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

Purpose: To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (k(w)) across the blood-brain barrier (BEE) 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-PurcellMeiboom-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/mm(2)). 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/mm(2), given similar to 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.