Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity

Abstract

Purpose Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology coregistration with the aim of studying intra-tumoral 11 C-methionine (MET) uptake in relation to tumor perfusion and the protein expression of histological cell markers in corresponding areas. Methods Consecutive histological sections of four tumors covering the entire en bloc-removed tumor were immunostained with antibodies against IDH1-mutated protein (tumor cells), Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for anatomical landmarks-based co-registration of subsequent histological images, which were overlaid on corresponding MET PET scans and MRI perfusion maps. Regions of interest (ROIs) on PET were selected throughout the entire tumor volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders with infiltrating zone. Tumor-to-normal tissue (T/ N) ratios of MET uptake and mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein expression of histological cell markers was quantified in corresponding regions. Statistical correlations were calculated between MET uptake, rCBV, and quantified protein expression. Results A total of 84 ROIs were selected in four oligodendrogliomas. A significant correlation (p < 0.05) between MET uptake and tumor cell density was demonstrated in all tumors separately. In two tumors, MET correlated with the density of proliferating cells and vessel cell density. There were no significant correlations between MET uptake and rCBV, and between rCBV and histological cell markers. Conclusions The MET uptake in hot spots, outside hotspots, and in infiltrating tumor edges unanimously reflects tumor cell density. The correlation between MET uptake and vessel density and density of proliferating cells is less stringent in infiltrating tumor edges and is probably more susceptible to artifacts caused by larger blood vessels surrounding the tumor. Although based on a limited number of samples, this study provides histological proof for MET as an indicator of tumor cell density and for the lack of statistically significant correlations between rCBV and histological cell markers in oligodendrogliomas.

18F-Trifluoromethylated D-Cysteine as a Promising New PET Tracer for Glioma Imaging: Comparative Analysis With MRI and Histopathology in Orthotopic C6 Models

“…The higher the S- [ 18 F]CF 3 -D-CYS uptakes were, the higher the tumor cell proliferation was. These findings are consistent with previous reports that [ 11 C]-MET uptake correlated with the proliferative Ki67 index ( 27 – 29 ). On the other hand, we found that the tumor hemorrhage region, which was confirmed by SWI-MRI and histopathology, had a pretty low S- [ 18 F]CF 3 -D-CYS uptake.…”

Combined Amino Acid Positron Emission Tomography and Advanced Magnetic Resonance Imaging in Glioma Patients

“…These findings were confirmed by another study [49]. Subsequently, Roodakker et al [50] compared regional MET PET and PWI at 3 T with local neuropathology in patients with en bloc-resected oligodendrogliomas. They showed that MET uptake correlated with tumor cell density throughout the entire tumor volume in all patients.…”

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

“…They concluded that MET PET, but not PWI, has a value as an indicator of tumor cell density in oligodendrogliomas. While in a very small study, this result differs from that of the GBM studies above and may indicate an important tumor type difference, wherein the value of PWI may be negligible for oligodendrogliomas specifically [ 39 ].…”

“…Studying these imaging modalities in oligodendrogliomas, Roodakker et al compared MET PET and PWI images acquired asynchronously, with histology as the ground truth, in four oligodendrogliomas [ 39 ]. MET PET uptake was significantly correlated to tumor cell density, but PWI was not correlated with MET PET or histology.…”