Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials.

Benjamin, P; Zeestraten, E; Lambert, C; Ster, IC; Williams, OA; Lawrence, AJ; Patel, B; MacKinnon, AD; Barrick, TR; Markus, HS (2015) Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials. Journal of Cerebral Blood Flow & Metabolism, 36 (1). ISSN 1559-7016
SGUL Authors: Barrick, Thomas Richard Lawrence, Andrew John Lambert, Christian Paul Chis Ster, Delizia Irina Benjamin, Philip

PDF Published Version
Available under License Creative Commons Attribution.

Download (177kB) | Preview


Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George's Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n=121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.113.

Item Type: Article
Additional Information: This article is distributed under the terms of the Creative Commons Attribution 3.0 License ( which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (
Keywords: Cerebral small vessel disease, clinical trials, diffusion tensor imaging, magnetic resonance imaging, vascular cognitive impairment, Neurology & Neurosurgery, 1103 Clinical Sciences, 1109 Neurosciences, 1102 Cardiovascular Medicine And Haematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Journal of Cerebral Blood Flow & Metabolism
ISSN: 1559-7016
Language: ENG
3 June 2015Published
Publisher License: Creative Commons: Attribution 3.0
Project IDFunderFunder ID
081589Wellcome Trust
ARUK-PG2013-2Alzheimer’s Research UK
PubMed ID: 26036939
Web of Science ID: WOS:000367166000018
Go to PubMed abstract
Publisher's version:

Actions (login required)

Edit Item Edit Item