Transient Oxygen Depletion and FLASH: Are We Ruling It Out Too Soon?

The contribution of transient oxygen depletion (TOD) to the FLASH effect has been challenged, primarily because measurements indicate both insufficient depletion rates and normal tissue oxygenation levels that are too high. We argue that these parameters have been overly constrained, and that realistic ranges of tissue oxygen heterogeneity and reported ranges of oxygen consumption rates still enable meaningful depletion in regions of healthy tissue during ultra-high dose rate irradiation. Further evaluation of these measures is essential; TOD is a recognized protective phenomenon which, together with other mechanisms, can contribute towards a unified understanding of the FLASH effect.