Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

SIMPLE SUMMARY: Contrast-enhanced (CE) X-ray imaging techniques have been used to assess angiogenesis in patients and animal models of cancer in order to overcome the limitations of histological quantification of angiogenesis, such as spatial and temporal heterogeneity of tumors. Some studies have compared the quantitative imaging parameters obtained with static and dynamic CE X-ray imaging techniques, but their association with histological biomarkers of angiogenesis has never been directly compared. This study aimed to provide such a comparison in a suitable animal model for the study of angiogenesis, namely, the subcutaneous C6 glioma model. We found an agreement among the quantitative imaging parameters obtained with these techniques, and we also found an association between a set of them with angiogenesis and necrosis descriptors. This set of quantitative imaging parameters demonstrated a high potential to describe angiogenesis and could be used to assess treatment response in further studies with this animal model. ABSTRACT: The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (C(I)), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (K(trans)) were quantified from dynamic contrast-enhanced (DCE) planar images. C(I) and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and K(trans) in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in C(I) and E quantified with SE and DE protocols. Significant strong correlations (Pearson r > 0.7, p < 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and C(I) in tumor periphery were associated with microvessel density (MVD) and necrosis, E and C(I) in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model.