A novel approach with “skeletonised MTR” measures tract-specific microstructural changes in early primary-progressive MS

Authors

  • Benedetta Bodini,

    Corresponding author
    1. Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, United Kingdom
    • Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. E-mail: b.bodini@ucl.ac.uk

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    • Benedetta Bodini and Mara Cercignani contributed equally to this work.

  • Mara Cercignani,

    Corresponding author
    1. Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy
    2. Clinical Imaging Science Centre, Brighton and Sussex Medical School, Brighton, United Kingdom
    • Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. E-mail: b.bodini@ucl.ac.uk

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  • Ahmed Toosy,

    1. Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, United Kingdom
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  • Nicola De Stefano,

    1. Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy
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  • David H. Miller,

    1. Department of Neuroinflammation, University College London Institute of Neurology, London, United Kingdom
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  • Alan J. Thompson,

    1. Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, United Kingdom
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  • Olga Ciccarelli

    1. Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, United Kingdom
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  • This study was performed at the University College London Institute of Neurology, Queen Square, London, United Kingdom, WC1N 3BG.

Abstract

We combined tract-based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract-specific short-term changes in early primary-progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty-one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co-registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow-up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal-appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract-specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross-subject and tract-specific changes in MTR. Hum Brain Mapp 35:723–733, 2014. © 2013 Wiley Periodicals, Inc.

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