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Randomized Controlled Trial
. 2017 Jun 7;131(12):1361-1373.
doi: 10.1042/CS20170146. Print 2017 Jun 1.

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

Affiliations
Randomized Controlled Trial

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

Iain D Croall et al. Clin Sci (Lond). .

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.

Keywords: biomarkers; cerebral small vessel disease; clinical trials; cognition; diffusion tensor imaging.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1
Cognitive profile of the SVD patient group. This figure shows average, age-matched z-scores for cognitive indices. Error bars represent ± 1 S.E.M. Index score significantly different from zero: ** P≤ 0.001, * P≤0.005.
Figure 2
Figure 2
A scatterplot showing the relationship between WM FA median and Mental flexibility, stratified by study site. In addition to individual site regression lines, the regression line for the total is also included with accompanying 95% CI limits (black, dashed line).

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