Comparison of iron and myelin changes in U‑fiber regions of relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders.

OBJECTIVE: To explore iron and myelin changes in U-fiber regions of relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorders (NMOSD) by susceptibility separation imaging, and to evaluate the clinical relevance of these changes. METHODS: This study included 119 RRMS patients, 47 NMOSD patients, and 93 healthy controls (HC). The U-fiber region was defined as the white matter within 4 mm beneath the gray-white matter boundary. Susceptibility separation imaging was reconstructed from 3D multi-echo gradient echo data, and total susceptibility, positive susceptibility (χpos) and negative susceptibility (χneg) were extracted from each U-fiber subregion. General linear models were performed to compare these metrics among the three groups. Partial correlation analyses were conducted to explore the associations between susceptibility metrics and clinical characteristics. RESULTS: Compared with HC, RRMS patients showed significantly decreased χpos in multiple temporal and limbic U-fiber regions, and significantly increased χneg in widespread U-fiber subregions. However, no significant differences in susceptibility metrics were observed between NMOSD patients and HC in any U-fiber subregion. Notably, after adjusting for potential confounding effects of disease severity and lesion burden, there were no significant differences in susceptibility metrics between RRMS and NMOSD patients. In RRMS patients, χneg in U-fiber subregions was significantly correlated with Expanded Disability Status Scale, particularly in the left superior frontal region. CONCLUSION: Susceptibility separation imaging provided surrogate markers suggestive of iron loss and demyelination in the U-fiber region of RRMS patients. These metrics were closely associated with lesion burden and may hold promise as imaging correlates of clinical disability.