title: Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis.
abstract: BACKGROUND
  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-R (2) = 0.4), attention (P = 0.0005, Adj-R (2) = 0.6), and disability (P = 0.03, Adj-R (2) = 0.4).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI Lausanne, Switzerland ; Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland ; LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bonnier
authors.affiliation: Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI Lausanne, Switzerland ; LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland ; Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.
authors.forename: Alexis
authors.initials: A
authors.lastname: Roche
authors.affiliation: Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI Lausanne, Switzerland ; LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Romascano
authors.affiliation: Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.
authors.forename: Samanta
authors.initials: S
authors.lastname: Simioni
authors.affiliation: LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Djalel
authors.initials: D
authors.lastname: Meskaldji
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Rotzinger
authors.affiliation: Department of Computer Science, University of Verona Verona, Italy.
authors.forename: Ying-Chia
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Computer Science, University of Verona Verona, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Menegaz
authors.affiliation: Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.affiliation: Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.
authors.forename: Renaud
authors.initials: R
authors.lastname: Du Pasquier
authors.affiliation: Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry Goettingen, Germany.
authors.forename: Tilman Johannes
authors.initials: TJ
authors.lastname: Sumpf
authors.affiliation: Biomedizinische NMR Forschungs GmbH, Max Planck Institute for Biophysical Chemistry Goettingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.affiliation: LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Thiran
authors.affiliation: Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI Lausanne, Switzerland ; Healthcare Sector IM&WS S, Siemens Schweiz AG Renens, Switzerland.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Krueger
authors.affiliation: Advanced Clinical Imaging Technology group, Siemens Healthcare IM BM PI Lausanne, Switzerland ; Neuro-immunology and Laboratoire de recherché en neuroimagérie, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland ; LTS5, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Granziera