Analysis of tumor morphology and vasculature in an animal model of colorectal cancer using in vivo contrast-enhanced endoluminal ultrasound biomicroscopy

Colorectal cancer (CRC) has a high incidence in the world, being the third leading cause of cancer-related mortality in the United States. Ninety percent of the malignant tumors can be cured if diagnosed in the early stages of localized disease and this motivates a great interest in the development and design of experimental models for CRC detection, staging and monitoring. The aim of this work was to use VEGFR2 (vascular endothelial growth factor receptor 2)-targeted ultrasound contrast agent (UCA) coupled to an endoluminal ultrasound biomicroscopy (eUBM) system to diagnose colon tumors and to analyze tumor vasculature. Colon tumors were induced in mice by using azoxymethane/dextran sulfate sodium and according to histopathology, 55% of colon tumors were adenomas and 45% were adenocarcinomas. Images of the lesion were obtained before and 2-15 minutes after VEGFR2-targeted UCA injection into the mice tail. Compared to post-mortem histopathology, all colonic lesions (lymphoid hyperplasias, ulcerations, thickened mucosa and tumors) were correctly diagnosed by eUBM. In addition, when coupled to a VEGFR2-targeted UCA, the eUBM system provided hyperechoic image areas compatible with intense VEGFR2 staining by immunohistochemical diagnosis. The results suggest that eUBM associated to UCA is a promising tool for histopathologycal and molecular imaging, and could be used to diagnose, stage and monitor colon tumor morphology and vasculature.