Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain

Abstract

Background: The blood-brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in the BBB occurring with healthy aging.

Purpose: To investigate age-related changes in the BBB permeability to water using multiple-echo-time (multi-TE) arterial spin labeling (ASL) MRI.

Study type: Prospective, cohort.

Population: Two groups of healthy humans-older group (≥50 years, mean age = 56 ± 4 years, N = 13, females = 5) and younger group (≤20 years, mean age = 18 ± 1, N = 13, females = 7).

Field strength/sequence: A 3T, multi-TE Hadamard pCASL with 3D Gradient and Spin Echo (GRASE) readout.

Assessment: Two different approaches of variable complexity were applied. A physiologically informed biophysical model with a higher complexity estimating time ( $T_{\mathrm{ex}}$ ) taken by the labeled water to move across the BBB and a simpler model of triexponential decay measuring tissue transition rate ( $k_{\mathrm{lin}})$ .

Statistics: Two-tailed unpaired Student t-test, Pearson's correlation coefficient and effect size. P < 0.05 was considered significant.

Results: Older volunteers showed significant differences of 36% lower $T_{\mathrm{ex}}$ , 29% lower cerebral perfusion, 17% pronged arterial transit time and 22% shorter intra-voxel transit time compared to the younger volunteers. Tissue fraction ( $f_{\mathrm{EV}}$ ) at the earliest TI = 1600 msec was significantly higher in the older group, which contributed to a significantly lower $k_{\mathrm{lin}}$ compared to the younger group. $f_{\mathrm{EV}}$ at TI = 1600 msec showed significant negative correlation with $T_{\mathrm{ex}}$ (r = -0.80), and $k_{\mathrm{lin}}$ and $T_{\mathrm{ex}}$ showed significant positive correlation (r = 0.73).

Data conclusions: Both approaches of Multi-TE ASL imaging showed sensitivity to detect age-related changes in the BBB permeability. High tissue fractions at the earliest TI and short $T_{\mathrm{ex}}$ in the older volunteers indicate that the BBB permeability increased with age.

Evidence level: 2 TECHNICAL EFFICACY: Stage 1.

Keywords: MRI; aging; arterial spin labeling; blood-brain barrier; multi-TE; permeability.