Iron accumulation in the corpus callosum: a quantitative MRI study in relapsing-remitting multiple sclerosis

PURPOSE: This study quantitatively evaluated iron accumulation in the normal-appearing corpus callosum (CC) of multiple sclerosis (MS) patients using multi-parametric magnetic resonance imaging (MRI), including quantitative susceptibility mapping, MTR, T1/T2 mapping, and volumetry, and examined associations with white matter lesions, disease duration (DD), and Expanded Disability Status Scale (EDSS). METHODS: Brain MRI of 58 patients with RRMS (32 females, 26 males; mean age 37 ± 9.07 years; age range 19-58 years) along with 58 age and gender-matched healthy controls (HCs) (27 females, 31 males; mean age 38 ± 8.8 years; age range 19-57 years) were extracted and analyzed. 3D-high resolution T1, T2-FLAIR, and T2* images, along with MTR, T1 and T2 maps were used for volumetric segmentation, WM lesions extraction, iron calculation, MTR, T1 and T2 relaxation times of CC, respectively. RESULTS: RRMS patients exhibited significantly higher iron concentrations across all corpus callosum (CC) regions compared with healthy controls (p < 0.01). Subregional analyses revealed that associations between iron concentration and imaging variables were confined primarily to anterior CC segments, most notably the mid-anterior CC, with no associations observed for disease duration, EDSS, or white matter lesion load. Among MRI metrics, iron achieved the highest discriminative performance (AUC = 0.74; sensitivity 100%, specificity 50%), while volume provided more balanced classification (AUC = 0.66). CONCLUSIONS: Quantitative MRI revealed iron accumulation in the corpus callosum of RRMS patients compared to HCs. Iron was the most sensitive marker for distinguishing patients, supporting its potential as an MS biomarker.