Cerebrovascular pulsatility differs across vascular compartments and is altered by hypercapnic stimuli: a BOLD fMRI...

Cerebral small vessel disease and neurodegenerative disorders have been associated with increased cerebrovascular pulsatility. Recently, BOLD fMRI-based methods have emerged for assessing pulsatility, however their interpretability is limited because the relation between estimated pulsatility indices ( PI ) and vascular anatomy and physiology remains poorly understood. To improve interpretability, we introduce a cardiac-specific BOLD fMRI- based PI , investigate its relationship to the cortical vasculature, and validate its sensitivity by introducing the known physiological vascular modulation of hypercapnia. Using high-resolution 7T BOLD fMRI with gradient-echo (GE) and spin-echo (SE) sequences, we disentangled macro- and microvascular contributions to the PI and quantified it across cortical depth. PI maps revealed anatomically plausible patterns, with elevated GE- PI near large veins and in white matter while SE- PI remained largely constant across cortical depth. GE- PI decreased during hypercapnia consistent with altered vascular tone, SE- PI on the other hand did not. PI correlated with cerebrovascular reactivity and venous blood volume suggesting sensitivity to vascular density and vessel mechanics. Our findings demonstrate that BOLD-derived PI provides a spatially and physiologically specific measure of vascular pulsatility. The BOLD fMRI-based PI method is readily applicable to existing datasets and has potential for assessing potential microvascular damage in cerebrovascular and neurodegenerative disease.