Serial endoscopy in azoxymethane treated mice using ultra-high resolution optical coherence tomography

Abstract

Purpose: Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be implemented in a small diameter endoscope for imaging mouse models of colorectal cancer (CRC). In this study, we utilized ultrahigh resolution (UHR) OCT to serially image the lower colon of azoxymethane (AOM) treated A/J mouse models of CRC in order to monitor the progression of neoplastic transformations and determine if OCT is capable of identifying early disease. Experimental Design: Thirteen AOM treated A/J and two control A/J mice were surveyed at four timepoints (8, 14, 22, and 26 weeks post AOM treatment) using a 2.0 mm diameter UHR OCT endoscopic system with 3.2 µm axial and 4.4 µm lateral resolution. Histological samples obtained at the final timepoint served as the diagnostic reference. A blinded expert panel of mouse colon pathologists provided diagnoses from the OCT images based on criteria developed from a separate training set of OCT images. Panel results were compared to histological diagnoses assigned by a blinded pathologist. Results: At the final imaging timepoint, 95% of adenomas and 23% of gastrointestinal neoplasias (38% protruding GINs and 9% non-protruding GINs) were correctly diagnosed. The panel identified 68% of disease foci (95% adenoma, 76% protruding GINs, and 13% non-protruding GINs). Over the OCT imaging timepoints, disease progression followed a typical succession, with normal or GIN preceding adenoma. Conclusions: Endoscopic UHR OCT enabled accurate diagnosis of adenomas, identification of protruding GIN, and non-destructive visualization of CRC progression, providing a tool for cancer research in animal models.