Exploring MGMT Methylation-Driven Structural Connectivity Changes in Insular Gliomas: A Tractography and Graph Theoretical Analysis

Abstract

Abstract Objectives To investigate the correlation between methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter levels and structural connectivity in insular gliomas across hemispheres. Methods We analyzed 61 left insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. Results The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.012) and uncinate fascicle (UF, p = 0.030) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. Conclusion MGMT methylation levels are significantly associated with structural connectivity changes in insular gliomas, displaying hemisphere-dependent differences.