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

S Schön,C Preibisch,J Keupp,I Yakushev,J Cabello,M Molina-Romero,A Hock,T Pyka,W Weber,P Eichinger,C Zimmer,F Liesche-Starnecker,J Gempt,M Metz,I Karimov,B Wiestler,B Meyer

doi:10.1007/s00259-019-04677-x

Abstract

PurposeImaging 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.MethodsPreoperative 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.ResultsIn 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.ConclusionsWe 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.

Highlights

Materials and methodsTraditionally, tumor imaging has focused on visualizing anatomy
In glioblastomas, the largest hot-spot volumes (HSV) was found for amide proton transfer–weighted (APTw), followed by PET and Cerebral blood volume (CBV) (p < 0.05)
The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions

Summary

Introduction

Materials and methodsTraditionally, tumor imaging has focused on visualizing anatomy. Among the most extensively studied imaging modalities for this purpose are O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging: Using FET as a tracer, PET can visualize the amino acid uptake in gliomas and metabolically active tumor cells [1]. MR-based DSC perfusion provides evidence of neoangiogenesis [5]—a hallmark of malignant gliomas—and thereby helps to distinguish between gliomas of different WHO grade and malignancy [6]. DSC has been shown to reflect differences in angiogenic pathways between isocitrate dehydrogenase (IDH) mutant and wild type gliomas [7] and to help predict patient survival [8] and response to antiangiogenic therapy (bevacizumab) [9]

Objectives

Results

Discussion

Conclusion