Background Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients which is ‘normal appearing’ on T1-weighted and T2-weighted magnetic resonance images. Objectives With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods Nine relapsing-remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to AC-PC line. Results The MT ratio of regions encompassing the normal appearing white matter (NAWM) was different in MS patients as compared with controls (p=0.043); however the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups (p=0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p=0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical grey matter for any relaxation parameter. Conclusions The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.