title: Spinal cord normalization in multiple sclerosis.
abstract: BACKGROUND
  Spinal cord (SC) pathology is common in multiple sclerosis (MS), and measures of SC-atrophy are increasingly utilized. Normalization reduces biological variation of structural measurements unrelated to disease, but optimal parameters for SC volume (SCV)-normalization remain unclear. Using a variety of normalization factors and clinical measures, we assessed the effect of SCV normalization on detecting group differences and clarifying clinical-radiological correlations in MS.
  
  
  METHODS
  3T cervical SC-MRI was performed in 133 MS cases and 11 healthy controls (HC). Clinical assessment included expanded disability status scale (EDSS), MS functional composite (MSFC), quantitative hip-flexion strength ("strength"), and vibration sensation threshold ("vibration"). SCV between C3 and C4 was measured and normalized individually by subject height, SC-length, and intracranial volume (ICV).
  
  
  RESULTS
  There were group differences in raw-SCV and after normalization by height and length (MS vs. HC; progressive vs. relapsing MS-subtypes, P < .05). There were correlations between clinical measures and raw-SCV (EDSS:r = -.20; MSFC:r = .16; strength:r = .35; vibration:r = -.19). Correlations consistently strengthened with normalization by length (EDSS:r = -.43; MSFC:r = .33; strength:r = .38; vibration:r = -.40), and height (EDSS:r = -.26; MSFC:r = .28; strength:r = .22; vibration:r = -.29), but diminished with normalization by ICV (EDSS:r = -.23; MSFC:r = -.10; strength:r = .23; vibration:r = -.35). In relapsing MS, normalization by length allowed statistical detection of correlations that were not apparent with raw-SCV.
  
  
  CONCLUSIONS
  SCV-normalization by length improves the ability to detect group differences, strengthens clinical-radiological correlations, and is particularly relevant in settings of subtle disease-related SC-atrophy in MS. SCV-normalization by length may enhance the clinical utility of measures of SC-atrophy.
authors.affiliation: Department of Neurology, Johns Hopkins University.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Neurology, Johns Hopkins University.
authors.forename: Michaela
authors.initials: M
authors.lastname: Seigo
authors.affiliation: Department of Neurology, Johns Hopkins University.
authors.forename: Shiv
authors.initials: S
authors.lastname: Saidha
authors.affiliation: Department of Neurology, Johns Hopkins University.
authors.forename: Elias
authors.initials: E
authors.lastname: Sotirchos
authors.affiliation: Department of Physical Medicine and Rehabilitation, Johns Hopkins University.|Motion Analysis Laboratory, Kennedy Krieger Institute.
authors.forename: Kathy
authors.initials: K
authors.lastname: Zackowski
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University.|Department of Computer Science, Johns Hopkins University.
authors.forename: Jerry
authors.initials: J
authors.lastname: Prince
authors.affiliation: Department of Biostatistics, Johns Hopkins University.
authors.forename: Marie
authors.initials: M
authors.lastname: Diener-West
authors.affiliation: Department of Neurology, Johns Hopkins University.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.affiliation: Department of Neurology, Johns Hopkins University.|Department of Biostatistics, Johns Hopkins University.|Department of Radiology and Radiological Science, Johns Hopkins University.|Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000592:standards*; D008279:Magnetic Resonance Imaging / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000473:pathology*
keywords: MRI; Multiple sclerosis; atrophy; normalization; spinal cord