FLASH辐照过程中辐解氧耗的计算模型及其对氧增强率的影响
A computational model of radiolytic oxygen depletion during FLASH irradiation and its effect on the oxygen enhancement ratio
摘要：
最近的动物辐照研究结果重新点燃了人们对超高剂量率辐照（也称为FLASH）降低正常组织毒性潜力的兴趣。然而，尽管有越来越多的证据表明“闪光效应”，但其机制尚未阐明。这篇文章假设，FLASH照射的辐射防护作用可能是由于低氧干细胞壁龛的特异性保留，这已经在包括骨髓和大脑在内的几个器官中被确定。为了探索这一假设，提出了一个新的计算模型，框架瞬态辐解氧耗（ROD）在闪光灯照射的氧增强比（OER）的影响。该模型考虑了通过组织的氧扩散、代谢细胞的氧消耗及其辐解消耗，以估计接受FLASH照射的细胞的放射敏感性的相对降低。基于该模型，提出了几个可在未来实验中检验的预测：（1）当辐射脉冲持续时间从<1 s增加到10 s时，闪光效应将逐渐消失：（2）为了获得最大的闪光效应，应使用最少的辐射脉冲数沉积剂量;（3）FLASH效应应该仅在照射时已经缺氧的细胞中观察到;和（4）毛细血管氧张力的变化（增加或减少）应该减弱FLASH效应。
英文摘要：
Recent results from animal irradiation studies have rekindled interest in the potential of ultra-high dose rate irradiation (also known as FLASH) for reducing normal tissue toxicity. However, despite mounting evidence of a "FLASH effect", a mechanism has yet to be elucidated. This article hypothesizes that the radioprotecting effect of FLASH irradiation could be due to the specific sparing of hypoxic stem cell niches, which have been identified in several organs including the bone marrow and the brain. To explore this hypothesis, a new computational model is presented that frames transient radiolytic oxygen depletion (ROD) during FLASH irradiation in terms of its effect on the oxygen enhancement ratio (OER). The model takes into consideration oxygen diffusion through the tissue, its consumption by metabolic cells, and its radiolytic depletion to estimate the relative decrease in radiosensitivity of cells receiving FLASH irradiation. Based on this model, several predictions are made that could be tested in future experiments: (1) the FLASH effect should gradually disappear as the radiation pulse duration is increased from <1s to 10 s; (2) dose should be deposited using the smallest number of radiation pulses to achieve the greatest FLASH effect; (3) a FLASH effect should only be observed in cells that are already hypoxic at the time of irradiation; and (4) changes in capillary oxygen tension (increase or decrease) should diminish the FLASH effect.
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