In Vivo Endoluminal Ultrasound Biomicroscopic Imaging in a Mouse Model of Colorectal Cancer

Rationale and Objectives

The gold-standard tool for colorectal cancer detection is colonoscopy, but it provides only mucosal surface visualization. Ultrasound biomicroscopy allows a clear delineation of the epithelium and adjacent colonic layers. The aim of this study was to design a system to generate endoluminal ultrasound biomicroscopic images of the mouse colon, in vivo, in an animal model of inflammation-associated colon cancer.

Materials and Methods

Thirteen mice ( Mus musculus ) were used. A 40-MHz miniprobe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope. Control mice ( n = 3) and mice treated with azoxymethane and dextran sulfate sodium ( n = 10) were subjected to simultaneous endoluminal ultrasound biomicroscopy and white-light colonoscopy. The diagnosis obtained with endoluminal ultrasound biomicroscopy and colonoscopy was compared and confirmed by postmortem histopathology.

Results

Endoluminal ultrasound biomicroscopic images showed all layers of the normal colon and revealed lesions such as lymphoid hyperplasias and colon tumors. Additionally, endoluminal ultrasound biomicroscopy was able to detect two cases of mucosa layer thickening, confirmed by histology. Compared to histologic results, the sensitivities of endoluminal ultrasound biomicroscopy and colonoscopy were 0.95 and 0.83, respectively, and both methods achieved specificities of 1.0.

Conclusions

Endoluminal ultrasound biomicroscopy can be used, in addition to colonoscopy, as a diagnostic method for colonic lesions. Moreover, experimental endoluminal ultrasound biomicroscopy in mouse models is feasible and might be used to further develop research on the differentiation between benign and malignant colonic diseases.

Colorectal cancer (CRC) has a high incidence in the world, being the third most common cancer and the third leading cause of cancer-related mortality in the United States, irrespective of gender . Ninety percent of malignant tumors can be cured if diagnosed in the early stages of localized disease , and this motivates great interest in the development and design of new tools for the early detection and staging of CRC. The gold-standard tool for CRC detection as well as for neoplastic alterations such as polyps and flat lesions in the mucosa is colonoscopy . However, it provides only mucosal surface visualization.

Polyps and flat lesions in the mucosa are mostly benign and can often be adequately resected endoscopically . Nevertheless, differentiation from carcinomatous lesions that invade the muscularis mucosa is paramount to provide the correct approach . Regarding malignant tumors, the determination of their penetration depth through the colonic layers is also important for accurate lesion staging and treatment strategy . Therefore, some cases may require the colonoscopic results to be complemented with additional information obtained with a diagnostic technique able to determine tumor penetration depth through the colonic wall. In this context, the use of endoscopic ultrasonography in the diagnosis and determination of the malignant potential and depth of colonic lesions has been proposed by some authors . For the rectum, endoscopic ultrasound staging has already been a standard for several years, along with magnetic resonance imaging (MRI) .

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Materials and methods

Animals

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Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) Carcinogenesis Protocol

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Endoluminal UBM (eUBM) System

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Simultaneous eUBM and Endoscopic Image Acquisition

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Histologic Analysis

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Results

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Table 1

Mouse Colon Findings Detected Simultaneously by Endoluminal Ultrasound Biomicroscopy and Colonoscopy and the Corresponding Histologic Diagnosis

Animal Lesion Findings Endoluminal Ultrasound Biomicroscopy Colonoscopy Histology Yes No Yes No Lymphoid Hyperplasia Tumor Thickened Mucosa 1 L 1-1 ✓ ✓ ✓ 1 L 2-1 ✓ ✓ ✓ 2 L 1-2 ✓ ✓ ✓ 2 L 2-2 ✓ ✓ ✓ 2 L 3-2 ✓ ✓ ✓ 3 L 1-3 ✓ ✓ ✓ 4 L 1-4 ✓ ✓ ✓ 4 L 2-4 ✓ ✓ ✓ 5 L 1-5 ✓ ✓ ✓ 5 L 2-5 ✓ ✓ ✓ 6 L 1-6 ✓ ✓ ✓ 7 L 1-7 ✓ ∗ ∗ ✓ 7 L 2-7 ✓ ✓ ✓ 7 L 3-7 ✓ ✓ ✓ 8 L 1-8 ✓ ✓ ✓ 9 L 1-9 ✓ ✓ ✓ 10 L 1-10 ✓ ✓ ✓ 10 L 2-10 ✓ ✓ ✓ 10 L 3-10 ✓ ✓ ✓

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Discussion

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Conclusions

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In Vivo Endoluminal Ultrasound Biomicroscopic Imaging in a Mouse Model of Colorectal Cancer

Rationale and Objectives

Materials and Methods

Results

Conclusions

Materials and methods

Animals

Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) Carcinogenesis Protocol

Endoluminal UBM (eUBM) System

Simultaneous eUBM and Endoscopic Image Acquisition

Histologic Analysis

Results

Discussion

Conclusions

References

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