Visualizing cellularity and angiogenesis in newly-diagnosed glioblastoma with diffusion and perfusion MRI and FET-PET imaging

Purpose: Combining imaging modalities has become an essential tool for assessment of tumor biology in glioblastoma (GBM) patients. Aim of this study is to understand how tumor cellularity and neovascularization are reflected in O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography ([18F] FET PET) and magnetic resonance imaging (MRI) parameters, including cerebral blood volume (CBV), fractional anisotropy (FA) and mean diffusivity (MD). Methods: In this prospective cohort, 162 targeted biopsies of 43 patients with therapy-naive, isocitrate dehydrogenase (IDH) wildtype GBM were obtained after defining areas of interest based on imaging parameters [18F] FET PET, CBV, FA and MD. Histopathological analysis of cellularity and neovascularization was conducted and results correlated to imaging data. Results: ANOVA analysis showed a significant increase of CBV in areas with high neovascularization. For diffusion metrics, and in particular FA, a trend for inverse association with neovascularization was found. [18F] FET PET showed a significant positive correlation to cellularity, while CBV also showed a trend towards correlation with cellularity, not reaching significant levels. In contrast, MD and FA were negatively associated with cellularity. Conclusion: Our study confirms that amino acid PET and MR imaging parameters are indicative of histological tumor properties in glioblastoma and highlights the ability of multimodal imaging to assess tumor biology non-invasively.