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

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 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 multi-site, further studies are required to determine whether associations with cognition of similar strength can be detected in a multi-centre setting. 109 patients (mean age=68) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across 6 sites as part of the PRESERVE DTI sub-study. After handling of missing data, 3T-MRI scanning was available from 5 sites on 5 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 normalised-brain volume, WMH lesion load, and n(o) 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 (standardised β=.268), Mental Flexibility (β=.306), Verbal Fluency (β=.376), and MoCA (β=.273). The magnitudes of these associations were comparable to those previously reported from single-centre studies found in a systematic literature review. In this multi-centre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. This study supports the use of DTI metrics as biomarkers of disease progression in multi-centre studies.