Sex differences in grey matter, white matter, and regional brain perfusion in young, healthy adults

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between grey and white matter, or without assessing regional CBF. Thus, fundamental sex differences in regional or whole-brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total grey and white matter perfusion as well as regional grey matter perfusion. Adults 18-30 years old (females=22, males=26), were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by Computational Anatomy Toolbox (CAT12) analysis in Statistical Parametric Mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females =62±9, males=45±10mL/100g/min, p<0.001), grey matter (females=75±11, males=54±12mL/100g/min, p<0.001), and white matter (females=44±6, males=32±7mL/100g/min, p<0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14-66% higher. A second MRI approach (4D flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, grey, and white matter levels and across dozens of brain regions, and offer new clarity into fundamental sex differences in global and regional CBF regulation prior to aging or pathology.