title: Identifying the start of multiple sclerosis injury: a serial DTI study.
abstract: BACKGROUND
  The events leading up to the development of new multiple sclerosis (MS) lesions on conventional imaging are unknown. The purpose of this study is to use diffusion tensor imaging (DTI) to investigate prelesional changes in MS to better understand the pathological changes that lead to lesion development.
  
  
  METHODS
  Twenty-one patients with relapsing MS starting natalizumab therapy underwent serial DTI for 12-18 months. Regions of interest were outlined within normal-appearing white matter and new gadolinium-enhancing lesions that developed over the course of the study. Images from all time points were coregistered and nonparametric regression was used to assess DTI changes prior to lesion appearance.
  
  
  RESULTS
  A total of 31 newly enhancing lesions were identified. Significant changes in transverse diffusivity (TD) (P < .001), longitudinal diffusivity (LD) (P = .025), mean diffusivity (MD) (P < .001), and fractional anisotropy (FA) (P = .04) were observed prior to gadolinium enhancement. A progressive increase in TD and LD occurred up to 10 months prior to lesion development. DTI measures in normal appearing white matter remained unchanged over the study period.
  
  
  CONCLUSIONS
  A significant change in diffusion measures can be seen prior to gadolinium enhancement. Changes in TD drove changes in FA and MD, providing evidence for impaired myelin integrity prior to gadolinium enhancement. DTI may be a sensitive measure for early detection of inflammatory disease activity in MS.
authors.affiliation: Mellen Center, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ontaneda
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Ken
authors.initials: K
authors.lastname: Sakaie
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lowe
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Phillips
authors.affiliation: Mellen Center, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D042241:Early Diagnosis; D004660:Encephalitis / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab; D012008:Recurrence; D016896:Treatment Outcome; D066127:White Matter / Q000187:drug effects / Q000473:pathology*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: DTI; MRI; T2 lesions; multiple sclerosis; natalizumab; prelesional