Detection of Mice Colorectal Tumors by Endoluminal Ultrasound Biomicroscopic Images and Quantification of Image Augmented Gray Values Following Injection of VEGFR-2 Targeted Contrast Agent.

RATIONALE AND OBJECTIVES: Ultrasound biomicroscopy (UBM) is a noninvasive imaging technique that can be applied in detecting colonic tumors and, once associated with an ultrasound contrast agent (UCA), can identify the molecular expression of cancer-related biomarkers, such as the vascular endothelial growth factor receptor 2 (VEGFR-2). The present work aimed to detect colonic tumors and quantify augmented gray values of endoluminal UBM (eUBM) images from colonic tumors following the injection of VEGFR-2 targeted UCA (VEGFR2-UCA) into a mouse model of colorectal cancer. MATERIAL AND METHODS: A 40 MHz miniprobe catheter inserted through the biopsy channel of a pediatric flexible bronchofiberscope was used to obtain colonoscopic and B-mode eUBM images simultaneously. Seventeen tumor-bearing mice had their colons inspected and six of them were subjected to a VEGFR2-UCA injection to predict VEGFR-2 expression. RESULTS: All animals developed distal colon tumors and eUBM was able to detect all of them and also to characterize the tumors, with 71.4% being in situ lesions and 28.6% being tumors invading the mucosa + muscularis mucosae + submucosa layers, as confirmed by histopathology. After VEGFR2-UCA injection, gray values from the eUBM tumoral images increased significantly (p < 0.01). Tumor sites with increased eUBM image gray values corresponded to areas with increased VEGFR-2 expression, as confirmed by immunohistochemistry. CONCLUSION: The results confirm eUBM as a powerful noninvasive and real-time tool for detecting colon tumor and its invasiveness and once associated with VEGFR2-UCA may become a tool for the detection of VEGFR-2 expression in colonic tumors.

Endoluminal ultrasound biomicroscopy as a reliable tool for in vivo assessment of colonic inflammation in rats.

PURPOSE: Endoscopic ultrasound (EUS) imaging of the colon is an important diagnostic tool for early neoplasia, although usually restricted to the rectum in inflammatory bowel disease (IBD). This study aimed to evaluate the ability of an endoluminal ultrasound biomicroscopic (eUBM) system to detect and characterize lesions simulating Crohn's disease in the colon of rats in vivo. METHODS: Colitis was induced with trinitrobenzene sulfonic acid instillated in the distal colon. Eighteen Wistar rats were submitted to eUBM in three time points: week 1 group (18 animals examined on day 3 after colitis induction), week 2 group (12 animals on days 3 and 10), and week 3 group (7 animals on days 3, 10, and 17). This design yielded distinct inflammation intensities. Three untreated rats were used for acquisition of control images. Scores were used for comparison with histology. RESULTS: Scores for eUBM and histology in the different moments of examination achieved a Spearman's rank correlation coefficient of 0.87 (p < 0.001). Findings of wall thickening presented positive predictive value (PPV) and sensitivity of 94 and of 100 %, respectively. Superficial and deep ulcers presented a PPV of 89 and 80 %, respectively, and negative predictive values of 100 and 85 %, respectively. CONCLUSION: Accurate detection and analysis of the lesions was achieved. The model is essential for the clinical development of the technique and a reproducible method for the evaluation of experimental colitis. eUBM might be applicable in different segments of the gut, developing into a novel adjunct method for IBD evaluation.