Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis

Authors

  • Guillaume Bonnier,

    1. Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI, Lausanne, Switzerland
    2. Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    3. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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  • Alexis Roche,

    1. Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI, Lausanne, Switzerland
    2. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    3. Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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  • David Romascano,

    1. Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI, Lausanne, Switzerland
    2. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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  • Samanta Simioni,

    1. Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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  • Djalel Meskaldji,

    1. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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  • David Rotzinger,

    1. Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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  • Ying-Chia Lin,

    1. Department of Computer Science, University of Verona, Verona, Italy
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  • Gloria Menegaz,

    1. Department of Computer Science, University of Verona, Verona, Italy
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  • Myriam Schluep,

    1. Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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  • Renaud Du Pasquier,

    1. Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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  • Tilman Johannes Sumpf,

    1. Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany
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  • Jens Frahm,

    1. Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany
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  • Jean-Philippe Thiran,

    1. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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  • Gunnar Krueger,

    1. Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI, Lausanne, Switzerland
    2. Healthcare Sector IM&WS S, Siemens Schweiz AG, Switzerland
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  • Cristina Granziera

    Corresponding author
    1. Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI, Lausanne, Switzerland
    2. Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    3. LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    • Correspondence

      Cristina Granziera, Department of Clinical Neurosciences, Neurology, CHUV, 1011 Lausanne, Switzerland. Tel: +41 79 5565687; Fax: +41 21 3141291; E-mail: cristina.granziera@chuv.ch

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Abstract

Introduction

In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients.

Methods

Brain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates.

Results

Quantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: −4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R2 = 0.4), attention (P = 0.0005, Adj-R2 = 0.6), and disability (P = 0.03, Adj-R2 = 0.4).

Conclusion

Advanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical–radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

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