Glioma BOLD connectivity profile and its relationship to patients’ survival

Abstract Background Presence of residual neurovascular activity within glioma lesions have been recently demonstrated via functional MRI (fMRI) along with active electrical synapses between glioma cells and healthy neurons that influence survival. In this study, we aimed to investigate whether gliomas demonstrate synchronized neurovascular activity with the rest of the brain, by measuring Blood Oxygen Level Dependent (BOLD) signal synchronization, i.e. functional connectivity-FC, while also testing whether the strength of such connectivity might predict patients’ overall survival (OS). Methods Resting-state fMRI scans of patients who underwent presurgical brain mapping were analysed (total sample, n=54; newly diagnosed patients, n=18; recurrent glioma group, n=36). A seed to voxel analysis was conducted to estimate the FC signal profile of the tumor mass. A regression model was then built to investigate the potential correlation between tumor FC and individual OS. Finally, an unsupervised, cross-validated clustering analysis was performed including tumor FC and clinical OS predictors (e.g., KPS, tumor volume, genetic profile) to verify the performance of tumor FC in predicting OS with respect to validated radiological, demographic, genetic and clinical prognostic factors. Results In both newly diagnosed and recurrent gliomas patients a significant pattern of BOLD synchronization between the solid tumor and distant brain regions was found. Crucially, glioma-brain functional connectivity positively correlated with variance in individual survival in both newly diagnosed patients (r=0.90-0.96; p<0.001; R 2=81-92%) and in the recurrent glioma group (r=0.72; p<0.001; R 2=52%), outperforming standard clinical, radiological and genetic predictors. Conclusions Results suggest glioma’s synchronization with distant brain regions should be further explored as a possible diagnostic and prognostic biomarker.