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Investigating the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) in stroke survivors

Research output: Contribution to journalArticlepeer-review

Wasim Khan, Mohamed Salah Khlif, Remika Mito, Thijs Dhollander, Amy Brodtmann

Original languageEnglish
Article number117839
Published15 May 2021

Bibliographical note

Funding Information: This work is supported by the National Health and Medical Research Council (NHMRC) Dementia Research Team Grant ( APP1094974 ) at the Florey Institute of Neuroscience and Mental Health , Melbourne, Australia. Funding Information: We thank our participants who generously contributed their time to the study. The Florey acknowledges the strong support from the Victorian Government, including funding from the Operational Infrastructure Support Grant. The authors acknowledge the facilities, and the scientific and technical assistance of the National Imaging Facility at the Florey Node. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Using advanced diffusion MRI, we aimed to assess the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) using 3-tissue diffusion signal compositions in ischemic stroke. Data were obtained from the Cognition and Neocortical Volume After Stroke (CANVAS) study. Diffusion-weighted MR and high-resolution structural brain images were acquired 3- (baseline) and 12-months (follow-up) post-stroke. WMHs were automatically segmented and longitudinal assessment at 12-months was used to retrospectively delineate NAWM voxels at baseline converting to WMHs. NAWM voxels converting to WMHs were further dichotomized into either: “growing” WMHs if NAWM adhered to existing WMH voxels, or “isolated de-novo" WMHs if NAWM was unconnected to WMH voxels identified at baseline. Microstructural properties were assessed using 3-tissue diffusion signal compositions consisting of white matter-like (WM-like: TW), gray matter-like (GM-like: TG), and cerebrospinal fluid-like (CSF-like: TC) signal fractions. Our findings showed that NAWM converting to WMHs already exhibited similar changes in tissue compositions at baseline to WMHs with lower TW and increased TC (fluid-like, i.e. free-water) and TG compared to persistent NAWM. We also found that microstructural properties of persistent NAWM were related to overall WMH burden with greater free-water content in patients with high WMH load. These findings suggest that NAWM preceding conversion to WMHs are accompanied by greater fluid-like properties indicating increased tissue water content. Increased GM-like properties may indicate a more isotropic microstructure of tissue reflecting a degree of hindered diffusion in NAWM regions vulnerable to WMH development. These results support the usefulness of microstructural compositions as a sensitive marker of NAWM vulnerability to WMH pathogenesis.

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