Researcher Profile and Settings

Affiliation

• Faculty of Health Sciences　Health Sciences　Biomedical Science and Engineering

Job Title

• Lecturer

Degree

• Bachelor（Hokkaido University）
• Master（Hokkaido University）
• PhD（Hokkaido University）

Research funding number

• 20826929

J-Global ID

• 201801002869649377

Research Interests

• Mathematical modelling   Radiation therapy   Bayes estimation   Monte Carlo simulation   Radiation biology   

Research Areas

• Energy / Quantum beam science
• Life sciences / Radiology

Academic & Professional Experience

• 2024/04 - Today 公益社団法人日本アイソトープ協会 理工・ライフサイエンス部会放射線照射標的分子探索専門委員会専門委員
• 2023/04 - Today 学校法人西野学園 札幌医学技術福祉歯科専門学校 臨床工学技士科 非常勤講師
• 2023/01 - Today Japan Atomic Energy Agency Nuclear Science and Engineering Center cross-appointment staff
• 2022/11 - Today Hokkaido University Faculty of Health Sciences Lecturer
• 2021/04 - 2022/10 Japan Atomic Energy Agency Nuclear Science and Engineering Center
• 2018/04 - 2022/10 Hokkaido University Faculty of Health Sciences
• 2018/04 - 2021/03 Japan Atomic Energy Agency Nuclear Science and Engineering Center Postdoc researcher
• 2016/04 - 2018/03 Japan Society for the Promotion of Science Research fellow

Education

• 2015/04 - 2018/03  Hokkaido University  Graduate School of Health Sciences  Ph.D. course
• 2017/05 - 2017/09  Queens University Belfast  Centre for Cancer Research and Cell Biology  (Visiting Ph.D. student)
• 2013/04 - 2015/03  Hokkaido University  Graduate School of Health Sciences  Master course
• 2009/04 - 2013/03  Hokkaido University  Department of Health Sciences

Association Memberships

• 公益社団法人日本放射線腫瘍学会   JAPAN HEALTH PHYSICS SOCIETY   THE JAPANESE RADIATION RESEARCH SOCIETY   JAPAN SOCIETY OF MEDICAL PHYSICS   公益社団法人 日本放射線技術学会   

Research Activities

Published Papers

• Reply to comment on ‘Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation’

  Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga

  Physics in Medicine & Biology 69 (10) 108002 - 108002 0031-9155 2024/05/03 [Refereed]
   

  Abstract Liew and Mairani commented on our paper ‘Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation’ (Shiraishi et al 2024a Phys. Med. Biol.69 015017), which proposed a biophysical model to predict the dose–response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model’s parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions.
• Changes in molecular conformation and electronic structure of DNA under 12C ions based on first-principles calculations

  Takuya Sekikawa, Yusuke Matsuya, Beomju Hwang, Masato Ishizaka, Hiroyuki Kawai, Yoshiaki Ōno, Tatsuhiko Sato, Takeshi Kai

  Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 548 165231 - 165231 0168-583X 2024/03 [Refereed]
  
• Meeting Report on “The 9th Educational Symposium on Radiation and Health by Young Scientists (ESRAH2022)

  H. Hashimoto, R. Nakayama, H. Kuwata, W. Poltabtim, R. Seino, R. Fukuda, K. Kheamsiri, R. Pradana, Y. Oda, M. Kiso, A. Sampei, C. Kranrod, H. Yoshino, Y. Matsuya, M. Hosoda

  Radiation Environment and Medicine 13 (1) 35 - 43 2024/02 [Refereed]
  
• Development of a model for evaluating the luminescence intensity of phosphors based on the PHITS track-structure simulation

  Yuho Hirata, Takeshi Kai, Tatsuhiko Ogawa, Yusuke Matsuya, Tatsuhiko Sato

  Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 547 165183 - 165183 0168-583X 2024/02 [Refereed]
  
• Possible mechanisms and simulation modeling of FLASH radiotherapy

  Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga

  Radiological Physics and Technology 1865-0333 2024/01/06 [Refereed]
  
• Generality assessment of a model considering heterogeneous cancer cells for predicting tumor control probability for stereotactic body radiotherapy against non-small cell lung cancer

  Ryo Saga, Yusuke Matsuya, Hideki Obara, Fumio Komai, Hironori Yoshino, Masahiko Aoki, Yoichiro Hosokawa

  Advances in Radiation Oncology 101437 - 101437 2452-1094 2024/01 [Refereed]
  
• A step-by-step simulation code for estimating yields of water radiolysis species based on electron track-structure mode in the PHITS code

  Yusuke Matsuya, Yuji Yoshii, Tamon Kusumoto, Ken Akamatsu, Yuho Hirata, Tatsuhiko Sato, Takeshi Kai

  Physics in Medicine & Biology 0031-9155 2023/12/29 [Refereed]
   

  Abstract Objective. Time-dependent yields of chemical products resulting from 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 simulates atomic interactions originating from discrete energy levels of ionizations and electronic excitations as well as molecular excitations as physical stages. However, no chemical code for simulating water radiolysis products exists in the PHITS package. Approach. Here, we developed a chemical simulation code dedicated to the PHITS code, hereafter called PHITS-Chem code, which enables the calculation of the G values of water radiolysis species (^•OH, e_aq^-, H₂, H₂O₂ etc.) by electron beams. Main results. The estimated G values during 1 μs are in agreement with the experimental ones and other simulations. This PHITS-Chem code also simulates the radiolysis in the presence of OH radical scavengers, such as tris(hydroxymethyl)aminomethane and dimethyl sulfoxide. Thank to this feature, the contributions of direct and indirect effects on DNA damage induction under various scavenging capacities can be analyzed. Significance. This chemical code coupled with PHITS could contribute to elucidating the mechanism of radiation effects by connecting physical, physicochemical, and chemical processes.
• Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

  Yuta Shiraishi, Yusuke Matsuya, Tamon Kusumoto, Hisanori Fukunaga

  Physics in Medicine & Biology 69 (1) 015017 - 015017 0031-9155 2023/12/26 [Refereed]
   

  Abstract Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s⁻¹) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s⁻¹ have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR-irradiation enabling the prediction of surviving fraction after UHDR irradiation. Approach. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. Main results. The estimate by the developed model could successfully reproduce the in vitro experimental dose–response curve for various cell line types and dose rates. Significance. The developed model would be useful for predicting the biological effects under the UHDR irradiation.
• Recent improvements of the particle and heavy ion transport code system – PHITS version 3.33

  Tatsuhiko Sato, Yosuke Iwamoto, Shintaro Hashimoto, Tatsuhiko Ogawa, Takuya Furuta, Shin-Ichiro Abe, Takeshi Kai, Yusuke Matsuya, Norihiro Matsuda, Yuho Hirata, Takuya Sekikawa, Lan Yao, Pi-En Tsai, Hunter N. Ratliff, Hiroshi Iwase, Yasuhito Sakaki, Kenta Sugihara, Nobuhiro Shigyo, Lembit Sihver, Koji Niita

  Journal of Nuclear Science and Technology 1 - 9 0022-3131 2023/10/31 [Refereed]
  
• First-principles simulation of an ejected electron produced by monochromatic deposition energy to water at the femtosecond order.

  Takeshi Kai, Tomohiro Toigawa, Yusuke Matsuya, Yuho Hirata, Tomoya Tezuka, Hidetsugu Tsuchida, Akinari Yokoya

  RSC advances 13 (46) 32371 - 32380 2023/10/31 [Refereed]
   

  This study uses a time-dependent first-principles simulation code to investigate the transient dynamics of an ejected electron produced in the monochromatic deposition energy from 11 to 19 eV in water. The energy deposition forms a three-body single spur comprising a hydroxyl radical (OH˙), hydronium ion (H3O+), and hydrated electron (eaq-). The earliest formation involves electron thermalization and delocalization dominated by the molecular excitation of water. Our simulation results show that the transient electron dynamics primarily depends on the amount of deposition energy to water; the thermalization time varies from 200 to 500 fs, and the delocalization varies from 3 to 10 nm in this energy range. These features are crucial for determining the earliest single-spur formation and facilitating a sequential simulation from an energy deposition to a chemical reaction in water photolysis or radiolysis. The spur radius obtained from the simulation correlates reasonably with the experimental-based estimations. Our results should provide universalistic insights for analysing ultrafast phenomena dominated by the molecular excitation of water in the femtosecond order.
• Development of an electron track-structure mode for arbitrary semiconductor materials in PHITS

  Yuho Hirata, Takeshi Kai, Tatsuhiko Ogawa, Yusuke Matsuya, Tatsuhiko Sato

  Japanese Journal of Applied Physics 62 (10) 106001 - 106001 0021-4922 2023/10/01 [Refereed]
   

  Abstract Optimizing the design of semiconductor detector requires an electron track-structure code that can trace an incident electron motion with energies down to a few eV and simulate the production process of excited electrons in semiconductors. We therefore developed an Electron Track Structure mode applicable to ARbitrary Targets (ETSART) and implemented it into Particle and Heavy Ion Transport code System (PHITS). ETSART can simulate the electrons’ motion in arbitrary semiconductor materials using their bandgap energies. The accuracy of ETSART was validated by comparing the calculated electron path lengths in semiconductor materials with the corresponding data in the ICRU Report 37. Using ETSART, we also computed the mean energy required to produce an electron–hole pair (epsilon value) in various semiconductors and found that the epsilon value varies nonlinearly with the bandgap energy. Thus, ETSART can be useful for initial and mechanistic evaluations of electron–hole pair formation in new materials.
• Biophysical Simulations for Estimating Biological Effects after Exposure to Ionizing Radiation: Current State and Future Prospects

  Yusuke Matsuya, Ryo Saga

  Radiation Environment and Medicine 12 (2) 81 - 90 2423-9097 2023/08/29 [Refereed][Invited]
  
• Improvement of the hybrid approach between Monte Carlo simulation and analytical function for calculating microdosimetric probability densities in macroscopic matter

  Tatsuhiko Sato, Yusuke Matsuya, Tatsuhiko Ogawa, Takeshi Kai, Yuho Hirata, Shuichi Tsuda, Alessio Parisi

  Physics in Medicine & Biology 68 155005  0031-9155 2023/08/07 [Refereed]
   

  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.
• Translational study for stereotactic body radiotherapy against non-small cell lung cancer, including oligometastases, considering cancer stem-like cells enable predicting clinical outcome from in vitro data

  Ryo Saga, Yusuke Matsuya, Hikari Sato, Kazuki Hasegawa, Hideki Obara, Fumio Komai, Hironori Yoshino, Masahiko Aoki, Yoichiro Hosokawa

  Radiotherapy and Oncology 181 109444 - 109444 0167-8140 2023/04 [Refereed]
  
• Modelling oxygen effects on the in- and out-of-field radiosensitivity of cells exposed to intensity-modulated radiation fields

  Yusuke Matsuya, Stephen J McMahon, Karl T Butterworth, Yoshie Yachi, Ryo Saga, Tatsuhiko Sato, Kevin M Prise

  Physics in Medicine & Biology 0031-9155 2023/03/23 

  Abstract Objective: The delivery of intensity-modulated radiation fields has improved the conformity of dose to tumour targets during radiotherapy (RT). Previously, it has been shown that intercellular communication between cells positioned in- and outside of the radiation field impacts cellular radiosensitivity under hypoxic and normoxic conditions. However, the mechanism of intercellular communication in hypoxia remains to be fully understood. In this study, the cell-killing effects of intercellular communication in hypoxia were modelled in an effort to better understand the underlying mechanisms of response. 
Approach: By irradiating a 50% area of the culture dish (half-field exposure), experimental dose-response curves for cell survival and residual DNA double-strand breaks (DSBs) were generated in prostate (DU145) and non-small cell lung cancer (H1299) cells. The oxygen enhancement ratio (OER) was determined from early DSB yields (corresponding to relative direct damage) and used to model the in- and out-of-field radiosensitivity. 
Main results: The developed integrated microdosimetric-kinetic (IMK) model successfully predicted the experimental dose responses for survival and lethal lesions, and provides a mechanistic interpretation that the probability of hits for releasing cell-killing signals is dependent on oxygen. This experimental and modelling study also suggests that residual DSBs correspond to logarithmic survival fraction (meaning lethal lesions) for in- and out-of-field cells. Our data suggest that the OER value determined using uniform-field exposure can be applied to predict the in- and out-of-field radiosensitivity of cells following exposure to intensity modulated beams. 
Significance: The developed IMK model facilitates a more precise understanding of intercellular signalling following exposure to intensity-modulated radiation fields.
• Author Correction: Impact of the Lorentz force on electron track structure and early DNA damage yields in magnetic resonance-guided radiotherapy.

  Yoshie Yachi, Takeshi Kai, Yusuke Matsuya, Yuho Hirata, Yuji Yoshii, Hiroyuki Date

  Scientific reports 13 (1) 2239 - 2239 2023/02/08
• An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation

  Yoshie Yachi, Yusuke Matsuya, Yuji Yoshii, Hisanori Fukunaga, Hiroyuki Date, Takeshi Kai

  International Journal of Molecular Sciences 24 (2) 1386 - 1386 2023/01/10 

  Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay.
• Initial yield of hydrated electron production from water radiolysis based on first-principles calculation

  Takeshi Kai, Tomohiro Toigawa, Yusuke Matsuya, Yuho Hirata, Tomoya Tezuka, Hidetsugu Tsuchida, Akinari Yokoya

  RSC Advances 13 (11) 7076 - 7086 2023 

  For water radiolysis, conventional simulation methods estimate free radical yields based on the cross-sections. Our results indicated that electron dynamic motion must be further solved to predict the initial yields of hydrated electrons.
• 放射線の挙動を原子サイズで計算できるPHITSの新機能

  小川達彦, 平田悠歩, 松谷悠佑, 甲斐健師

  Isotope News 784 13 - 16 2022/12 [Refereed][Invited]
  
• Application of a simple DNA damage model developed for electrons to proton irradiation.

  Yusuke Matsuya, Takeshi Kai, Alessio Parisi, Yuji Yoshii, Tatsuhiko Sato

  Physics in medicine and biology 67 (21) 2022/10/31 

  Proton beam therapy allows irradiating tumor volumes with reduced side effects on normal tissues with respect to conventional x-ray radiotherapy. Biological effects such as cell killing after proton beam irradiations depend on the proton kinetic energy, which is intrinsically related to early DNA damage induction. As such, DNA damage estimation based on Monte Carlo simulations is a research topic of worldwide interest. Such simulation is a mean of investigating the mechanisms of DNA strand break formations. However, past modellings considering chemical processes and DNA structures require long calculation times. Particle and heavy ion transport system (PHITS) is one of the general-purpose Monte Carlo codes that can simulate track structure of protons, meanwhile cannot handle radical dynamics simulation in liquid water. It also includes a simple model enabling the efficient estimation of DNA damage yields only from the spatial distribution of ionizations and excitations without DNA geometry, which was originally developed for electron track-structure simulations. In this study, we investigated the potential application of the model to protons without any modification. The yields of single-strand breaks, double-strand breaks (DSBs) and the complex DSBs were assessed as functions of the proton kinetic energy. The PHITS-based estimation showed that the DSB yields increased as the linear energy transfer (LET) increased, and reproduced the experimental and simulated yields of various DNA damage types induced by protons with LET up to about 30 keVμm-1. These results suggest that the current DNA damage model implemented in PHITS is sufficient for estimating DNA lesion yields induced after protons irradiation except at very low energies (below 1 MeV). This model contributes to evaluating early biological impacts in radiation therapy.
• Implementation of the electron track-structure mode for silicon into PHITS for investigating the radiation effects in semiconductor devices

  Yuho Hirata, Takeshi Kai, Tatsuhiko Ogawa, Yusuke Matsuya, Tatsuhiko Sato

  Japanese Journal of Applied Physics 61 (10) 106004 - 106004 0021-4922 2022/10/01 

  Abstract In order to elucidate the mechanism of radiation effects in silicon (Si) devices, such as pulse-height defects and semiconductor soft errors, we developed an electron track-structure model dedicated to Si and implemented it into particle and heavy ion transport code system (PHITS). Then, we verified the accuracy of our developed model by comparing the ranges and depth-dose distributions of electrons in Si obtained from this study with 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 in crystalline Si. Our calculated result agreed with the experimental data when the threshold energy for generating secondary electrons was set to 2.75 eV, consistent with the corresponding data deduced from past studies. This result suggested that the improved PHITS can contribute to the precise understanding of the mechanisms of radiation effects in Si devices.
• Impact of the Lorentz force on electron track structure and early DNA damage yields in magnetic resonance-guided radiotherapy.

  Yoshie Yachi, Takeshi Kai, Yusuke Matsuya, Yuho Hirata, Yuji Yoshii, Hiroyuki Date

  Scientific reports 12 (1) 16412 - 16412 2022/09/30 

  Magnetic resonance-guided radiotherapy (MRgRT) has been developed and installed in recent decades for external radiotherapy in several clinical facilities. Lorentz forces modulate dose distribution by charged particles in MRgRT; however, the impact of Lorentz forces on low-energy electron track structure and early DNA damage induction remain unclear. In this study, we estimated features of electron track structure and biological effects in a static magnetic field (SMF) using a general-purpose Monte Carlo code, particle and heavy ion transport code system (PHITS) that enables us to simulate low-energy electrons down to 1 meV by track-structure mode. The macroscopic dose distributions by electrons above approximately 300 keV initial energy in liquid water are changed by both perpendicular and parallel SMFs against the incident direction, indicating that the Lorentz force plays an important role in calculating dose within tumours. Meanwhile, DNA damage estimation based on the spatial patterns of atomic interactions indicates that the initial yield of DNA double-strand breaks (DSBs) is independent of the SMF intensity. The DSB induction is predominantly attributed to the secondary electrons below a few tens of eV, of which energy deposition patterns are not considerably affected by the Lorentz force. Our simulation study suggests that treatment planning for MRgRT can be made with consideration of only changed dose distribution.
• Microdosimetry Study of Proton Quality Factor Using Analytic Model Calculations

  Alexis Papadopoulos, Ioanna Kyriakou, Yusuke Matsuya, Sebastien Incerti, Ioannis A. Daglis, Dimitris Emfietzoglou

  Applied Sciences 12 (18) 8950 - 8950 2022/09/06 

  The quality factor (Q) is formally linked to the stochastic (e.g., carcinogenic) risk of diverse ionizing radiations at low doses and/or low dose rates. Q can be a function of the non-stochastic physical quantity Linear Energy Transfer (LET) or the microdosimetric parameter lineal energy (y). These two physical quantities can be calculated either by Monte Carlo (MC) track-structure simulations or by analytic models. In this work, various generalized analytical models were utilized and combined to determine the proton lineal energy spectra in liquid water spheres of various sizes (i.e., 10–3000 nm diameter) over the proton energy range of 1–250 MeV. The calculated spectra were subsequently used within the Theory of Dual Radiation Action (TDRA) and the ICRU Report 40 microdosimetric methodologies to determine the variation of Q¯ with proton energy. The results revealed that the LET-based Q values underestimated the microdosimetric-based Q¯ values for protons with energy below ~100 MeV. At energies relevant to the Bragg peak region (<20–30 MeV), the differences were larger than 20–50%, while reaching 200–500% at ~5 MeV. It was further shown that the microdosimetric-based Q¯ values for protons below ~100 MeV were sensitive to the sphere size. Finally, condensed-phase effects had a very small (<5%) influence on the calculated microdosimetric-based Q¯ over the proton energy range considered here.
• Microdosimetric modeling of relative biological effectiveness for skin reactions: Possible linkage between in vitro and in vivo data

  Tatsuhiko Sato, Yusuke Matsuya, Nobuyuki Hamada

  International Journal of Radiation Oncology*Biology*Physics 0360-3016 2022/05 [Refereed]
  
• Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle

  Yusuke Matsuya, Nobuyuki Hamada, Yoshie Yachi, Yukihiko Satou, Masayori Ishikawa, Hiroyuki Date, Tatsuhiko Sato

  Cancers 14 (4) 1045 - 1045 2022/02/18 [Refereed]
   

  Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.
• Features of accelerator-based neutron source for boron neutron capture therapy calculated by particle and heavy ion transport code system (PHITS)

  Yusuke Matsuya, Tamon Kusumoto, Yoshie Yachi, Yuho Hirata, Misako Miwa, Masayori Ishikawa, Hiroyuki Date, Yosuke Iwamoto, Shigeo Matsuyama, Hisanori Fukunaga

  AIP Advances 12 (2) 025013 - 025013 2022/02/01 [Refereed]
   

  Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the 7Li(p,n)7Be near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the 7Li(p,n)7Be reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.
• Track-structure modes in particle and heavy ion transport code system (PHITS): application to radiobiological research

  Yusuke Matsuya, Takeshi Kai, Tatsuhiko Sato, Tatsuhiko Ogawa, Yuho Hirata, Yuji Yoshii, Alessio Parisi, Thiansin Liamsuwan

  International Journal of Radiation Biology 98 (2) 148 - 157 0955-3002 2022/02/01 [Refereed]
   

  Purpose In radiation physics, Monte Carlo radiation transport simulations are powerful tools to evaluate the cellular responses after irradiation. When investigating such radiation-induced biological effects, it is essential to perform track structure simulations by explicitly considering each atomic interaction in liquid water at the sub-cellular and DNA scales. The Particle and Heavy-Ion Transport code System (PHITS) is a Monte Carlo code which enables to calculate track structure at DNA scale by employing the track-structure modes for electrons, protons and carbon ions. In this paper, we review the recent development status and future prospects of the track-structure modes in the PHITS code. Conclusions To date, the physical features of these modes have been verified using the available experimental data and Monte Carlo simulation results reported in literature. These track-structure modes can be used for calculating microdosimetric distributions to estimate cell survival and for estimating initial DNA damage yields. The use of PHITS track-structure mode is expected not only to clarify the underlying mechanisms of radiation effects but also to predict curative effects in radiation therapy. The results of PHITS simulations coupled with biophysical models will contribute to the radiobiological studies by precisely predicting radiation-induced biological effects based on the Monte Carlo approach.
• Tumor radioresistance caused by radiation-induced changes of stem-like cell content and sub-lethal damage repair capability

  Roman Fukui, Ryo Saga, Yusuke Matsuya, Kazuo Tomita, Yoshikazu Kuwahara, Kentaro Ohuchi, Tomoaki Sato, Kazuhiko Okumura, Hiroyuki Date, Manabu Fukumoto, Yoichiro Hosokawa

  Scientific Reports 12 (1) 2045-2322 2021/12 [Refereed]
   

  Abstract Cancer stem-like cells (CSCs) within solid tumors exhibit radioresistance, leading to recurrence and distant metastasis after radiotherapy. To experimentally study the characteristics of CSCs, radioresistant cell lines were successfully established using fractionated X-ray irradiation. The fundamental characteristics of CSCs in vitro have been previously reported; however, the relationship between CSC and acquired radioresistance remains uncertain. To efficiently study this relationship, we performed both in vitro experiments and theoretical analysis using a cell-killing model. Four types of human oral squamous carcinoma cell lines, non-radioresistant cell lines (SAS and HSC2), and radioresistant cell lines (SAS-R and HSC2-R), were used to measure the surviving fraction after single-dose irradiation, split-dose irradiation, and multi-fractionated irradiation. The SAS-R and HSC2-R cell lines were more positive for one of the CSC marker aldehyde dehydrogenase activity than the corresponding non-radioresistant cell lines. The theoretical model analysis showed that changes in both the experimental-based ALDH (+) fractions and DNA repair efficiency of ALDH (−) fractions (i.e., sub-lethal damage repair) are required to reproduce the measured cell survival data of non-radioresistant and radioresistant cell lines. These results suggest that the enhanced cell recovery in SAS-R and HSC2-R is important when predicting tumor control probability in radiotherapy to require a long dose-delivery time; in other words, intensity-modulated radiation therapy is ideal. This work provides a precise understanding of the mechanism of radioresistance, which is induced after irradiation of cancer cells.
• Development and validation of proton track-structure model applicable to arbitrary materials

  Tatsuhiko Ogawa, Yuho Hirata, Yusuke Matsuya, Takeshi Kai

  Scientific Reports 11 (1) 2045-2322 2021/12 [Refereed]
   

  Abstract A novel transport algorithm performing proton track-structure calculations in arbitrary materials was developed. Unlike conventional algorithms, which are based on the dielectric function of the target material, our algorithm uses a total stopping power formula and single-differential cross sections of secondary electron production. The former was used to simulate energy dissipation of incident protons and the latter was used to consider secondary electron production. In this algorithm, the incident proton was transmitted freely in matter until the proton produced a secondary electron. The corresponding ionising energy loss was calculated as the sum of the ionisation energy and the kinetic energy of the secondary electron whereas the non-ionising energy loss was obtained by subtracting the ionising energy loss from the total stopping power. The most remarkable attribute of this model is its applicability to arbitrary materials, i.e. the model utilises the total stopping power and the single-differential cross sections for secondary electron production rather than the material-specific dielectric functions. Benchmarking of the stopping range, radial dose distribution, secondary electron energy spectra in liquid water, and lineal energy in tissue-equivalent gas, against the experimental data taken from literature agreed well. This indicated the accuracy of the present model even for materials other than liquid water. Regarding microscopic energy deposition, this model will be a robust tool for analysing the irradiation effects of cells, semiconductors and detectors.
• Track-structure mode for electrons, protons and carbon ions in the PHITS code

  Yusuke Matsuya, Takeshi Kai, Tatsuhiko Ogawa, Yuho Hirata, Tatsuhiko Sato

  Hoshasen Kagaku 112 15 - 20 2021/11 [Refereed][Invited]
  
• Model development for estimating effects of boron neutron capture therapy.

  Hisanori Fukunaga, Yusuke Matsuya

  Radiation Biology Research Communications 56 (2) 208 - 223 2021/06 [Refereed][Invited]
  
• Oxygen enhancement ratios of cancer cells after exposure to intensity modulated x-ray fields: DNA damage and cell survival

  Yusuke Matsuya, Stephen J McMahon, Karl T Butterworth, Shingo Naijo, Isshi Nara, Yoshie Yachi, Ryo Saga, Masayori Ishikawa, Tatsuhiko Sato, Hiroyuki Date, Kevin M Prise

  Physics in Medicine & Biology 66 (7) 075014 - 075014 0031-9155 2021/04/07 [Refereed]
   

  Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field (OF) cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains to be fully clarified. Here, we investigate the impact of hypoxia on in-field and OF radio-sensitivities using two types of cancer cells, DU145 and H1299. Using a nBIONIX hypoxic culture kit and a shielding technique to irradiate 50% of a cell culture flask, oxygen enhancement ratios for double-strand breaks (DSB) and cell death endpoints were determined. Thesein vitromeasurements indicate that hypoxia impacts OF cells, although the hypoxic impacts on OF cells for cell survival were dose-dependent and smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of OF cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in advanced radiotherapy dose-distributions such as with intensity-modulated radiotherapy.
• 4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

  Ryo Saga, Yusuke Matsuya, Rei Takahashi, Kazuki Hasegawa, Hiroyuki Date, Yoichiro Hosokawa

  Scientific Reports 11 (1) 8258 - 8258 2021/04 [Refereed]
   

  Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.
• Verification of KURBUC-based ion track structure mode for proton and carbon ions in the PHITS code

  Yusuke Matsuya, Takeshi Kai, Tatsuhiko Sato, Thiansin Liamsuwan, Kohei Sasaki, Hooshang Nikjoo

  Physics in Medicine & Biology 66 (6) 06NT02 - 06NT02 0031-9155 2021/03/21 [Refereed]
   

  The Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo radiation transport simulation code. It has the ability to handle diverse particle types over a wide range of energy. The latest PHITS development enables the generation of track structure for proton and carbon ions (1H+,12C6+) based on the algorithms in the KURBUC code, which is considered as one of the most verified track-structure codes worldwide. This ion track-structure mode is referred to as the PHITS-KURBUC mode. In this study, the range, radial dose distributions, and microdosimetric distributions were calculated using the PHITS-KURBUC mode. Subsequently, they were compared with the corresponding data obtained from the original KURBUC and from other studies. These comparative studies confirm the successful inclusion of the KURBUC code in the PHITS code. As results of the synergistic effect between the macroscopic and microscopic radiation transport codes, this implementation enabled the detailed calculation of the microdosimetric and nanodosimetric quantities under complex radiation fields, such as proton beam therapy with the spread-out Bragg peak.
• Development of a new microdosimetric biological weighting function for the RBE10 assessment in case of the V79 cell line exposed to ions from 1H to 238U

  Alessio Parisi, Tatsuhiko Sato, Yusuke Matsuya, Yuki Kase, Giulio Magrin, Claudio Verona, Linh Tran, Anatoly Rosenfeld, Anna Bianchi, Pawel Olko, Lara Struelens, Filip Vanhavere

  Physics in Medicine & Biology 65 (23) 235010 - 235010 1361-6560 2020/12/04 [Refereed]
  
• Relation between biomolecular dissociation and energy of secondary electrons generated in liquid water by fast heavy ions

  Hidetsugu Tsuchida, Takeshi Kai, Kensei Kitajima, Yusuke Matsuya, Takuya Majima, Manabu Saito

  The European Physical Journal D 74 (10) 1434-6060 2020/10 [Refereed]
  
• Radiation Safety and Public Health for Radiological Professionals: Meeting Report on The 5th Educational Symposium on Radiation and Health (ESRAH) by Young Scientists in 2018

  Hiroko Yamashina, Marin Terashima, Joma Oikawa, Shingo Naijo, Tamao Miyao, Yoshie Yachi, Yusuke Matsuya, Masaru Yamaguchi, Takakiyo Tsujiguchi, Ryo Saga, Hu Jun, Goh Valerie, Swee Ting, Toshiya Nakamura, Yoichiro Hosokawa, Hiroyuki Date

  Radiation Environment and Medicine 10 (1) 48 - 54 2020/07
• Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: A radiobiological perspective.

  Hisanori Fukunaga, Yusuke Matsuya, Koichi Tokuuye, Motoko Omura

  British Journal of Radiology 93 20200311  2020/05/06 [Refereed][Not invited]
   

  Boron neutron capture therapy (BNCT) has great potential to selectively destroy cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly used in clinical practice, even although there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of radiation microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of compound biological effectiveness. Radiobiological perspectives provide insight into the effectiveness of BNCT in creating a synergy effect in the field of clinical oncology.
• A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.

  Yusuke Matsuya, Hisanori Fukunaga, Motoko Omura, Hiroyuki Date

  Cells 9 (5) 1117  2020/04/30 [Refereed][Not invited]
   

  Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric-kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.
• A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy

  Yusuke Matsuya, Tatsuhiko Sato, Rui Nakamura, Shingo Naijo, Hiroyuki Date

  Physics in Medicine & Biology 65 (9) 095006 - 095006 1361-6560 2020/04/28 [Refereed][Not invited]
  
• A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

  Yusuke Matsuya, Toshiaki Nakano, Takeshi Kai, Naoya Shikazono, Ken Akamatsu, Yuji Yoshii, Tatsuhiko Sato

  International Journal of Molecular Sciences 21 (5) 1701 - 1701 2020/03/02 [Refereed]
   

  Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.
• Verification of dose estimation of Auger electrons emitted from Cu-64 using a combination of FNTD measurements and Monte Carlo simulations

  Tamon Kusumoto, Yusuke Matsuya, Kentaro Baba, Ryo Ogawara, Mark S. Akselrod, Jonathan Harrison, Vasiliy Fomenko, Takeshi Kai, Masayori Ishikawa, Sumitaka Hasegawa, Satoshi Kodaira

  Radiation Measurements 132 1350-4487 2020/03 [Refereed][Not invited]
   

  © 2020 Elsevier Ltd We report the dose measurement technique for emitted particles from Cu-64 source using a combination of Fluorescent Nuclear Track Detector (FNTD), which is Al2O3 single crystal doped with C and Mg, and Monte Carlo simulations in the PHITS code and Geant4 toolkit. The relatively high fluorescence intensity induced by Auger electrons is observed at the FNTD surface. Then, the fluorescence intensity monotonically reduces as the depth from the surface increases. The results obtained using the PHITS Monte Carlo simulation code is very similar to that of Geant4. Also, the simulations are in good agreement with experimental results. These findings prove that the signal induced by Auger electrons is successfully measured using FNTD. Additionally, the high signal at the FNTD surface implies that Auger electrons can work effectively to kill cancer cells proximal to a Cu-64 source while minimizing damage effects on normal cells distal to the source. At 15 μm depth in the crystal, which is the mean tissue cell radius, the relative dose of beta particles is about 24% of that at the FNTD surface. Therefore, the contribution of free radicals created by beta particles should be accounted for to clarify the impact of Cu-64 on tissues.
• DNA damage induction during localized chronic exposure to an insoluble radioactive microparticle

  Yusuke Matsuya, Yukihiko Satou, Nobuyuki Hamada, Hiroyuki Date, Masayori Ishikawa, Tatsuhiko Sato

  Scientific Reports 9 (1) 2019/12 [Refereed][Not invited]
  
• Track Structure Study for Energy Dependency of Electrons and X-rays on DNA Double-Strand Break Induction

  Yachi T, Yoshii Y, Matsuya Y, Mori R, Oikawa J, Date H

  Scientific Reports 9 (17649) 17649 - 17649 2019/11 [Refereed][Not invited]
   

  Radiation weighting factor wR for photons and electrons has been defined as unity independently of the energy of the particles. However, the biological effects depend on the incident energies according to in vitro experimental data. In this study, we have quantified the energy concentration along electron tracks in terms of dose-mean lineal energy (yD) on chromosome (micro-meter) and DNA (nano-meter) order scales by Monte Carlo simulations, and evaluated the impact of photon energies on DNA double-strand break (DNA-DSB) induction from an experimental study of irradiated cells. Our simulation result shows that the yD values for diagnostic X-rays (60-250 kVp) are higher than that for therapeutic X-rays (linac 6 MV), which agrees well with the tissue equivalent proportional counter (TEPC) measurements. The relation between the yD values and the numbers of γ-H2AX foci for various photon energy spectra suggests that low energy X-rays induce DNA-DSB more efficiently than higher energy X-rays even at the same absorbed dose (e.g., 1.0 Gy). The relative biological effectiveness based on DNA-DSBs number (RBEDSB) is proportionally enhanced as the yD value increases, demonstrating that the biological impact of the photon irradiation depends on energy concentration along radiation tracks of electrons produced in the bio-tissues. Ultimately, our study implies that the value of wR for photons varies depending on their energies.
• Modeling of yield estimation for DNA strand breaks based on Monte Carlo simulations of electron track structure in liquid water

  Yusuke Matsuya, Takeshi Kai, Yuji Yoshii, Yoshie Yachi, Shingo Naijo, Hiroyuki Date, Tatsuhiko Sato

  Journal of Applied Physics 126 (12) 124701 - 124701 0021-8979 2019/09/28 [Refereed][Not invited]
  
• Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects.

  Matsuya Y, McMahon SJ, Ghita M, Yoshii Y, Sato T, Date H, Prise KM

  Scientific Reports 9 (9483) 9483 - 9483 2019/07 [Refereed][Not invited]
   

  In advanced radiotherapy, intensity modulated radiation fields and complex dose-delivery are utilized to prescribe higher doses to tumours. Here, we investigated the impact of modulated radiation fields on radio-sensitivity and cell recovery during dose delivery. We generated experimental survival data after single-dose, split-dose and fractionated irradiation in normal human skin fibroblast cells (AGO1522) and human prostate cancer cells (DU145). The dose was delivered to either 50% of the area of a T25 flask containing the cells (half-field) or 100% of the flask (uniform-field). We also modelled the impact of dose-rate effects and intercellular signalling on cell-killing. Applying the model to the survival data, it is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure for the same delivered dose; (ii) the importance of sub-lethal damage repair (SLDR) in AGO1522 cells is reduced under half-field exposure; (iii) the yield of initial DNA lesions measured with half-field exposure is smaller than that with uniform-field exposure. These results suggest that increased cell survival under half-field exposure is predominantly attributed not to rescue effects (increased SLDR) but protective effects (reduced induction of initial DNA lesions). In support of these protective effects, the reduced DNA damage leads to modulation of cell-cycle dynamics, i.e., less G1 arrest 6 h after irradiation. These findings provide a new understanding of the impact of dose-rate effects and protective effects measured after modulated field irradiation.
• Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model.

  Ryo Saga, Yusuke Matsuya, Rei Takahashi, Kazuki Hasegawa, Hiroyuki Date, Yoichiro Hosokawa

  Journal of radiation research 60 (3) 298 - 307 2019/05/01 [Refereed][Not invited]
   

  In radiotherapy, cancer stem cells (CSCs) are well recognized as one of the radioresistant cell types. Even in a small subpopulation, CSCs may have an influence on tumor control probability, represented by cell killing after irradiation. However, the relationship between the percentage content of CSCs and the cell survival dose-response curve has not yet been quantitatively clarified. In this study, we developed a cell-killing model for two cell populations (CSCs and progeny cells) to predict the surviving fractions, and compared it with the conventional linear-quadratic (LQ) model. Three prostate cancer cell lines (DU145, PC3 and LNCaP) were exposed to X-rays at doses ranging from 0 to 10 Gy. After the irradiation, we performed clonogenic survival assays to generate the cell survival curves, and carried out flow-cytometric analyses to estimate the percentage content of CSCs for each cell line. The cell survival curves for DU145 cells and PC3 cells seemed not to follow the conventional LQ model in the high dose range (>8 Gy). However, the outputs of the developed model agreed better with the experimental cell survival curves than those of the LQ model. The percentage content of CSCs predicted by the developed model was almost coincident with the measured percentage content for both DU145 cells and PC3 cells. The experiments and model analyses indicate that a small subpopulation of radioresistant CSCs has lower radiosensitivity in the high-dose range, which may lessen the clinical outcome for patients with prostate cancer after high-dose radiation therapy.
• Meeting Report on "The 4th Educational Symposium on Radiation and Health (ESRAH) by Young Scientists in 2017"

  Saga R, Tsujiguchi T, Yamaguchi M, Fukushi Y, Fujishima Y, Matsuya Y, Oikawa J, Terashima M, Date H, Nakamura T, Hosokawa Y

  Radiation environment and medicine : covering a broad scope of topics relevant to environmental and medical radiation research Hirosaki University [編] 7 (2) 121 - 124 2423-9097 2018/08 [Refereed][Not invited]
  
• Investigation of dose-rate effects and cell-cycle distribution under protracted exposure to ionizing radiation for various dose-rates.

  Yusuke Matsuya, Stephen J McMahon, Kaori Tsutsumi, Kohei Sasaki, Go Okuyama, Yuji Yoshii, Ryosuke Mori, Joma Oikawa, Kevin M Prise, Hiroyuki Date

  Scientific reports 8 (1) 8287 - 8287 2018/05/29 [Refereed][Not invited]
   

  During exposure to ionizing radiation, sub-lethal damage repair (SLDR) competes with DNA damage induction in cultured cells. By virtue of SLDR, cell survival increases with decrease of dose-rate, so-called dose-rate effects (DREs). Here, we focused on a wide dose-rate range and investigated the change of cell-cycle distribution during X-ray protracted exposure and dose-response curves via hybrid analysis with a combination of in vitro experiments and mathematical modelling. In the course of flow-cytometric cell-cycle analysis and clonogenic assays, we found the following responses in CHO-K1 cells: (1) The fraction of cells in S phase gradually increases during 6 h exposure at 3.0 Gy/h, which leads to radio-resistance. (2) Slight cell accumulation in S and G2/M phases is observed after exposure at 6.0 Gy/h for more than 10 hours. This suggests that an increase of SLDR rate for cells in S phase during irradiation may be a reproducible factor to describe changes in the dose-response curve at dose-rates of 3.0 and 6.0 Gy/h. By re-evaluating cell survival for various dose-rates of 0.186-60.0 Gy/h considering experimental-based DNA content and SLDR, it is suggested that the change of S phase fraction during irradiation modulates the dose-response curve and is possibly responsible for some inverse DREs.
• Estimation of the radiation-induced DNA double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus

  Ryosuke Mori, Yusuke Matsuya, Yuji Yoshii, Hiroyuki Date

  Journal of Radiation Research 59 (3) 253 - 260 1349-9157 2018/05/01 [Refereed][Not invited]
   

  DNA double-strand breaks (DSBs) are thought to be the main cause of cell death after irradiation. In this study, we estimated the probability distribution of the number of DSBs per cell nucleus by considering the DNA amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by X-ray irradiation. The probability estimation of DSB induction was made following these procedures: (i) making use of the Chinese Hamster Ovary (CHO)-K1 cell line as the target example, the amounts of DNA per nucleus in the logarithmic and the plateau phases of the growth curve were measured by flow cytometry with propidium iodide (PI) dyeing (ii) the probability distribution of the DSB number per cell nucleus for each phase after irradiation with 1.0 Gy of 200 kVp X-rays was measured by means of 3-H2AX immunofluorescent staining (iii) the distribution of the cell-specific energy deposition via secondary electrons produced by the incident X-rays was calculated by WLTrack (in-house Monte Carlo code) (iv) according to a mathematical model for estimating the DSB number per nucleus, we deduced the induction probability density of DSBs based on the measured DNA amount (depending on the cell cycle) and the calculated dose per nucleus. The model exhibited DSB induction probabilities in good agreement with the experimental results for the two phases, suggesting that the DNA amount (depending on the cell cycle) and the statistical variation in the local energy deposition are essential for estimating the DSB induction probability after X-ray exposure.
• Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

  Yusuke Matsuya, Kohei Sasaki, Yuji Yoshii, Go Okuyama, Hiroyuki Date

  Scientific reports 8 (1) 4849 - 4849 2018/03/19 [Refereed][Not invited]
   

  Intercellular communication after ionizing radiation exposure, so-called non-targeted effects (NTEs), reduces cell survival. Here we describe an integrated cell-killing model considering NTEs and DNA damage along radiation particle tracks, known as DNA-targeted effects (TEs) based on repair kinetics of DNA damage. The proposed model was applied to a series of experimental data, i.e., signal concentration, DNA damage kinetics, cell survival curve and medium transfer bystander effects (MTBEs). To reproduce the experimental data, the model considers the following assumptions: (i) the linear-quadratic (LQ) function as absorbed dose to express the hit probability to emit cell-killing signals, (ii) the potentially repair of DNA lesions induced by NTEs, and (iii) lower efficiency of repair for the damage in NTEs than that in TEs. By comparing the model results with experimental data, we found that signal-induced DNA damage and lower repair efficiency in non-hit cells are responsible for NTE-related repair kinetics of DNA damage, cell survival curve with low-dose hyper-radiosensitivity (HRS) and MTBEs. From the standpoint of modelling, the integrated cell-killing model with the LQ relation and a different repair function for NTEs provide a reasonable signal-emission probability and a new estimation of low-dose HRS linked to DNA repair efficiency.
• Markov chain Monte Carlo analysis for the selection of a cell-killing model under high-dose-rate irradiation

  Yusuke Matsuya, Takaaki Kimura, Hiroyuki Date

  MEDICAL PHYSICS 44 (10) 5522 - 5532 0094-2405 2017/10 [Refereed][Not invited]
   

  Purpose: High-dose-rate irradiation with 6 MV linac x rays is a wide-spread means to treat cancer tissue in radiotherapy. The treatment planning relies on a mathematical description of surviving fraction (SF), such as the linear-quadratic model (LQM) formula. However, even in the case of high-dose-rate treatment, the repair kinetics of DNA damage during dose-delivery time plays a function in predicting the dose-SF relation. This may call the SF model selection into question when considering the dose-delivery time or dose-rate effects (DREs) in radiotherapy and invitro cell experiments. In this study, we demonstrate the importance of dose-delivery time at high-dose-rate irradiations used in radiotherapy by means of Bayesian estimation. Methods: To evaluate the model selection for SF, three types of models, the LQM and two microdosimetric-kinetic models with and without DREs (MKMDR and MKM) were applied to describe invitroSF data (our work and references). The parameters in each model were evaluated by a Markov chain Monte Carlo (MCMC) simulation. Results: The MCMC analysis shows that the cell survival curve by the MKMDR fits the experimental data the best in terms of the deviance information criterion (DIC). In the fractionated regimen with 30 fractions to a total dose of 60 Gy, the final cell survival estimated by the MKMDR was higher than that by the LQM. This suggests that additional fractions are required for attaining the total dose equivalent to yield the same effect as the conventional regimen using the LQM in fractionated radiotherapy. Conclusions: Damage repair during dose-delivery time plays a key role in precisely estimating cell survival even at a high dose rate in radiotherapy. Consequently, it was suggested that the cell-killing model without repair factor during a short dose-delivery time may overestimate actual cell killing in fractionated radiotherapy. (C) 2017 American Association of Physicists in Medicine
• Educational Activity for the Radiation Emergency System in the Northern Part of Japan: Meeting Report on "The 3rd Educational Symposium on Radiation and Health (ESRAH) by Young Scientists in 2016''

  Yusuke Matsuya, Takakiyo Tsujiguchi, Masaru Yamaguchi, Takaaki Kimura, Ryosuke Mori, Ryota Yamada, Ryo Saga, Yohei Fujishima, Hiroyuki Date

  RADIATION RESEARCH 187 (6) 641 - 646 0033-7587 2017/06 [Refereed][Not invited]
   

  In the northern part of Japan, close cooperation is essential in preparing for any possible emergency response to radiation accidents because several facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho Village (Aomori Prefecture). After the accident at Fukushima Daiichi Nuclear Power Plant in 2011, special attention should be given to the relationship between radiation and human health, as well as establishing a system for managing with a radiation emergency. In the area of Hokkaido and Aomori prefectures in Japan, since 2008 an exchange meeting between Hokkaido University and Hirosaki University has been held every year to have opportunities to discuss radiation effects on human health and to collect the latest news on monitoring environmental radiation. This meeting was elevated to an international meeting in 2014 titled "Educational Symposium on Radiation and Health (ESRAH) by Young Scientists''. The 3rd ESRAH meeting took place in 2016, with the theme "Investigating Radiation Impact on the Environmental and Health''. Here we report the meeting findings on the continuing educational efforts after the Fukushima incident, what was accomplished in terms of building a community educational approaches, and future goals. (C) 2017 by Radiation Research Society
• Modeling cell survival and change in amount of DNA during protracted irradiation

  Yusuke Matsuya, Kaori Tsutsumi, Kohei Sasaki, Yuji Yoshii, Takaaki Kimura, Hiroyuki Date

  JOURNAL OF RADIATION RESEARCH 58 (3) 302 - 312 0449-3060 2017/05 [Refereed][Not invited]
   

  Hyper-radiosensitivity (HRS) is a well-known bioresponse under low-dose or low-dose-rate exposures. Although disorder of the DNA repair function, non-targeted effects and accumulation of cells in G(2) have been experimentally observed, the mechanism for inducing HRS by long-term irradiation is still unclear. On the basis of biological experiments and a theoretical study, we have shown that change in the amount of DNA associated with accumulation of cells in G(2) enhances radiosensitivity. To demonstrate continuous irradiation with 250 kVp X-rays, we adopted a fractionated regimen of 0.186 or 1.00 Gy per fraction at intervals of 1 h (i.e. 0.186 Gy/h, 1.00 Gy/h on average) to Chinese Hamster Ovary (CHO)-K1 cells. The change in the amount of DNA during irradiation was quantified by flow cytometric analysis with propidium iodide (PI). Concurrently, we attempted a theoretical evaluation of the DNA damage by using a microdosimetric-kinetic (MK) model that was modified to incorporate the change in the amount of DNA. Our experimental results showed that the fraction of the cells in G(2)/M phase increased by 6.7% with 0.186 Gy/h and by 22.1% with 1.00 Gy/h after the 12th irradiation. The MK model considering the change in amount of DNA during the irradiation exhibited a higher radiosensitivity at a high dose range, which could account for the experimental clonogenic survival. The theoretical results suggest that HRS in the high dose range is associated with an increase in the total amount of DNA during irradiation.
• Inorganic polyphosphate enhances radio-sensitivity in a human non-small cell lung cancer cell line, H1299

  Kaori Tsutsumi, Yusuke Matsuya, Tomoki Sugahara, Manami Tamura, Satoshi Sawada, Sagiri Fukura, Hisashi Nakano, Hiroyuki Date

  Tumor Biology 39 (6) 1010428317705033  1423-0380 2017/01/01 [Refereed][Not invited]
   

  Inorganic polyphosphate is a linear polymer containing tens to hundreds of orthophosphate residues linked by highenergy phosphoanhydride bonds. Polyphosphate has been recognized as a potent anti-metastasis reagent. However, the molecular mechanism underlying polyphosphate action on cancer cells is poorly understood. In this study, we investigated the involvement of polyphosphate in radio-sensitivity using a human non-small cell lung cancer cell line, H1299. We found that polyphosphate treatment decreases cellular adenosine triphosphate levels, suggesting a disruption of energy metabolism. We also found that the induction of DNA double-strand breaks was enhanced in polyphosphatetreated cells after X-ray irradiation and colony formation assay revealed that cell survival decreased compared with that of the control groups. These findings suggest that polyphosphate is a promising radio-sensitizer for cancer cells. Therefore, we hypothesized that polyphosphate treatment disrupts adenosine triphosphate-mediated energy transfer for cellular survival and DNA repair, thereby reducing the cellular capability to resist X-ray irradiation.
• Report on the 2nd Educational Symposium on RADIATION AND HEALTH by Young Scientists (ESRAH2015)

  Tsujiguchi Takakiyo, Nanashima Naoki, Chiba Mitsuru, Terashima Shingo, Fujishima Yohei, Matsuya Yusuke, Kwon Jihun, Nakamura Toshiya

  Radiation environment and medicine : covering a broad scope of topics relevant to environmental and medical radiation research Hirosaki University [編] 5 (1) 65 - 71 2423-9097 2016/03 [Refereed][Not invited]
  
• Cluster analysis for the probability of DSB site induced by electron tracks

  Y. Yoshii, K. Sasaki, Y. Matsuya, H. Date

  NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS 350 (1) 55 - 59 0168-583X 2015/05 [Refereed][Not invited]
   

  To clarify the influence of bio-cells exposed to ionizing radiations, the densely populated pattern of the ionization in the cell nucleus is of importance because it governs the extent of DNA damage which may lead to cell lethality. In this study, we have conducted a cluster analysis of ionization and excitation events to estimate the number of double-strand breaks (DSBs) induced by electron tracks. A Monte Carlo simulation for electrons in liquid water was performed to determine the spatial location of the ionization and excitation events. The events were divided into clusters by using the density-based spatial clustering of applications with noise (DBSCAN) algorithm. The algorithm enables us to sort out the events into the groups (clusters) in which a minimum number of neighboring events are contained within a given radius. For evaluating the dumber of DSBs in the extracted clusters, we have introduced an aggregation index (AI). The computational results show that a sub-key electron produces DSBs in a dense formation more effectively than higher energy electrons. The root-mean square radius (RMSR) of the cluster size is below 5 nm, which is smaller than the chromatin fiber thickness. It was found that this size of clustering events has a high possibility to cause lesions in DNA within the chromatin fiber site. (C) 2015 Elsevier B.V. All rights reserved.
• The Report of the 2nd Educational Symposium on Radiation and Health by Young Scientists (ESRAH2015)

  Tsujiguchi Takakiyo

  Japanese Journal of Radiological Technology 公益社団法人 日本放射線技術学会 71 (11) 1132 - 1137 0369-4305 2015 [Not refereed]
  
• Evaluation of the cell survival curve under radiation exposure based on the kinetics of lesions in relation to dose-delivery time

  Yusuke Matsuya, Kaori Tsutsumi, Kohei Sasaki, Hiroyuki Date

  JOURNAL OF RADIATION RESEARCH 56 (1) 90 - 99 0449-3060 2015/01 [Refereed][Not invited]
   

  We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric-kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate.
• Quantitative estimation of DNA damage by photon irradiation based on the microdosimetric-kinetic model

  Yusuke Matsuya, Yosuke Ohtsubo, Kaori Tsutsumi, Kohei Sasaki, Rie Yamazaki, Hiroyuki Date

  JOURNAL OF RADIATION RESEARCH 55 (3) 484 - 493 0449-3060 2014/05 [Refereed][Not invited]
   

  The microdosimetric-kinetic (MK) model is one of the models that can describe the fraction of cells surviving after exposure to ionizing radiation. In the MK model, there are specific parameters, k and y(D), where k is an inherent parameter to represent the number of potentially lethal lesions (PLLs) and y(D) indicates the dose-mean lineal energy in keV/mu m. Assuming the PLLs to be DNA double-strand breaks (DSBs), the rate equations are derived for evaluating the DSB number in the cell nucleus. In this study, we estimated the ratio of DSBs for two types of photon irradiation (6 MV and 200 kVp X-rays) in Chinese hamster ovary (CHO-K1) cells and human non-small cell lung cancer (H1299) cells by observing the surviving fraction. The estimated ratio was then compared with the ratio of gamma-H2AX foci using immunofluorescent staining. For making a comparison of the number of DSBs among a variety of radiation energy cases, we next utilized the survival data in the literature for both cells exposed to other photon types, such as Co-60 gamma-rays, Cs-137 gamma-rays and 100 kVp X-rays. The ratio of DSBs based on the MK model with conventional data was consistent with the ratio of gamma-H2AX foci numbers, confirming that the gamma-H2AX focus is indicative of DSBs. It was also shown that the larger y(D) is, the larger the DSB number is. These results suggest that k and y(D) represent the characteristics of the surviving fraction and the biological effects for photon irradiation.

Conference Activities & Talks

• 放射線誘起正孔がもたらすDNAの分子構造と電子状態変化の第一原理計算II  [Not invited]

  関川卓也, Hwang Beomju, 石坂優人, 松谷悠佑, 川井弘之, 大野義章, 佐藤達彦, 甲斐健師

  日本物理学会 2024年春季大会  2024/03
• 飛跡構造解析によるナノ規模分解能の放射線挙動計算  [Invited]

  小川達彦, 平田悠歩, 松谷悠佑, 甲斐健師

  日本金属学会 2024年春季大会  2024/03
• 放射線生物影響の最初期過程に関する計算機シミュレーション―DNAの放射線損傷による電子状態への影響―  [Invited]

  関川卓也, 松谷悠佑, ファン ボンジュ, 石坂優人, 大野義章, 佐藤達彦, 甲斐健師

  第3回 日本量子医科学会学術大会  2023/12
• 放射線生物影響の最初期過程に関する計算機シミュレーション―DNA損傷の直接効果と間接効果―  [Invited]

  甲斐健師, 樋川智洋, 松谷悠佑, 平田悠歩, 手塚智哉, 土田秀次, 伊東祐真, 横谷明徳

  第3回 日本量子医科学会学術大会  2023/12
• PHITSを用いた口腔内金属を有する頭部四面体ファントムに対する放射線シミュレーション

  長野拓也, 松谷悠佑, 戒田篤志, 野島瞳, 古田琢哉, 佐藤薫, 吉村亮一, 三浦雅彦

  日本放射線腫瘍学会第36回学術大会  2023/11
• First-principles calculations of DNA irradiated with a proton and a carbon ion beam

  T. Sekikawa, Y. Matsuya, H. Beomju, M. Ishizaka, H. Kawai, Y. Ōno, T. Sato, T. Kai

  The International Symposium on Quantum Science, Technology and innovation  2023/11
• PHITSにおける物理・化学過程のシミュレーションコードの開発状況  [Invited]

  松谷悠佑, 甲斐健師, 吉井勇治, 楠本多聞, 赤松憲, 平田悠歩, 佐藤達彦

  2023年度核データ+PHITS合同研究会  2023/11
• ヒト由来水晶体上皮細胞での線量率効果

  松谷悠佑, 佐藤達彦, 浜田信行

  日本保健物理学会第56回研究発表会  2023/11
• PHITS飛跡構造シミュレーションに基づく、電子・陽子・炭素イオン誘発DNA損傷推定モデルの開発

  松谷悠佑, 甲斐健師, 赤松憲, 中野敏彰, 吉井勇治, 鹿園直哉, 佐藤達彦

  第66回日本放射線影響学会  2023/11
• 不均質な放射線感受性を考慮した放射線治療効果推定モデルを用いた肺癌に対する体幹部定位放射線治療の局所制御率分析

  嵯峨涼, 松谷悠佑, 小原秀樹, 駒井史雄, 吉野浩教, 青木昌彦, 細川洋一郎

  第66回日本放射線影響学会  2023/11
• Track-structure simulation analysis for biological impacts in magnetic resonance-guided radiotherapy

  M. Shimoma, Y. Matsuya

  The 10th meeting of educational symposium of radiation and health (ESRAH)  2023/10
• 原子サイズで人体への放射線影響を予測する計算コードの開発

  松谷悠佑

  第9回北海道大学部局横断シンポジウム「新領域創成に向けた若手連携の挑戦」  2023/10
• A predictive model of surviving fraction under ultra-high dose-rate irradiation based on DNA damage responses

  Y. Shiraishi, Y. Matsuya, T. Kusumoto, H. Fukunaga

  The 6th Faculty of Health Sciences (FHS) International Conference  2023/10
• Monte Carlo simulation for dose distribution around dental metal crown

  K. Kudo, Y. Matsuya, T. Nagano

  The 10th meeting of educational symposium of radiation and health (ESRAH)  2023/09
• Model assessment for the impact of cancer stem cells on in vitro cell survival and clinical tumor control

  D. Ishiyama, R. Saga, Y. Matsuya

  The 10th meeting of educational symposium of radiation and health (ESRAH)  2023/09
• スポットスキャニング陽子線治療下における二次中性子線のモンテカルロシミュレーション

  岩田樂久, 高田健太, 松谷悠佑, 山中将史, 守屋駿佑, 松本和樹, 熊田博明, 榮武二

  第126回日本医学物理学会学術集会  2023/09
• Analysis of radiation interactions in phosphors using the PHITS track-structure mode for evaluating the response of radiation detectors

  Y. Hirata, T. Kai, T. Ogawa, Y. Matsuya, T. Sato

  21th International Conference on Radiation Effects in Insulators (REI-21)  2023/09
• Radiolysis of liquid water occurring around ion tracks of carbon beams

  H. Tsuchida, T. Tezuka, T. Kai, Y. Matsuya, T. Majima, M. Saito

  The 7th International Conference "Dynamics of Systems on the Nanoscale" (DySoN 2023)  2023/04
• PHITSを用いたDNA損傷計算 –マクロからミクロへの挑戦–

  佐藤達彦, 松谷悠佑, 甲斐健師, 小川達彦, 平田悠歩, 関川卓也

  日本原子力学会 2023年秋の大会  2023
• 放射線誘起正孔がもたらすDNAの分子構造と電子状態変化の第一原理計算

  関川卓也, ファン・ボンジュ, 石坂優人, 松谷悠佑, 川井弘之, 大野義章, 甲斐健師, 佐藤達彦

  日本物理学会第78回年次大会  2023
• FLASH放射線治療効果を再現する生物効果予測モデルの開発

  白石祐太, 松谷悠佑, 楠本多聞, 福永久典

  第60回日本放射線腫瘍学会生物部会学術大会  2023

MISC

• Dose calculation for 320-row ADCT by using PMMA phantom-consideration of heel effect-

  寺嶋真凛, 溝延数房, 松谷悠佑, 伊達広行  北海道放射線技術雑誌(Web)  86-  2019
• 診療用X線によって生じる複雑なDNA二本鎖切断数の推定

  吉井 勇治, 松谷 悠佑, 佐々木 恒平, 森 諒輔, 伊達 広行  北海道放射線技術雑誌  (82)  45  -46  2017/03  [Not refereed][Not invited]
  
• 診断用X線によって生じる複雑なDNA二本鎖切断数の推定

  吉井 勇治, 松谷 悠佑, 佐々木 恒平, 森 諒輔, 伊達 広行  北海道放射線技術雑誌  (81)  126  -126  2016/10  [Not refereed][Not invited]
  
• 放射線の長時間照射中における細胞周期と放射線感受性の解析

  松谷 悠佑, 吉井 勇治, 堤 香織, 伊達 広行, 森 諒輔, 佐々木 恒平, 及川 青亮  北海道放射線技術雑誌  (81)  127  -127  2016/10  [Not refereed][Not invited]
  
• 標的・非標的効果を考慮した低線量X線被ばく後の細胞生存率モデル

  松谷 悠佑, 佐々木 恒平, 吉井 勇治, 木村 尭朗, 伊達 広行  北海道放射線技術雑誌  (81)  128  -128  2016/10  [Not refereed][Not invited]
  
• 計算シミュレーションによる放射線生物研究 照射・非照射細胞混在環境を模擬した確率的モデルによる細胞応答に関する研究

  佐々木 恒平, 松谷 悠佑, 吉井 勇治, 伊達 広行  日本放射線影響学会大会講演要旨集  59回-  10  -10  2016/10  [Not refereed][Not invited]
  
• Non-Targeted Effectを含めた細胞生存率に対する数理モデルの開発

  松谷 悠佑, 佐々木 恒平, 吉井 勇治, 伊達 広行  日本放射線影響学会大会講演要旨集  59回-  1  -1  2016/10  [Not refereed][Not invited]
  
• Participation/Dispatch Reports on International Conferences (Held in Japan) in 2014

  Matsuya Yusuke, Shimizu Yoichiro, Kimata Hirona, Kato Hideki, Takenaga Tomomi, Takegami Kazuki, Hirosawa Ayaka, Yabe Hitoshi, Ito Yuya  Japanese Journal of Radiological Technology  71-  (4)  391  -401  2015  [Not refereed][Not invited]
  
• 微視的エネルギー付与の空間分布が及ぼすDNA二本鎖切断の誘導への影響

  YOSHII YUJI, MATSUYA YUSUKE, SASAKI KOHEI, DATE HIROYUKI  日本放射線技術学会雑誌  70-  (9)  986  -986  2014/09/20  [Not refereed][Not invited]
  
• 線量率の違いを考慮した細胞生存率モデルの有用性

  MATSUYA YUSUKE, SASAKI KOHEI, TSUTSUMI KAORI, DATE HIROYUKI  北海道放射線技術雑誌  75-  (75)  135  -135  2013/10/25  [Not refereed][Not invited]
  
• モンテカルロ法を用いた23kVpX線の生物効果比の推定

  吉井 勇治, 佐々木 恒平, 三浦 貴智, 松谷 悠佑, 伊達 広行  日本放射線影響学会大会講演要旨集  56回-  97  -97  2013/10  [Not refereed][Not invited]
  
• 放射線によるDNA損傷の定量的モデル解析と生物学的効果比

  MATSUYA YUSUKE, OTSUBO YOSUKE, TSUTSUMI KAORI, YAMAZAKI RIE, SASAKI KOHEI, DATE HIROYUKI  日本放射線影響学会大会講演要旨集  56th-  97  -97  2013/10/01  [Not refereed][Not invited]
  
• コンフルエント単層細胞環境における放射線誘発バイスタンダー効果のシミュレーション

  SASAKI KOHEI, MATSUYA YUSUKE, TSUTSUMI KAORI, ITO AKIO, DATE HIROYUKI  日本放射線影響学会大会講演要旨集  56th-  111  -111  2013/10/01  [Not refereed][Not invited]
  
• モンテカルロ法を用いた28kVpX線の生物効果比の推定

  YOSHII YUJI, SASAKI KOHEI, MIURA TAKATOMO, MATSUYA YUSUKE, DATE HIROYUKI  日本放射線影響学会大会講演要旨集  56th-  97  2013/10/01  [Not refereed][Not invited]
  

Awards & Honors

• 2023/11 56th Annual Meeting of Japan Health Physics Society Excellent Presentation Award
   Dose-rate effects in human lens epithelial cells 

  受賞者: Y. Matsuya,T Sato, N. Hamada
• 2023/10 Hokkaido University The best poster presentation award. The 9th Hokkaido University Cross-Departmental Symposium
   Development of a calculation code that predicts radiation effects on the human body at atomic scale 

  受賞者: Y. Matsuya
• 2022 Japan Atomic Energy Agency 2020 Chairman's Commendation (Research and Development Achievement Award/Implementation of epoch-making research and development)
   Development of track structure analysis code to elucidate irradiation effects from nano scale 

  受賞者: T. Ogawa, T. Kai, Y. Matsuya
• 2018/03 Hokkaido University Graduate School of Health Sciences President’s special award in Graduate School of Health Sciences Hokkaido University
   

  受賞者: Yusuke Matsuya
• 2017/10 The 60th Japansese Radiation Research Society, Excellent Presentation Award
   Investigation of cell survival under protracted exposure for various dose rates in consideration of cell cycle distribution 

  受賞者: Y. Matsuya;S. J. McMahon;K. Tsutsumi;K. Sasaki;Y. Yoshii;R. Mori;J. Oikawa;H. Date;K. M. Prise
• 2017/09 European Radiation Research Society (ERRS) Travel Award ERRS-GBS-2017
   Application of the IMK model to cell survival curves following the exposure to intensity modulated radiation fields 

  受賞者: Y. Matsuya;S. J. McMahon;K. M. Prise;H. Date
• 2016/12 The 22nd International Conference on Medical Physics (ICMP) ICMP2016 Anchali Krisanachinda Award (3rd)
   Optimization of the irradiation scheme in radiotherapy focusing on the dose and dose rate to the tumor and organs at risk 

  受賞者: R. Yamada;Y. Matsuya;H. Date
• 2016/12 The 22nd International Conference on Medical Physics (ICMP) ICMP2016 Anchali Krisanachinda Award (1st)
   Biophysical modeling for targeted and non-targeted effects on cells after irradiation 

  受賞者: Y. Matsuya;K. Sasaki;Y. Yoshii;H. Date
• 2016/11 The 72nd annual meeting of Japanese Society of Radiological Technology Hokkaido branch Excellent Presentation Award (Radiation Therapy)
   Analysis of cell-cycle dynamics under long-term exposure at low dose rate 

  受賞者: Oikawa J;Matsuya Y;Mori R;Date H
• 2016/10 The 59th Japansese Radiation Research Society Excellent Presentation Award
   Development of mathematical model for cell surviving fraction including non-targeted effect 

  受賞者: Matsuya Y;Sasaki K;Yoshii Y;Date H
• 2016/10 The 3rd Educational Symposium on Radiation and Health by Young Scientists Poster Prize Winner (1st)
   A Cell-Killing Model of Targeted and Non-Targeted Effects Based on Microdosimetry and Biological Processes 

  受賞者: Y. Matsuya;K. Sasaki;Y. Yoshii;G. Okuyama;T. Kimura;H. Date
• 2015/03 Hokkaido University Graduate School of Health Sciences President’s special award in Graduate School of Health Sciences Hokkaido University
   

  受賞者: Yusuke Matsuya
• 2014/10 The 2nd International Conference on Radiological Sciences and Technology President’s special award
   Quantitative Estimation of DNA Lesions in the Cell nucleus in Consideration of the Dose Rate 

  受賞者: Y. Matsuya;Y. Yoshii;K. Tsutsumi;K. Sasaki;H. Date
• 2013/03 Clark Memorial Foundation, Hokkaido University Clark award
   

  受賞者: Yusuke Matsuya
• 2013/01 Hokkaido University Excellent Presentation Award
   Microdosimetric study on the lesions in cell nucleus after photon beam irradiations 

  受賞者: Yusuke Matsuya
• 2012/09 Hokkaido University President’s special award in Department of Health Sciences Hokkaido University
   

  受賞者: Yusuke Matsuya
• 2010/06 Hokkaido University Nitobe Award
   

  受賞者: Yusuke Matsuya

Research Grants & Projects

• Bottom-up analysis of radiation microscopic transport

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2023/04 -2028/03 

  Author : 小川 達彦, 安部 晋一郎, 松谷 悠佑
• Development of DNA damage estimation system based on spatial pattern of radiation track structure

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2022/04 -2026/03 

  Author : 松谷 悠佑, 福永 久典, 松山 成男, 赤松 憲, 甲斐 健師, 楠本 多聞

   

  令和4年度は、DNA損傷を高速に推定可能なDNA損傷予測システムの開発に向けて、(1)化学モデルの開発、(2)イオン線照射実験の準備、(3)光子線や炭素線照射後のDNA損傷測定データの蓄積を進めた。開発や測定を進める中で得られた成果の一部は、国際的に著名なジャーナルにて3報の発表を行った。 当該年度の化学モデルの開発においては、既存の放射線輸送計算コードPHITSに実装されているイオン飛跡構造解析モードKURBUCを応用し、陽子線照射後のDNA損傷収率の計算を行うことで、高LET照射時の化学過程の重要性を確認した。同時に、当初予定していなかったが、PHITSによる計算から得られる相互作用の空間情報から、ラジカルの初期収量と時間変化を計算するコード開発に成功し、DNA損傷の発生メカニズムに関する研究を一層進めている。このコード開発に基づき、DNA損傷予測を高精度に再現する化学モデルの開発に着手した。 次に、当該年度の照射実験の準備については、東北大学高速中性子実験室の陽子ビームと中性子線の物理特性の評価を進めた。同時に、高崎量子応用研究所に設置されている低エネルギー炭素イオン源（TIARA）を使用した照射実験を行い、原子間力顕微鏡を使用することで、25 MeV/nおよび10 MeV/n炭素線（高LETイオン線）照射後に発生する様々なDNA損傷（一本鎖切断、二本鎖切断、クラスター損傷）収量の定量的測定に成功した。現在、得られた実測値に基づき、開発中の化学モデルの妥当性の確認を進めている。 以上の化学モデル開発ならびにイオン線照射実験の蓄積から、高LET放射線後の化学過程の重要性が確認され、化学モデル開発の開発ならびに検証を大いに進展させることに成功した。したがって、様々な放射線タイプにより生じるDNA損傷を高速に推定可能なDNA損傷予測システムの開発に向けて大幅に研究が進展したと思われる。
• 低線量生物影響を考慮したCT被曝線量指標の開発 －計算科学と生物学の分野間融合ー

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  Date (from‐to) : 2021/04 -2024/03 

  Author : 佐々木 恒平, 松谷 悠佑

   

  R3年度は低線量被ばくに対応したDNA損傷推定モデルの構築を実施した。 放射線物理過程を模擬する放射線輸送計算コード（Particle and Heavy Ion Transport code System：PHITS）を用いて、コンピュータ断層撮影（CT）検査時の生体内環境を模擬し、被ばく細胞集団のDNA損傷収率を理論計算で評価する体系構築に取り組んだ。この評価体系を構築するには2つの要素がある。（１）実際のCT検査時に装置から発生し、患者体内に到達するX線の質を正確に再現すること、（２）患者体内の細胞へ誘導されるDNA損傷数を推定し損傷の体内分布を作成すること、である。 （１）では細胞実験で用いるCT装置から発生するX線を正確に再現することが必要となる。CT装置から発生するX線は制動X線と呼ばれるものであり、そのエネルギーが広範囲に及ぶ。また、X線を発生するX線管や付加フィルタの材質や形状によって光子エネルギーは様々な分布を呈する。さらに、CT装置のコリメータなどでX線が相互作用することによっても様々なエネルギーのX線が発生し、X線管から発生するX線に混入する。よって、患者体内へ入射するX線を再現するにはそのX線のエネルギースペクトルの実測が必要となる。我々はCdTeスペクトロメータ（EMF123型）を用いてエネルギースペクトルの実測を試みたが、測定位置の制限から正確な測定が困難であった。そのため、実測した半価層とTucker式によってエネルギースペクトルを推定した。現在、PHITSに得られたエネルギースペクトルを入力したX線源モデルを作成している。 （２）以前より取り組んできた非照射細胞へ誘導されるDNA損傷を推定する細胞間シグナル伝達シミュレーションについて、本研究で扱う実験体系に合わせてパラメータを最適化した。最適化が不十分な箇所が存在するので、引き続き取り組んでいく。
• 不均一放射線場における放射線影響推定へ向けたモデル開発

  日本学術振興会：学術研究助成基金助成（若手研究）

  Date (from‐to) : 2019/04 -2022/03 

  Author : 松谷悠佑
• 低線量率被ばく時における放射線感受性のモデル解析

  日本学術振興会：科学研究費補助金

  Date (from‐to) : 2016 -2018 

  Author : 松谷悠佑

Social Contribution

Social Contribution

Social Contribution

• 北大保健同窓会 副会長

  Date (from-to) : 2024/01-Today

  Role : Organizing member
• ミクロな視点で放射線を分析!

  Date (from-to) : 2023/11/03

  Role : Lecturer

  Sponser, Organizer, Publisher  : 北海道大学 保健科学研究院

  Event, Program, Title : 保健科学研究院公開講座2023「ようこそ！ヘルスサイエンスの世界へ」
• DEI (Diversity, Equity & Inclusion) パネルディスカッション

  Date (from-to) : 2023/10/11

  Role : Panelist

  Sponser, Organizer, Publisher  : 北海道大学

  Event, Program, Title : 第9回北大・部局横断シンポジウム
• 10th Educational Symposium of Radiation and Health by Young Scientist (ESRAH2023)

  Date (from-to) : 2023/09/23-2023/09/24

  Role : Organizing member
• 目に見えない放射線 体の中では どんな反応をおこすのか？

  Date (from-to) : 2023/08/06

  Role : Lecturer

  Sponser, Organizer, Publisher  : 北海道大学 医学部 保健学科

  Event, Program, Title : 2023年度 オープンキャンパス
• The 9th meeting of educational symposium of radiation and health (ESRAH)

  Date (from-to) : 2022/12/03-2022/12/04

  Role : Organizing member
• An integrated theoretical model for estimating cell death based on the DNA damage response

  Date (from-to) : 2021/11/12-2021/11/14

  Role : Panelist

  Sponser, Organizer, Publisher  : 日本放射線影響学会第64回大会
• 放射線生物学へのPHITSコードの応用

  Date (from-to) : 2021/05/21

  Role : Others

  Event, Program, Title : PHITSプロモーション動画公開記念オンラインセミナー

Media Coverage

• がん放射線治療の効果を予測 弘前大など研究G成功、世界初

  Date : 2023/02/25

  Publisher, broadcasting station: デーリー東北デジタル

  Internet
• 肺がん放射線治療の効果を正確に予測 弘前大

  Date : 2023/02/24

  Publisher, broadcasting station: Web東奥

  Internet
• 放射線治療の効果 正確な予測に成功 世界初 （青森県）

  Date : 2023/02/24

  Publisher, broadcasting station: Yahoo! ニュース

  Internet
• ［弘前大学］世界初！がん幹細胞の考慮により臨床の放射線治療効果の予測に成功 -- 基礎細胞実験と臨床研究をつなぐ予測モデルを開発（Digital PR Platform）

  Date : 2023/02/14

  Program, newspaper magazine: 毎日新聞

  Internet
• 【弘前大学】世界初！がん幹細胞の考慮により臨床の放射線 治療効果の予測に成功 -- 基礎細胞実験と臨床研究をつなぐ予 測モデルを開発

  Date : 2023/02/14

  Program, newspaper magazine: 北海道新聞

  Internet
• 【弘前大学】世界初！がん幹細胞の考慮により臨床の放射線治療効 果の予測に成功 -- 基礎細胞実験と臨床研究をつなぐ予測モデルを 開発

  Date : 2023/02/14

  Publisher, broadcasting station: 紀伊民報AGARA

  Internet
• がん幹細胞の考慮により臨床の放射線治療効果の予測に成功～基礎細胞実験と臨床研究をつなぐ予測モデルを開発～

  Date : 2023/02/14

  Publisher, broadcasting station: Tii生命科学

  Internet
• 【弘前大学】世界初！がん幹細胞の考慮により臨床の放射線治療効果の予測に成功 -- 基礎細胞実験と臨床研究をつなぐ予測モデルを開発

  Date : 2023/02/14

  Publisher, broadcasting station: Mapionニュース

  Internet
• 世界初！がん幹細胞の考慮により臨床の 放射線治療効果の予測に成功 ―基礎細胞実験と臨床研究をつなぐ予測モデルを開発―

  Date : 2023/02

  Writer: Myself

  Publisher, broadcasting station: RAB青森放送

  Program, newspaper magazine: Yahoo! ニュース

  Media report
• 世界初！あらゆる物質中の放射線の動きを原子サイズで予測 －人体や物質への放射線影響に微細世界から迫る－

  Date : 2021/12

  Writer: Myself

  Program, newspaper magazine: 日刊工業新聞

  Paper