MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing-Remitting Multiple Sclerosis

Background: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. Purpose: To apply susceptibility separation (chi separation) to follow lesion evolution in MS with comparison to R-2*/R-2(')/QSM. Study Type: Longitudinal, prospective. Subjects: Twenty relapsing-remitting MS subjects (mean age: 42.5 +/- 9.4 years, 13 females; mean years of symptoms: 4.3 +/- 1.4 years). Field Strength/Sequence: Three-dimensional multiple echo gradient echo (QSM and R-2* mapping), two-dimensional dual echo fast spin echo (R-2 mapping), T-2-weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T. Assessment: Data were analyzed from two scans separated by a mean interval of 14.4 +/- 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R-2* or separated into positive/negative components from chi separation. Statistical Tests: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between chi separation and R-2*/R-2(')/QSM. Significant level: P < 0.005. Results: A total of 183 lesions were quantified. Categorizing lesions into groups based on chi separation demonstrated significant annual changes in QSM//R-2*/R-2('). When lesions were grouped based on changes in QSM and R-2*, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and chi separation. Data Conclusion: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R-2* and QSM alone.