Biological sex impacts intracranial vasomotor and hemodynamic responses during light intensity exercise: a 4D flow MRI study

Biological sex modifies cerebrovascular responses to physiological challenges such as chemical stimuli. Yet, the impact of biological sex on cerebrovascular responses to aerobic exercise remain unclear. This uncertainty stems, in part, from the reliance on intracranial blood velocity assessment which does not consider possible sex differences in vasomotor responses. Also, measures are typically made in one vessel, overlooking possible regional variations in cerebrovascular responses. 4D flow magnetic resonance imaging (MRI) enables simultaneous assessment of intracranial vasomotor and hemodynamic responses in multiple arteries. This research leveraged 4D flow MRI to evaluate the impact of biological sex on cerebrovascular responses during light intensity exercise in multiple intracranial arteries. We tested the hypothesis that cerebrovascular responses during light intensity exercise would differ between females and males, and regional variations would be observed. 34 young, healthy adults (31 ± 5 years of age, 18 females) underwent 3T MRI and performed supine exercise at 30-35% Formula: see textO 2 max in the MRI bore using an MRI compatible stepper exercise device. 4D flow MRI captured cross-sectional area (CSA), blood flow, and cerebral pulsatility (PI) in the internal carotid arteries (ICA), middle cerebral arteries (MCA), anterior cerebral arteries (ACA), vertebral arteries (VA), basilar artery, and the posterior cerebral arteries (PCA), and cerebrovascular conductance (CVC) was calculated. Biological sex influenced blood flow responses to exercise in the left VA (P = 0.03) and left ACA (P = 0.03). Despite no sex difference in left VA blood flow at baseline (females: 99 ± 39 mL/min, males: 75 ± 19 mL/min, P = 0.06), females demonstrated an increase in left VA blood flow with exercise (P < 0.01) while blood flow did not change in males (P = 0.053), leading to greater left VA blood flow during exercise in females (115 ± 43 mL/min) compared with males (88 ± 22 mL/min; P = 0.02). In the left ACA, no sex differences were observed in blood flow at baseline (P = 0.12); however, males demonstrated a larger increase in left ACA blood flow with exercise (∆16 ± 9 mL/min) compared with females (∆9 ± 7 mL/min; P = 0.03). Biological sex did not influence blood flow responses in other arteries (all P ≥ 0.18) and did not impact CSA responses (all P ≥ 0.07). In contrast, biological sex impacted CVC in the left VA, left and right MCA, and left and right PCA (all P ≤ 0.03) wherein females demonstrated greater CVC than males during baseline and exercise (all P ≤ 0.049). Further, despite no difference in left ICA CVC at baseline (females: 2.8 ± 0.5 mL/min/mmHg, males: 2.5 ± 0.6 mL/min/mmHg, P = 0.06), females demonstrated greater left ICA CVC during exercise (2.6 ± 0.4 mL/min/mmHg) than males (2.3 ± 0.4 mL/min/mmHg; P = 0.03). Lastly, biological sex did not impact PI responses to exercise (all P ≥ 0.13). Overall, modest sex differences were observed in cerebrovascular responses during light intensity exercise with regional variations. Exercise at higher intensities may further provoke sex differences in cerebrovascular responses to aerobic exercise, and further research may aide in intervention implementation in various populations. This research was supported by funding from the NIH (RF1 1NS117746-01 to JNB; T32HL007936 to UW-Madison CVRC and SHAGM), a Virginia Horne Henry Research Grant (AAK1123 to JNB), and the Wisconsin Alumni Research Foundation (to JNB). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.