Voxel-wise analysis of dynamic 18F-FET PET: a novel approach for non-invasive glioma characterisation

Background: Glioma grading with dynamic F-18-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour. This work aimed to ensure a reader-independent glioma characterisation and identification of aggressive sub-volumes by performing a voxel-based analysis with diagnostically relevant kinetic and static 18F-FET PET parameters. One hundred sixty-two patients with a newly diagnosed glioma classified according to histologic and molecular genetic properties were evaluated. The biological tumour volume (BTV) was segmented in static 20-40 min p.i. F-18-FET PET images using the established threshold of 1.6 x background activity. For each enclosed voxel, the time-to-peak (TTP), the late slope (Slope(15-40)), and the tumour-to-background ratios (TBR5-15, TBR20-40) obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The percentage portion of these values within the BTV was evaluated with percentage volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The ability to differentiate histologic and molecular genetic classes was assessed and compared to volume-of-interest (VOI)-based parameters. Results: Aggressive WHO grades III and IV and IDH-wildtype gliomas were dominated by a high proportion of voxels with an early peak, negative slope, and high TBR, whereby the PVHs with TTP < 20 min p.i., Slope(15-40) < 0 SUV/h, and TBR5-15 and TBR20-40 > 2 yielded the most significant differences between glioma grades. We found significant differences of the parameters between WHO grades and IDH mutation status, where the effect size was predominantly higher for voxel-based PVHs compared to the corresponding VOI-based parameters. A low overlap of BTV sub-volumes defined by TTP < 20 min p.i. and negative Slope(15-40) with TBR5-15 (>) (2)- and TBR20-40 (> 2)-defined hotspots was observed. Conclusions: The presented approach applying voxel-wise analysis of dynamic F-18-FET PET enables an enhanced characterisation of gliomas and might potentially provide a fast identification of aggressive sub-volumes within the BTV. Parametric 3D F-18-FET PET information as investigated in this study has the potential to guide individual therapy instrumentation and may be included in future biopsy studies.