Journal Article

DZNE-2025-00043

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI.

Voorter, P. H. M. ; Stringer, M. S. ; van Dinther, M. ; Kerkhofs, D. ; Dewenter, A. ; Blair, G. W. ; Thrippleton, M. J. ; Jaime Garcia, D. ; Chappell, F. M. ; Janssen, E. ; Kopczak, A. ; Staals, J. ; Ingrisch, M. ; Duering, M. ; Doubal, F. N. ; Dichgans, M.DZNE* ; van Oostenbrugge, R. J. ; Jansen, J. F. A. ; Wardlaw, J. M. ; Backes, W. H. ; Consortium, S. (Collaboration Author)

2025
Lippincott Williams & Wilkins Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1161/STROKEAHA.124.047910

Abstract: 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.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.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.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.URL: https://www.isrctn.com; Unique identifier: ISRCTN10514229.

Keyword(s): Humans (MeSH) ; White Matter: diagnostic imaging (MeSH) ; White Matter: pathology (MeSH) ; Middle Aged (MeSH) ; Male (MeSH) ; Female (MeSH) ; Cerebral Small Vessel Diseases: diagnostic imaging (MeSH) ; Cerebral Small Vessel Diseases: pathology (MeSH) ; Aged (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Prospective Studies (MeSH) ; Blood-Brain Barrier: diagnostic imaging (MeSH) ; Blood-Brain Barrier: pathology (MeSH) ; Diffusion Magnetic Resonance Imaging: methods (MeSH) ; blood-brain barrier ; cerebral small vessel diseases ; diffusion ; magnetic resonance imaging ; perfusion

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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