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

Publication Type	Academic Article
Authors	Ford J, Zhang Q, Sweeney E, Merkler A, de Leon M, Gupta A, Nguyen T, Ivanidze J
Journal	Front Aging Neurosci
Volume	14
Pagination	867452
Date Published	04/08/2022
ISSN	1663-4365
Abstract	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_W) 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_W in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k_W values in the cerebral cortex (mean = 81.51 min^-1, SD = 15.54) compared to cerebral white matter (mean = 75.19 min^-1, SD = 13.85) (p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k_W as an outcome showed that age was statistically significant in the cerebral cortex (p = 0.013), cerebral white matter (p = 0.033), hippocampi (p = 0.043), orbitofrontal cortices (p = 0.042), and precunei cortices (p = 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 (p = 0.026) and precunei cortices (p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k_W and WMH volume (r = -0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume (r = -0.44, p = 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.
DOI	10.3389/fnagi.2022.867452
PubMed ID	35462701
PubMed Central ID	PMC9024318