Comparison of blood-brain barrier water exchange rate in young and older adults with diffusion-weighted and multi-echo arterial spin labeling MRI

Abstract Background Water exchange rate (Kw) across the blood-brain barrier (BBB) has emerged as a candidate biomarker for assessing aging and neurological disease. This work sought to compare the diffusion-weighted (DW) and multi-echo (ME) arterial spin labeling (ASL) MRI sequences that assess Kw across the BBB in a young and an older healthy cohort to examine Kw changes in different brain regions associated with age group. Methods 12 young healthy (21–30 years, 26 ± 3 years, 8 female) and 18 older healthy (66–84 years, 75 ± 7 years, 13 female) participants underwent DW and ME ASL imaging along with structural T 1 -weighted scans on a 3T MRI. Kw, arterial transit time (ATT), and cerebral blood flow (CBF) maps were linearly registered to the structural images, which were then segmented using FreeSurfer into masks with 35 bilateral gray matter regions to extract regional Kw measures. Global and regional values were compared between younger and older participants using mixed-effect linear regression and two-sample t-tests with false discovery rate (FDR) correction. Additional linear regressions were utilized to directly correlate Kw, CBF, and ATT from the two ASL methods. Results DW and ME ASL produced opposite age-group differences in Kw in the whole brain and across all four lobes. Substantially higher absolute Kw values were observed using ME ASL compared to DW ASL. CBF exhibited a strong positive association (β = 1.15, p < 0.001) between DW and ME ASL while ATT showed a moderate positive relationship (β = 0.46, p < 0.001). Kw, on the other hand, was negatively associated (β = −0.62, p < 0.001) between the two ASL methods. ME ASL detected higher Kw in older adults within medial orbitofrontal, inferior frontal, anterior cingulate, inferior temporal, transverse temporal, sensorimotor, and insula regions. Conclusions DW and ME ASL detected distinctive patterns of BBB Kw change between young and older adults, with ME ASL identifying a greater number of statistically significant regional age-group differences in this cohort. Discrepancy in absolute values suggest method-dependent differences in ASL-derived Kw estimates, in addition to opposite age-group trends. Further validation is needed to understand contexts in which DW ASL and ME ASL are interchangeable versus complementary quantitative markers of BBB water exchange.