Fig. 2.

FLASH effect depends on tissue partial pressure of oxygen (pO₂) and reduced ROS production. WT mice anesthetized under normoxia or carbogen breathing (O₂ groups) were subjected to the NOR test 2 mo postirradiation. (A) Increase in normal brain pO₂ caused by carbogen breathing before and during the irradiation delivery reversed the neurocognitive sparing induced by FLASH found under normoxia to levels observed after CONV irradiation. Data are expressed as mean DI ± SD (n = 5–16 animals per group). P values were derived from the Mann–Whitney U test: ***P < 0.001 compared with the control nonirradiated group and ⁺P < 0.05; ⁺⁺P < 0.01 compared with the control + O₂ group. ns, not significant. (B) Water equilibrated at a 4% O₂ tension was irradiated with CONV and FLASH-RT, and H₂O₂ production was quantified by Amplex Red measurements. FLASH irradiation produces significantly less H₂O₂ than CONV at equivalent doses. Mean ± SD P values were derived from Mann–Whitney U test: ***P < 0.001.