title: Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis.
abstract: BACKGROUND
  Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([11C]PiB) can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS.
  
  
  METHODS
  Patients with active relapsing-remitting MS (n = 20) and healthy controls (n = 8) were included in a longitudinal trial combining PET with [11C]PiB and magnetic resonance imaging. Voxel-wise maps of [11C]PiB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination.
  
  
  RESULTS
  At baseline, there was a progressive reduction in [11C]PiB binding from the normal-appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow-up, high between-patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p = 0.006 and beta-coefficient = -0.67 with the Expanded Disability Status Scale; p = 0.003 and beta-coefficient = -0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index.
  
  
  CONCLUSIONS
  [11C]PiB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. Ann Neurol 2016;79:726-738.
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.|Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.|Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Lorenzo
authors.affiliation: Department of Behavioral and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglini
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Poirion
authors.affiliation: Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.|APHP Hôpital Saint-Antoine, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Chardain
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.|Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.|APHP, Hopital Pitié-Salpetrière, Paris, France.
authors.forename: Léorah
authors.initials: L
authors.lastname: Freeman
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Louapre
authors.affiliation: APHP, Hopital Pitié-Salpetrière, Paris, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Tchikviladze
authors.affiliation: APHP, Hopital Pitié-Salpetrière, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papeix
authors.affiliation: Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.|APHP, Hopital Pitié-Salpetrière, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.affiliation: Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Turkheimer
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR S 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France.|Service Hospitalier Fréderic Joliot, SHFJ, I2BM-DSV, CEA, Orsay, France.|APHP Hôpital Saint-Antoine, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff