A GPU‐based Monte Carlo model for water radiolysis under ultra‐high dose rate irradiation: Development and validation with MPEXS2.1‐DNA

The purpose of this study was to characterize more exactly the hydroxyl radical and the hydrogen atom produced in the radiolysis of water. This was done by comparing properties of the hydroxyl radical produced by photolysis of hydrogen peroxide, and of the hydrogen atom produced by reaction of H2 with this hydroxyl radical, with the corresponding properties, previously determined, of the species produced in the radiolysis of water. The comparison was made by accurate evaluation of relative rate constants for reaction of H202 and H2 with the hydroxyl radicals, and for reaction of H202 and 02 with the hydrogen atoms produced in the two systems. The effect of pH on these ratios was also studied. There is little or no direct information based on physical measurements concerning the reactive intermediates produced in the radiolysis of liquid water. The identity of these species is inferred from observations on water vapor and ice, and from chemical kinetic studies of various solutions as a function of concentration, total radiation dose, dose rate, LET (linear energy transfer), pH, temperature, isotopic content, etc. (1, 2). Chemical studies indicate radiation decomposition of liquid water to OH radicals and H atoms or their chemical equivalents. Evidence, based mostly on pH studies, suggests more than one form of each, but the actual identity and molecular constitution of these species is not known. It is also not known whether only one form of each is produced in the initial processes of the radiation decomposition of water. For example, very recent results of Czapski and Allen (3) indicate that only one form of hydrogen atom is produced initially, whereas other results (4, 5) suggest about 20 % of a second form. It is conceivable that hydroxyl

Introduction: While the operator radiation dose rates are correlated to patient radiation dose rates, discrepancies may exist in the effect size of each individual radiation dose predictors. An operator dose rate prediction model was developed, compared with the patient dose rate prediction model, and converted to an instant operator risk chart. Materials and Methods: The radiation dose rates (DRoperator for the operator and DRpatient for the patient) from 12,865 abdomen X-ray acquisitions were selected from 50 unique patients undergoing standard or complex endovascular aortic repair (EVAR) in the hybrid operating room with a fixed C-arm. The radiation dose rates were analyzed using a log-linear multivariable mixed model (with the patient as the random effect) and incorporated varying (patient and C-arm) radiation dose predictors combined with the vascular access site. The operator dose rate models were used to predict the expected radiation exposure duration until an operator may be at risk to reach the 20 mSv year dose limit. The dose rate prediction models were translated into an instant operator radiation risk chart. Results: In the multivariate patient and operator fluoroscopy dose rate models, lower DRoperator than DRpatient effect size was found for radiation protocol (2.06 for patient vs 1.4 for operator changing from low to medium protocol) and C-arm angulation. Comparable effect sizes for both DRoperator and DRpatient were found for body mass index (1.25 for patient and 1.27 for the operator) and irradiated field. A higher effect size for the DRoperator than DRpatient was found for C-arm rotation (1.24 for the patient vs 1.69 for the operator) and exchanging from femoral access site to brachial access (1.05 for patient vs 2.5 for the operator). Operators may reach their yearly 20 mSv year dose limit after 941 minutes from the femoral access vs 358 minutes of digital subtraction angiography radiation from the brachial access. Conclusion: The operator dose rates were correlated to patient dose rate; however, C-arm angulation and changing from femoral to brachial vascular access site may disproportionally increase the operator radiation risk compared with the patient radiation risk. An instant risk chart may improve operator dose awareness during EVAR.

The emerging FLASH radiotherapy technique employs "Ultra-High Dose Rate" (UHDR) irradiations and offers the potential to spare normal tissue while maintaining iso-effective tumor treatment. Given the physical and biological advantages inherent to high "Linear Energy Transfer" (LET) particles, the combination of UHDR and high LET has the capability to enhance the normal tissues sparing, as indicated by initial in vivo trials. However, to ensure a safe implementation of this combined modality, it is essential to establish robust dosimetric protocols utilizing dose-, dose rate-, and LET-independent detectors. The objective of this study is to characterize the dose, dose rate, and LET dependency of two diamond detectors with high LET carbon and oxygen ion irradiation under "Standard Dose Rate" (SDR) and UHDR conditions. The "microDiamond" (mD) and a "flashDiamond" (fD) prototype were benchmarked against measurements with a monitoring ionization chamber, Advanced Markus chamber (AMC), and simulations for carbon and oxygen irradiation, with energies of 274.98MeV/u and 325.98MeV/u under SDR and UHDR conditions. First, the entire depth-dose profiles obtained during SDR irradiations and the partial in-depth profiles of the Bragg peak region in UHDR were compared to the corresponding simulation values. Secondly, the linearity of the diamond detector response during dose escalation measurements was investigated for both dose rates. The two detectors exhibited alignment with the simulated depth-dose distributions for oxygen and carbon irradiations across both dose rate conditions. The mD overestimated the dose values for carbon and oxygen measurements. This overestimation increased with "dose-averaged LET" (LETd) during SDR irradiation and maintained a stable value of 5% for UHDR. Meanwhile, the fD demonstrated a high degree of agreement with the simulation, with a maximum discrepancy of 5% across all irradiation modalities in the plateau and "Bragg Peak" (BP). Deviations were observed in the BP fall-off region, while both diamond detectors exhibited a strong alignment with the AMC measurements. Furthermore, both detectors exhibited dose linearity under SDR and UHDR irradiation for both carbon and oxygen irradiation, with a coefficient of determination (R2) above 0.99. In the context of heavy ion carbon and oxygen irradiation in UHDR and SDR, the two diamond detectors demonstrated dose-rate independence. While the mD exhibited a tendency to overestimate dose values with increasing LETd, the fD was found to be LET-independent. The fD appears to offer accurate and reliable dose assessments for UHDR heavy ion experiments.

Research and analysis of environmental gamma-radiation dose rates have been carried out in several locations in West Kalimantan as potential Nuclear Power Point (NPP) sites. Aim of this study is as a baseline data for environmental gamma radiation dose rates in Indonesia, especially in the Bengkayang area from points with a radius of 0 to 10 km, and in locations around the city of Pontianak (both on land and rivers). The zero-point km is at the point of Pantai Gosong, Bengkayang District. This study was conducted an environmental evaluation based on the Dosage Limit Value (NBD) of PERKA BAPETEN No. 7/2013 and Safety Report Series No. 47 of IAEA. The study of environmental gamma-radiation dose rates was carried out using a Portable Gamma Ray Survey meter device, the Ludlum brand, while to determine its geographic location a GPS (Global Positioning System) was used from the Garmin tool that plotted into the Google Maps program. The division of the area in the Bengkayang area made a radius of 0 - 1 km, 1 - 2.5 km, 2.5 - 5 km and 5 - 10 km, and there are 16 sections. The division of the area around the city of Pontianak, measurements were carried out by measuring the dose rate of environmental gamma radiation on roadside land every 3 km and in rivers every 3 km. The results of monitoring the level of gamma radiation dose rates in the Bengkayang Regency area were a radius of 0-1 km (0.015-0.120 µSv/h, an average of 0.047 µSv/h), 1-2.5 km (0.013-0.075 µSv/h, an average of 0.042 µSv/h), 2.5-5 km (0.027 - 0.104 µSv/h, an average of 0.039 µSv/h), and 5-10 km (0.010-0.089 µSv/h, an average of 0.037 µSv/h). The results of monitoring the level of gamma radiation dose rates at 14 land locations and 17 river locations in Pontianak City were ranged from 0.010 to 0.150 µSv/h with an average of 0.080 µSv/h. The lowest dose rate of Kapuas River water location, Pontianak city, was 0.01 µSv/h at the PLTD (Diesel Power Plant), Pengharapan, Kapur village, Sungai Raya sub-district, Kubu Raya district, while the highest gamma-radiation dose rate was 0.150 µSv/h at Supadio Airport, Pontianak. The average gamma-radiation dose rates in the Bengkayang monitoring area with a radius of 0 to 10 km, and several locations in the Pontianak area were still lower than the effective dose rate for the general population of 1 mSv / year or 0.5 µSv/h (PERKA BAPETEN No. 7/2013 and Safety Report Series No. 47 IAEA).

Feasibility of Clinically Practical Ultra-High Dose Rate (FLASH) Radiation Delivery by a Reversible Configuration of a Standard Clinical-Use Linear Accelerator

It has been observed that healthy tissues are spared at ultra-high dose rate (UHDR: >40 Gy/s), so called FLASH effect. To elucidate the mechanism of FLASH effect, we evaluate changes in radiation chemical yield (G value) of 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), which is formed by the reaction of hydroxyl radicals with coumarin-3-carboxylic acid (C3CA), under carbon ions (140 MeV/u) and protons (27.5 and 55 MeV) in a wide-dose-rate range up to 100 Gy/s. The relative G value, which is the G value at each dose rate normalized by that at the conventional dose (CONV: 0.1 Gy/s >), 140 MeV/u carbon-ion beam is almost equivalent to 27.5 and 55 MeV proton beams. This finding implies that UHDR irradiations using carbon-ion beams have a potential to spare healthy tissues. Furthermore, we evaluate the G value of 7OH-C3CA under the de-oxygenated condition to investigate roles of oxygen to the generation of 7OH-C3CA effect. The G value of 7OH-C3CA under the de-oxygenated condition is lower than that under the oxygenated condition. The G value of 7OH-C3CA under the de-oxygenated condition is higher than those under UHDR irradiations. By direct measurements of the oxygen concentration during 55 MeV proton irradiations, the oxygen concentration drops by 0.1%/Gy, which is independent of the dose rate. When the oxygen concentration directly affects to yields of 7OH-C3CA, the rate of decrease in the oxygen concentration may be correlated with that of decrease in the G value of 7OH-C3CA. However, the reduction rate of G value under UHDR is significantly higher than the oxygen consumption. This finding implied that the influence of the reaction between water radiolysis species formed by neighborhood tracks could be strongly related to the mechanisms of UHDR effect.

This article considers quantitative comparisons of radiation effectiveness across a large range of dose rates, including low (LDR), medium, conventional or high (HDR) and ultra-high (or FLASH) dose rates.For comparisons of different continuous radiotherapy prescriptions, the linear quadratic model was used to derive ‘biological effective dose’ (BED) equations which included time-dependent enzymatic DNA repair in the low to high dose rate range for monophasic or biphasic repair kinetics. In a recent publication, much higher dose rates, associated with increasing overall radioresistance, was thought to be governed by a cube root (or similar) function of dose rate (which expresses the intensification of micro-volumetric linear energy transfer per unit volume and correlates with average inter-track distances) with resultant increases in the apparent α/β ratios. Explicit equations for assessments of BED* (defined as the excess BED beyond the threshold BED) are presented for dose rates ranging from around 0.1–5 × 106 Gy per hr. The method can also be adapted for tumour control comparisons.Graphical presentations are used to determine iso-effective doses of similar BED* values at different dose rates, for specified radiation doses. The threshold BEDs for radio-tolerance reduce in proportion to the change in the α radiosensitivity parameter. For dose rates above the HDR range, the intrinsic α/β ratio, which is independent of dose rate, continues to influence the magnitude of the changes in BED and dose required for a specified bio-effect, but in a modified form.For further research purposes, these tentative methods can provide isoeffective dose estimates to guide radiation use at different dose rates, but require further specific experimental validation. The methods may seem complex and contain many pitfalls. Further research is also required to identify residual enigmas, such as the exact dose rate and dose at which biological FLASH effects begin to operate and to validate these isoeffective dose predictions.

Associated normal tissue toxicity from current radiotherapy (RT) treatments limits effective dose escalation in the tumor to achieve nominal treatment results. Gold nanoparticles (GNPs) as radiosensitizing agents to locally increase photoelectron production have gained interest as a safe and viable method to improve therapeutic results. Among many other factors, the dose rate of the incident radiation has been shown to affect the radiosensitizing properties of GNPs significantly. To evaluate GNP-induced radiosensitization during variable dose rate delivery from the decay of a high dose rate brachytherapy 192-Ir source and a clinical 6MV linear accelerator (LINAC). HEC-1A endometrial cancer cells were seeded into 35mm petri dishes with or without 10µg/mL with spherical 11nm GNPs functionalized with polyethylene glycol and integrin binding domain RGD to improve intracellular uptake. Variable dose rate delivery from the 192-Ir source was achieved at two source strengths of 37.95 mGy m2/h and 18.97 mGy m2/h, corresponding to dose rates of 1.1 and 0.55Gy/min, respectively. For 6MV irradiations, dose rate variability was controlled by adjusting the distance to the target from 91cm to 129cm, yielding identical dose rates of 1.1 and 0.55Gy/min, respectively. Cellular viability was measured using a clonogenic assay after irradiations between 0 and 8Gy, and a DNA double-strand break assay after 2Gy irradiations. GNP-induced radiosensitization was significantly greater with higher dose rates than lower. Clonogenic loss with GNPs was increased from 1.00 to 1.19 (p<0.001) with higher dose rates from 192-Ir source and from 1.03 to 1.16 (p<0.001) with higher dose rate LINAC irradiations. DNA damage increase from GNPs was not significant at lower dose rates for both 192-Ir (p>0.05) and LINAC (p>0.05) irradiations; however, DNA damage was significantly increased at higher dose rates (192-Ir: p<0.01; 6MV: p<0.05). We have successfully demonstrated in vitro that clinically plausible GNP concentrations can induce variable radiosensitization based on the administered dose rate from both 192-Ir and LINAC irradiations. This work demands future research into the clinical translation of GNPs into high-dose-rate environments.

Background: A number of studies, including our own, have indicated that low dose rate of ionizing radiation might be (within some range) more effective in killing cells than high dose rate. This phenomenon is defined as “inverse dose-rate effect” and is mediated mainly by post radiation oxidative reactions, as radiation peroxidative damage increases with decreased dose rate. Knowledge of biological dose rate-dependent effects might have influence upon the extension of therapeutic maneuvers and limitation of normal tissue reaction. Aim: The aim of the present study was to evaluate the dose-rate effects on lymphoblastic cells since this type of cells is a target in total body irradiation. Materials and methods: Lymphoblastic K562 cells were exposed to 2 Gy X-ray dose (using a 6 MeV accelerator for therapeutic purposes), at high dose rate (2Gy/min), low dose rate (0.07 Gy/min) and at high dose rate, but total dose was given as short separated pulses delivered during the same time as low dose rate (28 min 34 sec). Cells were suspended in RPMI medium supplemented with serum and irradiated in culture flasks. After irradiation cells were incubated for 0.5 – 60 h and micronuclei, apoptotic, necrotic and mitotic cells were scored under fluorescent microscope. Activity of superoxide dismutase isoenzymes (MnSOD and CuZuSOD), and glutathione peroxidise as well as end-product of lipid peroxidation (malondialdehyde) were also measured. Results and discussion: Our results indicated that 2 Gy dose at high dose rate induced higher yield of micronuclei than the same dose at low dose rate or 2 Gy dose given in many pulses. At the same time high dose-rate was less effective in apoptosis induction in K562 cells than low dose-rate or pulsed dose. This effect may differ in different cell lines, since our study on murine carcinoma AT478 cells indicated opposite trend. Furthermore, there was no dose-rate effect in the activation of antioxidant enzymes in lymphoblastic cells, whereas inverse dose rate effect was observed for carcinoma cells. The observed differences may also result from the type of cell growth, K562 grow in suspension, but AT478 are adherent cells. The adherent cells may suffer higher damage from low dose rate during long time of irradiation, in part due to bystander effects. The ongoing study is aimed at evaluating the mechanisms responsible for observed differences and possible signalling activated at different dose rate irradiation. Supported by the Polish Ministry of Science and High Education, grant no N406 101/31/3870

The goal of this study is to investigate the effect of the location and width of a single lead shield on the dose rate of staff and caregivers in a hospital room with an I-131 patient. The best orientation of the patient and caregiver relative to the shield was determined based on minimizing staff and caregiver radiation dose rates. Shielded and unshielded dose rates were simulated using a Monte Carlo computer simulation and validated using real-world ionisation chamber measurements. Based on a radiation transport analysis using an adult voxel phantom published by the International Commission on Radiological Protection, placing the shield near the caregiver yielded the lowest dose rates. However, this strategy reduced the dose rate in only a tiny area of the room. Furthermore, positioning the shield near the patient in the caudal direction provided a modest dose rate reduction while shielding a large room area. Finally, increased shield width was associated with decreasing dose rates, but only a four-fold dose-rate reduction was observed for standard width shields. The recommendations of this case study may be considered as potential candidate room configurations where radiation dose rates are minimized, however these findings must be weighed against additional clinical, safety, and comfort considerations.

An extensive survey of natural γ radiation dose rate levels was measured throughout the Melaka State, Malaysia. The main objective of the present study is to verify the influence of different soil types γ radiation exposures in air using statistical analyses. One-way analysis of variances ANOVA and post hoc test using Fisher’s least significant difference (LSD) were used to test the probability of significance difference between the dose rates and soil types. The survey involved 541 measurement points of terrestrial gamma radiation dose rates in an area of 1650 km2 which covers five major soil groups based on six FAO/UNESCO soil orders. The spatial dose distributions and descriptive statistics of all measured γ radiation dose rates are presented. It has the mean value of 183 nGy h−1. The significance test using ANOVA shows that all dose rates for four soil groups were significantly different from each other with p sig. value <0.005 and the f-ratio lies in the rejection region, f-critical (Fα,(2, n−2)). The post hoc test using Fisher’s LSD shows that there are two main groups of dose rates with each range 152–175 nGy h−1 and 218–233 nGy h−1. These two classification groups indicated the low and high range of dose rates due to the different soil groups derived from different parent rocks. An estimation of average annual effective dose equivalent to the individual in the study area was 1.12 mSv year−1. For granitic soil region, the public is expected to receive slightly high effective dose of 2 mSv year−1. The statistical significance test shows that the soil types significantly influenced the γ radiation exposures received by the public on the ground level.

An extensive terrestrial gamma radiation dose (TGRD) rate survey has been conducted in Perak State, Peninsular Malaysia. The survey has been carried out taking into account geological and soil information, involving 2930 in situ surveys. Based on geological and soil information collected during TGRD rate measurements, TGRD rates have been predicted in Perak State using a statistical regression analysis which would be helpful to focus surveys in areas that are difficult to access. An equation was formulated according to a linear relationship between TGRD rates, geological contexts and soil types. The comparison of in situ measurements and predicted TGRD dose rates was tabulated and showed good agreement with the linear regression equation. The TGRD rates in the study area ranged from 38 nGy h−1 to 1039 nGy h−1 with a mean value of 224 ± 138 nGy h−1. This value is higher than the world average as reported in UNSCEAR . The TGRD rates contribute an average dose rate of 1.37 mSv per year. An isodose map for the study area was developed using a Kriging method based on predicted and in situ TGRD rate values.

A methodology recently developed by the U.S. EPA for estimating the carcinogenic risks from ionizing radiation is described. For most cancer sites, the risk model is one in which age-specific, relative risk coefficients are obtained by taking a geometric mean of the coefficients derived from the atomic bomb survivor data using two different methods for transporting risks from the Japanese to the U.S. population. The risk models are applied to estimate organ-specific risks per unit dose for a stationary population with mortality rates governed by 1980 U.S. vital statistics. With the exception of breast cancer, low-LET radiogenic cancer risk estimates are reduced by a factor of 2 at low doses and dose rates compared to acute high dose exposure conditions. For low dose (or dose rate) conditions, the risk of inducing a premature cancer death from uniform, whole body, low-LET irradiation is calculated to be 5.1 x 10(-2) Gy-1. Neglecting nonfatal skin cancers, the corresponding incidence risk is 7.6 x 10(-2) Gy-1. High-LET (alpha particle) risks are presumed to increase linearly with dose and to be independent of dose rate. High-LET risks are estimated to be 20 times the low-LET risks estimated under low dose rate conditions, except for leukemia and breast cancer where RBEs of 1 and 10 are adopted, respectively.

The effect of dose rate on the response of austenitic stainless steels to neutron radiation

Spycher et al. conducted a nationwide census-based cohort study to investigate whether the incidence of childhood cancer is associated with external exposure to natural background radiation from terrestrial gamma and cosmic rays. The authors claim their results suggest an increased risk of cancer among children exposed to external dose rates of background ionizing radiation of ≥ 200 nSv/h (1.8 mSv/yr) when compared with those exposed to < 100 nSv/h (0.9 mSv/yr). Furthermore, they claim the hazard ratios for each mSv increase in cumulative dose of external radiation are 1.028 (95% confidence interval [CI]: 1.008, 1.048) for any cancer, 1.036 (95% CI: 0.997, 1.077) for leukemia, 1.007 (95% CI: 0.964, 1.052) for lymphoma, and 1.042 (95% CI: 1.008, 1.084) for central nervous system tumors. Regarding the claimed increasing hazard ratios for childhood cancer for each mSv increase in cumulative dose of external radiation, this would be expected to be the case irrespective of the cause of childhood cancer. This is because childhood cancer cumulative incidence increases with follow-up time, which is positively correlated with cumulative radiation dose from birth. Had cumulative exposure to air pollution, cumulative food intake, or cumulative water intake been used as the risk factor, a similar outcome would be expected because all are positively correlated with follow-up time. The authors used in their analyses the doubly weighted (via radiation and tissue weighting factors) hypothetical effective dose rate and effective dose related to total-body irradiation from sources outside the body. They were apparently unaware that tissue weighting factors used are based on detriment rather than solely on cancer and that all significant contributions to radiation absorbed dose need to be accounted for. The authors omitted the very important contributions to radiation dose from radionuclides inside the body and from medical procedures. For example, the internal radiation dose to active bone marrow from radon and thoron can be significant (Richardson et al. 1991). Thus, misclassification of individuals to effective dose and dose rate groups likely occurred more frequently than acknowledged by Spycher et al. In addition, when focusing on a specific type of potential outcome (e.g., leukemia) and its association with radiation exposure of a specific target tissue (e.g., active bone marrow), it is better to use the equivalent dose, which involves only the radiation weighting factor, when a mixture of different radiations are involved (National Research Council 2006). This guards against unnecessary systematic error associated with using both the subjective radiation and tissue weighting factors to get the effective dose that was used by the authors. The individual-specific radiation doses and dose rates assigned by Spycher et al. likely involved significant errors (statistical and systematic), with the dose error possibly being larger than the effective dose assigned to the individual. Part of the systematic error relates to neglected doses from other sources (e.g., internal radionuclides). Because the focus of the research was on very small radiation dose rates and small cumulative doses, it is important to address dose and dose rate errors when conducting such analyses. It is also important to address uncertainty associated with other confounding factors studied (traffic-related air pollution, electromagnetic fields from radio and TV transmitters and from high-voltage power lines, degree of urbanization of municipality, socioeconomic status, etc.) as well as errors related to the use of probabilistic record linkage between the Swiss Childhood Cancer Registry and the Swiss National Cohort. If such errors and uncertainty had been addressed in the authors’ logistic regression analyses, then it is likely that no association between background radiation and childhood leukemia would have been suggested by the research results obtained.