Increasing Dose Rate Research Articles

Consideration of the conversion factor from air dose rates to individual external dose per hour after the Fukushima accident—individual external dose measurements of a TEPCO employee in Fukushima prefecture over a 9 year period—

The accident at Fukushima Daiichi Nuclear Power Plant (FDNPP) in 2011 resulted in the dispersion of radioactive materials throughout the surrounding area and an increase in the air dose rate was even confirmed in Fukushima City, which is located approximately 60 km northeast of FDNPP. A Tokyo Electric Power Company (TEPCO) Holdings employee, who has lived and worked in Fukushima City since the FDNPP accident, measured individual external doses, GPS data, and his activities in Fukushima Prefecture over a 9 year period beginning in 2014. This data provides valuable information about the area. The data show the following results. (i) Comparison of the air dose rate at the home location to the individual external dose per hour at the home shows that the average conversion factor has increased over the 9 years and exceeded 0.3 since 2019, indicating an overall relatively good correlation. (ii) Individual external doses measured in the office on the fourth floor of a concrete structure in Fukushima City have not changed significantly from 2014 to 2022, when air dose rates showed a decrease. (iii) Outdoor individual external doses, such as those measured when commuting on foot, have a relatively strong correlation with air dose rates from airborne monitoring with the conversion factor of about 0.6. The conversion factor do not differ significantly from 2014 to 2022.In this study, the individual external dose data is applicable to the TEPCO measurer and is not necessarily representative of all residents of Fukushima City. However individual external dose data for 9 consecutive years will be useful for estimating individual external doses from air dose rates, and estimating annual additional exposure doses, if even some of them are applicable to similar life patterns and lifestyles.

Methodological principles of searching for disposal sites of radioactively contaminated materials by geophysical methods

This article is devoted to radiometric studies at one of the sites of the Chornobyl nuclear power plant (the “Sandy Plateau” site), which is located on the south-eastern outskirts of the city of Pripyat. Radioactive substances, both artificial and natural, resulting from incidents and disasters at nuclear facilities pose the greatest danger. The disposal sites for radioactively contaminated materials considered in this work are sources of groundwater pollution. Currently, there is a problem of searching for their location for reburial in specialized stationary burial grounds, to solve which detailed complex geophysical studies are used. Various geophysical methods are considered, including micro-sensing and radiometric studies, to determine the location of burials. Particular attention is paid to the analysis and interpretation of geophysical data, as well as the economic and practical aspects of the application of these methods. As a result of the study, it was established: that when searching and studying burial sites of radioactively contaminated materials, the use of surface gamma photography makes it possible to assess the level of radioactive contamination of the upper layers of the soil (to a depth of 0.8-1 m). However, if the thickness of buried radioactively contaminated materials exceeds a certain level, which leads to weak contamination of rocks at a depth of more than 1-1.5 m, then burial objects may go undetected when using only gamma-ray imaging. In such cases, microgamma probing becomes an effective method. Increased values of exposure dose rate and the nature of microgamma sounding curves serve as indicators of the presence (increase in exposure dose rate with depth) or absence (sharp decrease in exposure dose rate with depth) of radioactively contaminated materials in the studied area.

Effect of red osier dogwood extract on in vitro gas production, dry matter digestibility, and fermentation characteristics of forage-based diet or grain-based diet

This in vitro batch culture study investigated the effects of red osier dogwood (ROD) extract supplementation on gas production (GP), dry matter disappearance (DMD), and fermentation characteristics in high forage (HF) and high grain (HG) diets with varying media pH level. The experiment was a factorial arrangement of treatments in a completely randomized design with 2 media pH (5.8 and 6.5) × 4 dose rates of ROD extract (0, 1, 3, and 5% of DM substrate). An additional treatment of monensin was added as a positive control for each pH level. The HF substrate consisted of 400 and 600 g/kg DM barley-based concentrate and barley silage, respectively, while the HG substrate contained 100 and 900 g/kg DM barley silage and barley-based concentrate, respectively. Treatments were incubated for 24 h with GP, DMD and fermentation parameters determined. No interaction was detected between the media pH level and ROD extract dose rate on GP, DMD and most of the fermentation parameters. The GP, DMD, and total volatile fatty acid (VFA) concentration were greater (P = 0.01) with media pH of 6.5 in both HF and HG diets. The GP were not affected by increasing ROD dose rate, except that GP linearly decreased in the HF (P = 0.04) and HG (P = 0.01) diets at 24 h; the DMD tended to linearly decrease at pH 6.5 (P = 0.06) for both HF and HG diets and at pH 5.8 (P = 0.02) for the HG diet. Adding ROD extract to the HF and HG diets linearly (P = 0.01) increased the acetate molar proportion at high or low media pH and consequently, the acetate to propionate (A:P) ratio linearly (P ≤ 0.04) increased. Supplementation of ROD extract to the HF diet linearly (P = 0.04) decreased the molar proportion of propionate at pH 6.5 (interaction between pH and ROD extract; P = 0.05), but had no effect on propionate proportion when added to the HG diet. Moreover, the proportion of branched-chain fatty acids linearly (P = 0.03) decreased with ROD extract supplementation at low pH (interaction, P < 0.05) for HF diet and linearly decreased (P = 0.05) at pH 6.5 for HG diet (interaction, P < 0.05). The NH3–N concentration was not affected by ROD supplementation in the HF diet but it linearly (P = 0.01) decreased with increasing dose rate in the HG diet. Methane concentration tended to linearly (P = 0.06) increase with ROD extract supplementation at high pH for HF diet and linearly increased at pH 5.8 (P = 0.06) and pH 6.5 (P = 0.02) for HG diet. These results indicate that the decreased DMD and increased A:P ratio observed with addition of ROD extract may be beneficial to HG-fed cattle to reduce the risk of rumen acidosis without negatively impacting fiber digestion.

Biological activity of sod-podzolic soils at different levels of radioactive contamination

The biological (enzymatic) activity of sod-podzolic soils has been investigated in the zone of mandatory resettlement and in the alienation zone of the Chornobyl Nuclear Power Plant (CNPP) under the influence of ionizing radiation. Gas chromatographic methods were used to determine potential nitrogenfixing (nitrogenase) activity, biochemical methods were applied to study the activity of hydrolytic enzymes (cellulase and protease) responsible for the decomposition of plant residues in the soil, as well as enzymes involved in oxidative-reductive reactions of organic matter transformation (catalase and polyphenoloxidases). Statistical analysis was also employed. The results of the conducted research indicate that a relatively low increase in the total dose rate in the radioactive contamination area (from 0.2 to 1.6 µGy/h) at Polygon No. 1 (the zone of mandatory resettlement near the village of Khrystynivka, Narodychi district, Zhytomyr region) stimulated potential nitrogenase activity of soil diazotrophs and the activity of both hydrolytic enzymes and oxidoreductases. High dose rates (up to 22.2, 61.6, and especially up to 84.0 mGy/h) at Polygon No. 2, located in the alienation zone of the CNPP directly in the area of the former Red Forest, led to a decrease in soil enzymatic activity. Thus, the obtained results unequivocally demonstrate the different nature of the impact of ionizing radiation levels on the biological activity of sod-podzolic soils. The more radioactive soil in the zone of mandatory resettlement stimulates the enzymatic activity of soil microbiota. This could be attributed to adaptive changes in the development and activity of microorganisms or changes in the composition of their communities, with a prevalence of radio-tolerant microbiota representatives. It is also possible that the manifestation of a radiobiological effect, such as radiation stimulation (radiation hormesis), accelerating the growth and development of microorganisms, may occur. In the alienation zone of the CNPP, with high radioactive contamination, the negative influence of ionizing radiation on the metabolism of soil microorganisms is preserved. The obtained results are highly correlated with the indicators of the abundance of nitrogen-fixing microorganisms in the investigated soils, as well as microorganisms representing the saccharolytic (fungi and cellulolytic bacteria) and peptolytic (ammonifiers) pathways of plant residue degradation, as previously demonstrated by us.

Dose Rate Effects on Hydrated Electrons, Hydrogen Peroxide, and a OH Radical Molecular Probe Under Clinical Energy Protons.

We report the dose rate dependence of radiation chemical yields (G value) of water radiolysis products under clinical energy protons (230 MeV) to understand mechanisms of the FLASH radiotherapy performed at ultra-high dose rate (>40 Gy/s). The G value of 7-hydoroxy-coumarin-3-carboxylic acid (7OH-C3CA) produced by reactions of coumarin-3-carboxylic acid (C3CA) with OH radicals and oxygen is evaluated by fluorescence method. Also, those of hydrated electrons and hydrogen peroxide are derived by absorption method using Saltzman and Ghomley techniques, respectively. Both G values of 7OH-C3CA and hydrated electrons decrease with increasing dose rate. The relative evolution of 7OH-C3CA is -39 ± 2% between 0.1 and 50 Gy/s. This value is higher than that of hydrated electrons, measured at -21 ± 4%. The G value of hydrogen peroxide in ultra-pure water also decreases with increasing dose rate. In comparison to these findings, we represent the increase of the G value of hydrogen peroxide with increasing dose rate in the mixture solution of MeOH and NaNO3, which act as scavengers of OH radicals and hydrated electrons, respectively, that decompose hydrogen peroxide. This finding indicates that a complex track structure can be expected with increasing dose rate and the reduction of OH radicals by forming hydrogen peroxide would be related to the sparing effect of healthy tissues.

Evaluation of natural radioactivity and assessment of dose increase due to the use of fertilizers produced in Poland

Some types of fertilizers may contain various amounts of natural radionuclides like 238U, 232Th, 226Ra, 40K (Kuzmanoviæ et al. in J Radioanal Nucl Chem 331(12):5825–5834, 2022. 10.1007/s10967-022-08646-x; H Hamamo et al. in J Radioanal Nucl Chem 194(2): 331–336, 1995. 10.1007/BF02038431; M García-León et al. in J Radioanal Nucl Chem 197(1): 173–184, 1995. 10.1007/BF02040229). In this study 16 samples of commercially available fertilizers produced in Poland were selected for preliminary radiological evaluation. The samples were measured by means of low background gamma spectrometry. The results showed high concentrations of 40K in potassium and multinutrient fertilizers (2.3–13.8 kBq kg−1), and relatively high concentrations of uranium and radium isotopes in phosphate fertilizers. The obtained results allowed to calculate radium equivalent activity, absorbed dose rate increase and increase in annual effective dose equivalent.

Radiochemical Oxygen Depletion Depends on Chemical Environment and Dose-Rate: Implications for FLASH Effect

FLASH (dose rates > 40 Gy/s) radiotherapy (RT) protects normal tissues from radiation damage, compared with conventional RT (∼Gy/min). Radiation-chemical oxygen depletion (ROD) has been the leading and most-studied mechanism to explain FLASH. Previous studies have reported low ROD values of ∼0.35 µM/Gy, however, they do not accurately model (utilizing water or oxidized substrates such as albumin) the intracellular environment. It has been proposed that the intracellular environment may support higher ROD values due to its specific chemical makeup. As chemical reducing agents, which play a critical role in the cell, may promote ROD, we measured ROD for several well-known cellular reducing agents. Precision polarographic oxygen sensors were used to measure ROD over a ∼100-0 µM oxygen concentration range in solutions containing various types of intracellular reducing agents, either alone or combined with glycerol (1M; to simulate the intracellular hydroxyl-radical-scavenging capacity). A Cs irradiator and a research proton beamline were used for radiation beam generation over a 10,000-fold (0.0085 to 100 Gy/s) dose rate range. Reagents were grouped generally into primary free-radical scavengers (glycerol & lysozyme) and reducing agents (cysteamine, cysteine, glutathione, dextrin-conjugated linoleic acid, NAD(P)H, ascorbate and uric acid). Reducing agents at 1 mM significantly altered ROD values. ROD, at 0.1 Gy/s varied from greater than 1 µM/Gy for NADPH to less than 0.1 µM/Gy for uric acid. Even higher RODs were found at lower dose rates and/or higher reducing agent concentrations. Although most greatly increased ROD, ascorbate and uric acid decreased ROD and additionally imposed an oxygen dependence of ROD at low oxygen concentrations. Interestingly, all agents having high rates of ROD at low dose rates show a decrease at FLASH dose rates and this seems to be a proportional response (i.e., the greater the ROD at low dose rate, the greater the inhibition by FLASH). At FLASH dose rates our data for a simple mixture of glycerol and glutathione showed the same trend as recent studies that, in general, FLASH had ∼25% lower ROD rates than conventional demonstrating agreement between polarographic sensors and optical phosphorescence decay methods. ROD was greatly augmented by some intracellular reducing agents but others effectively reversed this effect. Ascorbate had its greatest impact at low oxygen concentrations. ROD decreased with increasing dose rate and in all cases was less than 1 µM/Gy at 100 Gy/s, potentially posing a fundamental limit of max ROD for FLASH.

Increased flexibility and efficiency of a double-scattering FLASH proton beamline configuration for in vivo SOBP radiotherapy treatments

Objective. To commission a proton, double-scattering FLASH beamline by maximizing efficiency and field size, enabling higher-linear energy transfer FLASH radiotherapy to cells and small animals using a spread-out Bragg peak (SOBP) treatment configuration. We further aim to provide a configuration guide for the design of future FLASH proton double-scattering (DS) beamlines. Approach. Beam spot size and spread were measured with film and implemented into TOol for PArticle Simulation (TOPAS). Monte Carlo simulations were optimized to verify the ideal positioning, dimensions, and material of scattering foils, secondary scatterers, ridge filters, range compensators, and apertures. A ridge filter with three discrete heights was used to create a spread-out Bragg peak (SOBP) and was experimentally verified using our in-house experimental FLASH beamline. The increase in dose rate was compared to nominal shoot-through techniques. Results. The configuration and scatterer distance producing the largest field size of acceptable flatness, without drastically compromising dose rate was determined to be an elliptical field of 2 cm × 1.5 cm (25% larger than a previous configuration). SOBP testing yielded three distinct but connected spikes in dose with flatness under 5%. Reducing the thickness of the (first) scattering foil by a factor of two was found to increase efficiency by 50%. The new settings increased the field size, provided a Bragg peak treatment option, and increased the maximum available dose rate by 85%, as compared to the previous, shoot through method. Significance. Beam line updates established FLASH dose rates of over 135 Gy s−1 (potentially higher) at our double-scattering beamline, increased the efficiency and field size, and enabled SOBP treatments by incorporating an optimized ridge filter. Based on our simulations we provide parametric suggestions when commissioning a new proton DS beamline. This enhanced FLASH beamline for SOBP irradiations with higher dose rates and larger field sizes will enable a wider variety of experimentation in future studies.

Changes in air dose rates due to soil moisture content in the Fukushima prefecture forests

Radionuclides released and deposited because of the 2011 Fukushima Dai-ichi Nuclear Power Plant accident caused an increase in air dose rates in Fukushima Prefecture forests. Although an increase in air dose rates during rainfall was previously reported, the air dose rates in the Fukushima forests decreased during rainfall. This study aimed to develop a method to estimate rainfall-related changes in air dose rates, even in the absence of soil moisture data, in Namie-Town and Kawauchi-Village, Futaba-gun, Fukushima Prefecture. Moreover, we examined the relationship between preceding rainfall (Rw) and soil moisture content. The air dose rate was estimated by calculating the Rw in Namie-Town from May to July 2020. We found that the air dose rates decreased with increasing soil moisture content. The soil moisture content was estimated from Rw by combining short-term and long-term effective rainfall using half-live values of 2 h and 7 d and considering the hysteresis of water absorption and drainage processes. Furthermore, the soil moisture content and air dose rate estimations showed a good agreement with coefficient of determination (R2) scores >0.70 and >0.65, respectively. The same method was tested to estimate the air dose rates in Kawauchi-Village from May to July 2019. At the Kawauchi site, variation in estimated value is relatively large due to the presence of water repellency in dry conditions, and the amount of 137Cs inventory was low, so estimating air dose from rainfall remained a challenge. In conclusion, rainfall data were successfully used to estimate soil moisture and air dose rates in areas with high 137Cs inventories. This leads to the possibility of removing the influence of rainfall on measured air dose rate data and could contribute to the improvement of methods currently used to estimate the external air dose rates for humans, animals, and terrestrial forest plants.

Irradiation temperature and dose rate dependence of void swelling in RAFM steel during irradiation: Reaction rate theory analysis

Reaction rate theory analysis has performed to investigate the irradiation temperature and dose rate dependence of void swelling of RAFM steel under a wide range of irradiation temperatures and dose rates (250 to 620 °C and 10−7 to 10−3 dpa/s) with focusing on nucleation behavior of voids. In the rate theory analysis, an improved nucleation model is employed where the stable nucleus size of voids is estimated by the vacancy flux into/from voids which depends on irradiation condition and void size. The calculation says that the void swelling strongly depends on irradiation temperature and dose rate, and there is one unique peak temperature for each dose rate. As dose rate increases, the peak temperature shifts to higher temperatures and the peak swelling decreases; this results from the enhancement and suppression of void nucleation. The calculated stable nucleus size of voids remarkably depends on irradiation conditions and varies widely from 5 to about 50: the nucleus size drastically increases at higher temperatures, while it decreases at higher dose rates. For the dose rate dependence of the peak temperature of void swelling, the calculation provides a good agreement with the experiment more than a conventional model.

Chornobyl radiation spikes are not due to military vehicles disturbing soil

On 25th February 2022, increased gamma radiation dose rates were reported within the Chornobyl Exclusion Zone (CEZ). This coincided with Russian military vehicles entering the Ukrainian part of the CEZ from neighbouring Belarus. It was speculated that contaminated soil resuspension by vehicle movements or a leak from the Chornobyl Nuclear Power Plant complex may explain these spikes in radiation dose rates. The gamma dose rate monitoring network in the CEZ provides a crucial early warning system for releases of radioactivity to the environment and is part of the international safeguards for nuclear facilities. With the potential for further military action in the CEZ and concerns over nuclear safety, it is essential that such anomalous readings are investigated. We evaluate the hypotheses suggested to explain the apparent gamma dose rate increases, demonstrating that neither military vehicle-induced soil resuspension nor a leak from the Chornobyl Nuclear Power Plant are plausible. However, disruption of the Chornobyl base-station's reception of wireless signals from the gamma dose rate monitoring network in the CEZ may potentially explain the dose rate increases recorded.

Developing CAR‐T‐sparing Radiotherapy ‐ early dosimetric results

Background/objective: Radiotherapy (RT) is an effective treatment for residual lymphoma following CD19 chimeric antigen receptor T-cell (CAR-T) therapy. However, there are concerns regarding the potential effect of RT on CAR-T, particularly early after infusion. We initiated a prospective protocol to explore the effect of different RT planning parameters and techniques on dose to the blood, and thus CAR-T cells, in order to develop a “CAR-T sparing RT” for early RT after CAR-T therapy. Methods: We analysed 33 RT treatment plans for 11 lesions in 7 patients. Each lesion was planned 3 times; (1) a conventional plan using volumetric modulated arc therapy (VMAT) technique, (2) a plan with optimisation for blood vessels in the region as well as blood-rich organs and bone marrow, and (3) same as plan 2 but delivered with Flattening Filter-Free (FFF) beams to increase dose rate. Plans were compared with regards to planning target volume (PTV) coverage, dose homogeneity, organs at risk (OAR) doses including blood vessels, dose rate and beam-on time. Results: Using CAR-T sparing techniques, the mean dose to major blood vessels was reduced by a mean of 12% compared to the conventional VMAT plan. The beam-on time was reduced by a mean of 60% due to the increase in dose rate. The blood-rich organ doses were not significantly affected. There was no detrimental effect on the overall quality of plans in terms of PTV coverage and dose homogeneity. The effect of different planning measures employed varied in different cases depending on the PTV volume, the anatomical location, and the proximity of blood vessels. Examples of clinical cases will be presented in the meeting. Conclusion: Reduction of radiation dose to the blood is possible using a variety of technical adjustments as well as reduction of the beam-on time. Further work continues to understand the relative contribution of the individual parameters and optimise RT in the post-CAR-T setting. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Radiation Therapy Conflicts of interests pertinent to the abstract. N. G. Mikhaeel Honoraria: Gilead, Educational meeting honoraria, Oct 2022

Modeling of Ionizing Radiation Effects for Negative Capacitance Field-Effect Transistors

A theoretical model for simulating ionizing radiation effects on negative capacitance field-effect transistors (NCFETs) with a metal–ferroelectric–insulator–semiconductor (MFIS) structure was established. Based on the model, the effects of total ionizing dose (TID) and dose rate on the surface potential, ferroelectric capacitance, voltage amplification factor, and transfer characteristics of NCFETs were investigated. The simulation results demonstrated that, with the increase in total dose, the curves of surface potential versus gate voltage and driving current versus gate voltage shift left significantly, resulting in the point of voltage amplification shifting left. Meanwhile, with the increase in dose rate, the amplitude of both the surface potential and driving current decreases slightly. Meanwhile, the derived result indicated that relatively thin ferroelectric thickness can effectively reduce the effect of TID. It is expected that this model can be helpful for analyzing the radiation effects of NCFETs.

Radiation-Chemical Oxygen Depletion Depends on Chemical Environment and Dose Rate: Implications for the FLASH Effect

FLASH (dose rates >40 Gy/s) radiation therapy protects normal tissues from radiation damage, compared with conventional radiation therapy (∼Gy/m). Radiation-chemical oxygen depletion (ROD) occurs when oxygen reacts with radiation-induced free radicals, so a possible mechanism for FLASH involves radioprotection by the decreased oxygen as ROD occurs. High ROD rates would favor this mechanism, but prior studies have reported low ROD values (∼0.35 µM/Gy) in chemical environments such as water and protein/nutrient solutions. We proposed that intracellular ROD might be much larger, possibly promoted by its strongly reducing chemical environment. ROD was measured, using precision polarographic sensors, from ∼100 µM to zero in solutions containing intracellular reducing agents ± glycerol (1M), to simulate intracellular reducing and hydroxyl-radical-scavenging capacity. Cs irradiators and a research proton beamline allowed dose rates from 0.0085 to 100 Gy/s. Reducing agents significantly altered ROD values. Most greatly increased ROD but some (eg, ascorbate) actually decreased ROD and additionally imposed an oxygen dependence of ROD at low oxygen concentrations. The highest values of ROD were found at low dose rates, but these montonically decreased with increasing dose rate. ROD was greatly augmented by some intracellular reducing agents but others (eg, ascorbate) effectively reversed this effect. Ascorbate had its greatest effect at low oxygen concentrations. ROD decreased with increasing dose rate in most cases.

Evaluation of plan quality and treatment efficiency in cranial stereotactic radiosurgery treatment plans with a variable source-to-axis distance.

Radiotherapy deliveries with dynamic couch motions that shorten the source-to-axis distance (SAD) on a C-arm linac have the potential to increase treatment efficiency through the increase of the effective dose rate. In this investigation, we convert clinically deliverable volumetric modulated arc therapy (VMAT) and dynamic conformal arc (DCA) plans for cranial radiosurgery into virtual isocenter plans through implementation of couch trajectories that maintain the target at a shortened but variable SAD throughout treatment. A randomly sampled population of patients treated with cranial radiosurgery from within the last three years were separated into groups with one, two, and three lesions. All plans had a single isocenter (regardless of number of targets), and a single prescription dose. Patient treatment plans were converted from their original delivery at a standard isocenter to a dynamic virtual isocenter in MATLAB. The virtual isocenter plan featured a variable isocenter position based upon the closest achievable source-to-target distance (referred to herein as a virtual source-to-axis distance [vSAD]) which avoided collision zones on a TrueBeam STx platform. Apertures were magnified according to the vSAD and monitor units at a given control point were scaled based on the inverse square law. Doses were calculated for the plans with a virtual isocenter in the Eclipse (v13.6.23) treatment planning system (TPS) and were compared with the clinical plans. Plan metrics (MU, Paddick conformity index, gradient index, and the volume receiving 12 Gy or more), normal brain dose-volume differences, as well as maximum doses received by organs at risk (OARs) were assessed. The values were compared between standard and virtual isocenter plans with Wilcoxon Sign Ranked tests to determine significance. A subset of the plans were mapped to the MAX-HD anthropomorphic phantom which contained an insert housing EBT3 GafChromic film and a PTW 31010 microion chamber for dose verification on a linac. Delivering plans at a virtual isocenter resulted in an average reduction of 20.9% (p = 3×10-6 ) and 20.6% (p = 3.0×10-6 ) of MUs across all VMAT and all DCA plans, respectively. There was no significant change in OAR max doses received by plans delivered at a virtual isocenter. The low dose wash (1.0-2.0 Gy or 5-11% of the prescription dose) was increased (by approximately 20 cc) for plans with three lesions. This was equivalent to a 2.7%-3.8% volumetric increase in normal tissue receiving the respective dose level when comparing the plan with a virtual isocenter to a plan with a standard isocenter. Gamma pass rates with a 5%/1mm analysis criteria were 96.40% ± 2.90% and 95.07% ± 3.10% for deliveries at standard and virtual isocenter, respectively. Absolute point dose agreements were within -0.36% ± 3.45% and -0.55% ± 3.39% for deliveries at a standard and virtual isocenter, respectively. Potential time savings per arc were found to have linear relationship with the monitor units delivered per arc (savings of 0.009 s/MU with an r2 = 0.866 when fit to plans with a single lesion). Converting clinical plans at standard isocenter to a virtual isocenter design did not show any losses to plan quality while simultaneously improving treatment efficiency through MU reductions.

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

PurposeRadiation-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 MaterialsWe 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. ResultsThe 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. ConclusionsWe 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.

An Integrated Physical Optimization Framework for Proton Stereotactic Body Radiation Therapy FLASH Treatment Planning Allows Dose, Dose Rate, and Linear Energy Transfer Optimization Using Patient-Specific Ridge Filters

Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LETd). We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT. The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LETd, using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LETd, while maintaining dose coverage within the beam specific planning target volume. This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LETd simultaneously.

Effects of Flash Radiotherapy on Blood Lymphocytes in Humans and Small Laboratory Animals.

A mathematical model, which describes the level of surviving lymphocytes in the blood after ultra-high (FLASH) and lower dose rates of partial-body irradiation, is developed. The model is represented by simple analytic formulae that involve a few parameters, namely, physiologic parameters (characteristics of the blood flow through the blood circulatory system and its irradiated part), a biophysical parameter (a characteristic of the blood lymphocytes radiosensitivity), and the physical parameters (characteristics of irradiation). The model predicts that the level of surviving blood lymphocytes increases as the dose rate increases and approaches the limiting level of (1 - vR), where vR is the fraction of the blood volume in the irradiated part of the blood circulatory system. The model also predicts that the level of surviving blood lymphocytes after the same exposure is higher for lower vR. It is found that FLASH irradiation in humans with doses of 10 to 40 Gy and with exposure times significantly less (<1 s) than the blood circulation time (∼60 s) leads to the maximal blood lymphocyte sparing. Simple formula, which determines effective dose rates for optimal blood lymphocyte sparing, is derived in the framework of the developed model. For the dose range specified above, the obtained modeling prediction of the range of effective dose rates for optimal blood lymphocyte sparing in humans (namely, N ≥40 Gy/s) coincides with the dose rate range in FLASH radiation therapy. It is revealed that the respective effective dose rates for mice are higher than those for humans (for the same dose range) due to the shorter blood circulation time in mice than in humans. Proceeding from the findings obtained in this paper, a hypothesis elucidating the mechanisms of the abscopal effect of FLASH radiation therapy (namely, an antitumor response on metastases located outside of irradiated part of a body) is proposed.

Multi-objective genetic algorithm for synchrotron radiation beamline optimization

In beamline design, there are many floating parameters that need to be tuned; manual optimization is time-consuming and laborious work, and it is also difficult to obtain well optimized results. Moreover, there are always several objectives that need to be considered and optimized at the same time, making the problem more complicated. For example, asking for both the flux and energy to be as large as possible is a usual requirement, but the changing trends of these two variables are often contradictory. In this study, a novel optimization method based on a multi-objective genetic algorithm is introduced, the first attempt to optimize a beamline with multiple objectives. In order to verify this method, beamline ID17 of the European Synchrotron Radiation Facility (ESRF) is taken as an example for simulation, with energy and dose rate as objectives. The result shows that this method can be effective for beamline optimization, and an optimal solution set can be obtained within 30 generations. For the solutions whose objectives are both improved compared with those of ESRF beamline ID17, the maximums of energy and dose rate increase by around 7% and 20%, respectively.

Flash-Effect in Radiotherapy of Tumors and the Problems of its Radiobiological Substantiation

The published data regarding radiation therapy of tumors treatment with ultrahigh dose rate radiation has been analyzed. In 2014, the authors, among whom the most mentioned are Vincent Favaudon and MarieCatherine Vozenin, named it the flash effect. Note, however, that a member of our laboratory, S.V. Kozin in the collaboration with ITEP researchers, back in 1984, having studied the reaction of a graft tumors and the mice skin after the proton irradiation with the ultrahigh and ordinary dose rates, concluded that: ‘... an increase in the radiation dose rate to ultrahigh, without significantly changing radiation reactions of tumors, leads to the protection of the mice skin, which is associated with the manifestation of the effect of radiation-chemical absorption of oxygen. Thus, under certain conditions of radiotherapy, one can expect to receive a therapeutic gain due to use the radiation with a high dose rate’. Consideration of the expediency and possibility of using a single irradiation with a dose rate of tens of Gy/s in radiation therapy of tumors is now given a special attention. It can be considered as established that less damage to the skin, lungs, intestines, and some other tissues occurs in this case in comparison with the usual dose rates used for the radiation therapy. Moreover, a number of studies indicate an increase in radiation damage to the tumors, or at least a much smaller decrease in the degree of their damage. The radiobiological mechanisms remain unclear. The effect itself is of undoubted clinical and experimental interest and justifies the conduct of experimental and clinical studies, as well as the need to take it into account when developing new equipment for radiation therapy and dosimetry accompanying the treatment process.