Current therapies for multiple sclerosis (MS) inhibit the inflammatory response, but neither sufficiently inhibits ongoing degeneration within the brain nor provide potential repair to injured brain tissue. Consequently, there are no therapies with demonstrated efficacy in slowing, stopping, or reversing the progressive stage of MS, therefore representing an extreme unmet need in neurologic disease. Complicating matters, there are no biological or imaging markers with demonstrated utility for use in Phase 2 trials to screen putative therapies for progressive MS. This study proposes to both test the activity of a potential neuroprotection therapy - ibudilast - in progressive MS and test several candidate imaging measures for their utility in future studies of neuroprotection in progressive MS. We plan to conduct a 2-year; placebo-controlled trial of ibudilast in progressive MS. Multiple advanced imaging modalities will be used to evaluate the activity of ibudilast. At the conclusion of the tril, we will have a clear understanding of the effect of ibudilast on advanced imaging metrics and its safety and potential clinical benefit in progressive MS. Through additional analyses, we will determine which imaging metric provides the most robust and practical outcome for implementation in future clinical trials in progressive MS. Hopefully, this study will show efficac of ibudilast that leads to the first primary neuroprotective drug. Even if ibudilast is not found beneficial, the study will be crucial to the MS field by comparing imaging metrics to support practical Phase II trials for a group of MS patients for whom there is no treatment option.