Advanced quantitative MRI reveals a unique pattern of metabolic alterations and iron-pathology linked to glial...

Baló's concentric sclerosis (BCS) is a rare demyelinating disorder with concentric ring lesions on MRI, which can mimic tumefactive demyelinating lesions (TDL), especially present in tumefactive multiple sclerosis (TMS). Recent neuropathological studies suggest the involvement of activated microglia and astrocytes in BCS lesion expansion. However, advanced imaging techniques like Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have not been fully utilized to differentiate BCS from other TDL or explore their metabolic differences.

We retrospectively analyzed MRI data from 12 BCS patients (mean age 29.6 years, 50 % male) and 16 patients with TDL (mean age 30.9 years, 37.5 % male). MRS and QSM data were stratified into acute/subacute and chronic phases. Long echo-time acquisitions (TE =144 ms) were used for metabolite ratio analysis, while short echo-time (TE =35 ms) allowed absolute quantification of 34 metabolites. Lesion, peri-lesional, and normal-appearing white matter (NAWM) regions were compared. Patients tested positive for MOG or AQP4 were excluded.

In long echo-time MRS, BCS lesions demonstrated lower Cho/Cr (p = 0.0029) and Cho/NAA (p = 0.019) ratios compared to TDL, indicating greater axonal preservation and lower cellular turnover in BCS. When compared to their respective NAWM, BCS lesions exhibited significantly reduced NAA/Cr (p = 0.001) and TDL reduced NAA/Cr (p = 0.002), Cho/Cr (p = 0.001), and increased Cho/NAA (p < 0.0001). Absolute quantification showed increased myo-inositol in BCS lesions, while TDL showed increased glutamate metabolism. Layer-wise QSM analysis revealed a centrifugal gradient in BCS lesions, with the core exhibiting the highest susceptibility.

BCS presents distinct metabolic and structural features compared to TDL, with biomarkers such as lower Cho/Cr ratios, elevated myo-inositol, and centrifugal QSM gradients, which may enhance diagnostic accuracy and provide insight into lesion expansion.