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.
Does the Use of IV Contrast Enhanced CT for Attenuation Correction Affect Clinical Interpretation of Head and Neck PET/CT?