Background:Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that 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 the 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 gray 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.