title: Effect of treatment with interferon beta-1a on changes in voxel-wise magnetization transfer ratio in normal appearing brain tissue and lesions of patients with relapsing-remitting multiple sclerosis: a 24-week, controlled pilot study.
abstract: BACKGROUND
  This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT) and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR), in patients with relapsing-remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN β-1a SC) three times weekly versus healthy controls (HCs) (NCT01085318).
  
  
  METHODS
  Increasing (suggestive of remyelination) and decreasing (suggestive of demyelination) VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd)-enhancing lesion volume were measured over 24 weeks in 23 patients treated with IFN β-1a SC and in 15 HCs (where applicable). VW-MTR changes were tested using the Wilcoxon signed-rank or Wilcoxon rank-sum test.
  
  
  RESULTS
  A trend for greater volume of NABT with increasing VW-MTR at 24 weeks was observed for patients versus HCs (median [range] 1206 [0-15278]; 342 [0-951] mm3; p = 0.061). NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6-11577]; 360 [0-1755] mm3; p = 0.028). Similar findings were detected for lesion volumes. Two patients with notably high numbers of Gd-enhancing lesions at baseline had a markedly greater volume of tissue with increasing VW-MTR compared with other patients. Volume of NABT tissue with decreasing VW-MTR was significantly greater in patients versus HCs at 24 weeks (942 [0-6141]; 297 [0-852] mm3; p<0.001).
  
  
  CONCLUSIONS
  The significant change in NABT volume with increasing VW-MTR at 12 weeks suggests that active remyelination in patients with RRMS may occur during treatment with IFN β-1a SC. Findings from two patients with the highest number of Gd-enhancing lesions at baseline suggest that extensive remyelination in NABT may occur in patients with high disease activity. Tissue volume with decreasing VW-MTR was greater in patients than in HCs, despite treatment, validating the sensitivity of this technique for detecting MS disease activity.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01085318.
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America; Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dwyer
authors.affiliation: Department of Neurology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Deepa P
authors.initials: DP
authors.lastname: Ramasamy
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Durfee
authors.affiliation: Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Hojnacki
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts, United States of America.
authors.forename: Brooke
authors.initials: B
authors.lastname: Hayward
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts, United States of America.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dangond
authors.affiliation: Department of Neurology, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D009186:Myelin Sheath / Q000378:metabolism; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000068556:Interferon beta-1a