Quantification of tumor angiogenesis with contrast-enhanced x-ray imaging in preclinical studies: a review

Tissue contrast is a major challenge in the application of computed tomography (CT) and micro-computed tomography (micro-CT) techniques for imaging cancer. Contrast medium is used in order to enhance contrast of certain organs of interest, as well as tumors. Several types of contrast media have been used to assess tumor vasculature, perfusion and angiogenesis in preclinical studies. In general, low molecular weight contrast media have been used to characterize the first pass vascular dynamics of tumors with fast CT systems, while blood pool agents have been preferred to explore the delayed vascular dynamics with micro-CT systems. Together, these approaches provide qualitative, semi-quantitative, and quantitative information of the vascular architecture and vascular functionality of tumors in the preclinical scenario. Herein, we present an overview of contrast media, imaging techniques, image analysis methods, and quantitative parameters that have been used to evaluate tumor angiogenesisin vivoin recent preclinical studies. Preclinical applications on lesion detection and characterization, evaluation of vascular parameters as prognostic and predictive biomarkers, and evaluation of treatment response are also reviewed. These applications have demonstrated the potential of contrast-enhanced x-ray imaging to provide, in a noninvasive manner, a landscape of the spatial and temporal heterogeneity of the angiogenic process underlying tumor development.