Quantitative MRI would be beneficial in evaluating tissue damage in Multiple Sclerosis (MS), but existing quantitative techniques are not yet widely used. Recently developed SMART MRI technique generates quantitative magnetization transfer and MR relaxometry data from a single protocol. Herein we present data suggesting that the SMART metrics can serve as biomarkers for MS tissue damage. Our results showed that SMART metrics readily distinguish RRMS from progressive MS subtypes, and correlate with clinical assessments of MS patients. These data suggest that SMART MRI is a highly promising technique for MS monitoring, and for use as an endpoint in clinical trials.