title: Profilometry: A new statistical framework for the characterization of white matter pathways, with application to multiple sclerosis.
abstract: OBJECTIVE
  describe a new "profilometry" framework for the multimetric analysis of white matter tracts, and demonstrate its application to multiple sclerosis (MS) with radial diffusivity (RD) and myelin water fraction (MWF).
  
  
  METHODS
  A cohort of 15 normal controls (NC) and 141 MS patients were imaged with T1, T2 FLAIR, T2 relaxometry and diffusion MRI (dMRI) sequences. T1 and T2 FLAIR allowed for the identification of patients having lesion(s) on the tracts studied, with a special focus on the forceps minor. T2 relaxometry provided MWF maps, while dMRI data yielded RD maps and the tractography required to compute MWF and RD tract profiles. The statistical framework combined a multivariate analysis of covariance (MANCOVA) and a linear discriminant analysis (LDA) both accounting for age and gender, with multiple comparison corrections.
  
  
  RESULTS
  In the single-case case study the profilometry visualization showed a clear departure of MWF and RD from the NC normative data at the lesion location(s). Group comparison from MANCOVA demonstrated significant differences at lesion locations, and a significant age effect in several tracts. The follow-up LDA analysis suggested MWF better discriminates groups than RD.
  
  
  CONCLUSIONS
  While progress has been made in both tract-profiling and metrics for white matter characterization, no single framework for a joint analysis of multimodality tract profiles accounting for age and gender is known to exist. The profilometry analysis and visualization appears to be a promising method to compare groups using a single score from MANCOVA while assessing the contribution of each metric with LDA.
authors.affiliation: Weill Cornell Medicine, Deparment of Radiology, New York, NY.
authors.forename: Michael
authors.initials: M
authors.lastname: Dayan
authors.affiliation: Weill Cornell Medicine, Deparment of Neurology, New York, NY.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Monohan
authors.affiliation: Weill Cornell Medicine, Deparment of Radiology, New York, NY.
authors.forename: Sneha
authors.initials: S
authors.lastname: Pandya
authors.affiliation: Weill Cornell Medicine, Deparment of Radiology, New York, NY.|Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY.
authors.forename: Amy
authors.initials: A
authors.lastname: Kuceyeski
authors.affiliation: Weill Cornell Medicine, Deparment of Radiology, New York, NY.
authors.forename: Thanh D
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Weill Cornell Medicine, Deparment of Radiology, New York, NY.|Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY.
authors.forename: Ashish
authors.initials: A
authors.lastname: Raj
authors.affiliation: Weill Cornell Medicine, Deparment of Neurology, New York, NY.|Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Gauthier
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D016002:Discriminant Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D009103:Multiple Sclerosis / Q000473:pathology*; D015999:Multivariate Analysis; D009434:Neural Pathways / Q000473:pathology; D012727:Sex Characteristics; D066127:White Matter / Q000473:pathology*
keywords: LDA; MANCOVA; diffusion MRI; multiple sclerosis; myelin water fraction; profilometry; tractography