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Evaluation of dose recalculation vs dose deformation in a commercial platform for deformable image registration with a computational phantom

Deformable image registration (DIR) is an important tool for mapping both dose and contours of a new set of planning images when recurrent, that is, adaptive radiotherapy, or further treatment, that is, re-treatment, is required. The aim of this study was to evaluate the need for plan recalculation in deformed anatomies and to develop a reliable workflow for validating the DIR algorithm to be applied to dose warping such as dose accumulation (DA) for adaptive radiation therapy, and dose summation (DS) in the case of re-treatment. A set of 3 computational phantoms was developed to validate the application of B-Spline-based registrations for dose mapping among the various computed tomography image data sets. Two different versions were defined for each phantom to simulate clinical needs: adaptive radiotherapy and re-treatment; a DIR was performed to obtain a displacement vector field (DVF) for dose applications. Comparison of calculated and deformed doses was carried out by means of known markers inside the virtual phantoms. The differences were evaluated using a 3% dose index as acceptance criteria. A paired Wilcoxon signed-rank test was carried out to test the statistical significance of differences within the markers. Significant differences were only observed for the deformed dose in the DA test; no significant differences were observed for recalculated dose values in the DA and DS tests. The dose index is in accordance with these results. The warping dose process obtained by registering various sets of images was validated; a recalculation approach seems to be more accurate for DA purposes and image-guided adaptive radiation therapy (IGART) applications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

TU-G-204-05: The Effects of CT Acquisition and Reconstruction Conditions On Computed Texture Feature Values of Lung Lesions

Purpose: Texture features have been investigated as a biomarker of response and malignancy. Because these features reflect local differences in density, they may be influenced by acquisition and reconstruction parameters. The purpose of this study was to investigate the effects of radiation dose level and reconstruction method on features derived from lung lesions. Methods: With IRB approval, 33 lung tumor cases were identified from clinically indicated thoracic CT scans in which the raw projection (sinogram) data were available. Based on a previously-published technique, noise was added to the raw data to simulate reduced-dose versions of each case at 25%, 10% and 3% of the original dose. Original and simulated reduced dose projection data were reconstructed with conventional and two iterative-reconstruction settings, yielding 12 combinations of dose/recon conditions. One lesion from each case was contoured. At the reference condition (full dose, conventional recon), 17 lesions were randomly selected for repeat contouring (repeatability). For each lesion at each dose/recon condition, 151 texture measures were calculated. A paired differences approach was employed to compare feature variation from repeat contours at the reference condition to the variation observed in other dose/recon conditions (reproducibility). The ratio of standard deviation of the reproducibility to repeatability was used as the variation measure for each feature. Results: The mean variation (standard deviation) across dose levels and kernel was significantly different with a ratio of 2.24 (±5.85) across texture features (p=0.01). The mean variation (standard deviation) across dose levels with conventional recon was also significantly different with 2.30 (7.11) (p=0.025). The mean variation across reconstruction settings of original dose has a trend in showing difference with 1.35 (2.60) among all features (p=0.09). Conclusion: Texture features varied considerably with variations in dose and reconstruction condition. Care should be taken to standardize these conditions when using texture as a quantitative feature. This effort supported in part by a grant from the National Cancer Institute’s Quantitative Imaging Network (QIN): U01 CA181156; The UCLA Department of Radiology has a Master Research Agreement with Siemens Healthcare; Dr. McNitt-Gray has previously received research support from Siemens Healthcare.

60 APPLIED LIFE SCIENCES↗

EPRI Report: Review of Geostatistical Approaches to Characterization of Subsurface Contamination - 17442

The key metric in the final release of a nuclear facility from radiological controls following plant decommissioning is the potential long-term radiation exposure to future users of the site. This is estimated from modeling of the exposure that could conceivably result from residual contamination remaining on the site in buildings, soil and groundwater after the completion of decontamination, dismantlement and remediation activities. A key input to such modelling is characterization data obtained from surveys and sampling. To date, the regulatory guidance for conducting the final status survey required to show compliance with regulator approved site release limits (i.e., radionuclide concentrations or contamination levels) has been limited to surface contamination. EPRI has completed a project that provides guidance for use of geo-statistics in the development of a site final status survey that will address the impact of dose to a future user of the site from subsurface contamination. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Impact of respiratory motion correction on SPECT myocardial perfusion imaging using a mechanically moving phantom assembly with variable cardiac defects

Background: The aim of this study was to determine the impact of respiratory motion correction on SPECT MPI and on defect detection using a phantom assembly. Methods: SPECT/CT data were acquired using an anthropomorphic phantom with inflatable lungs and with an ECG beating and moving cardiac compartment. The heart motion followed the respiratory pattern in the cranio-caudal direction to simulate normal or deep breathing. Small or large transmural defects were inserted into the myocardial wall of the left ventricle. SPECT/CT images were acquired for each of the four respiratory phases, from exhale to inhale. A respiratory motion correction was applied using an image-based method with transformation parameters derived from the SPECT data by a non-rigid registration algorithm. A report on defect detection from two physicians and a quantitative analysis on MPI data were performed before and after applying motion correction. Results: Respiratory motion correction eliminated artifacts present in the images, resulting in a uniform uptake and reduction of motion blurring, especially in the inferior and anterior regions of the LV myocardial walls. The physicians’ report after motion correction showed that images were corrected for motion. Conclusions: A combination of motion correction with attenuation correction reduces artifacts in SPECT MPI. AC-SPECT images with and without motion correction should be simultaneously inspected to report on small defects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Challenges and Practical Solutions for Conducting Structural MARSSIM Surveys in Elevated Radon Environments - 20413

The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) [1] provides comprehensive guidance for the development and implementation of radiological surveys conducted to demonstrate compliance with a dose- or risk-based cleanup goal during final status survey. The MARSSIM methodology follows an integrated strategy combining direct measurements and sampling to assess uniform residual contamination, and scanning surveys to identify localized areas of elevated activity. Building surveys assessing residual surface contamination present unique challenges from reliance on field measurements that may be subject to less than ideal environmental conditions. Additionally, limited characterization and excessive conservatism incorporated into the conceptual site model may result in derived concentration guideline levels (DCGL) and, as a consequence of relatively inefficient field instrumentation, corresponding attributable count rates generally comparable to background. The presence of elevated ambient radon concentrations and associated progeny deposition both exacerbate these intrinsic survey challenges and introduce a series of technical, logistic, and administrative obstacles that can wreak havoc on the statistical legitimacy of each component of the MARSSIM process. Short-lived radon progeny including polonium-218, lead-214, bismuth-214, and polonium-214 produce excessive alpha and beta radiation that may decrease instrument sensitivity through an increase in background count rates, and, at worst, may result in incorrect survey unit failure through the simulation of residual surface activity. Aside from the obvious solution of exhaustive radon mitigation, the primary objectives are to distinguish between radon progeny deposition and actual surface activity, and collect sufficient defensible data. The following is a technical discussion of the consequences of performing building MARSSIM surveys in the presence of elevated ambient radon atmospheres, conceptual examples, and an overview of practical strategies to minimize the effects of radon interference while collecting sufficient defensible data to complete the survey. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Theoretical substantiation of biological efficacy enhancement for β-delayed particle decay {sup 9}C beam: A Monte Carlo study in combination with analysis with the local effect model approach

Purpose: To improve the efficacy of heavy ion therapy, β-delayed particle decay {sup 9}C beam as a double irradiation source for cancer therapy has been proposed. The authors’ previous experiment showed that relative biological effectiveness (RBE) values at the depths around the Bragg peak of a {sup 9}C beam were enhanced and compared to its stable counterpart {sup 12}C beam. The purpose of this study was to explore the nature of the biological efficacy enhancement theoretically. Methods: A Monte Carlo simulation study was conducted in this study. First a simplified cell model was established so as to form a tumor tissue. Subsequently, the tumor tissue was imported into the Monte Carlo simulation software package GATE and then the tumor cells were virtually irradiated with comparable {sup 9}C and {sup 12}C beams, respectively, in the simulations. The transportation and particle deposition data of the {sup 9}C and {sup 12}C beams, derived from the GATE simulations, were analyzed with the authors’ local effect model implementation so as to deduce cell survival fractions. Results: The particles emitted from the decay process of deposited {sup 9}C particles around a cell nucleus increased the dose delivered to the nucleus and elicited clustered damages around the secondary particles’ trajectories. Therefore, compared to the {sup 12}C beam, the RBE value of the {sup 9}C beam increased at the depths around their Bragg peaks. Conclusions: Collectively, the increased local doses and clustered damages due to the decayed particles emitted from deposited {sup 9}C particles led to the RBE enhancement in contrast with the {sup 12}C beam. Thus, the enhanced RBE effect of a {sup 9}C beam for a simplified tumor model was shown theoretically in this study.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-T-598: Parametric Equation for Quick and Reliable Estimate of Stray Neutron Doses in Proton Therapy and Application for Intracranial Tumor Treatments

Purpose: Development of a parametric equation suitable for a daily use in routine clinic to provide estimates of stray neutron doses in proton therapy. Methods: Monte Carlo (MC) calculations using the UF-NCI 1-year-old phantom were exercised to determine the variation of stray neutron doses as a function of irradiation parameters while performing intracranial treatments. This was done by individually changing the proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and the air gap size while their impact on neutron doses were put into a single equation. The variation of neutron doses with distance from the target volume was also included in it. Then, a first step consisted in establishing the fitting coefficients by using 221 learning data which were neutron absorbed doses obtained with MC simulations while a second step consisted in validating the final equation. Results: The variation of stray neutron doses with irradiation parameters were fitted with linear, polynomial, etc. model while a power-law model was used to fit the variation of stray neutron doses with the distance from the target volume. The parametric equation fitted well MC simulations while establishing fitting coefficients as the discrepancies on the estimate of neutron absorbed doses were within 10%. The discrepancy can reach ∼25% for the bladder, the farthest organ from the target volume. Finally, the validation showed results in compliance with MC calculations since the discrepancies were also within 10% for head-and-neck and thoracic organs while they can reach ∼25%, again for pelvic organs. Conclusion: The parametric equation presents promising results and will be validated for other target sites as well as other facilities to go towards a universal method.

61 RADIATION PROTECTION AND DOSIMETRY↗

Modeling the impact of extreme weather events and future climate on the radiologically contaminated sites of Enewetak Atoll

Enewetak Atoll underwent 43 historical nuclear tests from 1948 to 1958, including the first hydrogen bomb test, resulting in a substantial nuclear material fallout contaminating the Atoll and the lagoon waters. The radionuclide fallout material deposited in lagoon sediments and land soil will remain for decades to come. With intensifying climate and extreme weather events, the possibility of redistribution of deposited radionuclide material has become a great concern. This study uses a numerical modeling approach to estimate the potential elevated radionuclide concentrations that can be distributed during storm events under current and future climates. We simulated three historical storm scenarios that are most likely to impact Atoll’s environment and remobilize the radionuclide-bound sediments. WRF-ARW was used to reconstruct these storm scenarios under current year (2015) and future year (2090) climates. Storm-induced ocean hydrodynamics conditions were generated using FVCOM. FVCOM-ICM was externally coupled to simulate the fate and transport of radionuclides. Given that the 239 Pu is the largest inventory of the lagoon and Atoll islands, the model results show the highest average 239 Pu concentration that an island may be exposed to is 3.25E-4 Bq/m 3 (becquerel per cubic meters), which is an increase of 84 times the average baseline/existing 239 Pu concentration without the storm conditions. The overall increase in 239 Pu average over all the islands of Atoll is about 20 folds relative to the baseline concentration. Despite the high relative increase ratios, the significantly low activity concentrations may not pose an immediate exposure risk. However, due to the limitations of the study and uncertainties/biases in the historical data used, further research supported by field surveys to better characterize the current contamination level may be needed to make more accurate predictions.

54 ENVIRONMENTAL SCIENCES↗

The Potential of Computational Fluid Dynamics Simulation on Serial Monitoring of Hemodynamic Change in Type B Aortic Dissection

PurposeWe aimed to assess the potential of computational fluid dynamics simulation (CFD) in detecting changes in pressure and flow velocity in response to morphological changes in type B aortic dissection.Materials and MethodsPressure and velocity in four morphological models of type B aortic dissection before and after closure of the entry tear were calculated with CFD and analyzed for changes among the different scenarios. The control model (Model 1) was patient specific and built from the DICOM data of CTA, which bore one entry tear and three re-entry tears. Models 2–4 were modifications of Model 1, with two re-entry tears less in Model 2, one re-entry tear more in Model 3, and a larger entry tear in Model 4.ResultsThe pressure and velocity pertaining to each of the morphological models were unique. Changes in pressure and velocity findings were accountable by the changes in morphological features of the different models. There was no blood flow in the false lumen across the entry tear after its closure, the blood flow direction across the re-entry tears was reversed after closure of the entry tear.ConclusionCFD simulation is probably useful to detect hemodynamic changes in the true and false lumens of type B aortic dissection in response to morphological changes, it may potentially be developed into a non-invasive and patient-specific tool for serial monitoring of hemodynamic changes of type B aortic dissection before and after treatment.

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Application of Geant4 Monte Carlo simulation in dose calculations for small radiosurgical fields

The Geant4 toolkit was used to develop a Monte Carlo (MC)-based engine for accurate dose calculations in small radiation field sizes. The Geant4 toolkit (version 10.1.p02) was used to simulate 6-MV photon beam of a Varian2100C linear accelerator that is being used for stereotactic radiosurgery (SRS) treatment with small radiation fields. Geometric models of 3 in-house designed radiosurgical divergent cones, with the diameters of their projections at the isocenter being 10, 20, and 30 mm, were simulated. The accuracy of the MC simulation technique was examined by reproducing several different simulated dosimetric parameters of the primary beams with the experimental data. The dose distributions are first checked for single beams for each cone, then standard multiple field (SMF) techniques are applied. A sample set of DICOM files from computed tomography (CT) scan imaging of a patient's head was converted to the Geant4 geometry format to implement MC-based engine for a clinical test. To validate the accuracy of the MC-based calculations for SMF arrangements, the isodose lines from MC simulation in water phantom were compared with the measured isodose lines using EBT3 Gafchromic film in Solid Water phantoms. Agreements between measured and simulated depth dose values and beam profiles for SRS cones were generally within 2%/2 mm. For output factors, the largest discrepancy was observed for 10 mm SRS cone, which was 1.7%. For SMF techniques, in SRS cones, the MC simulation and EBT3 Gafchromic film dosimetry were in acceptable agreement (5%/5 mm). Excellent agreement between the results of the MC-based and measured dose values for both single and SMF techniques in SRS cones indicates the ability of the Geant4 toolkit to be applied as the platform for treatment planning of advanced radiotherapy techniques.

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TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology

The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

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Land and Water Use Characteristics and Human Health Input Parameters for use in Environmental Dosimetry and Risk Assessments at the Savannah River Site. 2016 Update

Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) regulatory guides. Within the regulatory guides, default values are provided for many of the dose model parameters, but the use of applicant site-specific values is encouraged. Detailed surveys of land-use and water-use parameters were conducted in 1991 and 2010. They are being updated in this report. These parameters include local characteristics of meat, milk and vegetable production; river recreational activities; and meat, milk and vegetable consumption rates, as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors (to be used in human health exposure calculations at SRS) are documented. The intent of this report is to establish a standardized source for these parameters that is up to date with existing data, and that is maintained via review of future-issued national references (to evaluate the need for changes as new information is released). These reviews will continue to be added to this document by revision.

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Synthesis of Post-fire Monitoring Activities in the Great Basin Desert, Mojave Desert, and Transition Zones

In the deserts of the American Southwest, fire return intervals of centuries to millennia are being replaced by fire return intervals of decades. This increased burn frequency has implications for post-closure management and long-term stewardship for Soils Corrective Action Units (CAUs) and Corrective Action Sites (CASs) on the Nevada National Security Site (NNSS), Tonopah Test Range, and Nevada Test and Training Range for which the U.S. Department of Energy (DOE), Environmental Management-Nevada (EM-NV) is responsible. For many CAUs and CASs, where closure-in-place alternatives were implemented or are being considered, there is a chance that these sites could burn over while they still pose a risk to the environment or human health given the long half-lives of some of the radionuclide contaminants of concern (COCs) (Shafer et al., 2007; Shafer and Gomes, 2009). Although it would have been ideal to conduct a fire-related study at a radionuclide contaminated site on the NNSS to determine how contaminated soils are transported post-fire, it was more practical to examine fires in environments analogous to where Soils Activity CAUs and CASs exist. Therefore, a series of studies were initiated at three radiologically uncontaminated analog sites to better understand the possible effects of wildfire on erosion and sediment transport by wind and water should vegetation at contaminated sites burn at the NNSS. The studies took place at the sites of the Gleason Fire, a prescribed burn that occurred near Ely, Nevada, which is in the Great Basin ecoregion; the White Rock Fire that occurred near Mesquite, Nevada, which is in the Mojave Desert ecoregion; and the Jacob Fire that occurred near Hiko, Nevada, in the transitional zone between the Great Basin Desert and the Mojave Desert. Each site was representative of one of the three ecoregions found on the NNSS. Erosion and vegetation characteristics were measured multiple times post-fire on both burned and unburned test plots at these study sites to compare and monitor the effects of fire over time. However, at the Mojave Desert site, there was an additional burn from nearly 25 years ago that was also compared with the more recent burned areas from 2013. Also, the time elapsed after the fire and the time when sampling began differed among the ecoregions. For example, at the Great Basin site, samples were collected prior to the fire and less than one month after the fire, whereas data collected at the Mojave Desert site did not occur until 22 months after the fire. The differences between the sample measurements and the time that elapsed after the fire may contribute to the variability in the data and the interpretations of the data. Runoff and water erosion were quantified through a series of rainfall and runoff simulation tests in which controlled amounts of water were delivered to the soil surface. Runoff data were collected from different microhabitats (e.g., undercanopies, interspace soils, ridges, and drainage areas). The data showed soil hydrophobicity (i.e., water repellency) on the Great Basin site for up to 12 months after the fire. The soil structure remained changed and weaker on the burned areas compared with the unburned areas for the three-year study period. Although runoff data at both the Great Basin site and transition zone site were highly variable, the post-fire runoff potential did not generally increase at either location after three years of monitoring. Mojave runoff did not differ much between fire ages or between burned and unburned areas, possibly because of the amount of vegetation growing on all three surfaces and because the fire intensity was likely lower relative to other ecoregions due to the amount of space between plants. Additionally, the measurements conducted on the Mojave fire occurred several years after the fire had burned and not within several months of the burn, which may also account for the lack of differences in runoff between burned and unburned locations. Wind erosion was assessed and quantified with a Portable In-Situ Wind ERosion Lab (PI-SWERL) on both the burned and unburned soils of different microhabitats (e.g., ridges, drainages, interspaces between plants, and plant undercanopies). Estimates of emissions (e.g., particulate matter with aerodynamic diameters less than or equal to 10 micrometers, or PM10) at different wind speeds were collected and filter samples were analyzed for chemical composition. The measurements among the fires were similar and the results of the wind erosion measurements indicate that there were seasonal influences on many parameters, but the potential for PM10 windblown dust emissions was higher on burned areas compared with unburned areas. Among the burned areas, drainages produced the most dust emissions, whereas burned ridges were the least emissive. Emissions at the Mojave site and transition zone site were similar between burned and unburned areas approximately three years after the respective fires. Emissions remained much greater on burned soils at the Great Basin site. However, site selection may have also contributed to the differences of emissions among the three study locations. Post-fire vegetation responses were documented for three years following each fire in different microhabitats (e.g., ridge, drainage, undercanopy, and interspace) at the Great Basin and transition zone sites. In 2013, at the Mojave fire site, random permanent plots were established in newly burned areas, areas that burned approximately 25 years ago, and an unburned control area. At each fire site, the regeneration of native plant species dominated the burned areas, but invasive annual grasses were present at each fire site. During the course of each three-year study, the invasive annual grasses increased in density or percentage at both the Great Basin and transition fire sites but not at the Mojave site, where annual invasive grasses remained high throughout the study period. However, the chronosequence data from the Mojave site indicate a transition to different invasive grass species with time. The post-burn vegetation at all three ecoregions is still in the early stages of succession, and shrub size should increase over time and shrub density should decrease over time. However, the recovery of the plant communities to pre-burn compositions may not occur for decades or centuries, or may not occur because of changes in climate and the presence of invasive annual grasses. Results from the three study locations suggested that contaminated soils on the NNSS that experienced wildfire had the potential for soil erosion and transport of contaminated soils. Both wind and soil runoff studies indicated that locations in the Great Basin and transition zone ecoregions were more susceptible to erosion than the Mojave Desert ecoregion, but the highest levels of erosion occurred during the early portions of the study (the first 24 months) and the Mojave Desert was not measured until 22 months after the burn. Additionally, data from the Great Basin indicated deeper soils may increase susceptibility to wind erosion. Historically, the Great Basin and transition zone ecoregions burned more frequently than the Mojave Desert because of fuel abundance and connectivity—and they continue to burn more frequently, particularly after the introduction of invasive grasses (Davies and Nafus, 2013). However, both ecoregions and the transition zone have burned with extensive, high-severity fires when certain weather and fuel conditions are met. For example, the high abundance and productivity of annual grasses and forbs—which are usually produced by above average winter precipitation—combined with early spring and summer warm, dry conditions. Future climate scenarios predict increased temperatures, variable to reduced precipitation, and larger, more extreme wildfires throughout western North America. These predictions suggest that future fires on the NNSS could increase in frequency, intensity, and severity similar to their analog ecosystems throughout the Great Basin and Mojave Desert (Dennison et al., 2014; Abatzoglou andWilliams, 2016; Westerling, 2016).

54 ENVIRONMENTAL SCIENCES↗

Computational Modeling of Micrometastatic Breast Cancer Radiation Dose Response

Purpose: Prophylactic cranial irradiation (PCI) involves giving radiation to the entire brain with the goals of reducing the incidence of brain metastasis and improving overall survival. Experimentally, we have demonstrated that PCI prevents brain metastases in a breast cancer mouse model. We developed a computational model to expand on and aid in the interpretation of our experimental results. Methods and Materials: MATLAB was used to develop a computational model of brain metastasis and PCI in mice. Model input parameters were optimized such that the model output would match the experimental number of metastases per mouse from the unirradiated group. An independent in vivo–limiting dilution experiment was performed to validate the model. The effect of whole brain irradiation at different measurement points after tumor cells were injected was evaluated in terms of the incidence, number of metastases, and tumor burden and was then compared with the corresponding experimental data. Results: In the optimized model, the correlation between the number of metastases per mouse and the experimental fits was >95. Our attempt to validate the model with a limiting dilution assay produced 99.9% correlation with respect to the incidence of metastases. The model accurately predicted the effect of whole-brain irradiation given 3 weeks after cell injection but substantially underestimated its effect when delivered 5 days after cell injection. The model further demonstrated that delaying whole-brain irradiation until the development of gross disease introduces a dose threshold that must be reached before a reduction in incidence can be realized. Conclusions: Our computational model of mouse brain metastasis and PCI correlated strongly with our experiments with unirradiated mice. The results further suggest that early treatment of subclinical disease is more effective than irradiating established disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Investigation of dose reduction in cardiac perfusion SPECT via optimization and choice of the image reconstruction strategy

Background: We investigated the extent to which the administered dose (activity) level can be reduced without sacrificing diagnostic accuracy for three reconstruction strategies for SPECT-myocardial perfusion imaging (MPI). Methods: We optimized the parameters of the three reconstruction strategies for perfusion-defect detection over a range of simulated administered dose levels using a set of hybrid studies (derived from 190 subjects) consisting of clinical SPECT-MPI data modified to contain realistic simulated lesions. The optimized strategies we considered are filtered backprojection (FBP) with no correction for degradations, ordered-subsets expectation-maximization (OS-EM) with attenuation correction (AC), scatter correction (SC), and resolution correction (RC), and OS-EM with scatter and resolution correction only. Each study was evaluated using a total perfusion deficit (TPD) score computed by the Quantitative Perfusion SPECT (QPS) software package. We conducted a receiver operating characteristics (ROC) study based on the TPD scores for each dose level and reconstruction strategy. Results: For FBP, the achieved optimum values of the area under the ROC curve (AUC) at 100%, 50%, 25%, and 12.5% of standard dose were 0.75, 0.74, 0.72, and 0.70, respectively, compared to 0.81, 0.79, 0.76, and 0.74 for OS-EM with AC–SC–RC and 0.78, 0.77, 0.74, 0.72 for OS-EM with SC–RC. Conclusions: Our results suggest that studies reconstructed by OS-EM with AC–SC–RC could possibly be reduced, on average, to 25% of the originally administered dose without causing diagnostic accuracy (AUC) to decrease below that of FBP.

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SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced machine learning methodologies need be consider in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Influence of Aqueous Dispersivity on Transport of Radiological Material at LANL MDA G - 20450

Aqueous dispersivity is a phenomenon by which a solute moving in groundwater mixes with water that does not contain the solute and becomes diluted. Solutes take paths of varying lengths through pore networks or experience slower velocities due to interactions with pore walls. Aqueous dispersivity leads to breakthrough curves with earlier arrival than expected in purely advective systems and persistent 'tails,' or late-arriving, dilute concentrations of the solute. Dispersivity can be longitudinal (in the direction of flow) or transverse (orthogonal to flow). LANL has disposed of radioactive material at Material Disposal Area (MDA) G since the late 1950's. Most of the disposed materials at MDA G are low-level waste (LLW), but other types of radioactive wastes are disposed or stored at the site. For example, there is a collection of remote-handled transuranic waste (RH-TRU) waste in 33 shafts, which were intended to be stored retrievably. Aqueous-phase radionuclides included in models of contaminant transport at MDA G are subject to dispersive processes in porous media of the vadose zone and saturated zone. To model dispersivity at MDA G probabilistically, we created site-specific distributions of aqueous dispersivity. First, we performed a comprehensive review of peer-reviewed publications, reports from other performance assessments of MDA G, and documentation from sites that were considered similar based on expert opinion, such as Yucca Mountain. Data were included from a wide range of sources, so that distributions developed based on the data reflect the current state of knowledge in properties of the subsurface environment. Data were grouped based on value type (e.g., determined via experiment or used in a different model), rock type, zone type (saturated or unsaturated), and site, and were weighted in the distributions according to their relevance to the site and zone type. We combined Monte Carlo simulation and bootstrapping techniques to produce approximate distributions of mean aqueous dispersivity. Distributions of dispersivity for saturated and unsaturated zone transport are differentiated by data weight and the length scales over which transport occurs. We find that underestimating or disregarding transverse dispersivity may lead to overstating simulated well capture in the saturated zone at MDA G. Neglecting transverse dispersivity is a common assumption due in part to use of one-dimensional transport models that do not consider solute spreading orthogonal to flow. Also, we find that variability in longitudinal dispersivity is associated with substantial travel time alterations in the MDA G unsaturated zone and in simulated contaminant breakthrough times at a downstream observation plane in the MDA G saturated zone. Finally, at large scales (>1000 m), a linear trend between the dispersivity coefficient and length over which transport occurs may overestimate the dispersivity coefficient. Future modeling work with application to solute spreading could include interacting advective and diffusive zones in the highly fractured basalt below MDA G. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗