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DOE OSTI2014

Calculated and Measured Dose Distributions in an Anthropomorphic RANDO Phantom - Paper 105

Patient-specific quality assurance (QA) is a major component of the Intensity Modulated Radiation Therapy (IMRT) clinical process. The objective of this often time-intensive measurement process is to verify that the prescribed dose is accurately delivered to the target volume while sparing surrounding healthy tissue. The IMRT dose distributions can be measured using a wide variety of techniques and measurement devices including film (radiographic and radiochromic), ion chamber arrays, diode arrays, and Electronic Portal Imaging Devices (EPIDs). Of all the available modalities, film is one of the most versatile and most frequently utilized measurement systems. In rotation delivery techniques (such as volume modulated arc therapy and helical tomotherapy), composite dose distributions are obtained by irradiating a test phantom containing dosimeter(s). When film is utilized as the dosimeter, it can be placed in coronal, sagittal, or transverse planes inside the phantom. Because the film is irradiated using the rotational delivery sequence used to treat the patient, the dose given to specific anatomical structures (such as the parotids, spinal cord, bladder, rectum etc...) can be evaluated. Thomas et al (Med Phys 32: 3793-3800) recently reported the results of IMRT verifications for ten patients planned and treated with helical tomotherapy. This study reported that nearly 92% of the film pixels within the analyzed region of interest were within a gamma criterion of 2 mm and 2%. Like most tomotherapy users, Thomas et al used a test phantom made of homogeneous water equivalent material. Heterogeneous phantoms that simulate the different tissue densities in the human body do exist, but are infrequently used for patient-specific IMRT QA. The potential advantage of using heterogeneous phantoms is that the measured dose distributions will more adequately reflect the clinical dose distributions in the patients. The use of homogenous phantoms during IMRT quality assurance can potentially mask errors that arise from limitations in the treatment planning system's modeling of density corrections. The purpose of this study was to evaluate the dosimetric accuracy of a helical tomotherapy system using an anthropomorphic RANDO phantom (The Phantom Laboratory, Salem, NY) for patient-specific QA. The results of this study will allow a benchmark to be established for dosimetric accuracy in heterogeneous materials. Performing patient-specific QA is an integral part of the IMRT patient treatment process. Test phantoms are typically homogeneous, and do test the treatment planning systems ability to account for heterogeneity corrections. In this study, an anthropomorphic RANDO phantom was used to evaluate the doses calculated by a helical tomotherapy system. The dosimetric agreement between calculated and measured was worse than published results in homogenous phantoms, especially for target volumes located in the lung. Further investigation will be needed to determine if these errors are due to film response at heterogeneous tissue interfaces or from actual dose calculation errors. (authors)

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2015

SU-E-T-09: A Clinical Implementation and Optimized Dosimetry Study of Freiberg Flap Skin Surface Treatment in High Dose Rate Brachytherapy

Purpose: This case study was designated to confirm the optimized plan was used to treat skin surface of left leg in three stages. 1. To evaluate dose distribution and plan quality by alternating of the source loading catheters pattern in flexible Freiberg Flap skin surface (FFSS) applicator. 2. To investigate any impact on Dose Volume Histogram (DVH) of large superficial surface target volume coverage. 3. To compare the dose distribution if it was treated with electron beam. Methods: The Freiburg Flap is a flexible mesh style surface mold for skin radiation or intraoperative surface treatments. The Freiburg Flap consists of multiple spheres that are attached to each other, holding and guiding up to 18 treatment catheters. The Freiburg Flap also ensures a constant distance of 5mm from the treatment catheter to the surface. Three treatment trials with individual planning optimization were employed: 18 channels, 9 channels of FF and 6 MeV electron beam. The comparisons were highlighted in target coverage, dose conformity and dose sparing of surrounding tissues. Results: The first 18 channels brachytherapy plan was generated with 18 catheters inside the skin-wrapped up flap (Figure 1A). A second 9 catheters plan was generated associated with the same calculation points which were assigned to match prescription for target coverage as 18 catheters plan (Figure 1B). The optimized inverse plan was employed to reduce the dose to adjacent structures such as tibia or fibula. The comparison of DVH’s was depicted on Figure 2. External beam of electron RT plan was depicted in Figure 3. Overcall comparisons among these three were illustrated in Conclusion: The 9-channel Freiburg flap flexible skin applicator offers a reasonably acceptable plan without compromising the coverage. Electron beam was discouraged to use to treat curved skin surface because of low target coverage and high dose in adjacent tissues.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Model‐Based Approach to Selecting Pegfilgrastim Dose for Pharmacokinetic and Pharmacodynamic Similarity Studies in Biosimilar Development

This study applied modeling and simulation (M&S) approaches to evaluate the sensitivity of pegfilgrastim pharmacokinetics (PKs) and pharmacodynamics (PDs) to changes in dose amount, and linear or nonlinear clearance (CL) over pegfilgrastim subcutaneous dose of 2–6 mg. A previously published model was adapted to better describe pegfilgrastim PK and PD data in healthy subjects and used in simulation. Nonlinear CL accounts for 98% and 77%, respectively, of the total CL of pegfilgrastim at 2 and 6 mg. The sensitivity analyses showed: (i) PK of 2 and 6 mg doses are similarly sensitive to detect differences for a 5% change in dose; (ii) PK of 2 mg dose is more sensitive to changes in receptor binding affinity, a model parameter for nonlinear CL, and a product quality attribute characterized with orthogonal methods as part of demonstrating analytical similarity between products; (iii) PK of approved 6 mg dose is more sensitive to changes in linear CL, which has not been associated with any specific product quality attributes, and (iv) the PDs are not sensitive to changes in linear or nonlinear CL. Taken together, our analyses support that the approved pegfilgrastim dose of 6 mg is appropriate for detecting differences between a biosimilar and the reference products in pegfilgrastim PK and PD similarity studies. The described M&S approaches can be adopted to support dose selection for biosimilars with nonlinear PK and complex PK–PD interplay.

Pharmacology & Pharmacy↗

DOE OSTI2019

An investigation of a novel reusable radiochromic sheet for 2D dose measurement

Purpose Radiochromic film remains a useful and versatile clinical dosimetry tool. Current film options are single use. Here, we introduce a novel prototype two‐dimensional (2D) radiochromic sheet, which optically clears naturally at room temperature after irradiation and can be reused. We evaluate the sheets for potential as a 2D dosimeter and as a radiochromic bolus with capability for dose measurement. Methods A novel derivative of reusable Presage ® was manufactured into thin sheets of 5 mm thickness. The sheets contained 2% cumin‐leucomalachitegreen‐diethylamine (LMG‐DEA) and plasticizer (up to 25% by weight). Irradiation experiments were performed to characterize the response to megavoltage radiation, including dose sensitivity, temporal decay rate, consistency of repeat irradiations, intra and inter‐sheet reproducibility, multi‐modality response (electrons and photons), and temperature sensitivity (22°C to 36°C). The local change in optical‐density (ΔOD), before and after radiation, was obtained with a flat‐bed film scanner and extracting the red channel. Repeat scanning enabled investigation of the temporal decay of ΔOD. Additional studies investigated clinical utility of the sheets through application to IMRT treatment plans (prostate and a TG119 commissioning plan), and a chest wall electron boost treatment. In the latter test, the sheet performed as a radiochromic bolus. Results The radiation induced OD change in the sheets was found to be proportional to dose and to exponentially decay to baseline in ~24 h (R2 = 0.9986). The sheet could be reused and had similar sensitivity (within 1% after the first irradiation) for at least eight irradiations. Importantly, no memory of previous irradiations was observed within measurement uncertainty. The consistency of dose response from photons (6 and 15 MV) and electrons (6–20 MeV) was found to be within calibration uncertainty (~1%). The dose sensitivity of the sheets had a temperature dependence of 0.0012 ΔOD/°C. For the short (1 min) single field IMRT QA verification, good agreement was observed between the Presage sheet and EBT film (gamma pass rate 97% at 3% 3 mm dose‐difference and distance‐to‐agreement tolerance, with a 10% threshold). For the longer (~13 min) TG‐119 9‐field IMRT verification the gamma agreement was lower at 93% pass rate at 5% 3 mm, 10% threshold, when compared with Eclipse. The lower rate is attributed to uncertainty arising from signal decay during irradiation and indicates a current limitation. For the electron cutout treatment, both Presage and EBT agreed well (within 2% RMS difference) but differed from the Eclipse treatment plan (~7% RMS difference) indicating some limitations to the Eclipse modeling in this case. The worst case estimates of uncertainty introduced by the signal decay for deliveries of 2, 5, and 10 min are 0.6%, 1.4%, and 2.8% respectively. Conclusions Reusable Presage sheets show promise for 2D dose measurement and as a radiochromic bolus for in vivo dose measurement. The current prototype is suitable for deliveries of length up to 5 min, where the uncertainty introduced by signal decay is anticipated to be ~1% (worst case 1.4%), or for longer deliveries where there is no temporal modulation (e.g. physical compensators, or open beams). Additionally, spatial resolution is limited by sheet thickness and scanner resolution, resulting in a practical resolution of 0.8 mm.

Collins, Cielle↗

DOE OSTI2018

Radiation dose rate distributions of spent fuel dry casks estimated with MAVRIC based on detailed geometry and continuous-energy models

This study presents a detailed comparison of the dose rate distributions of a dry TN–32 fuel cask with two geometry models and two cross-sectional datasets. The accuracies of radiation dose rate estimation and computational efficiencies of each geometry model with two cross-sectional data-sets are compared. The use of automated variance reduction techniques can significantly improve the computational efficiency of such a realistic, deep penetration problem that involves radiation transport from different volumetric sources, thereby eliciting only a small statistical error. Monaco with Automated Variance Reduction using Importance Calculations (MAVRIC) is a computational sequence within the SCALE 6.2 code package based on consistent adjoint driven importance sampling (CADIS), a type of automated variance reduction technique. Homogenous and full fuel assembly models are built herein, and two nuclear cross-section libraries (V7–200N47G and continuous energy) are applied in this work. Based on the detailed comparisons, we found that neutron dose rate estimation is more dependent on geometry modeling than on cross-section data. For neutron-induced gamma rays, the dose rate distribution depends on both the spatial self-shielding effect and the cross-section library. The primary gamma rays respectively contribute to the total dose rate by ~91% and ~ 99% on side and top surfaces, and the dose rate accuracy is more dependent on the cross-section library than on geometry modeling. In terms of the computation efficiency and efforts spent on geometry modeling, the homogenous fuel assembly model with the MG library can produce an acceptable dose rate distribution, but the detailed fuel assembly model with the continuous-energy library is required for more precise dose rate estimation.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2018

Dose-limiting Urinary Toxicity With Pembrolizumab Combined With Weekly Hypofractionated Radiation Therapy in Bladder Cancer

There is currently significant interest in the potential benefits of combining radiation and immune checkpoint blockade (ICB) to stimulate both regional and distant abscopal immune responses. In melanoma and lung cancer, patients who have received radiation therapy during ICB appear to have prolonged survival. The PLUMMB trial (Pembrolizumab in Muscle-invasive/Metastatic Bladder cancer) (NCT02560636) is a phase I study to test the tolerability of a combination of weekly radiation therapy with pembrolizumab in patients with metastatic or locally advanced urothelial cancer of the bladder. In the first dose-cohort, patients received pembrolizumab 100 mg 3-weekly, starting 2 weeks before commencing weekly adaptive bladder radiation therapy to a dose of 36 Gy in 6 fractions. The first dose-cohort was stopped after 5 patients, having met the predefined definition of dose-limiting toxicity. Three patients experienced grade 3 urinary toxicities, 2 of which were attributable to therapy. One patient experienced a grade 4 rectal perforation. In view of these findings, the trial has been paused and the protocol will be amended to reduce radiation therapy dose per fraction. The authors advise caution to those combining radiation therapy and ICB, particularly when radiation therapy is given at high dose per fraction for pelvic tumours. The PLUMMB trial met the protocol-defined definition of dose-limiting toxicity and will be amended to reduce radiation therapy dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2013

Association of brominated proteins and changes in protein expression in the rat kidney with subcarcinogenic to carcinogenic doses of bromate

The water disinfection byproduct bromate (BrO{sub 3}{sup −}) produces cytotoxic and carcinogenic effects in rat kidneys. Our previous studies demonstrated that BrO{sub 3}{sup −} caused sex-dependent differences in renal gene and protein expression in rats and the elimination of brominated organic carbon in their urine. The present study examined changes in renal cell apoptosis and protein expression in male and female F344 rats treated with BrO{sub 3}{sup −} and associated these changes with accumulation of 3-bromotyrosine (3-BT)-modified proteins. Rats were treated with 0, 11.5, 46 and 308 mg/L BrO{sub 3}{sup −} in drinking water for 28 days and renal sections were prepared and examined for apoptosis (TUNEL-staining), 8-oxo-deoxyguanosine (8-oxoG), 3-BT, osteopontin, Kim-1, clusterin, and p-21 expression. TUNEL-staining in renal proximal tubules increased in a dose-related manner beginning at 11.5 mg BrO{sub 3}{sup −}/L in female rats and 46 mg/L in males. Increased 8-oxoG staining was observed at doses as low as 46 mg/L. Osteopontin expression also increased in a dose-related manner after treatment with 46 mg/L, in males only. In contrast, Kim-1 expression increased in a dose-related manner in both sexes, although to a greater extent in females at the highest dose. Clusterin and p21 expression also increased in a dose-related manner in both sexes. The expression of 3-BT-modified proteins only increased in male rats, following a pattern previously reported for accumulation of α-2{sub u}-globulin. Increases in apoptosis in renal proximal tubules of male and female rats at the lowest doses suggest a common mode of action for renal carcinogenesis for the two sexes that is independent of α-2{sub u}-globulin nephropathy. - Highlights: • Bromate induced nephrotoxicity in both male and female rats by similar mechanisms. • Apoptosis was seen in both male and female rats at the lowest doses tested. • Bromate-induced apoptosis correlated to 8-oxo-deoxyguanosine formation. • Bromate increased the level of 3-bromotyrosine-modified proteins in male rats only. • These data identify possible novel mechanisms for bromate-induced nephrotoxicity.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Age-dependent comparison of monoenergetic photon organ and effective dose coefficients for pediatric stylized and voxel phantoms submerged in air

We report that dose rate coefficients computed using the University of Florida-National Cancer Institute (UF-NCI) pediatric series of voxel phantoms were compared with values computed using the Oak Ridge National Laboratory (ORNL) pediatric stylized phantoms in an air submersion exposure geometry. Simulations were conducted comparing phantoms classified within five ages: newborn, 1-year-old, 5-year-old, 10-year-old, and 15-year-old for both male and female sexes. This is a continuation of previous work comparing monoenergetic photon organ dose rate coefficients, as defined by ICRP Publication 103, for the male and female adult phantoms. With both the male and female data computed for each pediatric phantom age, effective dose rate coefficients and ratios were computed for voxel and stylized phantoms. Organ dose rate coefficients for the pediatric phantoms and ratios of organ dose rates for the voxel and stylized phantoms are provided for eight monoenergetic photon energies ranging from 30 keV to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Comparison of effective dose rates between the voxel and stylized phantoms was within 5% between 500 keV and 5 MeV and within 10% between 70 keV and 5 MeV for phantoms > 1-year-old. Lastly, stylized newborn effective dose rates were consistently ~20% higher than the voxel counterpart, over all energies.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2013

A COMPARISON OF DOSE RESULTS FROM THE CLEAN AIR ACT ASSESSMENT PACKAGE-1988, PERSONAL COMPUTER (CAP88-PC), VERSION 3 TO PREVIOUS VERSIONS

EPA-approved computer software packages, including CAP88-PC, are used by Department of Energy sites to demonstrate compliance with the radionuclide air emission standard under the Clean Air Act. The most recent update, CAP88-PC version 3, was approved by EPA in February 2006 for use by Department of Energy facilities. Version 3 incorporates several major changes that have the potential to affect calculated doses relative to calculations using earlier versions. This analysis examined the types and magnitudes of changes to dose estimates for specific radionuclides calculated using the version 3 software compared with the previous versions. Total effective dose calculated with version 3 was compared to effective dose equivalent calculated with previous versions for parent radionuclides and for the total dose from radionuclide chains. Various comparisons were also performed to determine which of the updates in version 3 accounted for changes in overall dose estimates. CAP88-PC version 3 would produce substantially different results relative to previous versions of the code for a number of radionuclides, including some isotopes that may be present at Department of Energy facilities, as well as those used for industrial and medical applications. In general, doses for many radionuclides are lower using version 3 but doses for a few key radionuclides would be higher.

Rhoads, Kathleen↗

DOE OSTI2022

Dose Rate Effects in the Aging of Nuclear Cable Insulation Subjected to Gamma Radiation

In nuclear power plants (NPPs), the aging of polymer-based electrical cable insulation must be effectively monitored to ensure the safe and reliable operation of NPPs. Gamma radiation is one of the main environmental stressors causing degradation of cable insulation. For a given total dose of absorbed gamma radiation, damage due to gamma irradiation may be dose rate dependent. The purpose of this work is to confirm whether a dose rate effect exists for the cable insulation made by crosslinked polyethylene (XLPE) and ethylene propylene rubber (EPR), quantify the relationship between degradation rate and dose rate, and explore the correlation of different measured properties. The dose rate effects at 1800 Gy/h, 200 Gy/h, and 100 Gy/h using 60Co gamma irradiation on cable aging was studied. Different types of cable insulation, including two XLPEs and one EPR, were irradiated at the different dose rates with a total dose around 300 kGy at 26 °C. The properties of unirradiated and irradiated samples were characterized by mass change, yellowness index, and other ongoing measurements. Dose rate effects were observed for mass change data of XLPE and EPR.

Li, Donghui↗

DOE OSTI2014

SU-E-T-115: Dose Perturbation Study of Self-Expandable Metal and Polyester Esophageal Stents in Proton Therapy Beams

Purpose: This work investigates dose perturbations due to Self-expandable metal and polyester esophageal stents undergoing proton radiotherapy for esophageal cancer. Methods: Five commercially available esophageal stents made of nitinol (Evolution, Wallflex and Ultraflex), stainless steel (Z-Stent) and polyester (Polyflex) were tested. Radiochromic film (GafChromic EBT3 film, Ashland, Covington, KY) wrapped around a stent and a 12cc syringe was irradiated with 2CGE (Cobalt Gray Equivalent) of proton beam in a custom fabricated acrylic phantom. An air-hollow syringe simulates the esophagus. Results: The Z-stent created the largest dose perturbations ranges from -14.5% to 6.1% due to the steel composition. The WallFlex, Evolution and Ultraflex stents produced the dose perturbation ranges of (−9.2%∼8.6%), (−6.8%∼5.7%) and (−6.2%∼6.2%), respectively. The PolyFlex stent contains the radiopaque tungsten markers located top, middle and bottom portions. When the focal cold spots induced by the markers were excluded in the analysis, the dose perturbation range was changed from (−11.6%∼6.4%) to (−0.6%∼5.0%). Conclusion: The magnitude of dose perturbation is related to material of a metallic stent. The non-metallic stent such as PolyFlex shows relatively lower dose perturbation than metallic stents except a radiopaque marker region. Overall Evolution and Ultraflex stent appear to be less dose perturbations. The largest dose perturbations (cold spots) were located at both edges of stents in distal area for the single proton beam irradiation study. The analysis of more than two proton beam which is more typical clinical beam arrangement would be necessary to minimize the doe perturbation effect in proton ratiotherapy.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2015

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number of fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-T-430: Validation of IBEAM Evo Couch Top for Different Relative Electron Density (RED) Combination During Photon Beam Dose Calculation in Monaco− Treatment Planning System

Purpose: Validation of iBEAM™ evo couch-top for different relative electron density (RED) combination during photon beam dose calculation in Monaco− TPS. Methods: The iBEAM™ evo couch-top has two layers:outer carbon fiber (CF) and inner foam core (FC). To study the beam intensity attenuation of couch-top, measured doses were compared with doses calculated for different REDs. Measurements were performed in solid water phantom with PTW-0.125cc ion-chamber positioned at center of the phantom with 5.3cm thickness slabs placed above and below the chamber. Similarly, in TPS, iBEAM™ evo couch-top was simulated and doses were calculated for different RED combinations (0.2CF-0.2FC, 0.4CF-0.2FC, 0.6CF-0.2FC, 0.8CF-0.2FC, and 1.0CF-0.2FC) by using Monte Carlo dose calculation algorithm in Monaco TPS (V5.1). Doses were measured for every 10 degree gantry angle separation, 10×10cm{sup 2} field size and 6MV photons. Then, attenuation is defined as the ratio of output at posterior gantry angle to output of its opposed anterior gantry angle (e.g.225°/45°). output fluctuation with different gantry angle was within ±0.21%. To confirm above results, dose-planes were measured for five pelvic VMAT plans (360°arc) in PTW two-dimensional array and compared with different calculated dose-planes of above-mentioned couch REDs. Gamma pass rates<1.00) were analyzed for 3%/2mm criteria. Results: Measured and calculated attenuation was in good agreement for the RED combination of 0.2CF-0.2FC and difference was within ±0.515%. However, other density combination showed difference of ±0.9841%, ±1.667%, ±2.9241% and ±2.8832% for 0.4CF-0.2FC, 0.6CF-0.2FC, 0.8CF-0.2FC, and 1.0CF-0.2FC, respectively. Maximum couch-top attenuation was observed at 110°–120° and 240°–250° and decreases linearly as the gantry angle approaches 180°. Moreover, gamma pass rate confirmed the above results and showed maximum pass rate of 96.23% for 0.2CF-0.2FC, whereas others were 95.72%, 95.12%, 94.31% and 93.24%. Conclusion: RED value of 0.2CF-0.2FC was found to be suitable for accurate couch-top modeling for 6MV photon beam Monte Carlo calculations in Monaco TPS.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2015

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris ) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2015

Consequences of Low Dose Ionizing Radiation Exposure on the Hippocampal Microenvironment

The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses ( ≥ 45 Gy), few studies have been conducted at much lower doses ( ≤ 2 Gy), where the response of the CNS (like many other tissues) may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT) animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2019

FGR 13 Dose Conversion Factor Files

The purpose of this document is to discuss the construction of two MACCS dose conversion factor (DCF) files in some detail, an older file created in 2007 named FGR13DCF.inp and a newer file created in 2018 called FGR13GyEquiv_RevA.inp. Very briefly, the difference between the two files is that the older file follows the standard conventions of assigning a radiation weighting factor of 20 for alpha radiation for all tissues and organs; whereas, the newer file complies with the FGR 13 health effects modeling and uses modified radiation weighting factors (referred to as relative biological effectiveness (RBE) factors) for alpha radiation of 10 for breast and of 1 for red bone marrow. During an intermediate period the creation of these two DCF files, a file called FGR13GyEquiv was created and used for the SOARCA calculations. This file was not released to the MACCS user community, but it is also discussed briefly in this document. DCF files are used by MACCS to convert air and ground radionuclide concentrations to doses to an organ or to the whole body. The MACCS calculation considers duration and shielding factor for each exposure pathway including cloudshine, groundshine, inhalation, and ingestion. Dose coefficients for cloudshine and groundshine are expressed as dose rates; dose coefficients for inhalation and ingestion are expressed as committed doses. In this document, dose coefficients (newer ICRP terminology) is used to describe the values contained in dose conversion factor (older ICRP terminology) files.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2023

Estimate of Gamma Dose Rates from Arrays of Fermi-1 Blanket Elements During the MEDE Process

The Enrico Fermi Atomic Power Plant Unit 1 (Fermi-1) was a sodium-cooled fast breeder reactor located in Monroe County, Michigan. The reactor was powered by a core of enriched uranium metal alloy driver fuel, which was enveloped by an axial and radial blanket material consisting of depleted uranium metal alloyed with 3 wt.% molybdenum. There are 406 axial and 559 radial irradiated sodium-bonded Fermi-1 blanket assemblies in storage at INL, totaling 34 metric tons of heavy metal. Disposal of the Fermi-1 blanket material directly into a geological repository is prohibited due to the reactive characteristic of its bond sodium. A melt drain evaporate (MEDE) process can effectively remove bond sodium from Fermi-1 blanket material. Consequently, planning is underway to apply a MEDE process to treat the 34 metric tons of heavy metal of irradiated Fermi-1 blanket material. Given the irradiated Fermi-1 blanket material’s relatively low power history and 50+ years of decay, it can be treated in a shielded glovebox. To assess the requisite shielding, the dose rates of the Fermi-1 blanket elements in various process configurations are needed. The method to perform the dose rate calculations is to first generate an average source term and associated photon source spectra for the Fermi-1 blanket material in SCALE and then use the associated photon spectra to calculate dose rates using MCNP6.2 in seven representative geometries. Dose rates in rem/h were calculated on contact (1 cm from outer geometry surface), 30 cm away from outer geometry surface, and 1 m from outer geometry surface at axial heights spanning the length of the blanket material within the geometry. The maximum average dose rate for the single Fermi-1 radial blanket element is ~0.60 rem/h, for the Fermi-1 radial blanket assembly ~1.10 rem/h, for the single Fermi-1 axial blanket element ~0.5 rem/h, for the Fermi-1 axial blanket assembly ~1.01 rem/h, for the MEDE can ~ 0.98 rem/h, for the Fermi Storage Canister ~ 0.83 rem/h, and for the MEDE cans in the DOE Standard Canister ~0.51 rem/h. Based on these maximum average values, the bounding dose rates are assumed to be 3× the average dose rates calculated for the axial blanket material and 7.6× the average dose rates calculated for the radial blanket material, based on the distribution of Fermi-1 blanket material assembly burnup.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2017

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.

60 APPLIED LIFE SCIENCES↗