Spinal Cord Normalization in Multiple Sclerosis

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.