Experiments have reported low normal tissue toxicities during FLASH irradiation, but the mechanism has not been elaborated. Several hypotheses have been proposed to explain the mechanism. One hypothesis is oxygen depletion. We analyze the time-dependent change of oxygen concentration in the tissue to study the oxygen depletion hypothesis using a computational model. The effects of physical, chemical and physiological parameters on oxygen depletion were explored. The kinetic equation of the model is solved numerically using the finite difference method with rational boundary conditions. Results of oxygen distribution is supported by the experiments of oxygen-sensitivity electrodes and experiments on the expression and distribution of the hypoxia-inducible factors. The analysis of parameters shows that the steady-state oxygen distribution before irradiation is determined by the oxygen consumption rate of the tissue and the microvessel density. The change of oxygen concentration after irradiation has been found to follow a negative exponential function, and the time constant is mainly determined by the microvessel density. The change of oxygen during exposure increases with dose rate and tends to be saturated because of oxygen diffusion. When the dose rate is high enough, the same dose results in the same reduction of oxygen concentration regardless of dose rate. The analysis of the FLASH effect in the brain tissue based on this model does not support the explanation of the oxygen depletion hypothesis. The oxygen depletion hypothesis remains controversial because the oxygen in most normal tissues cannot be depleted to radiation resistance level by FLASH irradiation.
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February 2022
Research Article|
October 21 2021
A Computational Model for Oxygen Depletion Hypothesis in FLASH Effect
Ankang Hu;
Ankang Hu
a Department of Engineering Physics, Tsinghua University, Beijing, China
b Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education, Beijing, China
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Rui Qiu;
Rui Qiu
1
a Department of Engineering Physics, Tsinghua University, Beijing, China
b Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education, Beijing, China
1 Address for correspondence: Department of Engineering Physics, Tsinghua University, Beijing, 100084, P.R. China; email: qiurui@tsinghua.edu.cn.
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Zhen Wu;
Zhen Wu
a Department of Engineering Physics, Tsinghua University, Beijing, China
c Nuctech Company Limited, Beijing, China
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Hui Zhang;
Hui Zhang
a Department of Engineering Physics, Tsinghua University, Beijing, China
b Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education, Beijing, China
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Wei Bo Li;
Wei Bo Li
d Institute of Radiation Medicine, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH) Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
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Junli Li
Junli Li
a Department of Engineering Physics, Tsinghua University, Beijing, China
b Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education, Beijing, China
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Radiat Res (2022) 197 (2): 175–183.
Article history
Received:
November 22 2020
Accepted:
September 23 2021
Citation
Ankang Hu, Rui Qiu, Zhen Wu, Hui Zhang, Wei Bo Li, Junli Li; A Computational Model for Oxygen Depletion Hypothesis in FLASH Effect. Radiat Res 1 February 2022; 197 (2): 175–183. doi: https://doi.org/10.1667/RADE-20-00260.1
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