Journal
PLOS ONE
Volume 11, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0147836
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Funding
- Wellcome Trust [081589]
- English National Institute for Health Research Senior Investigator award
- Academy of Medical Sciences (GB) Clinical Lecturer Start-Up Grant
- Alzheimer's Research UK [ARUK-PG2013-2]
- English National Institute of Health Research (NIHR) Clinical Stroke Research Network
- Academy of Medical Sciences (AMS) [AMS-SGCL8-Lambert] Funding Source: researchfish
- Alzheimers Research UK [ARUK-PG2013-2] Funding Source: researchfish
- National Institute for Health Research [CL-2012-16-501, NF-SI-0512-10019] Funding Source: researchfish
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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.
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