Lesion-Aware Myelin-Weighted Connectomics in the phase II SYNERGY Trial

Motivation: Microstructure-informed tractography methods face challenges in presence of focal lesions. Goal(s): This study aims to apply an extension of Myelin Streamline Decomposition (MySD) which accounts for lesions to patients with multiple sclerosis (MS) enrolled in a completed phase 2 clinical trial (SYNERGY) with conventional DTI acquisitions. Approach: We applied our novel approach to perform network analysis in SYNERGY’s secondary progressive (SP) and relapsing-remitting (RR) patients. Results: Using MySD applied to patients with focal pathology, we showed that SPMS patients had increased alterations in myelin-weighted network properties compared to RRMS. Myelin-weighted networks also exhibited correlations with motor and cognitive impairment. Impact: For the first time, we applied our novel connectomics approach explicitly designed to cope with focal pathology to MS patients in a clinical trial, demonstrating its sensitivity and adaptability to real-world clinical data.