| Summary: | Aims: I investigate potential MRI markers in cerebral small vessel disease (SVD), to determine their relationship to cognitive impairment and investigate whether they are feasible for use as surrogate outcome measures in clinical trials by estimating their sensitivity to longitudinal change and calculating sample sizes for a hypothetical clinical trial. I also carry out pilot work to investigate the potential use of 7T MRI in SVD. Methods: Data from the prospective St Georges Cognition and Neuroimaging in Stroke (SCANS) study of patients with symptomatic SVD was used (n=121). Neuropsychological testing was performed annually for a period of 3 years. Multimodal MRI was also acquired annually to evaluate brain volume, T2 White Matter Hyperintensities (WMH) volume, lacunes and white matter damage on diffusion tensor imaging (DTI). Results: At baseline, lacunes and brain volume were found be important predictors of cognitive impairment on conventional MRI. There is a specific association between lacunes in the anteromedial thalamus and impaired processing speed (Chapter 3). Perivascular spaces (PvS) were not associated with cognitive impairment but were associated with other MRI markers of SVD (Chapter 4). Over 3 years, longitudinal change was detectable in MRI markers but not in cognitive measures. WMH volume and diffusion tensor imaging parameters were most sensitive to change and therefore had the smallest sample size estimates for a hypothetical clinical trial (Chapter 5). The presence of new lacunes was the only MRI marker able to predict longitudinal change in cognition over a 3 year follow-up period (Chapter 6). Conclusion: Quantitative MRI markers could significantly reduce the size of clinical trials to screen treatments for efficacy in SVD, although further validation from studies with longer follow-up is required. 7T MRI has the potential to provide new information on underlying disease mechanisms and more specific surrogate markers of SVD progression (Chapter 7).
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