Characterizing venous hyperintense signal on ASL MRI as a marker of reduced oxygen extraction efficiency in older adults

Motivation: Venous hyperintense signal (VHS) on perfusion-weighted ASL images potentially marks microvascular flow disturbances resulting in reduced oxygen extraction efficiency. However, its physiological underpinnings in older adults, particularly those with APOE genotypes known to affect hemodynamics, remain unclear. Goal(s): To characterize VHS regarding macro- and microvascular cerebral hemodynamics and effects on OEF in typically aging older APOE ε4 carriers and non-carriers. Approach: We investigated associations between MRI-derived VHS, OEF and macro- and microvascular hemodynamic parameters, i.e., oxygen supply, flow, blood velocities and transit times. Results: VHS indicated lower OEF independently of other macro- and microvascular hemodynamic physiology, potentially more so in APOE ε4+ individuals. Impact: VHS may serve as a distinct marker of reduced oxygen extraction efficiency in older adults and could facilitate deeper insights into contributions of capillary dysfunction to age-related pathologies such as white matter lesions or neurodegeneration, especially in APOE ε4 carriers.