{
  "abstract": "Background Slowly expanding lesions (SELs) in multiple sclerosis (MS) are markers of chronic active lesions and seem to trigger disability. This study aimed to analyse spatial features of SELs through diffusion MRI and their clinical impact on progression independent of relapse activity (PIRA).Methods An observational study of MS subjects prospectively followed since 2011; inclusion required at least three longitudinal T1/T2-weighted and diffusion-weighted MRIs. Subjects followed clinical assessments, using Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale. At MRI, lesions were categorised using non-linear deformation as definite or possible SELs, and non-SELs. Fractional anisotropy (FA) was extracted from each lesion core and perilesional area. Differences in FA values across core and perilesional areas by SEL category were assessed using the Mann-Whitney test. Associations with PIRA and clinical outcomes were evaluated using mixed-effects, logistic and Cox regression models.Results 130 subjects underwent MRI (median 25 months) and clinical assessments (median follow-up 9.2 years), of which 29 (22%) developed PIRA. Of 4811 lesions, 8% were definite SELs. Definite SELs exhibited FA decline over time in core and perilesional areas compared with other lesions. Longitudinal core FA reductions within definite SELs were associated with worse MSFC z-score evolution (β=0.03, 95% CI 0.01 to 0.05, p=0.003), higher odds for PIRA (OR=0.01, 95% CI 0.01 to 0.12, p=0.001) and predicted faster time to reach first PIRA event (HR=0.03, 95% CI 0 to 0.49, p=0.015).Conclusions Definite SELs show distinct greater microstructural damage and are associated with PIRA, making their FA signature a potential predictor of MS progression.",
  "authors": [
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Alberto Calvi"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Francesc Vivó Pascual"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Elisabeth Solana"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Elisabet Lopez-Soley"
    },
    {
      "affiliations": [
        "Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK",
        "Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK",
        "National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre, London, UK"
      ],
      "name": "Baris Kanber"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Salut Alba-Arbalat"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Maria Sepulveda"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Eugenia Martínez-Hernández"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "José Maria Cabrera-Maqueda"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Elianet Fonseca"
    },
    {
      "affiliations": [
        "Neuroradiology Department, Centre de Diagnòstic per la Imatge (CDI), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Santiago Medrano-Martorell"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Albert Saiz"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Yolanda Blanco"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital del Mar, Pompeu Fabra University, Barcelona, Spain"
      ],
      "name": "Pablo Villoslada"
    },
    {
      "affiliations": [
        "Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK",
        "National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre, London, UK",
        "e-Health Centre, Universitat Oberta de Catalunya, Barcelona, Spain"
      ],
      "name": "Ferran Prados Carrasco"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Eloy Martinez-Heras"
    },
    {
      "affiliations": [
        "Neuroimmunology and Multiple Sclerosis Unit and Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain"
      ],
      "name": "Sara Llufriu"
    }
  ],
  "title": "Diffusivity anisotropy signature of slowly expanding lesions predicts progression independent of relapse activity in multiple sclerosis",
  "uid": "01b3f762-36bc-5283-af0e-1801b963ee26"
}