Disclosures: J. Oh has received personal compensation for consulting or speaking from EMD-Serono, Genzyme, Biogen-Idec, and Novartis; M. Seigo reports no disclosures; S. Saidha has received personal compensation for consulting from Medical Logix for the development of continuing medical education programs, and has received educational grant support from Teva Neurosciences and Novartis; E. Sotirchos reports no disclosures; M. Chen reports no disclosures; J. Prince has received consulting fees and holds stock in Diagnosoft, Inc.; M. Diener-West reports no disclosures; P. A. Calabresi has provided consultation services to Vertex and Abbott and MedImmune, and has received research funding from Biogen-IDEC, Abbott, Vertex, Novartis, and Bayer; D. S. Reich reports no disclosures.
Clinical Investigative Study
Spinal Cord Normalization in Multiple Sclerosis
Article first published online: 5 MAR 2014
Copyright © 2014 by the American Society of Neuroimaging
Journal of Neuroimaging
Volume 24, Issue 6, pages 577–584, November/December 2014
How to Cite
Oh, J., Seigo, M., Saidha, S., Sotirchos, E., Zackowski, K., Chen, M., Prince, J., Diener-West, M., Calabresi, P. A. and Reich, D. S. (2014), Spinal Cord Normalization in Multiple Sclerosis. Journal of Neuroimaging, 24: 577–584. doi: 10.1111/jon.12097
Study Funding: Multiple Sclerosis Society of Canada Decker Family Transitional Career Development Award (to J.O.). National Multiple Sclerosis Society (TR 3760-A-3 to P.A.C.). Intramural Research Program of the National Institute of Neurological Disorders and Stroke (to D.S.R.).
- Issue published online: 27 OCT 2014
- Article first published online: 5 MAR 2014
- Manuscript Accepted: 19 NOV 2013
- Manuscript Revised: 6 OCT 2013
- Manuscript Received: 7 APR 2013
- Multiple sclerosis;
- spinal cord;
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.
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).
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.
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.