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Tract-specific quantitative MRI better correlates with disability than conventional MRI in multiple sclerosis

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Abstract

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.

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Acknowledgments

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.

Ethical standards

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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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University, 600 North Wolfe Street, Pathology 622A, Baltimore, MD, 21287, USA

    Daniel M. Harrison, Scott D. Newsome, John N. Ratchford, Peter A. Calabresi & Daniel S. Reich

  2. Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore, MD, 21218, USA

    Navid Shiee & Dzung Pham

  3. Radiology and Imaging Sciences, National Institutes of Health, Building 10, Clinical Center, 10 Center Drive, MSC 1074, Bethesda, MD, 20892-1074, USA

    Navid Shiee & Dzung Pham

  4. Department of Radiology and Radiologic Science, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD, 21287, USA

    Navid Shiee & Daniel S. Reich

  5. Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

    Pierre-Louis Bazin

  6. Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation for the Advancement of Military Medicine, 10 Center Dr MSC 1400, Building 10 Rm B1N264B, Bethesda, MD, 20892, USA

    Dzung Pham

  7. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA

    Daniel S. Reich

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  1. Daniel M. Harrison
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  2. Navid Shiee
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  3. Pierre-Louis Bazin
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  4. Scott D. Newsome
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  5. John N. Ratchford
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  7. Peter A. Calabresi
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  8. Daniel S. Reich
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Correspondence to Daniel M. Harrison.

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Harrison, D.M., Shiee, N., Bazin, PL. et al. Tract-specific quantitative MRI better correlates with disability than conventional MRI in multiple sclerosis. J Neurol 260, 397–406 (2013). https://doi.org/10.1007/s00415-012-6638-8

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  • DOI: https://doi.org/10.1007/s00415-012-6638-8

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