Blood-brain barrier water permeability across the adult lifespan: A multi-echo ASL study

An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease. We evaluated Tex, cerebral blood flow (CBF) and arterial transit time (ATT) in 209 healthy adults between 26 and 87 years, over age and sex, using general linear models in gray matter, white matter, and regionally in cerebral lobes. After QC, 194 participants were included in the main analysis, and the results demonstrated that both gray matter (GM) and white matter (WM) BBB permeability was higher with higher age (Tex lower by 0.47 ms per year in GM [p < 0.05], and by 0.49 ms in WM, for females; no significant for males), with the largest Tex difference in the frontal lobes (0.64 ms decrease per year, p = 0.011, population average). CBF was lower with higher age in the GM (-0.71 mL/min/100g per year, p < 0.001, for females; -0.31 mL/min/100g per year, p < 0.05, for males). When correcting Tex models for CBF and ATT, effect of age on Tex disappears in the GM, but not in the WM (β=-0.28, p = 0.08). The CBF findings of this study are in line with previous studies, demonstrating the validity of the new sequence. The BBB water permeability variation over age and sex described in this study provides a reference for future BBB research.