Axonal loss, a crucial pathological process in multiple sclerosis (MS), can be disentangled non-invasively by the CHARMED diffusion model. 8 early MS subjects were scanned at baseline and after 1 year follow-up. At follow-up, TBSS analysis showed statistically significant changes (decrease in FR/FA, increase in MD) compared to baseline in widespread brain regions. The most extensive change was evident in FR, which also showed the greatest sensitivity, especially in areas of fiber-crossing. FR was the only index which detected longitudinal change in axonal density in lesions and therefore holds promise as a biomarker for early diagnosis and disease-monitoring purposes.