BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between F_IO₂ and CBF is necessary to establish F_IO₂ levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study’s objective was to determine whether a dose-response relationship exists between F_IO₂ and CBF and, if so, the F_IO₂ at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose F_IO₂ of 30%, 40%, 50%, and 100% (Arm 1) or high dose F_IO₂ of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% F_IO₂, with subsequent CBF measurements obtained at each predetermined F_IO₂ level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose F_IO₂ ≤ 50% did not affect CBF. In contrast, high dose F_IO₂ ≥ 60% significantly reduced CBF. Exposure to 100% F_IO₂ led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing F_IO₂ levels in a dose dependent manner, with significant reductions in CBF with F_IO₂ exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493–498.