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Article Abstract
Objectives: Quantitative susceptibility mapping (QSM) has been used to classify chronic white matter lesions (WMLs) in multiple sclerosis (MS), which exhibit varying myelin and iron content. Compared to QSM, subvoxel-QSM can further differentiate susceptibility alterations arising from demyelination and iron accumulation. This study aims to evaluate the performance of subvoxel-QSM in classifying chronic WMLs in relapsing-remitting MS (RRMS) and explore their heterogeneity.
Methods: In 57 RRMS patients, WMLs segmented manually were classified into 5 QSM lesion types (isointense, hypointense, hyperintense, lesions with hypointense rim, and paramagnetic rim lesions [PRLs]). Then, visual and quantitative characteristics in subvoxel-QSM (χ and χ) were compared within each subtype. Next, PRLs were classified into two subgroups by hyperintensity presence in χ and compared as above. Meanwhile, the neurite density index (NDI), from the multi-compartment diffusion model, quantified lesional microstructural damage.
Results: A total of 1002 WMLs from 57 RRMS patients underwent QSM classification, demonstrating the following distribution: 119 (11.88%) QSM-isointense, 665 (66.37%) QSM-hyperintense, 17 (1.70%) QSM-hypointense, 3 (0.30%) QSM-hypointense rim, and 198 (19.76%) PRLs. Subvoxel-QSM analysis identified 199 PRLs in χ (195 from QSM-PRL and 4 from QSM-hyperintense), grouped as 130 (65.33%) χ-PRL without myelin and 69 (34.67%) with myelin. The χ-PRL without myelin exhibited significantly lower NDI than those with myelin (P =0.006). In QSM-isointense lesions, 84.03% (100/119) showed χ-isointensity and χ-isointensity, while 15.97% (19/119) exhibited χ-hypointensity and χ-hypointensity. Moreover, the χ-isointense/χ-isointense subgroup exhibited significantly higher χ values (P =0.019). Among QSM-hyperintense lesions, 92.78% (617/665) displayed χ-hyperintensity with χ-hypointensity and 6.62% (44/665) showed χ-isointensity with χ-hypointensity, while 0.60% (4/665) appeared as PRLs in χ. Moreover, the χ-hyperintense/χ-hypointense exhibited significantly lower NDI and χ values (all P <0.01).
Conclusion: Subvoxel-QSM enhances lesion heterogeneity characterization in RRMS, providing complementary biomarkers for myelin integrity beyond conventional QSM, and its detection of repair gradations may help with personalized therapeutic strategies and clinical trial endpoint optimization.
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| http://dx.doi.org/10.1016/j.msard.2025.106698 | DOI Listing |
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