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

Andrew M. Blamire,Robin G. Morris,David J. Werring,Valerie Lohner,Victoria C. Cambridge,Barry Moynihan,Hugh S. Markus,Daniel J. Tozer,Ahamad Hassan,Iain D. Croall,John T. O’Brien,Thomas R. Barrick,Usman Khan,Kirsty Harkness,Gary A. Ford

doi:10.1042/cs20170146

Abstract

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 (β =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.

Highlights

Cerebral small vessel disease (SVD) causes a quarter of all ischaemic strokes, is the most common pathology underlying vascular cognitive impairment and dementia [1] and contributes to the severity of Alzheimer’s disease [2]
It is possible that individual cases of small Complex model β-values, and unusually ‘weak’/‘strong’ scatterplot fits are due to lack of power from low sample sizes. In this analysis of baseline data from a multicentre clinical trial of SVD, we found associations between Diffusion tensor imaging (DTI) metrics and cognition of a similar magnitude to those reported in previous single-centre studies
This provides support for the use of DTI measures as surrogate markers in clinical trials of SVD. We found that both DTI markers and lacunar infarct count were independently associated with Global cognition and Montreal Cognitive Assessment (MoCA) results

Summary

Introduction

Cerebral small vessel disease (SVD) causes a quarter of all ischaemic strokes, is the most common pathology underlying vascular cognitive impairment and dementia [1] and contributes to the severity of Alzheimer’s disease [2]. SVD affects the small vessels of the brain and results in a number of characteristic radiological appearances best seen on MRI, including lacunar infarcts, T2-white matter c 2017 The Author(s) While cognitive testing plays a central role in identifying the presence of cognitive impairment, it has proved to be relatively insensitive to longitudinal change [11] This has led to the suggestion that MRI might represent a useful surrogate marker to monitor disease progression and evaluate the efficacy of therapeutic interventions in smaller number of patients prior to larger phase III trials [3,12]

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Conclusion