Purpose: FLASH RT has sparked significant interest due to its potential for increasing the therapeutic ratio. Though the mechanism of FLASH has not been elucidated, oxygen concentration was found to be a significant factor in several experiments. However, in vivo measurements of oxygen depletion tend to underestimate the true extent of the phenomenon due to the re-diffusion of oxygen during irradiation, heterogeneity, and volume averaging effects. This computational study investigates these factors and discusses the implications for measuring oxygen depletion in vivo during FLASH RT.
Methods: A 3D computational model of normal mouse brain vasculature was constructed based on a public dataset. The dynamic oxygen distribution during 20 Gy FLASH dose was modeled by a partial differential equation considering oxygen diffusion, metabolism and radiolytic depletion assuming dose rates of 100, 300, and 1000 Gys⁻¹. The true oxygen depletion was compared to the apparent depletion measured in vivo by a simulated oximeter.
Results: Our study shows how the location and spatial resolution of oximeters as well as FLASH dose rates may affect the measurement accuracy of oxygen depletion. Due to oxygen recovery during FLASH radiation, the measured apparent oxygen depletion can be substantially lower than the real depletion. Furthermore, the accuracy of the measurement also depends on the spatial distribution of the soluble oxygen probes within the tissue with respect to the vasculature, and on the spatial resolution of the detector. With increasing dose rate, the apparent oxygen depletion is closer to the actual oxygen depletion due to the shorter irradiation time.
Conclusion: Measurement accuracy of oxygen depleted during FLASH RT in vivo is dependent on multiple factors. Ideally, oximeters should have high spatial and temporal resolution and irradiation time should be short enough to downplay the effects of oxygen heterogeneity and diffusion kinetics.
Modeling, Finite Element Analysis, Hypoxia
TH- Radiobiology(RBio)/Biology(Bio): Bio- tissue and microenvironment