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

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

doi:10.1016/j.neuroimage.2021.117839

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

Neuroimage. 2021 May 15:232:117839. doi: 10.1016/j.neuroimage.2021.117839. Epub 2021 Feb 9.

Authors

Wasim Khan¹, Mohamed Salah Khlif², Remika Mito³, Thijs Dhollander⁴, Amy Brodtmann⁵

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, United Kingdom. Electronic address: will.khan@monash.edu.
² Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia. Electronic address: mohamed.khlif@florey.edu.au.
³ Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia. Electronic address: remika.mito@florey.edu.au.
⁴ Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁵ Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; Melbourne Dementia Research Centre, University of Melbourne, Victoria, Australia. Electronic address: agbrod@unimelb.edu.au.

PMID: 33577935
DOI: 10.1016/j.neuroimage.2021.117839

Abstract

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: T_W), gray matter-like (GM-like: T_G), and cerebrospinal fluid-like (CSF-like: T_C) signal fractions. Our findings showed that NAWM converting to WMHs already exhibited similar changes in tissue compositions at baseline to WMHs with lower T_W and increased T_C (fluid-like, i.e. free-water) and T_G 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.

Keywords: 3-tissue; Compositional analysis; Diffusion MRI; Normal-appearing white matter; White matter hyperintensities.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Female
Follow-Up Studies
Humans
Leukoaraiosis / diagnostic imaging*
Leukoaraiosis / epidemiology
Male
Middle Aged
Retrospective Studies
Stroke / diagnostic imaging*
Stroke / epidemiology
Survivors*
White Matter / diagnostic imaging*