A pilot study on protocol consistency and graph metric reproducibility in microstructure-weighted connectomes

Microstructure-weighted connectomes incorporate diffusion parameters into structural networks, offering a rich characterisation of brain connectivity. While these biologically-informed connectomes have shown sensitivity to pathology-related alterations (for example in multiple sclerosis), their reproducibility remains largely unexplored. In this study, we evaluated the consistency of connectomes weighted with tensor and Bingham-NODDI parameters, employing a four-shell acquisition protocol to ensure accurate fibre reconstruction. Phantom and in vivo (N=4) data were acquired to assess temporal, inter-site and inter-protocol reproducibility of weighting parameters and inter-site stability of graph metrics. High reproducibility was observed for fractional anisotropy (FA), mean diffusivity (MD), and intra-neurite (INVF) and intra-cellular (ICVF) volume fractions, with coefficients of variation (CVs) below 5% and negligible Bland-Altman biases. Orientation dispersion index and β concentration parameter showed CVs above 5% and were excluded from connectome construction. Graph metrics extracted from FA-, MD- and INVF-weighted connectomes exhibited good consistency, except for modularity. Extra-cellular volume fraction (ECVF)-weighted connectomes showed poor reproducibility (CV>5%, intraclass correlation coefficient