Magnetic susceptibility and MR frequency shifts in MS lesions are sensitive measures of tissue damage. However, the sensitivity of FS and QSM to magnetic susceptibility effects as well as changes in tissue microarchitecture complicate data interpretation in biological systems. By contrasting QSM and resonance frequency shift maps these two mechanisms may be differentiated. We observed that the signal shifts at enhancement are reflective of microstructural changes indicating formation of myelin debris, as similar FS and QSM changes were observed. Signal reductions in MS lesions 5yrs-post-enhancement however are only present on QSM, suggesting removal of myelin debris and axonal loss as the underlying mechanisms.