Abstract
Simple SummaryContrast-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.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 (CI), 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 (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI 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 Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI 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 CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI 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.
Highlights
Angiogenesis is a mechanism of tumor vascularization characterized by the formation of new blood vessels from the pre-existing vasculature [1]
These results suggested that CI and relative blood volume (rBV), quantified in SE and DE micro-computed tomography (CT) images, allow better discernment between muscle and the tumor regions, both qualitatively and quantitatively, than attenuation, E, or the kinetic parameters quantified with dynamic contrast-enhanced (DCE) planar images
For SE images, E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD
Summary
Angiogenesis is a mechanism of tumor vascularization characterized by the formation of new blood vessels from the pre-existing vasculature [1]. Microvessel density (MVD) is a surrogate biomarker of angiogenesis, it is quantified by histology and provides useful prognostic and predictive information for the management of cancer patients [2,3]. The main limitation of histological quantification of MVD is related to the temporal and spatial heterogeneity of tumors. In order to overcome this limitation, contrast-enhanced (CE) imaging techniques have been proposed to evaluate the angiogenic status of tumors in vivo, taking advantage of the immature and leaky nature of angiogenic vessels [4]. Several imaging modalities have been used to evaluate tumor vasculature in the clinical setting and to assess the potential of the imaging parameters to provide diagnostic, prognostic, and predictive information, such as computed tomography (CT) and magnetic resonance imaging (MRI), among others [4,5,6]. Dynamic contrast-enhanced MRI (DCE-MRI), dynamic susceptibility contrast-enhanced MRI (DSC-MRI), and perfusion CT are the most widely used techniques, and each one of them has advantages and disadvantages related to technical, biological, and clinical factors [4]
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