Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma

Abstract

Background

This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly-diagnosed glioma.

Methods

A consecutive series of n=237 patients with newly diagnosed glioblastoma and n=131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute-152 space. Using a voxel-based lesion-symptom mapping (VSLM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n=17 molecular characteristics in the glioblastoma cohort and n=2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n=1000 iterations) was used to correct for multiple testing and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α=0.05, power >0.8).

Results

Tumor location predilection for isocitrate dehydrogenase (IDH)-mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted p=0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted p>0.05, each).

Conclusions

Our study highlights the unique properties of IDH-mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.