Exploring Molecular Glioblastoma: Insights from Advanced Imaging for a Nuanced Understanding of the Molecularly Defined Malignant Biology

Abstract

Molecular glioblastoma (molGB) does not exhibit the histologic hallmarks of a grade 4 glioma but is nevertheless diagnosed as glioblastoma when harboring specific molecular markers. MolGB can easily be mistaken for similar-appearing lower-grade astrocytomas. Here, we investigated how advanced imaging could reflect the underlying tumor biology. Clinical and imaging data were collected for 7 molGB grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. Four neuroradiologists performed VASARI-scoring of conventional imaging, and their inter-reader agreement was assessed using Fleiss ϰ coefficient. To evaluate the potential of advanced imaging, two-sample t-test, one-way ANOVA, Mann-Whitney-U, and Kruskal-Wallis-test were performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) that were extracted fully automatically from the whole tumor volume. While conventional VASARI imaging features did not allow for reliable differentiation between glioma entities, rCBV was significantly higher in molGB compared to astrocytomas for the 5th and 95th percentile, mean and median values (p < 0.05). ADC values were significantly lower in molGB than in astrocytomas for mean, median, and the 95th percentile (p < 0.05). Although no molGB showed contrast enhancement initially, we observed enhancement in the short-term follow-up of one patient. Quantitative analysis of diffusion and perfusion parameters shows potential in reflecting the malignant tumor biology of molGB. It may increase awareness of molGB in a non-enhancing, "benign" appearing tumor. Our results support the emerging hypothesis that molGB might present glioblastoma captured at an early stage of gliomagenesis.