Exploring the contribution of gray matter microstructure to R1 contrast via multi-compartment diffusion modelling in the healthy brain

• We investigated the relationship between SANDI diffusion metrics and R1=1/T1. • Soma-related metrics correlated negatively with R1 in grey matter. • Intra-neurite metrics correlated positively with R1 in white matter. • SANDI metrics are sensitive to regional myelin-dependent microstructural features. • R1 mapping combined with SANDI modelling enhances brain tissue architecture. The Soma And Neurite Density Imaging (SANDI) model enhances MRI-derived water diffusion metrics sensitivity to gray matter (GM) microstructural complexity. We investigated the hypothesis that the diffusion metrics derived from the SANDI three-compartment model contributed to the longitudinal relaxation rate R1(=1/T1) contrast in brain tissue. To this aim, twenty healthy volunteers underwent diffusion-weighted imaging and R1 mapping via MP2RAGE at 3 T. The diffusion metrics included intra-neurite signal fraction (fneurite), intra-soma signal fraction (fsoma), extra-neurite fraction (fextra), soma radii (Rsoma), and intra-neurite and extra-neurite diffusivities (D in and D e ). In GM, a moderate negative spatial correlation was observed between R1 and soma-related metrics (fsoma and Rsoma, with r = -0.47, -0.35, respectively), indicating that GM microstructure contributes to R1 contrast. These findings align with evidence suggesting structural heterogeneity in the cortex, where a different degree of cortical myelination modulates neuroplasticity. Notably, similar effects and trends were identified when evaluating across subjects’ correlations of the metrics of interest (fsoma and Rsoma, with r = -0.56, -0.48, respectively). In WM, moderate to strong positive spatial correlations were observed between R1 and intra-neurite metrics (D in and fneurite, with r = 0.53, 0.30, respectively), where myelinated axons host the pool of intra-neurite water. These results suggest that WM and GM microstructural characteristics contribute to the R1 contrast, where R1 depends, among other factors, to the degree of myelination within brain tissues, thus contributing to the understanding of the emerging relaxation differences across the brain parenchyma. Future research should explore these relationships in clinical populations with demyelination and neurodegeneration.