Abstract
BACKGROUND: The deep gray matter (DGM), especially the pulvinar, and the white matter surrounding chronic active lesions have demonstrated depleted iron levels, indicating a possible mechanistic link. However, no studies have investigated the potential relationship between these phenomena. OBJECTIVES: The study aimed to determine whether PRLs were associated with pulvinar iron depletion and, if so, whether this relationship was spatially mediated. METHODS: This retrospective analysis included 139 people with MS (pwMS) and 43 healthy controls (HCs) scanned at 3T MRI at baseline and after 5.4 ± 0.6 years. Pulvinar iron concentrations (cFe) and iron masses (mFe) were estimated from quantitative susceptibility maps and tested for associations with PRLs. A separate cohort of 96 pwMS with PRLs and propensity-matched HCs was included to evaluate peri‑plaque normal-appearing white matter (NAWM) abnormalities. RESULTS: PRL number was associated with greater decline in pulvinar cFe (β = -0.265, p = 0.005) and mFe (β = -0.256, p = 0.006). Peri-plaque NAWM susceptibility was increased 11 mm surrounding PRLs, outside which shorter PRL-to-pulvinar distance was associated with greater decline in pulvinar cFe (β = 0.380, p = 0.005) and mFe (β = 0.348, p = 0.022). CONCLUSIONS: Our findings support a spatially-mediated relationship between PRLs and chronic pulvinar iron depletion.