Multiple sclerosis (MS) is a brain network disconnection syndrome. Although the brain network topology in MS has been evaluated using diffusion MRI tractography, the mechanism underlying disconnection in the disorder remains unclear. In this study, we evaluated the brain network topology in MS using connectomes with connectivity strengths based on the ratio of the inner to outer myelinated axon diameter (i.e., g-ratio), thereby providing enhanced sensitivity to demyelination compared with the conventional measures of connectivity. We mapped g-ratio-based connectomes in 14 patients with MS and compared them with those of 14 age- and sex-matched healthy controls. For comparison, probabilistic tractography was also used to map connectomes based on the number of streamlines (NOS). We found that g-ratio- and NOS-based connectomes comprised significant connectivity reductions in patients with MS, predominantly in the motor, somatosensory, visual, and limbic regions. However, only the g-ratio-based connectome enabled detection of significant increases in nodal strength in patients with MS. Finally, we found that the g-ratio-weighted nodal strength in motor, visual, and limbic regions significantly correlated with inter-individual variation in measures of disease severity. The g-ratio-based connectome can serve as a sensitive biomarker for diagnosing and monitoring disease progression
