Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas

Abstract

Purpose Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. Methods Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. Results In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. Conclusions We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

Comparison of Amino Acid PET to Advanced and Emerging MRI Techniques for Neurooncology Imaging: A Systematic Review of the Recent Studies

“…They did not report on this imaging combination for any other tumor subtypes. In another study of 46 newly diagnosed gliomas, Schon et al [ 60 ] found the tumor volume to be larger by FET PET than by DSC PWI. For identifying cellularity, FET PET parameters performed the strongest, while for vascularity, both DSC PWI and FET PET performed well.…”

“…Even in low-grade gliomas, a similar trend was observed for the two imaging modalities (P = 0:085 for APTw and P = 0:045 for CBV). Reproduced with permission from Figure 2 of Schon et al [60]. 14 Molecular Imaging this discrepancy.…”

Sequential implementation of DSC-MR perfusion and dynamic [18F]FET PET allows efficient differentiation of glioma progression from treatment-related changes

“…Several analyses correlated [ 18 F]FET PET parameters with PWI-derived parameters like rCBV [19][20][21][22]. However, there is a general consensus that [ 18 F]FET uptake, especially at 20-40 min, is dominated by the expression of amino acid transporters [10,19], explaining why hotspot locations on [ 18 F]FET PET and PWI do often not coincide [22].…”

Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors

“…Data from initial studies revealed incongruent results, suggesting FET, DWI, and CEST evaluate different biologic processes and information in brain tumors [ 135 , 136 ]. However, a more recent study from 2020 utilized FET PET-MRI combined with amide-CEST and DSC perfusion to generate intra-lesional hot spot volumes (HSV) in 46 glioma patients [ 137 ]. HSVs generated with amide-CEST in GBM patients were larger than for FET or DSC HSVs.…”