Multimodal Quantitative MRI of White and Gray Matter: Associations with Myelin-Related Metrics in the Healthy Adult Brain Using Synthetic MRI and IVIM-DWI

Background/Objectives: Quantitative MRI may support non-invasive characterization of myelin-related tissue properties, but the relative association of synthetic MRI (SyMRI) metrics and IVIM-DWI parameters with myelin-related measures remains unclear. This study investigated associations between SyMRI-derived quantitative measures, IVIM-derived parameters, and myelin-related indices in healthy adult brain tissue. Methods: Twenty-six healthy adults underwent IVIM-DWI and SyMRI. ROI-based quantitative parameters were extracted, including ADC, D, D*, perfusion fraction (f), T1, T2, and proton density (PD). SyMRI-derived myelin-correlated parenchymal fraction (MyCPF) and myelin-correlated volume (MyC) were obtained. ROI-averaged WM–GM differences were assessed using the Wilcoxon signed-rank test, and associations were evaluated using Spearman correlation with false discovery rate correction. Results: IVIM-derived parameters were significantly higher in WM, whereas T1 and PD were significantly higher in GM (all p < 0.001); T2 did not differ significantly (p = 0.901). In WM, PD showed a strong inverse association with MyCPF (ρ = −0.736, p < 0.001, q < 0.001), whereas its association with MyC did not remain significant after correction. In GM, PD showed a moderate inverse association with MyCPF (ρ = −0.532, p = 0.005), but this was not significant after correction (q = 0.073). No IVIM-derived parameter showed significant associations with myelin-related metrics after correction. Conclusions: PD showed the strongest association with MyCPF, particularly in WM, supporting its potential as a non-invasive marker of myelin-related tissue composition. IVIM-derived parameters showed limited relevance for myelin assessment in this healthy cohort.