{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:58:47Z","timestamp":1793739527528,"version":"4.6.1"},"reference-count":37,"publisher":"Radiation Research Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1667\/rade-20-00260.1","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:25:27Z","timestamp":1636107927000},"page":"175-183","source":"Crossref","is-referenced-by-count":12,"title":["A Computational Model for Oxygen Depletion Hypothesis in FLASH Effect"],"prefix":"10.1667","volume":"197","author":[{"given":"Ankang","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Engineering Physics, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Engineering Physics, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Engineering Physics, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Engineering Physics, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Radiation Medicine, Helmholtz Zentrum M\u00fcnchen - German Research Center for Environmental Health (GmbH) Ingolst\u00e4dter Landstr. 1, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Engineering Physics, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"11","doi-asserted-by":"crossref","unstructured":"G Adrian, E Konradsson, M Lempart, et al.  \"Br J Radiol.\"  93, \"The FLASH effect depends on oxygen concentration.\" 20190702 (2020)","DOI":"10.1259\/bjr.20190702"},{"key":"27","doi-asserted-by":"crossref","unstructured":"CF Babbs  and MG Steiner  \"Free Radic Biol Med.\"  8, \"Simulation of free radical reactions in biology and medicine: a new two-compartment kinetic model of intracellular lipid peroxidation.\" 471 (1990)","DOI":"10.1016\/0891-5849(90)90060-V"},{"key":"26","doi-asserted-by":"crossref","unstructured":"P O'Neill  and P Wardman  \"Int J Radiat Biol.\"  85, \"Radiation chemistry comes before radiation biology.\" 9 (2009)","DOI":"10.1080\/09553000802640401"},{"key":"14","doi-asserted-by":"crossref","unstructured":"C Fouillade, S Curras-Alonso, L Giuranno, et al.  \"Clin Cancer Res.\"  26, \"FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence.\" 1497 (2020)","DOI":"10.1158\/1078-0432.CCR-19-1440"},{"key":"29","doi-asserted-by":"crossref","unstructured":"DR Grimes  and M Partridge  \"Biomed Phys Eng Express.\"  1, \"A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio.\" 045209 (2015)","DOI":"10.1088\/2057-1976\/1\/4\/045209"},{"key":"2","doi-asserted-by":"crossref","unstructured":"DA Simmons, FM Lartey, E Schuler, et al.  \"Radiother Oncol.\"  139, \"Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation.\" 4 (2019)","DOI":"10.1016\/j.radonc.2019.06.006"},{"key":"7","doi-asserted-by":"crossref","unstructured":"DR Spitz, GR Buettner, MS Petronek, et al.  \"Radiother Oncol.\"  139, \"An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.\" 23 (2019)","DOI":"10.1016\/j.radonc.2019.03.028"},{"key":"18","doi-asserted-by":"crossref","unstructured":"DR Spitz, GR Buettner, MS Petronek, et al.  \"Radiother Oncol.\"  139, \"An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.\" 23 (2019)","DOI":"10.1016\/j.radonc.2019.03.028"},{"key":"6","doi-asserted-by":"crossref","unstructured":"G Pratx  and DS Kapp  \"Phys Med Biol.\"  64, \"A computational model of radiolytic oxygen depletion during FLASH irradiation and its effect on the oxygen enhancement ratio.\" 185005 (2019)","DOI":"10.1088\/1361-6560\/ab3769"},{"key":"13","doi-asserted-by":"crossref","unstructured":"M Buonanno, V Grilj, DJ Brenner,  \"Radiother Oncol.\"  139, \"Biological effects in normal cells exposed to FLASH dose rate protons.\" 51 (2019)","DOI":"10.1016\/j.radonc.2019.02.009"},{"key":"3","doi-asserted-by":"crossref","unstructured":"P Wilson, B Jones, T Yokoi, et al.  \"Br J Radiol.\"  85, \"Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions.\" e933 (2012)","DOI":"10.1259\/bjr\/17827549"},{"key":"34","doi-asserted-by":"crossref","unstructured":"KL Talks, H Turley, KC Gatter, et al.  \"Am J Pathol.\"  157, \"The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages.\" 411 (2000)","DOI":"10.1016\/S0002-9440(10)64554-3"},{"key":"1","doi-asserted-by":"crossref","unstructured":"V Favaudon, L Caplier, V Monceau, et al.  \"Sci Transl Med.\"  6, \"Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.\" (2014)","DOI":"10.1126\/scitranslmed.3008973"},{"key":"4","doi-asserted-by":"crossref","unstructured":"M Durante, E Brauer-Krisch, M Hill,  \"Brit J Radiol.\"  91, \"Faster and safer? 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