Imaging G-ratio in multiple sclerosis using high-gradient diffusion MRI and macromolecular tissue volume

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 (b = -40.5, P = .001) and axonal volume fraction (b = -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.