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Updated: Dec 23, 2025
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Three-tissue compositional analysis reveals in-vivo microstructural heterogeneity of white matter hyperintensities
Wasim Khan1, Natalia Egorova2, Mohamed Salah Khlif3
1Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, UK.
Abstract:
White matter hyperintensities (WMHs) are frequently observed on brain scans of older individuals and are associated with cognitive impairment and vascular brain burden. Recent studies have shown that WMHs may only represent an extreme end of a diffuse pathological spectrum of white matter (WM) degeneration. The present study investigated the microstructural characteristics of WMHs using an advanced diffusion MRI modelling approach known as Single-Shell 3-Tissue Constrained Spherical Deconvolution (SS3T-CSD), which provides information on different tissue compartments within each voxel. The SS3T-CSD method may provide complementary information in the interpretation of pathological tissue through the tissue-specific microstructural compositions of WMHs. Data were obtained from stroke patients enrolled in the Cognition and Neocortical Volume After Stroke (CANVAS) study, a study examining brain volume and cognition after stroke. WMHs were segmented using an automated method, based on fluid attenuated inversion recovery (FLAIR) images. Automated tissue segmentation was used to identify normal-appearing white matter (NAWM). WMHs were classified into juxtaventricular, periventricular and deep lesions, based on their distance from the ventricles (3-10 mm). We aimed to compare in stroke participants the microstructural composition of the different lesion classes of WMHs and compositions of NAWM to assess the in-vivo heterogeneity of these lesions. Results showed that the 3-tissue composition significantly differed between WMHs classes and NAWM. Specifically, the 3-tissue compositions for juxtaventricular and periventricular WMHs both exhibited a relatively greater fluid-like (free water) content, which is compatible with a presence of interstitial fluid accumulation, when compared to deep WMHs. These findings provide evidence of microstructural heterogeneity of WMHs in-vivo and may support new insights for understanding the role of WMH development in vascular neurodegeneration.
Insights
White matter hyperintensities (WMHs) show microstructural differences based on location. Juxtaventricular and periventricular WMHs have more fluid than deep WMHs, indicating disease heterogeneity.
Area of Science:
- Neuroimaging
- White Matter Hyperintensities Research
- Diffusion MRI
Background:
- White matter hyperintensities (WMHs) are common in older adults and linked to cognitive decline.
- WMHs may represent a broader spectrum of white matter degeneration.
- Understanding WMH heterogeneity is crucial for neurodegeneration research.
Purpose of the Study:
- To investigate the microstructural characteristics of different white matter hyperintensity (WMH) classes.
- To compare WMH microstructural composition with normal-appearing white matter (NAWM).
- To assess in-vivo heterogeneity of WMHs in stroke patients.
Main Methods:
- Utilized Single-Shell 3-Tissue Constrained Spherical Deconvolution (SS3T-CSD) for advanced diffusion MRI analysis.
- Segmented WMHs and normal-appearing white matter (NAWM) from stroke patient data (CANVAS study).
- Classified WMHs into juxtaventricular, periventricular, and deep lesions based on proximity to ventricles.
Main Results:
- Significant differences in 3-tissue composition were found between WMH classes and NAWM.
- Juxtaventricular and periventricular WMHs showed higher fluid-like content compared to deep WMHs.
- This suggests interstitial fluid accumulation in specific WMH locations.
Conclusions:
- Provides in-vivo evidence for microstructural heterogeneity within white matter hyperintensities.
- Findings may offer new insights into the development of WMHs in vascular neurodegeneration.
- Highlights the utility of advanced MRI techniques for characterizing WMH pathology.
