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Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.

Abstract：

BACKGROUND AND PURPOSE:White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. METHODS:From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. RESULTS:NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. CONCLUSIONS:Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity.

journal_name

Stroke

journal_title

Stroke

authors

van Leijsen EMC,Bergkamp MI,van Uden IWM,Ghafoorian M,van der Holst HM,Norris DG,Platel B,Tuladhar AM,de Leeuw FE

doi

10.1161/STROKEAHA.118.020980

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1386-1393

issue

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.118.020980

journal_volume

pub_type

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Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.