Structural connectome quantifies tumor invasion and predicts survival in glioblastoma patients

Abstract:

Background Glioblastoma is characterized by extensive invasion into brain parenchymal tissue through white matter tracts. Systematically quantifying invasion, however, is limited by the conventional imaging tools, and could potentially be achieved by a structural connectome approach. Methods Two prospective patient cohorts of newly diagnosed glioblastoma were included for network construction. A fiber template was firstly derived by employing probabilistic tractography on healthy subjects. Through performing tract-based spatial statistics in patients and age-matched controls, the connectivity strength of each fiber was estimated in patients for network construction. Contrast-enhancing and non-enhancing tumors were segmented and overlaid to the network to identify connectome disruption in lesion and distant areas. The connectome disruption probabilities were calculated across all patients. Disruption indices and network topological features were examined using survival models. Results The distant areas accounted for higher proportion of disruption than the contrast-enhancing tumor (16.8 ± 12.0% vs 5.8 ± 5.1%, P < 0.001). Compared to healthy controls, patient networks demonstrated lower clustering coefficient, but higher characteristic path length (each P < 0.001). Higher distant area disruption (HR = 1.43, P = 0.027) and characteristic path length (HR = 1.59, P = 0.031) were associated with worse survival, while higher clustering coefficient (HR = 0.59, P = 0.016) was associated with prolonged survival. Conclusion The occult invasion in glioblastoma could be identified and quantified using structural connectome, which may confer benefits to precise patient management.