Although diffusion tensor imaging (DTI) and the magnetization transfer ratio (MTR) have been extensively studied in multiple sclerosis (MS), it is still unclear if they are more effective biomarkers of disability than conventional MRI. MRI scans were performed on 117 participants with MS in addition to 26 healthy volunteers. Mean values were obtained for DTI indices and MTR for supratentorial brain and three white matter tracts of interest. DTI and MTR values were tested for correlations with measures of atrophy and lesion volume and were compared with these more conventional indices for prediction of disability. All DTI and MTR values correlated to an equivalent degree with lesion volume and cerebral volume fraction (CVF). Thalamic volumes correlated with all indices in the optic radiations and with mean and perpendicular diffusivity in the corpus callosum. Nested model regression analysis demonstrated that, compared with CVF, DTI indices in the optic radiations were more strongly correlated with Expanded Disability Status Scale and were also more strongly correlated than both CVF and lesion volume with low-contrast visual acuity. Abnormalities in DTI and MTR are equivalently linked with brain atrophy and inflammatory lesion burden, suggesting that for practical purposes they are markers of multiple aspects of MS pathology. Our findings that some DTI and MTR indices are more strongly linked with disability than conventional MRI measures justifies their potential use as targeted, functional system-specific clinical trial outcomes in MS.
Multiple sclerosis Diffusion tensor imaging Magnetization transfer ratio MRI Disability
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The MRI data was acquired through National MS Society Tissue Repair grant TR3760A3 and through a grant from EMD Serono. Research support was also obtained through NINDS grant K99NS064098 from the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, and NINDS grant R01NS070906.
Conflicts of interest
Dr. Calabresi has received research support and consultation fees from EMD Serono. Otherwise, the authors declare no financial relationships with the supporting entities of this study.
All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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