AUTHOR=Ford Jeremy N. , Zhang Qihao , Sweeney Elizabeth M. , Merkler Alexander E. , de Leon Mony J. , Gupta Ajay , Nguyen Thanh D. , Ivanidze Jana 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.867452

DOI=10.3389/fnagi.2022.867452

ISSN=1663-4365

ABSTRACT=<p>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<sub>W</sub>) 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<sub>W</sub> in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k<sub>W</sub> values in the cerebral cortex (mean = 81.51 min<sup>–1</sup>, <italic>SD</italic> = 15.54) compared to cerebral white matter (mean = 75.19 min<sup>–1</sup>, <italic>SD</italic> = 13.85) (<italic>p</italic> &lt; 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k<sub>W</sub> as an outcome showed that age was statistically significant in the cerebral cortex (<italic>p</italic> = 0.013), cerebral white matter (<italic>p</italic> = 0.033), hippocampi (<italic>p</italic> = 0.043), orbitofrontal cortices (<italic>p</italic> = 0.042), and precunei cortices (<italic>p</italic> = 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 (<italic>p</italic> = 0.026) and precunei cortices (<italic>p</italic> = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k<sub>W</sub> and WMH volume (<italic>r</italic> = −0.51, <italic>p</italic> = 0.02), and normal-appearing white matter (NAWM) and WMH volume (<italic>r</italic> = −0.44, <italic>p</italic> = 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.</p>