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

• Published in: Magnetic resonance in medicine Vol. 81; no. 5; pp. 3065 - 3079
• Main Authors: Shao, Xingfeng, Ma, Samantha J., Casey, Marlene, D’Orazio, Lina, Ringman, John M., Wang, Danny J.J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2019
• Subjects: Adult; Aged; Algorithms; arterial spin labeling (ASL); Blood; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; blood–brain barrier (BBB); Brain; Brain - diagnostic imaging; Brain mapping; Cerebral Small Vessel Diseases - diagnostic imaging; Cognition; Cognitive ability; Cohort Studies; Correlation analysis; Correlation coefficient; Correlation coefficients; Dementia - diagnostic imaging; Dementia disorders; Diabetes mellitus; Diffusion; Diffusion barriers; Female; Geriatrics; gradient and spin echo (GRASE); Health risks; Healthy Volunteers; Humans; Hypercholesterolemia; Imaging, Three-Dimensional - methods; Labeling; Magnetic Resonance Imaging; Male; Mapping; Membrane permeability; Memory; Mental Status and Dementia Tests; Middle Aged; Modelling; Neuroimaging; Older people; Perfusion; Permeability; Regularization; Reproducibility; Reproducibility of Results; Risk analysis; Risk Factors; small vessel disease (SVD); Spin labeling; Spin Labels; Substantia alba; Tissues; Vascular dementia; Vascular diseases; Water exchange; water permeability; Weighting; White Matter - diagnostic imaging; Young Adult; water permeability; blood-brain barrier (BBB); diffusion; gradient and spin echo (GRASE); perfusion; small vessel disease (SVD); arterial spin labeling (ASL)
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.27632

Purpose
To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (kw) 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). kw 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 kw 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 kw measurements (intraclass correlation coefficient = 0.75) was achieved. Average kw was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min–1 for whole brain, gray and white matter. kw was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between kw 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. kw may serve as an imaging marker of cerebral SVD and associated cognitive impairment.