Fetal and Maternal Atomic Bomb Survivor Dosimetry Using the J45 Pregnant Female Phantom Series: Considerations of the Kneeling and Lying Posture with Comparisons to the DS02 System.

ABSTRACT: Organ dosimetry data of the atomic bomb survivors and the resulting cancer risk models derived from these data are currently assessed within the DS02 dosimetry system developed through the Joint US-Japan Dosimetry Working Group. In DS02, the anatomical survivor models are limited to three hermaphroditic stylized phantoms-an adult (55 kg), a child (19.8 kg), and an infant (9.7 kg)-that were originally designed for the preceding DS86 dosimetry system. As such, organ doses needed for assessment of in-utero cancer risks to the fetus have continued to rely upon the use of the uterine wall in the adult non-pregnant stylized phantom as the dose surrogate for all fetal organs regardless of gestational age. To address these limitations, the Radiation Effects Research Foundation (RERF) Working Group on Organ Dose (WGOD) has established the J45 (Japan 1945) series of high-resolution voxel phantoms, which were derived from the UF/NCI series of hybrid phantoms and scaled to match mid-1940s Japanese body morphometries. The series includes male and female phantoms-newborn to adult-and four pregnant female phantoms at gestational ages of 8, 15, 25, and 38 wk post-conception. In previous studies, we have reported organ dose differences between those reported by the DS02 system and those computed by the WGOD using 3D Monte Carlo radiation transport simulations of atomic bomb gamma-ray and neutron fields for the J45 phantoms series in their traditional "standing" posture, with some variations in their facing direction relative to the bomb hypocenter. In this present study, we present the J45 pregnant female phantoms in both a "kneeling" and "lying" posture and assess the dosimetric impact of these more anatomically realistic survivor models in comparison to current organ doses given by the DS02 system. For the kneeling phantoms facing the bomb hypocenter, organ doses from bomb source photon spectra were shown to be overestimated by the DS02 system by up to a factor of 1.45 for certain fetal organs and up to a factor of 1.17 for maternal organs. For lying phantoms with their feet in the direction of the hypocenter, fetal organ doses from bomb source photon spectra were underestimated by the DS02 system by factors as low as 0.77, while maternal organ doses were overestimated by up to a factor of 1.38. Organs doses from neutron contributions to the radiation fields exhibited an increasing overestimation by the DS02 stylized phantoms as gestational age increased. These discrepancies are most evident in fetal organs that are more posterior within the mother's womb, such as the fetal brain. Further analysis revealed that comparison of these postures to the original standing posture indicate significant dose differences for both maternal and fetal organ doses depending on the type of irradiation. Results from this study highlight the degree to which the existing DS02 system can differ from organ dosimetry based upon 3D radiation transport simulations using more anatomically realistic models of those survivors exposed during pregnancy.

Intra-brain vascular models within the ICRP mesh-type adult reference phantoms for applications to internal dosimetry.

Objective. Phantoms of the International Commission on Radiological Protection provide a framework for standardized dosimetry. The modeling of internal blood vessels-essential to tracking circulating blood cells exposed during external beam radiotherapy and to account for radiopharmaceutical decays while still in blood circulation-is, however, limited to the major inter-organ arteries and veins. Intra-organ blood is accounted for only through the assignment of a homogeneous mixture of parenchyma and blood [single-region (SR) organs]. Our goal was to develop explicit dual-region (DR) models of intra-organ blood vasculature of the adult male brain (AMB) and adult female brain (AFB).Approach. A total of 4000 vessels were created amongst 26 vascular trees. The AMB and AFB models were then tetrahedralized for coupling to the PHITS radiation transport code. Absorbed fractions were computed for monoenergetic alpha particles, electrons, positrons, and photons for both decay sites within the blood vessels and for tissues outside these vessels. RadionuclideS-values were computed for 22 and 10 radionuclides commonly employed in radiopharmaceutical therapy and nuclear medicine diagnostic imaging, respectively.Main results. For radionuclide decays, values ofS(brain tissue ← brain blood) assessed in the traditional manner (SR) were higher than those computed using our DR models by factors of 1.92, 1.49, and 1.57 for therapeutic alpha-emitters, beta-emitters, and Auger electron-emitters, respectively in the AFB and by factors of 1.65, 1.37, and 1.42 for these same radionuclide categories in the AMB. Corresponding ratios of SR and DR values ofS(brain tissue ← brain blood) were 1.34 (AFB) and 1.26 (AMB) for four SPECT radionuclides, and were 1.32 (AFB) and 1.24 (AMB) for six common PET radionuclides.Significance. The methodology employed in this study can be explored in other organs of the body for proper accounting of blood self-dose for that fraction of the radiopharmaceutical still in general circulation.

Predicting Severity of Radiation Induced Lymphopenia in Individual Proton Therapy Patients for Varying Dose Rate and Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations.

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters. METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute lymphocyte counts (ALCs) during RT and follow-up were available. We used HEDOS, a time-dependent, whole-body, blood flow computational framework, in combination with explicit liver blood flow modeling, to calculate the dose volume histograms for circulating lymphocytes for changing BOTs (1 second-300 seconds) and fractionations (5 fx, 15 fx). From this, we used the linear cell survival model and an exponential model to determine patient-specific lymphocyte radiation sensitivity, α, and recovery, σ, respectively. RESULTS: The in vivo-derived patient-specific α had a median of 0.65 Gy-1 (range, 0.30-1.38). Decreasing BOT to 1 second led to an increased average end-of-treatment ALC of 27.5%, increasing to 60.3% when combined with the 5-fx regimen. Decreasing to 5 fx at the conventional dose rate led to an increase of 17.0% on average. The benefit of both increasing dose rate and reducing the number of fractions was patient specificࣧpatients with highly sensitive lymphocytes benefited most from decreasing BOT, whereas patients with slow lymphocyte recovery benefited most from the shorter fractionation regimen. CONCLUSIONS: We observed that increasing dose rate at the same fractionation reduced ALC depletion more significantly than reducing the number of fractions. High-dose-rates led to an increased sparing of lymphocytes when shortening the fractionation regimen, particularly for patients with radiosensitive lymphocytes at elevated risk.

A mesh-based model of liver vasculature: implications for improved radiation dosimetry to liver parenchyma for radiopharmaceuticals.

PURPOSE: To develop a model of the internal vasculature of the adult liver and demonstrate its application to the differentiation of radiopharmaceutical decay sites within liver parenchyma from those within organ blood. METHOD: Computer-generated models of hepatic arterial (HA), hepatic venous (HV), and hepatic portal venous (HPV) vascular trees were algorithmically created within individual lobes of the ICRP adult female and male livers (AFL/AML). For each iteration of the algorithm, pressure, blood flow, and vessel radii within each tree were updated as each new vessel was created and connected to a viable bifurcation site. The vascular networks created inside the AFL/AML were then tetrahedralized for coupling to the PHITS radiation transport code. Specific absorbed fractions (SAF) were computed for monoenergetic alpha particles, electrons, positrons, and photons. Dual-region liver models of the AFL/AML were proposed, and particle-specific SAF values were computed assuming radionuclide decays in blood within two locations: (1) sites within explicitly modeled hepatic vessels, and (2) sites within the hepatic blood pool residing outside these vessels to include the capillaries and blood sinuses. S values for 22 and 10 radionuclides commonly used in radiopharmaceutical therapy and imaging, respectively, were computed using the dual-region liver models and compared to those obtained in the existing single-region liver model. RESULTS: Liver models with virtual vasculatures of ~ 6000 non-intersecting straight cylinders representing the HA, HPV, and HV circulations were created for the ICRP reference. For alpha emitters and for beta and auger-electron emitters, S values using the single-region models were approximately 11% (AML) to 14% (AFL) and 11% (AML) to 13% (AFL) higher than the S values obtained using the dual-region models, respectively. CONCLUSIONS: The methodology employed in this study has shown improvements in organ parenchymal dosimetry through explicit consideration of blood self-dose for alpha particles (all energies) and for electrons at energies below ~ 100 keV.

A dynamic blood flow model to compute absorbed dose to circulating blood and lymphocytes in liver external beam radiotherapy.

We have developed a novel 4D dynamic liver blood flow model, capable of accurate dose estimation to circulating blood cells during liver-directed external beam radiotherapy, accounting for blood recirculation and radiation delivery time structure. Adult male and adult female liver computational phantoms with detailed vascular trees were developed to include the hepatic arterial, hepatic portal venous, and hepatic venous trees. A discrete time Markov Chain approach was applied to determine the spatiotemporal distribution of 105blood particles (BP) in the human body based on reference values for cardiac output and organ blood volumes. For BPs entering the liver, an explicit Monte Carlo simulation was implemented to track their propagation along ∼2000 distinct vascular pathways through the liver. The model tracks accumulated absorbed dose from time-dependent radiation fields with a 0.1 s time resolution. The computational model was then evaluated for 3 male and 3 female patients receiving photon (VMAT and IMRT) and proton (passive SOBP and active PBS) treatments. The dosimetric impact of treatment modality, delivery time, and fractionation on circulating blood cells was investigated and quantified using the mean dose (µdose,b),V>0Gy,V>0.125Gy,andD2%. Average reductions inµdose,b,V>0Gy,V>0.125GyandD2%of 45%, 6%, 53%, 19% respectively, were observed for proton treatments as compared to photon treatments. Our simulation also showed thatV>0Gy,V>0.125Gy, andD2%were highly sensitive to the beam-on time. BothV>0GyandV>0.125Gyincreased with beam-on time, whereasD2%decreased with increasing beam-on time, demonstrating the tradeoff between low dose to a large fraction of blood cells and high dose to a small fraction of blood cells. Consequently, proton treatments are not necessarily advantageous in terms of dose to the blood simply based on integral dose considerations. Instead, both integral dose and beam-on time can substantially impact relevant dosimetric indices.

Japanese pediatric and adult atomic bomb survivor dosimetry: potential improvements using the J45 phantom series and modern Monte Carlo transport.

The radiation exposure estimates for the atomic bomb survivors at Hiroshima and Nagasaki have evolved over the past several decades, reflecting a constant strive by the Radiation Effects Research Foundation (RERF) to provide thorough dosimetry to their cohort. Recently, a working group has introduced a new series of anatomical models, called the J45 phantom series, which improves upon those currently used at RERF through greater age resolution, sex distinction, anatomical realism, and organ dose availability. To evaluate the potential dosimetry improvements that would arise from their use in an RERF Dosimetry System, organ doses in the J45 series are evaluated here using environmental fluence data for 20 generalized survivor scenarios pulled directly from the current dosimetry system. The energy- and angle-dependent gamma and neutron fluences were converted to a source term for use in MCNP6, a modern Monte Carlo radiation transport code. Overall, the updated phantom series would be expected to provide dose improvements to several important organs, including the active marrow, colon, and stomach wall (up to 20, 20, and 15% impact on total dose, respectively). The impacts were especially significant for neutron dose estimates (up to a two-fold difference) and within organs which were unavailable in the previous phantom series. These impacts were consistent across the 20 scenarios and are potentially even greater when biological effectiveness of the neutron dose component is considered. The entirety of the dosimetry results for all organs are available as supplementary data, providing confident justification for potential future DS workflows utilizing the J45 phantom series.

HEDOS-a computational tool to assess radiation dose to circulating blood cells during external beam radiotherapy based on whole-body blood flow simulations.

We have developed a time-dependent computational framework, hematological dose (HEDOS), to estimate dose to circulating blood cells from radiation therapy treatment fields for any treatment site. Two independent dynamic models were implemented in HEDOS: one describing the spatiotemporal distribution of blood particles (BPs) in organs and the second describing the time-dependent radiation field delivery. A whole-body blood flow network based on blood volumes and flow rates from ICRP Publication 89 was simulated to produce the spatiotemporal distribution of BPs in organs across the entire body using a discrete-time Markov process. Constant or time-varying transition probabilities were applied and their impact on transition time was investigated. The impact of treatment time and anatomical site were investigated using imaging data and dose distributions from a liver cancer and a brain cancer patient. The simulations revealed different dose levels to the circulating blood for brain irradiation compared to liver irradiation even for similar field sizes due to the different blood flow properties of the two organs. The volume of blood receiving any dose (V>0 Gy) after a single radiation fraction increases from 1.2% for a 1 s delivery time to 20.9% for 120 s delivery time for the brain cancer treatment, and from 10% (1 s) to 48.7% (120 s) for a liver cancer treatment. Other measures of the low-dose bath to the circulating blood such as the dose to small volumes of blood (D2%) decreases with longer delivery time. Furthermore, we demonstrate that the blood dose-volume histogram is highly sensitive to changes in the treatment time, indicating that dynamic modeling of blood flow and radiation fields is necessary to evaluate dose to circulating blood cells for the assessment of radiation-induced lymphopenia. HEDOS is publicly available and allows for the estimation of patient-specific dose to circulating blood cells based on organ DVHs, thus enabling the study of the impact of different treatment plans, dose rates, and fractionation schemes.

Organ and detriment-weighted dose rate coefficients for exposure to radionuclide-contaminated soil considering body morphometries that differ from reference conditions: adults and children.

The system of protection established by the International Commission on Radiological Protection (ICRP) provides a robust framework for ionizing radiation exposure justification, optimization, and dose limitation. The system is built upon fundamental concepts of a reference person, defined in ICRP Publication 89, and the radiation protection quantity effective dose, defined in ICRP Publication 103. For external exposures to radionuclide-contaminated soil, values of the organ dose rate coefficient (Gy/s per Bq/m2) and effective dose rate coefficient (Sv/s per Bq/m2) have been computed by several authors and national laboratories using ICRP-compliant reference phantoms-both stylized and voxelized. These coefficients are of great value in post-accident exposure assessments as seen in Japan following the 2011 Fukushima Daiichi nuclear power station disaster. Questions arise, however, among the general public regarding the accuracy of organ and effective dose estimates based upon reference phantom methodologies, especially for those individuals with height and/or total body mass that differ modestly or even substantially from the nearest age-matched reference person. In this pilot study, this issue is explored through use of the extended 351-member UF/NCI hybrid phantom library in which values of organ and detriment-weighted dose rate coefficients are computed for sex/height/mass-specific phantoms, and systematically compared to their values of the effective dose rate coefficient computed using corresponding reference phantoms. Results are given for monoenergetic photons, and then for some 33 different radionuclides, with all dose rate coefficient data provided in a series of electronic annexes. For environmentally relevant radionuclides such as 89Sr, 90Sr, 137Cs, and 131I, percent differences between the detriment-weighted dose rate coefficient computed using non-reference and the effective dose rate coefficient computed using reference phantoms vary only ± 5% for young children approximated by the reference 1-year-old phantom. With increased body size and age, the range of percent differences in these two quantities increases to + 7% to - 14% for the reference 5-year-old, to + 10% to - 27% for the reference 10-year-old, to + 33% to - 31% for the reference 15-year-old, and to + 15% to - 40% for male and female adults.