Sex comparison of cerebrovascular reactivity to CO2 at global, lobe, and regional levels in healthy young adults.

Cerebrovascular and neurologic diseases show sex-specific risks and regional variation, both of which are linked to changes in cerebral blood flow (CBF), suggesting that sex or sex hormones may influence cerebrovascular function. Cerebrovascular reactivity (CVR) to hypercapnia may help predict these outcomes, but the identification of fundamental sex differences in CVR remain equivocal. Most CVR studies use methods that cannot identify regional variation, which may be clinically relevant. This study examined if sex differences exist in CVR, at the whole brain, lobular, and regional levels while controlling for confounding factors like menstrual cycle and hormonal contraception. 87 young, healthy adults (38F, 49M; F:22±4yrs, M:23±4yrs, 18-37yrs) from two similar cohorts were studied using arterial spin labeling (pcASL) in a 3T magnetic resonance imaging (MRI) scanner to derive microvascular CBF at room-air and during hypercapnia (~+8 mmHg end-tidal CO2). The cohorts had identical inclusion criteria but used different hypercapnia methods. In a subset (n=37), CVR was measured using 4D flow MRI of 11 cerebral arteries. While females displayed greater resting CBF, no sex differences in CVR using pcASL were observed in whole-brain (females=4.1±1.9, males=4.9±3.0%/mmHg), grey matter, white matter, or regions of interest forming the grey matter (all p<0.05). Similarly, 4D flow-derived CVR was not different between sexes at a whole-brain (females=3.5±0.9, males=3.4±1.8%/mmHg) or individual artery level (all p<0.05). These results indicate that when controlling for the confounders of age, menstrual cycle, hormonal contraception, and comorbidities, no sex differences in CVR are detected at global, lobular, arterial, or regional levels.