3D computational model of oxygen depletion kinetics in brain vasculature during FLASH RT and its implications for in vivo oximetry experiments
3D computational model of oxygen depletion kinetics in brain vasculature during FLASH RT and its implications for in vivo oximetry experiments
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DOI：
10.1002/mp.15642
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发表时间：
2022-04-18
期刊：
影响因子：
3.8
通讯作者：
Pratx, Guillem
中科院分区：
文献类型：
--
作者：
Cui, Sunan;Pratx, Guillem
目的：超高剂量率照射，也被称为FLASH，已被证明可以提高放射治疗（RT）的治疗率。放射化学耗氧（ROD）假说部分解释了这一效应背后的机制，该假说将正常组织的保护归因于ROD诱导的短暂缺氧。为了更好地了解氧对FLASH效应的贡献，有必要测量FLASH辐照期间体内的氧（O-2）。本研究的目的是确定所需的时间分辨率，以准确测量闪光灯照射后立即快速变化的氧浓度。方法：我们使用从公共荧光显微镜数据集构建的真实血管模型进行了氧动力学的计算模拟。通过考虑氧扩散、代谢和ROD的偏微分方程（PDE）对FLASH RT期间和之后氧张力（p(o2)）的动态分布进行建模。假设氧气完全耗尽或部分耗尽，以及氧气扩散、消耗、血管p（o2）和血管密度等参数的可能值范围，对氧气回收导致的ROD低估进行了评估。结果：在FLASH rt后，O-2浓度迅速恢复。假设时间分辨率为0.5 s，在部分耗尽和完全耗尽情况下，估计的ROD分别仅为实际值的50.7%和36.7%。此外，ROD的低估高度依赖于血管密度。考虑到所涉及参数的不确定性，特别是组织中不同的血管密度，为了以90%的准确率估计ROD率，需要毫秒级的时间分辨率。结论：在FLASH rt中，O-2的快速恢复对体内ROD的测量提出了很大的挑战，建议在正常组织中测量ROD的时间分辨率为毫秒级。考虑到肿瘤的血管系统不规则，需要进一步研究是否同样的要求也适用于肿瘤。
Purpose: Ultra-high-dose-rate irradiation, also known as FLASH, has been shown to improve the therapeutic ratio of radiation therapy (RT). The mechanism behind this effect has been partially explained by the radiochemical oxygen depletion (ROD) hypothesis, which attributes the protection of the normal tissue to the induction of transient hypoxia by ROD. To better understand the contribution of oxygen to the FLASH effect, it is necessary to measure oxygen (O-2) in vivo during FLASH irradiation. This study's goal is to determine the temporal resolution required to accurately measure the rapidly changing oxygen concentration immediately after FLASH irradiation.Methods: We conducted a computational simulation of oxygen dynamics using a real vascular model that was constructed from a public fluorescence microscopy dataset. The dynamic distribution of oxygen tension (p(o2)) during and after FLASH RT was modeled by a partial differential equation (PDE) considering oxygen diffusion, metabolism, and ROD. The underestimation of ROD due to oxygen recovery was evaluated assuming either complete or partial depletion, and a range of possible values for parameters such as oxygen diffusion, consumption, vascular p(o2) and vessel density.Result: The O-2 concentration recovers rapidly after FLASH RT. Assuming a temporal resolution of 0.5 s, the estimated ROD is only 50.7% and 36.7% of its actual value in cases of partial and complete depletion, respectively. Additionally, the underestimation of ROD is highly dependent on the vascular density. To estimate ROD rate with 90% accuracy, temporal resolution on the order of milliseconds is required considering the uncertainty in parameters involved, especially, the diverse vascular density of the tissue.Conclusion: The rapid recovery of O-2 poses a great challenge for in vivo ROD measurements during FLASH RT. Temporal resolution on the order of milliseconds is recommended for ROD measurements in the normal tissue. Further work is warranted to investigate whether the same requirements apply to tumors, given their irregular vasculature.