Quantitative Water Permeability Mapping of Blood-Brain-Barrier Dysfunction in Aging.

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer's disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k values in the cerebral cortex (mean = 81.51 min, = 15.54) compared to cerebral white matter (mean = 75.19 min, = 13.85) ( < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k as an outcome showed that age was statistically significant in the cerebral cortex ( = 0.013), cerebral white matter ( = 0.033), hippocampi ( = 0.043), orbitofrontal cortices ( = 0.042), and precunei cortices ( = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex ( = 0.026) and precunei cortices ( = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k and WMH volume ( = -0.51, = 0.02), and normal-appearing white matter (NAWM) and WMH volume ( = -0.44, = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders.