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Sekikawa, Takuya; Matsuya, Yusuke; Hwang, B.*; Ishizaka, Masato*; Kawai, Hiroyuki*; Ono, Yoshiaki*; Sato, Tatsuhiko; Kai, Takeshi
Nuclear Instruments and Methods in Physics Research B, 548, p.165231_1 - 165231_6, 2024/03
Times Cited Count:0 Percentile:0.44(Instruments & Instrumentation)One of the main causes of radiation effects on the human body is thought to be damage to DNA, which carries genetic information. However, it is not fully understood what kind of molecular structural changes DNA undergoes upon radiation damage. Since it has been reported that various types of DNA damage are formed when DNA is irradiated, our group has investigated the relationship between DNA damage and various patterns of radiation-induced ionization induced by radiation. Although we have so far analyzed DNA damage in a simple system using a rigid body model of DNA, more detailed calculations are required to analyze the molecular structural changes in DNA, which are considered to be important in considering the effects on the human body. In this study, we attempted to clarify the molecular conformational changes of DNA using OpenMX, a first-principles calculation software that can discuss electronic states based on molecular structures. Specifically, we calculated the most stable structure, band dispersion, and wave function of DNA under the assumption that one and two electrons are ionized by various radiation. In the presentation, we will discuss the relationship between the energy dependence of each incident radiation type and the molecular conformational change of DNA. In addition, the radiation-induced changes in the basic physical properties of DNA (corresponding to the initial stage of DNA damage) will be discussed from the viewpoints of both radiation physics and solid state physics.
Hirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke; Sato, Tatsuhiko
Nuclear Instruments and Methods in Physics Research B, 547, p.165183_1 - 165183_7, 2024/02
Times Cited Count:0 Percentile:0.02(Instruments & Instrumentation)The luminescence efficiency of the phosphors for swift ions is known to decrease because of the quenching effects. To obtain the precise dose distributions using phosphor detectors, understanding the mechanisms of quenching effects is mandatory. Here, we developed a new model for estimating the luminescence intensity of phosphors based on the track-structure modes for arbitrary materials implemented in PHITS. The developed model enabled the simulation of the quenching effects of the BaFBr detector and was verified by comparing the results to the corresponding measured data. The present model is expected to contribute to developing phosphor detectors worldwide.
Shiraishi, Yuta*; Matsuya, Yusuke; Kusumoto, Tamon*; Fukunaga, Hisanori*
Physics in Medicine & Biology, 69(1), p.015017_1 - 015017_14, 2024/01
Times Cited Count:0 Percentile:0.05(Engineering, Biomedical)FLASH radiotherapy (FLASH-RT) using ultra-high dose rate ( 40 Gy/sec) is known as a new treatment which is expected to enable preserving normal tissue functions, compared to the conventional radiotherapy (CONV-RT) with high dose rate ( 6 Gy/min). To date, it is believed that the modulation of chemical processes caused by interactions between radiation tracks under FLASH-RT is a key factor in the functional preservation of normal tissues; however, the relationship between changes in chemical processes and cellular responses remains uncertain. In this study, we developed a prediction model (integrated microdosimetric-kinetic (IMK) model for FLASH-RT) taking into account of the relationship between the chemical process and the DNA damage yields (which is the initial response) under ultra-high dose rate irradiation, to investigate the cellular mechanisms. As a result, the developed model considering the chemical-processes dependent change in DNA damage yields successfully reproduced the measured cell-killing effects of both CONV-RT and FLASH-RT for various cell line types. This model development would contribute on not only precisely understanding of cellular mechanisms after FLASH-RT irradiation but also enabling the prediction of therapeutic effects with high precision.
Saga, Ryo*; Matsuya, Yusuke; Obara, Hideki*; Komai, Fumio*; Yoshino, Hironori*; Aoki, Masahiko*; Hosokawa, Yoichiro*
Advances in Radiation Oncology (Internet), 9 Pages, 2024/00
The curative effects after radiotherapy are evaluated by the index of tumor control probability (TCP), and the treatment regimen has been determined empirically based on clinical experiences. In recent years, in order to determine TCP for any treatment regimens based on cell experiments, it is necessary to consider the existence of radioresistant cancer stem cells, which are included in tumors at from a few to several tens of percent. Our previous study has proposed an integrated microdosimetric-kinetic (IMK) model that explicitly considers cancer stem cells, and successfully reproduced cancer cell death obtained from cell experiments and clinical TCP. However, the verification so far has been limited to comparison with the clinical data of Hirosaki University Hospital, and comparative verification with clinical data of other facilities has not been performed. In this study, we focused on the stereotactic radiotherapy against non-small cell lung cancer that prescribes a large dose at once, and compared the public data collected by meta-analysis with the IMK model. As a result, it was found that the IMK model considering cancer stem cells well reproduced the clinical TCP regardless of the observed facility type. This work would contribute to the development of technology for predicting curative effects of radiotherapy with high precision.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke; Hirata, Yuho; Tezuka, Tomoya*; Tsuchida, Hidetsugu*; Yokoya, Akinari*
RSC Advances (Internet), 13(46), p.32371 - 32380, 2023/11
Times Cited Count:0 Percentile:0(Chemistry, Multidisciplinary)Although scientific knowledge of photolysis and radiolysis of water is widely used in the life sciences and other fields, the formation mechanism of the spatial distribution of hydrated electrons (spur) resulting from energy deposition to water is still not well understood. The chemical reaction times of hydrated electrons, OH radicals, and HO in the spur strongly depend on the spur radius. In our previous study, we elucidated the mechanism at a specific given energy (12.4 eV) by first-principles calculations. In the present study, we performed first-principles calculations of the spur radius at the deposition energies of 11-19 eV. The calculated spur radius is 3-10 nm, which is consistent with the experimental prediction (~4 nm) for the energy range of 8-12.4 eV, and the spur radius gradually increases with increasing energy. The spur radius is a new scientific knowledge and is expected to be widely used for estimating radiation DNA damage.
Hirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke*; Sato, Tatsuhiko
Japanese Journal of Applied Physics, 62(10), p.106001_1 - 106001_6, 2023/10
Times Cited Count:2 Percentile:75.57(Physics, Applied)Optimization of semiconductor detector design requires theoretical analysis of the process of radiation conversion to carriers (excited electrons) in semiconductor materials. We, therefore, developed an electron track-structure code that can trace an incident electron trajectory down to a few eV and simulate many excited electron productions in semiconductors, named ETSART, and implemented it into PHITS. The accuracy of ETSART was validated by comparing calculated electron ranges in semiconductor materials with the corresponding data recommended in ICRU Report 37 and obtained from another simulation code. The average energy required to produce a single excited electron (epsilon value) is an important value that describes the characteristics of semiconductor detectors. Using ETSART, we computed the epsilon values in various semiconductors and found that the calculated epsilon values cannot be fitted well with a linear model of the band-gap energy. ETSART is expected to be useful for initial and mechanistic evaluations of electron-hole generation in undiscovered materials.
Matsuya, Yusuke; Saga, Ryo*
Radiation Environment and Medicine, 12(2), p.81 - 90, 2023/08
Monte Carlo radiation transport simulations and biophysical models are powerful tools to evaluate the biological effects after ionizing radiation in radiation protection and radiation therapy. When exposing human body to radiation, DNA lesions as an early biological response are induced by deposition energy, leading to cell death with a certain probability. To precisely evaluate such effects, it is needed to perform translational studies among radiation physics, chemistry, and biology. Here, we introduce two simulation tools for predicting biological effects, i.e., Particle and Heavy-Ion Transport code System (PHITS) and integrated microdosimetric-kinetic model (IMKM). First, PHITS track-structure calculation at DNA scale enables to estimate the DNA damage yields by electrons and protons. Meanwhile, the IMKM considering various biological factors such as DSB repair kinetics and cancer stem-liken cells can successfully reproduce in vitro cell survival and clinical outcome. This review shows the development history and future prospect of the PHITS and the IMKM, which can expect to be further applied to the research fields of radiation research and quantum life science.
Sato, Tatsuhiko; Matsuya, Yusuke*; Ogawa, Tatsuhiko; Kai, Takeshi; Hirata, Yuho; Tsuda, Shuichi; Parisi, A.*
Physics in Medicine & Biology, 68(15), p.155005_1 - 155005_15, 2023/07
Times Cited Count:2 Percentile:84.52(Engineering, Biomedical)In this study, we improved the microdosimetric function implemented in PHITS using the latest track-structure simulation codes. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the numbers of ionization events occurred in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1 um. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation.
Matsuya, Yusuke; McMahon, S. J.*; Butterworth, K. T.*; Yachi, Yoshie*; Saga, Ryo*; Sato, Tatsuhiko; Prise, K. M.*
Physics in Medicine & Biology, 68(9), p.095008_1 - 095008_12, 2023/04
Times Cited Count:1 Percentile:65.01(Engineering, Biomedical)Hypoxia induces radioresistance in tumors, leading to malignant progression in intensity-modulated radiation therapy. To date, it has been shown that intercellular signalling between cells positioned inside and outside radiation field impacts on cellular radiosensitivity under hypoxia and normoxia. However, the mechanistic role of intercellular communication in hypoxia remains to be fully understood. In this study, we modelled the cell-killing effects of intercellular signalling in hypoxia to better understand the underlying mechanisms of response. We used the oxygen enhancement ratio (OER) given from early DSB yields and modelled the in- and out-of-field radiosensitivity. As a result, the model analysis provides an mechanistical interpretation that the probability of hits for releasing cell-killing signals is dependent on oxygen. Our data also suggested that the field-type independent OER value, which can be given by uniform-field exposure, can be applied when predicting both in- and out-of-field radiosensitivity. These results would contribute to more precise understanding of intercellular signalling under heterogeneous exposure to intensity-modulated radiation fields.
Kai, Takeshi; Toigawa, Tomohiro; Matsuya, Yusuke*; Hirata, Yuho; Tezuka, Tomoya*; Tsuchida, Hidetsugu*; Yokoya, Akinari*
RSC Advances (Internet), 13(11), p.7076 - 7086, 2023/03
Times Cited Count:3 Percentile:81.33(Chemistry, Multidisciplinary)Scientific insights of water radiolysis are widely used in the life sciences and so on, however, the formation mechanism of radicals, a product of water radiolysis, is still not well understood. We are challenging to develop a simulation code to solve this formation mechanism from the viewpoint of radiation physics. Our first-principles calculations have revealed that the behavior of secondary electrons in water is governed not only by collisional effects but also by polarization effects. Furthermore, from the predicted ratio of ionization to electronic excitation, based on the spatial distribution of secondary electrons, we successfully reproduce the initial yield of hydrated electrons predicted in terms of radiation chemistry. The code provides us a reasonable spatiotemporal connection from radiation physics to radiation chemistry. Our findings are expected to provide newly scientific insights for understanding the earliest stages of water radiolysis.
Yachi, Yoshie*; Matsuya, Yusuke*; Yoshii, Yuji*; Fukunaga, Hisanori*; Date, Hiroyuki*; Kai, Takeshi
International Journal of Molecular Sciences (Internet), 24(2), p.1386_1 - 1386_14, 2023/01
Times Cited Count:2 Percentile:75.46(Biochemistry & Molecular Biology)When living cells are irradiated with radiation and complex damage is formed within a few nanometers of DNA, it is believed to induce biological effects such as cell death. In general, complex DNA damage formed in cells can be detected experimentally by fluorescence microscopy, because the area around the damage site emits light like a focus point when a fluorophore is used. However, this detection method has not been able to analyze the degree of complexity of DNA damage. Therefore, in this study, we addressed on the measured focus size and evaluated the degree of complexity of DNA damage using a track structure analysis code. As a result, we found that as DNA damage becomes more complex, the focus size also increases. Our findings are expected to provide a new analytical method for elucidating the initial factors of radiation biological effects.
Sato, Tatsuhiko; Iwamoto, Yosuke; Hashimoto, Shintaro; Ogawa, Tatsuhiko; Furuta, Takuya; Abe, Shinichiro; Kai, Takeshi; Matsuya, Yusuke; Matsuda, Norihiro; Hirata, Yuho; et al.
Journal of Nuclear Science and Technology, 9 Pages, 2023/00
Times Cited Count:5 Percentile:98.08(Nuclear Science & Technology)The Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo radiation transport code that can simulate the behavior of most particle species with energies up to 1 TeV (per nucleon for ions). Its new version, PHITS3.31, was recently developed and released to the public. In the new version, the compatibility with high-energy nuclear data libraries and the algorithm of the track-structure modes have been improved. In this paper, we summarize the upgraded features of PHITS3.31 with respect to the physics models, utility functions, and application software introduced since the release of PHITS3.02 in 2017.
Matsuya, Yusuke; Yoshii, Yuji*; Kusumoto, Tamon*; Akamatsu, Ken*; Hirata, Yuho; Sato, Tatsuhiko; Kai, Takeshi
Physics in Medicine & Biology, 19 Pages, 2023/00
Times Cited Count:0 Percentile:0.05(Engineering, Biomedical)Time-dependent yields of chemical products resulted in water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which allows to determine several atomic interactions such as ionizations and electronic excitations as physical stage. However, a chemical code for simulating products of water radiolysis does not exist in the PHITS package. Here, we developed a chemical simulation code dedicated for the PHITS code, hereafter called PHITS-Chem code, which enables calculating G values of water radiolysis species (OH radical, e, H, HO etc) by electron beams. The estimated G values during 1 s are in agreement with the experimental ones and other simulations. This PHITS-Chem code enables simulating the dynamics in the presence of OH radical scavenger, and is useful for evaluating contributions of direct and indirect effects on DNA damage induction. This code will be included and be available in the future version of PHITS.
Saga, Ryo*; Matsuya, Yusuke; Sato, Hikari*; Hasegawa, Kazuki*; Obara, Hideki*; Komai, Fumio*; Yoshino, Hironori*; Aoki, Masahiko*; Hosokawa, Yoichiro*
Radiotherapy and Oncology, p.109444_1 - 109444_9, 2023/00
Times Cited Count:2 Percentile:0(Oncology)When treating non-small cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) with high-dose irradiation is often utilized. The fractionation schemes and curative effects can be evaluated by mathematical models for predicting cell survival curve. Such model parameters can be determined from in vitro experiment, but they are empirically determined based on experiences in clinics. As such, there is a large gap between in vitro and clinical study. As such background, translational study between in vitro cell survival and clinical curative effects is necessary. In this study, explicitly considering existence of cancer stem-like cells (CSCs), we developed an all-in-one model for predicting both in vitro cell survival and clinical curative effects (integrated microdosimetric-kinetic (IMK) model) and performed retrospective evaluation of clinical outcomes following SBRT for NSCLC in Hirosaki University Hospital. As a result, the IMK model successfully reproduced both in vitro cell survival and the tumor control probability with various fractionation schemes (i.e., 6-10 Gy per fraction). The developed model would contribute on precisely understanding the impact of CSCs on curative effects after SBRT for NSCLC with high precision.
Ogawa, Tatsuhiko; Hirata, Yuho; Matsuya, Yusuke; Kai, Takeshi
Isotope News, (784), p.13 - 16, 2022/12
Track-structure calculation, a method to simulate every secondary electron production reaction explicitly, has been extensively used as an important techniques in various fields such as radiation biology, material irradiation effect, and radiation detection. However, it requires the dielectric function of the target materials, which is not well known except for liquid water. Therefore we developed a model to perform track-structure calculation based on a systematic formula of secondary electron production cross section and that of stopping power. The model can therefore perform track-structure calculation regardless of the availability of dielectric function measurement data. Stopping range, and energy deposition radial distribution calculated by this model agreed well with the earlier experimental data and calculation by precedent codes. The lineal energy in tissue-equivalent gas calculated by this model agreed with measurement data taken from literature, showing distinct difference from that in liquid water. This model was implemented to PHITS Ver3.25, the general-purpose radiation transport simulation code of JAEA, being distributed to users as the first track-structure calculation model applicable to arbitrary materials available in general-purpose transport code.
Matsuya, Yusuke; Kai, Takeshi; Parisi, A.*; Yoshii, Yuji*; Sato, Tatsuhiko
Physics in Medicine & Biology, 67(21), p.215017_1 - 215017_13, 2022/11
Times Cited Count:5 Percentile:78.03(Engineering, Biomedical)Proton beam therapy allows to irradiate tumor volumes with reduced side effects on normal tissues with respect to X-ray radiotherapy. Biological effects such as cell killing after proton beam irradiations depend on the proton kinetic energy, which is intrinsically related in the early DNA damage induction. As such, the estimation of DNA damage yields based on Monte Carlo simulations is a research topic of worldwide interest. In this study, we investigate the possibility of applying a simple model developed for electron to proton without any modification. The yields of single-strand breaks (SSB), double-strand breaks (DSB) and the complex DSB were assessed as a function of the proton kinetic energy. The PHITS-based estimation accurately reproduced the experimental and simulated yields of various DNA damage types induced by protons with linear energy transfer (LET) up to about 30 keV/m. These results suggest that current DNA damage model implemented in PHITS is sufficient for estimating DNA lesion yields induced after protons irradiation except for lower energies than MeV.
Hirata, Yuho; Kai, Takeshi; Ogawa, Tatsuhiko; Matsuya, Yusuke; Sato, Tatsuhiko
Japanese Journal of Applied Physics, 61(10), p.106004_1 - 106004_6, 2022/10
Times Cited Count:5 Percentile:67.2(Physics, Applied)Some radiation effects such as pulse-height defects and soft errors can cause problems in silicon (Si) devices. Local energy deposition in microscopic scales is essential information to elucidate the mechanism of these radiation effects. We, therefore, developed an electron track-structure model, which can simulate local energy deposition down to nano-scales, dedicated to Si and implemented it into PHITS. Then, we verified the accuracy of our developed model by comparing the ranges and depth-dose distributions of electrons obtained from this study with the corresponding experimental values and other simulated results. As an application of the model, we calculated the mean energies required to create an electron-hole pair, the so-called epsilon value. We found that the threshold energy for generating secondary electrons reproducing the epsilon value is 2.75 eV, consistent with the corresponding data deduced from past theoretical and computational studies. Since the magnitudes of the radiation effects on Si devices largely depend on the epsilon value, the developed code is expected to contribute to precisely understanding the mechanisms of pulse-height defects and semiconductor soft errors.
Papadopoulos, A.*; Kyriakou, I.*; Matsuya, Yusuke; Incerti, S.*; Daglis, I. A.*; Emfietzoglou, D.*
Applied Sciences (Internet), 12(18), p.8950_1 - 8950_20, 2022/09
Times Cited Count:2 Percentile:28.33(Chemistry, Multidisciplinary)The quality factor (Q) is the index which is used when evaluating the stochastic (e.g., carcinogenic) risk of diverse ionizing radiations. While the Q value can be commonly determined from the Linear Energy Transfer (LET), more elaborate approaches are based on the microdosimetric parameter lineal energy (y) calculated either by analytical model or Monte Carlo (MC) simulations. However, the developing of the model for determining the Q value is still ongoing worldwide for realizing the precise risk assessment. In this study, various generalized analytical models that account for both -ray transport and energy-loss straggling effects are utilized to evaluate the Q values over the proton energy range 1-250 MeV. The results revealed that the LET-based ICRP Report 60 recommendations underestimate the microdosimetric-based Q values of protons with energy below 100 MeV, which was also confirmed by using MC simulation data on the y values. The present work shows that analytic models may offer a practical alternative to computer-intensive MC simulations for calculating Q values based on the microdosimetric methodologies. In future study, we are planning to compare the y spectra and subsequent calculations of Q based on new MC data with the latest versions of Geant4-DNA and PHITS track structure codes which make use of different physics models.
Sato, Tatsuhiko; Matsuya, Yusuke; Hamada, Nobuyuki*
International Journal of Radiation Oncology, Biology, Physics, 114(1), p.153 - 162, 2022/09
Times Cited Count:6 Percentile:83.07(Oncology)The microdosimetric kinetic model, which was originally developed for estimating cell surviving fractions for various radiations, was improved to be capable of estimating the mean and uncertainty of RBE for skin reactions. The parameter used in the model was independently determined from in vitro measurements of dermal cell survival and in vivo measurements of skin reactions taken from 8 and 23 papers, respectively. Our model quantitatively revealed that RBE for skin reactions tend to be higher than that for dermal cell survival. RBE of various mono-energetic radiations calculated from this model confirmed that the past evaluations made by ICRP and NCRP a few decades ago are still supported by recent experimental data. Conclusions: Our model can play important roles not only in medical physics for avoiding unnecessary skin reactions in particle therapy and BNCT but also in radiation protection for future decision making of the recommended RBE values.
Yachi, Yoshie*; Kai, Takeshi; Matsuya, Yusuke; Hirata, Yuho; Yoshii, Yuji*; Date, Hiroyuki*
Scientific Reports (Internet), 12, p.16412_1 - 16412_8, 2022/09
Times Cited Count:2 Percentile:47.19(Multidisciplinary Sciences)Recently, magnetic resonance-guided radiotherapy (MRgRT) which can visualize tumors in real time has been developed and installed in several clinical facilities. It is known that Lorentz force modulate macroscopic dose distribution by a charged particle, however, the impact by the force on microscopic radiation-track structure and early DNA damage induction remain unclear. In this study, we simulated the electron-track structure in a static magnetic field using a PHITS, and estimated features of biological effects. We indicated that the macroscopic dose distributions are changed by the force, while early DNA damage such as double strand breaks is attributed to the secondary electrons below a few tens of eV which are independent of the force. We expect that our insight significantly contributes to the MRgRT.