%0 Journal Article
%T 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每Remitting Multiple Sclerosis: A 24-Week, Controlled Pilot Study
%A Robert Zivadinov
%A Michael G. Dwyer
%A Silva Markovic-Plese
%A Cheryl Kennedy
%A Niels Bergsland
%A Deepa P. Ramasamy
%A Jacqueline Durfee
%A David Hojnacki
%A Brooke Hayward
%A Fernando Dangond
%A Bianca Weinstock-Guttman
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0091098
%X 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每remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN 汕-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 汕-1a SC and in 15 HCs (where applicable). VW-MTR changes were tested using the Wilcoxon signed每rank or Wilcoxon rank每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每15278]; 342 [0每951] mm3; p = 0.061). NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6每11577]; 360 [0每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每6141]; 297 [0每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 汕-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. Trial Registration ClinicalTrials.gov NCT01085318.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0091098