Imaging G-Ratio in Multiple Sclerosis Using High-Gradient Diffusion MRI and Macromolecular Tissue Volume

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Abstract
BACKGROUND AND PURPOSE: Remyelination represents an area of great therapeutic interest in multiple sclerosis but currently lacks a robust imaging marker. The purpose of this study was to use high-gradient diffusion MRI and macromolecular tissue volume imaging to obtain estimates of axonal volume fraction, myelin volume fraction, and the imaging g-ratio in patients with MS and healthy controls and to explore their relationship to neurologic disability in MS. MATERIALS AND METHODS: Thirty individuals with MS (23 relapsing-remitting MS, 7 progressive MS) and 19 age-matched healthy controls were scanned on a 3T MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Macromolecular tissue volume imaging was performed to quantify the myelin volume fraction. Diffusion data were fitted to a 3-compartment model of white matter using a spheric mean approach to yield estimates of axonal volume fraction. The imaging g-ratio was calculated from the ratio of myelin volume fraction and axonal volume fraction. Imaging metrics were compared between groups using 2-sided t tests with a Bonferroni correction. RESULTS: The mean g-ratio was significantly elevated in lesions compared with normal-appearing WM (0.74 vs 0.67, P < .001). Axonal volume fraction (0.17 vs 0.23, P < .001) and myelin volume fraction (0.17 vs 0.25, P < .001) were significantly lower in lesions than normal-appearing WM. Myelin volume fraction was lower in normal-appearing WM compared with that in healthy controls (0.25 vs 0.27, P = .009). Disability, as measured by the Expanded Disability Status Scale, was significantly associated with myelin volume fraction (β = –40.5, P = .001) and axonal volume fraction (β = –41.0, P = .016) in normal-appearing WM. CONCLUSIONS: The imaging g-ratio may serve as a biomarker for the relative degree of axonal and myelin loss in MS.
Funding Information
  • National Institute of Biomedical Imaging and Bioengineering (R00EB015445)
  • Conrad N. Hilton Foundation
  • National Institute of Neurological Disorders and Stroke (K23NS078044, K23NS096056)
  • RSNA Research and Education Foundation (RSNA Resident Research Grant)
  • Altschul Foundation
  • American Heart Association Postdoctoral Fellowship
  • National Multiple Sclerosis Society (PR-1412-02194)

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