Two Patterns of White Matter Connection in Multiple Gliomas: Evidence from Probabilistic Fiber Tracking

Background: Multiple lesions are uncommon in brain gliomas, and their pathophysiology is poorly understood. Invasive growth along white matter tracts is an important clinicopathological characteristic of gliomas, and a major factor in a poor therapeutic outcome. Here, we used probabilistic fiber tracking and cluster analysis to investigate the inter-focal connectivity relationships of multiple gliomas, in order to seek inferential evidence of common origin. Methods: MRI scans of 46 patients with multiple gliomas were retrospectively analyzed. Before surgery, all patients underwent multimodal functional MR imaging, including diffusion tensor imaging, enhanced 3D T1-weighted imaging, diffusion-weighted imaging, 1H MR spectroscopy, and dynamic susceptibility contrast perfusion-weighted imaging. Probabilistic fiber tracking was used to quantify white matter connectivity between neoplastic foci. Hierarchical cluster analysis was performed to identify patterns of white matter connection. Results: Cluster analysis reveals two patterns of connectivity, one with smaller, and one with greater, connectivity (2675 +/- 1098 versus 30432 +/- 22707, p < 0.0001). The two subgroups show significant differences in relative cerebral blood volume (2.31 +/- 0.95 versus 1.73 +/- 0.48, p = 0.002) and lipid/creatine ratio (0.32 +/- 0.22 versus 0.060 +/- 0.051, p = 0.006). Conclusion: Two distinct patterns of white matter connection exist in multiple gliomas. Those with lower connectivity tend to have independent origins, and can be termed true multicentric glioma, whereas those with greater connectivity tend to share common origin, and spread along white matter tracts. True multicentric gliomas have higher vascularity and more intratumoral necrosis. These findings may help to develop personalized therapeutic strategies for multiple gliomas.