Venous arterial spin labeling MRI signal is associated with oxygen supply-independent reduction in cerebral oxygen extraction in typically aging older adults

Microvascular flow disturbances may reduce capillary oxygen extraction efficiency and contribute to the accumulation of structural and functional pathology over the course of the aging process. Venous hyperintense signal (VHS) on arterial spin labeling (ASL) magnetic resonance imaging (MRI) has recently been proposed as a noninvasive marker of disturbed capillary flow patterns and may be associated with an oxygen supply-independent reduction in cerebral oxygen extraction fraction (OEF) in clinical populations. However, the role of VHS in typically aging older individuals remains under-investigated. Much physiologic inter-subject variability exists in OEF, primarily due to differences in cerebral hemodynamics (e.g., macro- and microvascular flow, transit times or blood velocity), and it is not well understood if these hemodynamic factors confound associations between VHS and OEF. Moreover, it remains unclear to what degree the appearance of VHS might be associated with imaging-related artifacts, including motion. To better characterize these effects, we conducted a multi-modal MRI study in a cohort of 36 typically aging older adults (60-80 years). We measured VHS, whole brain OEF, cerebral blood flow, microvascular oxygen supply and arterial transit times, and bulk flow in the internal carotid arteries and the superior sagittal sinus. Associations between cerebral hemodynamic physiology, head motion, VHS, and OEF were analyzed using combined multivariable and stepwise regression models. We found that VHS was associated with lower OEF and that VHS remained independently associated with reduced OEF in multivariable models adjusting for other vascular parameters. Importantly, VHS was not related to head motion. These findings suggest that VHS in older individuals may be indicative of distinct physiological mechanisms leading to reduced OEF, but further work is needed to directly elucidate their underpinnings.