SSD values were also derived using joint probabilities of confidence error ellipses. The statistics of these major treatment plan parameters quantitatively evaluate the consistency of any treatment plans which facilitates automatic APDV checking procedures. Conclusion: APDV could be useful in detecting and preventing catastrophic errors immediately before treatment deliveries. Future plan including automatic patient identify and patient setup checks after patient daily images are acquired by the machine and become available on the TMS computer. This project is supported by the Agency for Healthcare Research and Quality (AHRQ) under award 1R01HS0222888. The senior author received research grants from ViewRay Inc. and Varian Medical System.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-H-BRC-03: Evaluation of Very High-Energy Electron (VHEE) Beams in Comparison to VMAT and PBS Treatment Plans

Purpose: The aim of this study was to evaluate the performance of very high-energy electron (VHEE) beams in comparison to clinically delivered treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PBS) technology. Methods: Three clinical cases were selected (prostate, lung, and pediatric CNS). The VHEE plans were calculated in the Monte Carlo EGSnrc code and pencil beam doses were calculated using the DOSxyznrc MC code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PBS were optimized in a research version of RayStation using an in house build script in order to minimize operator bias between the different techniques. Results: For the prostate cancer case, the PBS plan showed lower mean organ at risk (OAR) doses compared to the other modalities. An exception was the femoral heads, due to the lateral beam arrangements. The VMAT plan showed lower mean doses to the rectum and the bladder compared to the 100 MeV VHEE plan. The lung cancer case showed minor differences between the three modalities. However, the PBS plan showed a lower contralateral lung dose. The pediatric CNS case showed a better conformity and lower spinal cord dose for the 100 MeV VHEE plan. For all cases, the 200 MeV VHEE plans were found to be similar to or better than the 100 MeV VHEE plans. Conclusion: The present study showed that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses can be achieved. Funding: DoD, Award#:W81XWH-13-1-0165, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation. BL and PM are founders of TibaRay,Inc. BL and PM have received research grants from Varian and RaySearch Laboratory.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-H-207A-02: Relative Importance of the Various Factors Influencing the Accuracy of Monte Carlo Simulated CT Dose Index

Purpose: Monte Carlo simulation is a frequently used technique for assessing patient dose in CT. The accuracy of a Monte Carlo program is often validated using the standard CT dose index (CTDI) phantoms by comparing simulated and measured CTDI{sub 100}. To achieve good agreement, many input parameters in the simulation (e.g., energy spectrum and effective beam width) need to be determined. However, not all the parameters have equal importance. Our aim was to assess the relative importance of the various factors that influence the accuracy of simulated CTDI{sub 100}. Methods: A Monte Carlo program previously validated for a clinical CT system was used to simulate CTDI{sub 100}. For the standard CTDI phantoms (32 and 16 cm in diameter), CTDI{sub 100} values from central and four peripheral locations at 70 and 120 kVp were first simulated using a set of reference input parameter values (treated as the truth). To emulate the situation in which the input parameter values used by the researcher may deviate from the truth, additional simulations were performed in which intentional errors were introduced into the input parameters, the effects of which on simulated CTDI{sub 100} were analyzed. Results: At 38.4-mm collimation, errors in effective beam width up to 5.0 mm showed negligible effects on simulated CTDI{sub 100} (<1.0%). Likewise, errors in acrylic density of up to 0.01 g/cm{sup 3} resulted in small CTDI{sub 100} errors (<2.5%). In contrast, errors in spectral HVL produced more significant effects: slight deviations (±0.2 mm Al) produced errors up to 4.4%, whereas more extreme deviations (±1.4 mm Al) produced errors as high as 25.9%. Lastly, ignoring the CT table introduced errors up to 13.9%. Conclusion: Monte Carlo simulated CTDI{sub 100} is insensitive to errors in effective beam width and acrylic density. However, they are sensitive to errors in spectral HVL. To obtain accurate results, the CT table should not be ignored. This work was supported by a Faculty Research and Development Award from Cleveland State University.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation

Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated with 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion: These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM are founders of TibaRay,Inc.; BL and PM have received research grants from Varian and RaySearch Laboratory.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound

Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo: +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of FUS. This work was supported by NIH Grant R21 AR065010 (M.L. Fabiilli) and the Basic Radiologic Sciences Innovative Research Award (M.L. Fabiilli). A. Moncion is supported by the National Science Foundation Graduate Student Research Fellowship (Grant DGE 1256260).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

WE-DE-BRA-05: Monte Carlo Simulation of a Novel Multi-Layer MV Imager

Purpose: To develop and validate a Monte Carlo (MC) model of a novel multi-layer imager (MLI) for megavolt (MV) energy beams. The MC model will enable performance optimization of the MLI design for clinical applications including patient setup verification, tumor tracking and MVCBCT. Methods: The MLI is composed of four layers of converter, scintillator and light detector, each layer similar to the current clinical AS1200 detector (Varian Medical Systems, Inc). The MLI model was constructed using the Geant4 Application for Tomographic Emission (GATE v7.1) and includes interactions for x-ray photons, charged particles and optical photons. Computational experiments were performed to assess Modulation Transfer Function (MTF), Detective Quantum Efficiency (DQE) and Noise Power Spectrum normalized by photon fluence and average detector signal (qNNPS). Results were compared with experimental measurements. The current work incorporates, in one model, the complete chain of events occurring in the imager; i.e. starting from x-ray interaction to charged particle transport and energy deposition to subsequent generation, interactions and detection of optical photons. Results: There is good agreement between measured and simulated MTF, qNNPS and DQE values. Normalized root mean squared error (NRMSE) between measured and simulated values over all four layers was 2.18%, 2.43% and 6.05% for MTF, qNNPS and DQE respectively. The relative difference between simulated and measured values for qNNPS(0) was 1.68% and 1.57% for DQE(0). Current results were obtained using a 6MV Varian Truebeam™ spectrum. Conclusion: A comprehensive Monte Carlo model of the MLI prototype was developed to allow optimization of detector components. The model was assessed in terms of imaging performance using standard metrics (i.e. MTF, qNNPS, DQE). Good agreement was found between simulated and measured values. The model will be used to assess alternative detector constructions to facilitate advanced clinical imaging applications including MV-CBCT and tumor tracking. The project was supported, partially, by a grant from Varian Medical Systems, Inc., and Award No. R01CA188446-01 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

WE-DE-BRA-07: Megavoltage Spectral Imaging with a Layered Detector

Purpose: The aim of the current work is to investigate the feasibility of megavoltage spectral imaging using a multiple layered detector for enhancement of low contrast detectability through material segmentation and discrimination (such as bone, markers and metal implants). Potentially the technique can be applied to improve detection and reduce dose in Megavoltage Cone Beam Computed Tomography (MV-CBCT). Methods: Experiments were performed with a prototype multi-layer imager (MLI) which has higher detective efficiency and lower noise characteristics than conventional Electronic Portal Imaging Devices (EPIDs). Images of a solid water phantom were acquired at 2.5 MV, 6MV and 6MV without flattening filter (FFF). The following materials were placed within a stack of solid water: aluminum, copper and gold. Material separation was assessed based on Contrast-to-Noise Ratio (CNR) of the weighted image, formed by a weighted subtraction of the images from two layers of the MLI. A range of weighting factors were investigated for material separation. Results: CNR can be minimized for each material by appropriate selection of the subtraction weighting factor. This is equivalent to a selective subtraction of specific materials from the image. Using multiple layers simultaneously also decreases the dose requirement and removes any registration errors. The minimum CNR for aluminum, copper and gold at the weighted image formed with 2.5MV was obtained at weighting factors equal to 0.92, 0.76 and 0.64 respectively. The corresponding values at 6MVFFF were 0.99, 0.92 and 0.78 respectively. Conclusion: In the current work, an MV spectral imaging feasibility study was attempted using a novel multi-layer prototype EPID imager. Initial results suggest that material separation based on spectral differences between different layers is possible. This spectral imaging technique has potential advantages in MV-CBCT for real-time target tracking, patient set-up imaging and adaptive radiotherapy. The project was supported, partially, by a grant from Varian Medical Systems, Inc., and Award No. R01CA188446-01 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

60 APPLIED LIFE SCIENCES↗