title: Multicontrast connectometry: a new tool to assess cerebellum alterations in early relapsing-remitting multiple sclerosis.
abstract: BACKGROUND
  Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS.
  
  
  METHODS
  We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores.
  
  
  RESULTS
  In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage.
  
  
  CONCLUSIONS
  Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage.
authors.affiliation: Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI & Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne (CHUV), Lausanne, Switzerland; Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Romascano
authors.forename: Djalel-Eddine
authors.initials: DE
authors.lastname: Meskaldji
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bonnier
authors.forename: Samanta
authors.initials: S
authors.lastname: Simioni
authors.forename: David
authors.initials: D
authors.lastname: Rotzinger
authors.forename: Ying-Chia
authors.initials: YC
authors.lastname: Lin
authors.forename: Gloria
authors.initials: G
authors.lastname: Menegaz
authors.forename: Alexis
authors.initials: A
authors.lastname: Roche
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.forename: Renaud Du
authors.initials: RD
authors.lastname: Pasquier
authors.forename: Jonas
authors.initials: J
authors.lastname: Richiardi
authors.forename: Dimitri
authors.initials: D
authors.lastname: Van De Ville
authors.forename: Alessandro
authors.initials: A
authors.lastname: Daducci
authors.forename: Tilman
authors.initials: T
authors.lastname: Sumpf
authors.forename: Jens
authors.initials: J
authors.lastname: Fraham
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Thiran
authors.forename: Gunnar
authors.initials: G
authors.lastname: Krueger
authors.forename: Cristina
authors.initials: C
authors.lastname: Granziera
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D012146:Rest
keywords: connectometry; diffusion MRI; multicontrast; multiple sclerosis; resting-state MRI