“Evaluation of Mouse Models of Colorectal Cancer Using Optical Coherence Tomography and Laser Induced Flourescence Spectroscopy
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Abstract: Colorectal cancer (CRC) is the third leading cause of cancer related deaths. Rodent models of colorectal disease are useful for evaluating diagnostic tools, therapeutics, and disease progression; however, an appropriate imaging tool is needed. Optical coherence tomography (OCT) uses a near-infrared light source to generate structural images from refractive index mismatches with resolutions of 2-15 mm at imaging depths of up to 2 mm. In contrast, laser-induced fluorescence (LIF) spectroscopy provides information about biochemical composition, exciting tissues with ultraviolet to green wavelengths of light and measuring fluorescence emission from endogenous fluorophores. Both modalities are non-destructive and can be readily packaged into small diameter endoscopes
OCT and LIF are applied to mouse models of colorectal disease, beginning with a comprehensive ex-vivo evaluation of normal mouse gastrointestinal (GI) tract in various strains and ages and secondarily sampled colorectal neoplasia and inflammatory bowel disease (IBD) using a combined in-air OCT/LIF system. Characteristic features of OCT images were identified for normal GI tract, colorectal neoplasia, and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin.
Next, endoscopic OCT/LIF was evaluated in an in-vivo serial study using a prototype 2 mm diameter endoscope to image the lower colon of ApcMin and control mice. Adenoma development over OCT imaging timepoints was characterized as a progressive mucosal thickening to frank mass formation. LIF revealed decreased 405 nm emission intensity and the presence of an emission peak at 680 nm over adenoma.
In a final study, ultrahigh resolution OCT (UHR OCT) was used to serially image the lower colon of azoxymethane treated A/J mice to monitor colorectal neoplasm progression and determine OCT’s capability of identifying early disease. A panel of blinded mouse colon pathology experts assigned a diagnosis based the OCT images, which was then compared to a histological diagnosis assigned by a blinded pathologist. Endoscopic UHR OCT enabled accurate diagnosis of adenomas, identification of protruding GIN, and non-destructive visualization of colorectal neopslasm progression, providing a tool for cancer research in animal models. |