Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI

Abstract

Purpose: To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (k_w ) across the blood-brain barrier (BBB) without contrast, and to evaluate its clinical utility in a cohort of elderly subjects at risk of cerebral small vessel disease (SVD).

Methods: A diffusion preparation module with spoiling of non-Carr-Purcell-Meiboom-Gill signals was integrated with pseudo-continuous arterial spin labeling (pCASL) and 3D gradient and spin echo (GRASE) readout. The tissue/capillary fraction of the arterial spin labeling (ASL) signal was separated by appropriate diffusion weighting (b = 50 s/mm² ). k_w was quantified using a single-pass approximation (SPA) model with total generalized variation (TGV) regularization. Nineteen elderly subjects were recruited and underwent 2 MRIs to evaluate the reproducibility of the proposed technique. Correlation analysis was performed between k_w and vascular risk factors, Clinical Dementia Rating (CDR) scale, neurocognitive assessments, and white matter hyperintensity (WMH).

Results: The capillary/tissue fraction of ASL signal can be reliably differentiated with the diffusion weighting of b = 50 s/mm² , given ~100-fold difference between the (pseudo-)diffusion coefficients of the 2 compartments. Good reproducibility of k_w measurements (intraclass correlation coefficient = 0.75) was achieved. Average k_w was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min^-1 for whole brain, gray and white matter. k_w was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between k_w and vascular risk factors, CDR, executive/memory function, and the Fazekas scale of WMH were observed.

Conclusion: A diffusion prepared 3D GRASE pCASL sequence with TGV regularized SPA modeling was proposed to measure BBB water permeability noninvasively with good reproducibility. k_w may serve as an imaging marker of cerebral SVD and associated cognitive impairment.

Keywords: arterial spin labeling (ASL); blood-brain barrier (BBB); diffusion; gradient and spin echo (GRASE); perfusion; small vessel disease (SVD); water permeability.