Spinal Cord Normalization in Multiple Sclerosis

Jiwon Oh, Michaela Seigo, Shiv Saidha, Elias Sotirchos, Kathy Zackowski, Min Chen, Jerry Prince, Marie Diener-West, Peter A. Calabresi, Daniel S. Reich

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalJournal of Neuroimaging
Issue number6
StatePublished - Nov 1 2014


  • Atrophy
  • MRI
  • Multiple sclerosis
  • Normalization
  • Spinal cord

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology


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