Comparative Systematic Analysis of Gray Matter BiophysicalModels on a Public Dataset

Abstract

Biophysical models of diffusion tailored to characterize gray matter (GM) microstructure are gaining traction in the neuroimaging community. NEXI, SMEX, SANDI, and SANDIX represent recent efforts to incorporate different microstructural features,such as soma contributions and inter-compartment exchange, into the diffusion MRI (dMRI) signal. In this work, we present a comparative evaluation of these four gray matter models on a single, publicly available in vivo human dataset, the Connectome Diffusion Microstructure Dataset (CDMD), acquired with two diffusion times. Using the open-source Gray Matter Swiss Knife toolbox, we estimate cortical microstructure metrics in 26 healthy subjects and evaluate goodness of fit, anatomical patterns and consistency with previous studies. CDMD data yielded GM parameter estimates consistent with values reported in previous studies. This retrospective cross-model analysis establishes the feasibility of estimating exchange models from only two diffusion times and highlights trade-offs in biological specificity, model complexity, and fitting robustness, critical considerations when choosing a model for future clinical and research applications.