Matsuya, Yusuke; Sato, Tatsuhiko; Nakamura, Rui*; Naijo, Shingo*; Date, Hiroyuki*
Physics in Medicine and Biology, 65(9), p.095006_1 - 095006_12, 2020/05
Radio-resistance induced under low oxygen pressure plays an important role in malignant progression in fractionated radiotherapy. For the general approach to predict cell killing under hypoxia, cell-killing models (e.g., the Linear-Quadratic model) have to be fitted to experimental survival data for both normoxia and hypoxia to obtain the oxygen enhancement ratio (OER). However, model parameters for every oxygen condition needs to be considered by model-fitting approaches. This is inefficient for fractionated irradiation planning. Here, we present an efficient model for fractionated radiotherapy the integrated microdosimetric-kinetic model including cell-cycle distribution and the OER at DNA double-strand break endpoint. The cell survival curves described by this model can reproduce the experimental survival data for both acute and chronic low oxygen concentrations. The OER used for calculating cell survival agrees well with experimental DSB ratio of normoxia to hypoxia. This work provides biological effective dose (BED) under various oxygen conditions including its uncertainty, which can contribute to creating fractionated regimens for multi-fractionated radiotherapy. If the oxygen concentration in a tumor can be quantified by medical imaging, the present model will make it possible to estimate the cell-killing and BED under hypoxia in more realistic intravital situations.
Matsuya, Yusuke; Nakano, Toshiaki*; Kai, Takeshi; Shikazono, Naoya*; Akamatsu, Ken*; Yoshii, Yuji*; Sato, Tatsuhiko
International Journal of Molecular Sciences (Internet), 21(5), p.1701_1 - 1701_13, 2020/03
Among various DNA damage induced after irradiation, clustered damage composed of at least two vicinal lesions within from 10 to 20 base pairs is recognized as fatal damage to human tissue. Such clustered damage yields have been evaluated by means of computational approaches; however, the simulation validity has not been sufficiently made yet. Meanwhile, the experimental technique to detect clustered DNA damage has been evolved in the recent decades, so both approaches with simulation and experiment get used to be available for investigating clustered damage recently. In this study, we have developed a simple model for estimating clustered damage yield based on the spatial density of ionization and electronic excitation events obtained by the PHITS code, and compared the computational results to the experimental clustered damage coupled with base damage (BD) measured by gel electrophoresis and atomic force microscopy. The computational results agreed well with experimental fractions of clustered damage of strand breaks (SB) and BD, when the yield ratio of BD/SSB is assumed to be 1.3. From the comparison of complex DNA double-strand break coupled with BDs between simulation and experimental data, it was suggested that aggregation degree of the events along electron track reflects the complexity of DNA damage. The resent simulation enables to quantify the type of clustered damage which cannot be measured in in vitro experiment, which succeeded in interpreting the experimental detection efficiency for clustered BD.
Proton Beam Radiotherapy; Physics and Biology, p.61 - 72, 2020/00
Ionizing radiation heterogeneously deposits energy in matter via atomic interactions such as ionization and excitation. This heterogeneity complicatedly depends on the type and energy of ionization radiation, and influences the biological effect of the radiation exposure. Thus, the biological effects are expected to be different with radiations imparting the energy even for the same absorbed dose. In this chapter, a review of the definitions of microdosimetric quantities is given. Examples of calculated track structures and microdosimetric quantities of several mono-energetic radiations are shown for discussion. Then, past studies on the applications of microdosimetry in proton therapy are briefly reviewed and summarized.
Carter, L. M.*; Crawford, T. M.*; Sato, Tatsuhiko; Furuta, Takuya; Choi, C.*; Kim, C. H.*; Brown, J. L.*; Bolch, W. E.*; Zanzonico, P. B.*; Lewis, J. S.*
Journal of Nuclear Medicine, 60(12), p.1802 - 1811, 2019/12
Voxel human phantoms have been used for internal dose assessment. More anatomically accurate representation become possible for skins or layer tissues owing to recent developments of advanced polygonal mesh-type phantoms and thus internal dose assessment using those advanced phantoms are desired. However, the Monte Carlo transport calculation by implementing those phantoms require an advanced knowledge for the Monte Carlo transport codes and it is only limited to experts. We therefore developed a tool, PARaDIM, which enables users to conduct internal dose calculation with PHITS easily by themselves. With this tool, a user can select tetrahedral-mesh phantoms, set radionuclides in organs, and execute radiation transport calculation with PHITS. Several test cases of internal dosimetry calculations were presented and usefulness of this tool was demonstrated.
Ogawa, Tatsuhiko; Sato, Tatsuhiko; Yamaki, Tetsuya*
Hoshasen Kagaku (Internet), (108), p.11 - 17, 2019/11
Scintillators are generally used to detect various kinds of particles such as electrons, gammas, protons and heavy ions. Scintillators emit photons according to the energy deposited to the crystal. It is also known that light yield is suppressed for particles depositing energy densely owing to quenching. Moreover, it is suggested that quenching is attributed to transfer of energy from excited fluorescent molecules to damaged molecules (Frster mechanism or Dexter mechanism). In this study, energy deposition in a scintillator crystal by radiation was calculated using radiation transport codes to finally obtain excitation and damage of fluorescent molecules. Based on the calculation, spatial configuration of exited and damaged molecules. Then the probability that Frster mechanism takes place in excited molecules were estimated to obtain the number of fluorescent molecules that emit photons. As a result, light yield is proportionally increased with increase in the incident energy in case of electron incidence. On the other hand, light yield is increased non-linearly in case of proton incidence. This trend is in a good agreement with the experimental results.
Matsuya, Yusuke; Kai, Takeshi; Yoshii, Yuji*; Yachi, Yoshie*; Naijo, Shingo*; Date, Hiroyuki*; Sato, Tatsuhiko
Journal of Applied Physics, 126(12), p.124701_1 - 124701_8, 2019/09
Biological effects after ionizing radiation exposure arise from initial DNA strand breaks. DNA damage can be estimated from the simulation with both track structure analysis and diffusion of free radicals; however, the simulation is a time-consuming process. In this study, we present a simple model for estimating yields of strand breaks based only on spatial patterns of inelastic interactions (i.e., ionization and electronic excitation) generated by electrons, which are evaluated by PHITS code without considering the production and diffusion of free radicals. In this model, the number of events per track and that of the two events pair within 3.4 nm (corresponding to 10 base pair) were stochastically sampled for calculating SSB and DSB yields, respectively. The calculated results agreed well with other simulations and experimental data on DSB yield and yield ratio of DSB/SSB for the exposure to mono-energetic electrons. The present model also can demonstrate the relative biological effectiveness at the DSB endpoint for various photon exposures. This study indicated that the spatial pattern of inelastic events composed of ionization and electronic excitation is sufficient to obtain the impact of electrons on initial induction to DNA strand break.
Yamashiki, Yosuke*; Maehara, Hiroyuki*; Airapetian, V.*; Notsu, Yuta*; Sato, Tatsuhiko; Notsu, Shota*; Kuroki, Ryusuke*; Murashima, Keiya*; Sato, Hiroaki*; Namekata, Kosuke*; et al.
Astrophysical Journal, 881(2), p.114_1 - 114_24, 2019/08
The impact of Stellar flares on extrasolar planetary systems has been discussed and argued, especially whether there is a potential impact on their life systems. Here, we propose a comprehensive evaluation system for stellar flares, focusing on Stellar Proton Events (SPE) on selected extrasolar planets with hypothetical atmospheres and oceans. This is done by cross-linking KIC flare-observed and flare-estimated stars by their start pots that are directly linked with the Monte Carlo simulation system PHITS through the exoplanetary database system ExoKyoto. The estimated dose at ground level for each planetary surface did not exceed the critical dose for complex animals.
Sakashita, Tetsuya*; Sato, Tatsuhiko; Hamada, Nobuyuki*
PLOS ONE (Internet), 14(8), p.e0221579_1 - e0221579_20, 2019/08
Cataracts have long been known, but a biologically based mathematical model is still unavailable for cataratogenesis. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure.
Abe, Shinichiro; Liao, W.*; Manabe, Seiya*; Sato, Tatsuhiko; Hashimoto, Masanori*; Watanabe, Yukinobu*
IEEE Transactions on Nuclear Science, 66(7, Part2), p.1374 - 1380, 2019/07
Single event upsets (SEUs) caused by secondary cosmic-ray neutrons have recognized as a serious reliability problem for microelectronic devices. Acceleration tests at neutron facilities are convenient to validate soft error rates (SERs) quickly, but some corrections caused from measurement conditions are required to derive realistic SERs at actual environment or to compare other measured data. In this study, the effect of irradiation side on neutron-induced SEU cross sections was investigated by performing neutron transport simulation using PHITS. SERs for 65-nm bulk CMOS SRAMs are estimated using the sensitive volume model. It was found from simulation that SERs for the sealant side irradiation are 30-50% larger than those for the board side irradiation. This difference comes from the difference of production yield and angular distribution of secondary H and He ions, which are the main cause of SEUs. Thus the direction of neutron irradiation should be reported when the result of acceleration tests are published. This result also indicates that SERs can be reduced by equipping device with sealant side facing downward.
Matsuya, Yusuke; McMahon, S. J.*; Ghita, M.*; Yoshii, Yuji*; Sato, Tatsuhiko; Date, Hiroyuki*; Prise, K. M.*
Scientific Reports (Internet), 9(1), p.9483_1 - 9483_12, 2019/07
In radiotherapy, intensity modulated radiation fields and complex dose-delivery are used to prescribe doses to tumors. Here, we analyzed the impact of modulated field on radio-sensitivity and cell recovery during irradiation time. The dose was delivered to either 50% of the area of the flask containing cells (half-field) or 100% of the flask (uniform-field). We also modelled cell-killing considering dose-rate effects and intercellular signals. It is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure even with the same dose; (ii) the importance of sub-lethal damage repair in normal human skin fibroblast cells under the half-field is reduced; (iii) the increase of cell survival under half-field is predominantly attributed to not rescue effects (increased repair) but protective effects (reduced initial DNA lesion yield). These findings provide new understanding of radio-sensitivity for hit and non-hit cells under non-uniform exposure.
Matsuya, Yusuke; Satou, Yukihiko; Hamada, Nobuyuki*; Date, Hiroyuki*; Ishikawa, Masayori*; Sato, Tatsuhiko
Scientific Reports (Internet), 9(1), p.10365_1 - 10365_9, 2019/07
Insoluble radioactive microparticles (so called Cs-bearing particles) have been assumed to adhere in the long term to trachea after aspirated into respiratory system, leading to heterogeneous dose distribution within healthy tissue around the particles. The biological effects posed by such a particle remain unclear. Here, we show cumulative DNA damage in cultured cells proximal and distal to the particle under localized chronic exposure in comparison with uniform exposure. We placed the particle-contained microcapillary onto a glass-base dish containing normal human lung cells in vitro, and observed a significant change in nuclear -H2AX foci after 24 h or 48 h exposure to the particle. The dose calculation by a Monte Carlo simulation and the comparison with nuclear foci under uniform exposure suggested that the localized exposure to a Cs-bearing particle leads to not only signal-induced DNA damage to distal cells but also the reduction of DNA damage induction yield to proximal cells (protective effects). Considering the small organ dose, the conventional radiation risk assessment is adequate. This study is the first to quantify the spatial distribution of cumulative DNA lesions under heterogeneous exposure by insoluble Cs-bearing particles.
Sato, Tatsuhiko; Masunaga, Shinichiro*; Kumada, Hiroaki*; Hamada, Nobuyuki*
Radiation Protection Dosimetry, 183(1-2), p.247 - 250, 2019/05
As an application of Particle and Heavy Ion Transport code System PHITS, We have developed the stochastic microdosimetric kinetic (SMK) model for estimating the therapeutic effects of various kinds of radiation therapy. In this study, we improved the SMK model for estimating the therapeutic effect of boron neutron capture therapy, BNCT. The improved SMK model can consider not only the intra- and intercellular heterogeneity of B-10 distribution but also the dose rate effect. The accuracy of the model was well verified by comparisons made between calculated and measured surviving fractions of tumor cells, which we previously determined in vivo in mice with B-10 compounds exposed to reactor neutron beam. Details of the improved SMK model together with the verification results will be presented at the meeting.
Hashimoto, Shintaro; Sato, Tatsuhiko
Journal of Nuclear Science and Technology, 56(4), p.345 - 354, 2019/04
Particle transport simulations based on the Monte Carlo method have been applied to shielding calculations. Estimation of not only statistical uncertainty related to the number of trials but also systematic one induced by unclear physical quantities is required to confirm the reliability of calculated results. In this study, we applied a method based on analysis of variance to shielding calculations. We proposed random- and three-condition methods. The first one determines randomly the value of the unclear quantity, while the second one uses only three values: the default value, upper and lower limits. The systematic uncertainty can be estimated adequately by the random-condition method, though it needs the large computational cost. The three-condition method can provide almost the same estimate as the random-condition method when the effect of the variation is monotonic. We found criterion to confirm convergence of the systematic uncertainty as the number of trials increases.
Griffin, K.*; Paulbeck, C.*; Bolch, W.*; Cullings, H.*; Egbert, S.*; Funamoto, Sachiyo*; Sato, Tatsuhiko; Endo, Akira; Hertel, N.*; Lee, C.*
Radiation Research, 191(4), p.369 - 379, 2019/04
Due to computing limitations of the time, only three stylized phantoms were used in DS86 and DS02 to represent the entire Japanese population: an infant, child, and adult. Our study aimed to evaluate the dosimetric impact that should be expected from using an updated and age-expanded RERF phantom series with the survivor cohort. To this end, we developed a new series of hybrid phantoms, based on the Japanese population of 1945, which has greater anatomical realism and improved age resolution than those previously used by RERF. From the photon portion of the spectra, dose differences of up to nearly 25% are expected between the old and new series, while differences of up to nearly 70% are expected from the neutron portion. Overall, our new series of phantoms has shown to provide significant improvements to survivor organ dosimetry, especially to those survivors who were previously misrepresented in body size by their stylized phantom and to those who experienced a highly-directional irradiation field.
Yano, Tsuneo*; Hasegawa, Koki*; Sato, Tatsuhiko; Hachisuka, Akiko*; Fukase, Koichi*; Hirabayashi, Yoko*
Iyakuhin Iryo Kiki Regyuratori Saiensu, 50(3), p.122 - 134, 2019/03
This report provides an overview of alpha-particle-emitting radiopharmaceuticals applied by micro-dosimetry.
Sato, Tatsuhiko; Kataoka, Ryuho*; Shiota, Daiko*; Kubo, Yuki*; Ishii, Mamoru*; Yasuda, Hiroshi*; Miyake, Shoko*; Miyoshi, Yoshizumi*; Ueno, Haruka*; Nagamatsu, Aiko*
Journal of Space Weather and Space Climate (Internet), 9, p.A9_1 - A9_11, 2019/03
Real-time estimation of astronaut doses during solar particle events (SPE) is one of the most challenging tasks in cosmic-ray dosimetry. We therefore develop a new computational method that can nowcast the solar energetic particle (SEP) as well as galactic cosmic-ray (GCR) fluxes on any Earth orbit during a large SPE associating with ground level enhancement. It is an extended version of WArning System for AVIation Exposure to Solar Energetic Particle, WASAVIES. The extended version, called WASAVIES-EO, can calculate the GCR and SEP fluxes outside a satellite based on its two-line element data. Moreover, organ dose and dose-equivalent rates of astronauts in the International Space Station (ISS) can be estimated using the system, considering its shielding effect. The accuracy of WASAVIES-EO was validated based on the dose rates measured in ISS, as well as based on high-energy proton fluxes observed by POES satellites.
Kataoka, Ryuho*; Nishiyama, Takanori*; Tanaka, Yoshimasa*; Kadokura, Akira*; Uchida, Herbert Akihito*; Ebihara, Yusuke*; Ejiri, Mitsumu*; Tomikawa, Yoshihiro*; Tsutsumi, Masaki*; Sato, Kaoru*; et al.
Earth, Planets and Space (Internet), 71, p.9_1 - 9_10, 2019/01
Transient ionization of the mesosphere was detected at around 65 km altitude during the isolated auroral expansion occurred at 2221-2226 UT on June 30, 2017. A general-purpose Monte Carlo particle transport code PHITS suggested that significant ionization is possible in the middle atmosphere due to auroral X-rays from the auroral electrons of 10 keV.
Schuemann, J.*; McNamara, A. L.*; Warmenhoven, J. W.*; Henthorn, N. T.*; Kirkby, K.*; Merchant, M. J.*; Ingram, S.*; Paganetti, H.*; Held, K. D.*; Ramos-Mendez, J.*; et al.
Radiation Research, 191(1), p.76 - 93, 2019/01
We propose a new Standard DNA Damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modelling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
Isotope News, (760), p.2 - 5, 2018/12
Recently, we proposed a new model for estimating the biological effectiveness for Boron Neutron Capture Therapy (BNCT) based on the absorbed dose distributions in cellular scale. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. This paper reviews the basic features of the model.
Ishikawa, Tetsuo*; Matsumoto, Masaki*; Sato, Tatsuhiko; Yamaguchi, Ichiro*; Kai, Michiaki*
Journal of Radiological Protection, 38(4), p.1253 - 1268, 2018/12
The current knowledge on internal dose estimation and its health effect were reviewed in this paper. The goals were to discuss the uncertainty of current dose coefficients, to compare the effects of external and internal exposures, and to review recent epidemiological studies. Radionuclides focused on in this study were caesium-137 (Cs), caesium-134 (Cs), and iodine-131 (I), which primarily contributed to internal effective thyroid doses after the Fukushima Dai-ichi Nuclear Power Station accident. Current knowledge suggests that the risk of internal exposure could be generally the same as or less than that of external exposure, when they are compared at the same effective dose.