Sensitive outcome measures are required to test novel therapies designed to target neurodegeneration in Multiple Sclerosis(MS). We have previously shown that functional connectivity using resting-state fMRI (rs-fMRI) and anatomic connectivity using DTI are related in the transcallosal motor pathway and along the memory pathway connecting hippocampus to posterior cingulate. We propose a combined metric incorporating anatomic and functional connectivity along these pathways as a potential biomarker of disease progression in MS. In this study, we present results from a 2 year study that assessed this biomarker in 19 MS patients at six timepoints. We show that our metric is sensitive to changes in MS disease over this time interval. We also show that our metric is more sensitive to change than typically used imaging biomarkers.