Improving the Reliability of Network Metrics in Structural Brain Networks by Integrating Different Network Weighting Strategies into a Single Graph

Structural brain networks estimated from diffusion MRI (dMRI) via tractography have been widely studied in healthy controls and patients with neurological and psychiatric diseases. However, few studies have addressed the reliability of derived network metrics both node-specific and network-wide. Different network weighting strategies (NWS) can be adopted to weight the strength of connection between two nodes yielding structural brain networks that are almost fully-weighted. Here, we scanned five healthy participants five times each, using a diffusion-weighted MRI protocol and computed edges between 90 regions of interest (ROI) from the Automated Anatomical Labeling (AAL) template. The edges were weighted according to nine different methods. We propose a linear combination of these nine NWS into a single graph using an appropriate diffusion distance metric. We refer to the resulting weighted graph as an Integrated Weighted Structural Brain Network (ISWBN). Additionally, we consider a topological filtering scheme that maximizes the information flow in the brain network under the constraint of the overall cost of the surviving connections. We compared each of the nine NWS and the ISWBN based on the improvement of: (a) intra-class correlation coefficient (ICC) of well-known network metrics, both node-wise and per network level; and (b) the recognition accuracy of each subject compared to the remainder of the cohort, as an attempt to access the uniqueness of the structural brain network for each subject, after first applying our proposed topological filtering scheme. Based on a threshold where the network level ICC should be >0.90, our findings revealed that six out of nine NWS lead to unreliable results at the network level, while all nine NWS were unreliable at the node level. In comparison, our proposed ISWBN performed as well as the best performing individual NWS at the network level, and the ICC was higher compared to all individual NWS at the node level. Importantly, both network and node-wise ICCs of network metrics derived from the topologically filtered ISBWN (ISWBN(TF)), were further improved compared to the non-filtered ISWBN. Finally, in the recognition accuracy tests, we assigned each single ISWBN(TF) to the correct subject. We also applied our methodology to a second dataset of diffusion-weighted MRI in healthy controls and individuals with psychotic experience. Following a binary classification scheme, the classification performance based on ISWBN(TF) outperformed the nine different weighting strategies and the ISWBN. Overall, these findings suggest that the proposed methodology results in improved characterization of genuine between-subject differences in connectivity leading to the possibility of network-based structural phenotyping.