Objectives: 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: 133 individuals with MS and 14 healthy control subjects (HCs) underwent cervical SC-MRI at 3T and clinical assessment, including the expanded disability status scale(EDSS), multiple sclerosis functional composite (MSFC), and quantitative tests of hip-flexion strength(HFS) and vibration sensation threshold (VST). SCV was measured between C3-C4. SCV was normalized by individual factors: height, spinal cord length (SCL - yielding an average measure of cross-sectional area), and intracranial volume(ICV).
Results: There were significant group differences between MS cases and HCs in raw SCV, and SCV normalized by height and SCL (p<0.05). SCV normalized to either height or SCL was greater in relapsing vs. progressive MS subtypes (p<0.05), while raw SCV was not (p=0.32). There were significant correlations between clinical measures and raw SCV(EDSS:ρ=-0.20; MSFC:ρ=0.16; HFS:ρ=0.35, VST:ρ=-0.19, all p<0.05 except MSFC=0.06). Observed clinical-radiological correlations consistently strengthened with normalization by SCL(EDSS:ρ=-0.43; MSFC:ρ=0.33; HFS:ρ=0.38, VST:ρ=-0.40, all p<0.001) and height(EDSS:ρ=-0.26; MSFC:ρ=0.28; HFS:ρ=0.22, VST:ρ=-0.29, all p<0.05), but generally diminished with normalization by ICV(EDSS:ρ=-0.23,p=0.01; MSFC:ρ=-0.10;p=0.24; HFS:ρ=0.23,p=0.01; VST:ρ=-0.35,p<0.01). In relapsing patients, normalization by SCL allowed the detection of clinical-radiological correlations that were not apparent with raw SCV.
Conclusions: SCV normalization by SCL consistently improves the ability to detect group differences, strengthens clinical-radiological correlations, and seems to be of particular relevance in settings of subtle disease-related SC atrophy in MS. Normalization by SCL should be performed to maximize the clinical utility of measures of SC atrophy.