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


METHODS
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 microm axial and 4.4 microm 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.
Hariri
Lida P
LP
Division of Biomedical Engineering, The University of Arizona, Tucson, Arizona 85721, USA.
Qiu
Ziping
Z
Tumlinson
Alexandre R
AR
Besselsen
David G
DG
Gerner
Eugene W
EW
Ignatenko
Natalia A
NA
Povazay
Boris
B
Hermann
Boris
B
Sattmann
Harald
H
McNally
James
J
Unterhuber
Angelika
A
Drexler
Wolfgang
W
Barton
Jennifer K
JK
D000236:Adenoma / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D016099:Endoscopy, Gastrointestinal; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D051379:Mice; D041623:Tomography, Optical Coherence / Q000379:methods*
D001397:Azoxymethane