Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

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

Imaging age-related cognitive decline: A comparison of diffusion tensor and magnetization transfer MRI.

DTI appears the most sensitive imaging parameter to determine age-related white matter damage. The stronger relationship with FA suggests that axonal damage is important in age-related cognitive decline

Average DTI histogram distributions of the baseline longitudinal cohort and at 3 year follow-up.

<p>A. Fractional anisotropy. B. Mean diffusivity (mm²s^-1). C. Radial diffusivity (mm²s^-1). D. Axial diffusivity (mm²s^-1).</p

A. An axial fractional anisotropy and B. mean diffusivity map (mm²s^-1).

<p>Images are from a 78 year old male from the SCANS cohort and representative of DTI-derived maps of symptomatic cerebral small vessel disease patients.</p

SCANS longitudinal imaging cohort.

<p>All available DTI scans without EPI warping were used in our analyses. Exit event coding: Death = patient passed away; Dementia = patient developed a primary dementia syndrome; Heart implant = patient was unable to do further MR sessions due to a heart implant; ICH = subject met exclusion criteria after intracerebral haemorrhage; Cognition only = patient withdrew from MR sessions but remained in study for cognition; Withdrawal = patient formally withdrew from the study; Loss to follow-up = patient was lost to follow-up; Major stroke = patient met exclusion criteria after major ischaemic stroke; Cardiac arrest = major cognitive impairment related to hypoxia was seen in a patient after a cardiac arrest.</p

A. T1-weighted image B. FLAIR image C. Corresponding tissue segmentation map.

<p>Abbreviations: GM = grey matter; NAWM = normal appearing white matter; Lac. = lacune of presumed vascular origin; WMH = white matter hyperintensity.</p