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

Abstract

KEy WoRDSendoscopic imaging, imaging of tumor progression, gastrointestinal cancer, colorectal adenoma, gastrointestinal intraepithelial neoplasia, animal models for carcinogenesis, azoxymethane treated mouse model of colorectal neoplasm Research PaperSerial 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 mm axial and 4.4 mm 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.

Optical coherence tomography today: speed, contrast, and multimodality

“…Pan et al 185 suggested that an ALA fluorescence-guided endoscopic OCT could enhance the efficiency and sensitivity of early bladder cancer diagnosis and demonstrated in animal studies that the specificity of fluorescence detection of transitional cell carcinoma was significantly enhanced by fluorescence-guided OCT. Tumlinson et al 205 have demonstrated a combined miniaturized OCT and laser-induced fluorescence (LIF) spectroscopy imaging catheter for in vivo mouse colon imaging to monitor the disease progression in mouse colon longitudinally and to identify colorectal adenomatous mouse colon. [206][207][208] OCT images showed significant changes in mucosal layer thickness and loss of visibility of tissue boundary lines between healthy and diseased tissue. Similarly, the LIF spectra of healthy and diseased tissues were distinguishable by the emissions at 405 and 680 nm.…”

Chlorogenic Acid Differentially Alters Hepatic and Small Intestinal Thiol Redox Status Without Protecting Against Azoxymethane-Induced Colon Carcinogenesis in Mice

“…We selected our AOM dosing regimen to induce colon cancer based on existing evidence from studies in mice suggesting that this approach closely mimics the pathogenesis of colon cancer in humans (41,46,52,(66)(67)(68). We also specifically selected A/J mice for our studies because this strain is highly susceptible to AOM-induced colon cancer, thereby ensuring that we would be testing the hypothesis that CGA might inhibit colon cancer (69).…”

Development of a Fiber-Optic Optical Coherence Tomography Probe for Intraocular Use

“…19 The side-imaging OCT is a system with a scanning beam projected perpendicular to the probe axis. These probes are suitable for tissues within tubular organs, for example, the gastrointestinal tract, [20][21][22][23][24] vascular system, 25-29 respiratory system, 21,30-33 and urinary tract, 34 because the perpendicular angle of the scanning laser can make more efficient use of such a limited space and can obtain images over 3608. Further, threedimensional imaging 23,31 can also be obtained because circumferential scanning allows continuous images of tubular organs.…”