Abstract
Despite magnetic resonance imaging (MRI) being the gold-standard imaging modality in the glioblastoma (GBM) setting, the availability of rodent MRI scanners is relatively limited. CT is a clinically relevant alternative which is more widely available in the pre-clinic. To study the utility of contrast-enhanced (CE)-CT in GBM xenograft modelling, we optimized CT protocols on two instruments (IVIS-SPECTRUM-CT;TRIUMPH-PET/CT) with/without delivery of contrast. As radiomics analysis may facilitate earlier detection of tumors by CT alone, allowing for deeper analyses of tumor characteristics, we established a radiomic pipeline for extraction and selection of tumor specific CT-derived radiomic features (inc. first order statistics/texture features). U87R-Luc2 GBM cells were implanted orthotopically into NOD/SCID mice (n=25) and tumor growth monitored via weekly BLI. Concurrently mice underwent four rounds of CE-CT (IV iomeprol/iopamidol; 50kV-scan). N=45 CE-CT images were semi-automatically delineated and radiomic features were extracted (Pyradiomics 2.2.0) at each imaging timepoint. Differences between normal and tumor tissue were analyzed using recursive selection. Using either CT instrument/contrast, tumors > 0.4cm3 were not detectable until week-9 post-implantation. Radiomic analysis identified three features (waveletHHH_firstorder_Median, original_glcm_Correlation and waveletLHL_firstorder_Median) at week-3 and -6 which may be early indicators of tumor presence. These features are now being assessed in CE-CT scans collected pre- and post-temozolomide treatment in a syngeneic model of mesenchymal GBM. Nevertheless, BLI is significantly more sensitive than CE-CT (either visually or using radiomic-enhanced CT feature extraction) with luciferase-positive tumors detectable at week-1. In conclusion, U87R-Luc2 tumors > 0.4cm3 are only detectable by Week-8 using CE-CT and either CT instrument studied. Nevertheless, radiomic analysis has defined features which may allow for earlier tumor detection at Week-3, thus expanding the utility of CT in the preclinical setting. Overall, this work supports the discovery of putative prognostic pre-clinical CT-derived radiomic signatures which may ultimately be assessed as early disease markers in patient datasets.
Use of full-dose contrast-enhanced CT for extrahepatic staging using Gallium-68-DOTATATE PET/CT in patients with neuroendocrine tumors
