Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI
Paulien H M Voorter1,2, Michael S Stringer3, Maud van Dinther4,5
1Department of Radiology and Nuclear Medicine (P.H.M.V., J.F.A.J., W.H.B.), Maastricht University Medical Center, the Netherlands.
Background:
White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.
Methods:
Structural T2-weighted imaging, multishell diffusion imaging, and dynamic contrast-enhanced magnetic resonance imaging were performed at 3T in 44 participants with sporadic cerebral small vessel disease and 32 participants with monogenic cerebral small vessel disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; 59±12 years, 41 males) between June 2017 and May 2020 as part of the prospective, multicenter (Edinburgh, the United Kingdom; Maastricht, the Netherlands; and Munich, Germany), observational INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases). The mean diffusivity, free water content, and perfusion (all derived from multishell diffusion imaging), as well as the blood-brain barrier leakage and plasma volume fraction (derived from dynamic contrast-enhanced magnetic resonance imaging), were compared between deep and periventricular WMH types using paired t tests. Additional spatial analyses were performed inside and outside the WMH types to determine the internal heterogeneity and the extent of the penumbras, that is, adjacent white matter at risk for conversion to WMH.
Results:
Periventricular WMH had higher mean diffusivity, higher free water content, and more plasma volume compared with deep WMH (P<0.001, P=0.01, and P<0.001, respectively). No differences were observed in perfusion (P=0.94) and blood-brain barrier leakage (P=0.65) between periventricular and deep WMHs. The spatial analyses inside WMH and the adjacent white matter revealed a gradual gradient in white matter microstructure, free water content, perfusion, and plasma volume but not in blood-brain barrier leakage.
Conclusions:
We showed different pathophysiological heterogeneity of the 2 WMH types. Periventricular WMHs display more severe damage and fluid accumulation compared with deep WMH, whereas deep WMHs reflect stronger hypoperfusion in the lesion's core.
Registration:
URL: https://www.isrctn.com; Unique identifier: ISRCTN10514229.
Insights
White matter hyperintensities (WMHs) show distinct pathophysiological differences. Periventricular WMHs exhibit greater damage and fluid accumulation, while deep WMHs indicate more severe hypoperfusion, aiding understanding of cerebral small vessel disease.
Area of Science:
- Neuroimaging
- Cerebral Small Vessel Disease
- White Matter Hyperintensities
Background:
- White matter hyperintensities (WMHs) are key markers of cerebral small vessel disease (SVD).
- Conventional MRI cannot fully reveal the varied pathophysiology within WMHs and adjacent white matter.
- Understanding microstructural and microvascular alterations in WMHs is crucial for SVD research.
Purpose of the Study:
- To enhance the understanding of WMH pathophysiology and adjacent white matter injury.
- To investigate microstructural and microvascular differences between deep and periventricular WMH subtypes.
- To compare sporadic and genetic SVD using quantitative MRI.
Main Methods:
- Quantitative MRI (T2-weighted, multishell diffusion, dynamic contrast-enhanced) at 3T.
- Inclusion of 44 sporadic and 32 monogenic SVD patients (INVESTIGATE-SVDs study).
- Analysis of mean diffusivity, free water, perfusion, BBB leakage, and plasma volume in WMH subtypes and surrounding tissue.
Main Results:
- Periventricular WMHs showed higher mean diffusivity, free water content, and plasma volume than deep WMHs.
- No significant differences in perfusion or blood-brain barrier leakage between WMH types.
- Spatial analysis revealed gradual gradients in microstructure and microvasculature around WMHs, indicating penumbral regions.
Conclusions:
- Distinct pathophysiological heterogeneity exists between periventricular and deep WMHs.
- Periventricular WMHs are associated with more severe tissue damage and fluid accumulation.
- Deep WMHs are characterized by more pronounced hypoperfusion within the lesion core.
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