Inspired oxygen level and tension modulate the murine skin sparing FLASH effect in electron ultra-high dose rate irradiations

ObjectiveThis study evaluated the hypothesis that baseline tissue oxygen (pO2) would modulate FLASH damage sparing in murine skin, comparing MeV electron ultra-high dose rate (UHDR) versus conventional dose rate (CDR) irradiations. ApproachMurine leg skin pO2 was systematically varied and measured during irradiation from a Mobetron 9 MeV linac at 25 Gy, comparing UHDR ({approx}240 Gy/s) to CDR ({approx}0.16 Gy/s), for skin damage outcomes. Radiolytic oxygen consumption, go2 (mmHg/Gy), was also quantified in vivo. Baseline tissue pO2 was systematically modulated in 5 different treatment cohorts, using known methods of altering the inhaled gas (room air, 100% oxygen, or carbogen) and through applied limb vascular compression (partial or full). Induced skin damage was scored daily per mouse. Main ResultsFLASH skin sparing was observed in groups with partial leg clamping (pO2{approx}7{+/-}4mmHg), inhaled air (pO2{approx}12{+/-}6mmHg) and oxygen (tissue pO2{approx}16{+/-}4mmHg), while reduction in ulceration progression was significant just in the air inhalation group. No FLASH effect was observed at zero oxygen, via complete blood flow occlusion (pO2{approx}0{+/-}1mmHg), or when modulated by inhaled carbogen (pO2{approx}21{+/-}7mmHg). In vivo measurements of radiolytic consumption, go2, correlated to initial pO2 when FLASH was present (pO2{approx}4-16mmHg) and saturated above pO2>16mmHg. Inspired carbogen induced the highest pO2 and maximum damage at 25 Gy. Reductions in dose to 20 and 15 Gy reduced skin damage with carbogen, but did not result in FLASH sparing. SignificanceThese findings indicate that tissue pO2 directly modulates in vivo FLASH skin tissue sparing, requiring roughly room air or 100% oxygen anesthetic gas levels for this effect to be present. The effect is diminished by the absence of oxygen or from carbogen induced oxygen values. Variations in dose do not appear to alter this observation at carbogen induced pO2 levels.