Metabolic Insights into Iron Deposition in Relapsing-Remitting Multiple Sclerosis via 7T Magnetic Resonance Spectroscopic Imaging

Abstract

Objective To investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis(MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesions in vivo according to iron deposition. Methods 7T MR spectroscopic imaging and susceptibility-weighted-imaging was performed in 31 RRMS patients(16female/15male;mean age,36.9+-10.3years). Mean metabolic ratio were calculated for regions of interest(ROI) of normal appearing white matter(NAWM), 'non-iron', and three distinct types of iron-laden lesions, and for lesion layers of 'non-iron' and 'rim' lesions. Furthermore, newly emerging 'non-iron' and 'iron' lesions were compared longitudinally. Results 52% of iron-containing lesions showed no distinct paramagnetic rim. Of these, 'area' lesions exhibited a 65% higher mIns/tNAA(p=0.035) than 'rim' lesions. Comparing lesion layers of both 'non-iron' and 'rim' lesions, a steeper metabolic gradient of mIns/tNAA('non-iron'+15%,'iron'+40%) and tNAA/tCr('non-iron'-15%,'iron'-35%) was found in 'iron' lesions, with the lesion core showing +22% higher mIns/tNAA(p=0.005) and -23% lower tNAA/tCr(p=0.048) in 'iron' compared to 'non-iron' lesions. In newly emerging lesions, 46% showed iron accumulation, with the drop in tNAA/tCr after lesion formation remaining significantly lower compared to pre-lesional tissue over time in 'iron' lesions(year0:p=0.013,year1:p=0.041) as opposed to 'non-iron' lesions(year0:p=0.022,year1:p=0.231). Conclusion 7T MRSI allows in vivo characterization of different iron accumulation types showing metabolic differences. Furthermore, the larger extent of neuronal damage in lesions with a distinct iron rim was reconfirmed, but with metabolic differences in lesion development between (non)-iron-containing lesions. This highlights the ability of MRSI to further investigate different types of iron accumulation and suggests possible implications for disease monitoring. Clinical relevance statement: The clinical importance of differentiating various types of iron accumulation in MS lesions was shown, as contrasting metabolic profiles are likely associated with different levels of tissue damage.