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Research Paper

Serial Endoscopy in Azoxymethane Treated Mice Using Ultra-High Resolution Optical Coherence Tomography

Lida P. Hariri, Ziping Qiu, Alexandre R. Tumlinson, David G. Besselsen, Eugene W. Gerner, Natalia Ignatenko, Boris Povazay, Boris Hermann, Harald Sattmann, James McNally, Angelika Unterhuber, Wolfgang Drexler and Jennifer K. Barton

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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.

Authors

Lida P. Hariri

The University of Arizona, Tucson, AZ

Ziping Qiu

Medical University of Vienna, Vienna, Austria

Alexandre R. Tumlinson

The University of Arizona, Tucson, AZ

David G. Besselsen

The University of Arizona, Tucson, AZ

Eugene W. Gerner

Department of Cell Biology & Anatomy, Arizona Cancer Center, University of Arizona, Tucson, Arizona

Natalia Ignatenko

The University of Arizona, Tucson, AZ

Boris Povazay

Medical University of Vienna, Vienna, Austria

Boris Hermann

Medical University of Vienna, Vienna, Austria

Harald Sattmann

Medical University of Vienna, Vienna, Austria

James McNally

The University of Arizona, Tucson, AZ

Angelika Unterhuber

Medical University of Vienna , Vienna, Austria

Wolfgang Drexler

Medical University of Vienna , Vienna, Austria

Jennifer K. Barton

The University of Arizona, Tucson, AZ

Purchase article for $19

Subscribe to this journal for $129/year