Comparison between R2'-based and R2*-based χ-separation methods: A clinical evaluation in individuals with multiple sclerosis.

Susceptibility source separation, or χ-separation, estimates diamagnetic (χ) and paramagnetic susceptibility (χ) signals in the brain using local field and R2' (= R2* - R2) maps. Recently proposed R2*-based χ-separation methods allow for χ-separation using only multi-echo gradient echo (ME-GRE) data, eliminating the need for additional data acquisition for R2 mapping. Although this approach reduces scan time and enhances clinical utility, the impact of missing R2 information remains a subject of exploration. In this study, we evaluate the viability of two previously proposed R2*-based χ-separation methods as alternatives to their R2'-based counterparts: model-based R2*-χ-separation versus χ-separation and deep learning-based χ-sepnet-R2* versus χ-sepnet-R2'. Their performances are assessed in individuals with multiple sclerosis (MS), comparing them with their corresponding R2'-based counterparts (i.e., R2*-χ-separation vs. χ-separation and χ-sepnet-R2* vs. χ-sepnet-R2'). The evaluations encompass qualitative visual assessments by experienced neuroradiologists and quantitative analyses, including region of interest analyses and linear regression analyses. Qualitatively, R2*-χ-separation tends to report higher χ and χ values compared with χ-separation, leading to less distinct lesion contrasts, while χ-sepnet-R2* closely aligns with χ-sepnet-R2'. Quantitative analysis reveals a robust correlation between both R2*-based methods and their R2'-based counterparts (r ≥ 0.88). Specifically, in the whole-brain voxels, χ-sepnet-R2* exhibits higher correlation and better linearity than R2*-χ-separation (χ/χ from R2*-χ-separation: r = 0.88/0.90, slope = 0.79/0.86; χ/χ from χ-sepnet-R2*: r = 0.90/0.92, slope = 0.99/0.97). In MS lesions, both R2*-based methods display comparable correlation and linearity (χ/χ from R2*-χ-separation: r = 0.90/0.91, slope = 0.98/0.91; χ/χ from χ-sepnet-R2*: r = 0.88/0.88, slope = 0.91/0.95). Notably, χ-sepnet-R2* demonstrates negligible offsets, whereas R2*-χ-separation exhibits relatively large offsets (0.02 ppm in the whole brain and 0.01 ppm in the MS lesions), potentially indicating the false presence of myelin or iron in MS lesions. Overall, both R2*-based χ-separation methods demonstrated their viability as alternatives to their R2'-based counterparts. χ-sepnet-R2* showed better alignment with its R2'-based counterpart with minimal susceptibility offsets, compared with R2*-χ-separation that reported higher χ and χ values compared with R2'-based χ-separation.