氧耗竭假说仍存争议：FLASH放疗期间氧耗竭的数学模型
Oxygen depletion hypothesis remains controversial: a mathematical model of oxygen depletion during FLASH radiation
AI总结：
本研究构建了描述组织氧浓度动态变化的计算模型，以脑组织为例验证发现氧耗竭假说无法解释FLASH放疗的正常组织低毒性效应，指出该假说仍存争议。
摘要：
研究背景：已有实验报道FLASH放疗过程中正常组织毒性较低，但其作用机制尚未阐明。目前学界已提出多种假说以解释该机制，其中氧耗竭假说已被提出且大多仅开展了定性研究。研究方法：本文提出一种计算模型用于描述组织内氧浓度随时间的变化，采用有限差分法对模型的动力学方程进行数值求解。以脑组织为例，利用该模型基于氧耗竭假说分析FLASH效应。研究结果：氧分布由组织的氧消耗速率和毛细血管间距共同决定；辐射后氧浓度随时间的变化遵循负指数函数，时间常数由毛细血管间距决定；当剂量率足够高时，无论剂量率如何，相同剂量都会导致相同的氧浓度变化。基于该模型的脑组织FLASH效应分析结果不支持氧耗竭假说的解释。研究结论：结合本模型的数学分析以及缺氧诱导因子表达与分布相关实验结果，大多数正常组织中的氧无法被FLASH放疗耗竭，因此氧耗竭假说仍存在争议。
英文摘要：
Background: Experiments have reported low normal tissue toxicities during FLASH radiation, but the mechanism has not been elaborated. Several hypotheses have been proposed to explain the mechanism. The oxygen depletion hypothesis has been introduced and mostly studied qualitatively. Methods: We present a computational model to describe the time-dependent change of oxygen concentration in the tissue. The kinetic equation of the model is solved numerically using the finite difference method. The model is used to analyze the FLASH effect with the oxygen depletion hypothesis, and the brain tissue is chosen as an example. Results: The oxygen distribution is determined by the oxygen consumption rate of the tissue and the distance between capillaries. The change of oxygen concentration with time after radiation has been found to follow a negative exponential function, and the time constant is determined by the distance between capillaries. When the dose rate is high enough, the same dose results in the same change of oxygen concentration regardless of dose rate. The analysis of FLASH effect in the brain tissue based on this model does not support the explanation of the oxygen depletion hypothesis. Conclusions: The oxygen depletion hypothesis remains controversial because oxygen in most normal tissues cannot be depleted by FLASH radiation according to the mathematical analysis with this model and experiments on the expression and distribution of the hypoxia-inducible factors.
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