Background and ObjectiveColorectal cancer (CRC) remains the second deadliest cancer in the United States. Several screening methods exist; however, detection of small polyps remains a challenge. Optical coherence tomography (OCT) has been demonstrated to be capable of detecting lesions as small as 1mm in the mouse colon, but detection is based on measuring a doubling of the mucosa thickness. The colon microvasculature may be an attractive biomarker of early tumor development because tumor vessels are characterized by irregular structure and dysfunction. Our goal was to develop an endoscopic method of detecting and segmenting colon vessels using Doppler OCT to enable future studies for improving early detection and development of novel chemopreventive agents. MethodWe conducted in vivo colon imaging in an azoxymethane (AOM)-treated mouse model of colorectal cancer using a miniature endoscope and a swept-source OCT system at 1,040nm with a 16kHz sweep rate. We applied the Kasai autocorrelation algorithm to laterally oversampled OCT B-scans to resolve vascular flow in the mucosa and submucosa. Vessels were segmented by applying a series of image processing steps: (i) intensity thresholding; (ii) two-dimensional matched filtering; and (iii) histogram segmentation. ResultsWe observed differences in the vessels sizes and spatial distribution in a mature adenoma compared to surrounding undiseased tissue and compared the results with histology. We also imaged flow in four young mice (two AOM-treated and two control) showing no significant differences, which is expected so early after carcinogen exposure. We also present flow images of adenoma in a living mouse and a euthanized mouse to demonstrate that no flow is detected after euthanasia. ConclusionWe present, to the best of our knowledge, the first Doppler OCT images of in vivo mouse colon collected with a fiber-based endoscope. We also describe a fast and robust image processing method for segmenting vessels in the colon. These results suggest that Doppler OCT is a promising imaging modality for vascular imaging in the colon that requires no exogenous contrast agents. (C) 2016 Wiley Periodicals, Inc.