Conventional magnetic resonance imaging approaches currently used for the detection of myelin and demyelination, are suboptimal in the quantitative imaging of myelin. Novel MRI approach exploiting RAFF4 was better associated with myelin content during demyelination. For this study 22 rats were used. Of these, demyelinating lesions were induced in 13 rats of LPC. The remaining 9 animals were control. All animals were scanned in MRI system in demyelination stage and remyelination stage. MRI data was collected for quantification of RAFF4, DTI, T1sat and MTR. Histology was performed on all animals and brain sections were Nissl and myelin stained. All MRI metrics showed statistically significant differences between LPC group in the ipsilateral cc and the corresponding area in control animals, in demyelination stage at day 3. At 37 days, RAFF4 and MTR showed clear 70–80 % return towards normal values, likely corresponding to ongoing remyelination seen in histological sections. While similar recovery was detected in DTI metrics FA showed no recovery or even further increase during remyelination phase. was only diffusion parameter which did not show significant different between groups at 37 day. Our data indicates sensitivity of RAFF4 and MT to myelin content both in demyelinated lesions and during subsequent remyelination. DTI metrices seem to provide complementary information related not only myelin content but also architecture of the myelin sheets. Combination of RAFF4 and DTI has potential to differentiate between normal, demyelinated and remyelinated axonal bundles thus providing unique non-invasive characterization of white matter pathologies in various neurological diseases.