title: Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.
abstract: Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD.
authors.affiliation: Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: Eva Anna
authors.initials: EA
authors.lastname: Zeestraten
authors.affiliation: Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.|Department of Radiology, Charing Cross Hospital campus, Imperial College NHS trust, London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Benjamin
authors.affiliation: Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Lambert
authors.affiliation: Stroke Research Group, Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: Owen Alan
authors.initials: OA
authors.lastname: Williams
authors.affiliation: Department of Psychology, King's College Institute of Psychiatry, Psychology, and Neuroscience, London, United Kingdom.
authors.forename: Robin Guy
authors.initials: RG
authors.lastname: Morris
authors.affiliation: Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: Thomas Richard
authors.initials: TR
authors.lastname: Barrick
authors.affiliation: Stroke Research Group, Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hugh Stephen
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000368:Aged; D059345:Cerebral Small Vessel Diseases / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011788:Quality of Life
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