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Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

Lookup NU author(s): Iain Croall, Professor John O'Brien, Professor Andrew BlamireORCiD, Professor Gary Ford



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The Author(s). Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (ß =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

Publication metadata

Author(s): Croall ID, Lohner V, Moynihan B, Khan U, Hassan A, O'Brien JT, Morris RG, Tozer DJ, Cambridge VC, Harkness K, Werring DJ, Blamire AM, Ford GA, Barrick TR, Markus HS

Publication type: Article

Publication status: Published

Journal: Clinical Science

Year: 2017

Volume: 131

Issue: 12

Pages: 1361-1373

Online publication date: 07/06/2017

Acceptance date: 09/05/2017

Date deposited: 29/06/2017

ISSN (print): 0143-5221

ISSN (electronic): 1470-8736

Publisher: Portland Press Ltd


DOI: 10.1042/CS20170146


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