Quantitative Water Permeability Mapping of Blood-Brain-Barrier Dysfunction in Aging

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k W ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI....

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Published in:Frontiers in aging neuroscience Vol. 14; p. 867452
Main Authors: Ford, Jeremy N., Zhang, Qihao, Sweeney, Elizabeth M., Merkler, Alexander E., de Leon, Mony J., Gupta, Ajay, Nguyen, Thanh D., Ivanidze, Jana
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 08.04.2022
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ISSN:1663-4365, 1663-4365
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Summary:Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k W ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k W in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k W values in the cerebral cortex (mean = 81.51 min –1 , SD = 15.54) compared to cerebral white matter (mean = 75.19 min –1 , SD = 13.85) ( p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k W as an outcome showed that age was statistically significant in the cerebral cortex ( p = 0.013), cerebral white matter ( p = 0.033), hippocampi ( p = 0.043), orbitofrontal cortices ( p = 0.042), and precunei cortices ( p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex ( p = 0.026) and precunei cortices ( p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k W and WMH volume ( r = −0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume ( r = −0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders.
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This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience
Edited by: Eszter Farkas, University of Szeged, Hungary
Reviewed by: Alon Friedman, Dalhousie University, Canada; Donald Elbert, The University of Texas at Austin, United States; Istvan Krizbai, Hungarian Academy of Sciences (MTA), Hungary
ISSN:1663-4365
1663-4365
DOI:10.3389/fnagi.2022.867452