Quantitative image analysis applied in other microendoscopy studies include texture features of ovarian cancer confocal microendoscopy, cell density in mouse model sarcomas using wide-field structured illumination, and wavelet decomposition in color colonoscopic video frames.22–24 These algorithms quantify a range of image features, such as texture (including spatial-frequency content), cell nuclei image segmentation and counting, and discrete wavelet transform and covariance.22–24 There are numerous image features that could be extracted for quantification, depending on the data acquired by the imaging modality, but for the quantification of image features in fluorescence microendoscopy of nonspecific staining of bulk tissue, we chose image features that trained clinicians would typically consider in their analysis, namely crypt shape, size, and homogeneity. Pathologists who study en face histopathology of colorectal tissue for signs of dysplasia take into account image features such as elongated or branched crypts, clusters of crypts or crypts of abnormal size, irregular contours, and stratification of the nuclei surrounding the crypt. While pathologists commonly use nucleic patterns as a marker for abnormality, due to the length of the colorectal tract, it is of greater relevance during microendoscopic screening to use a fiber bundle with a larger field of view than to acquire images that resolve individual nuclei. Therefore, the algorithm we developed focuses on quantifying the larger structures of epithelial morphology such as crypt area and circularity. Additionally, the extent to which image morphology varies in clinically normal colorectal tissue in patients with different clinical histories, such as diagnosis, chemotherapy, radiation, prior surgeries, or other therapy, has not been described or quantified. There is a significant need for a quantitative benchmark for future detection of occult dysplasia in patients who have a range of diagnoses and/or prior treatment, and a need for generalized image analysis tools for advanced microendoscopy imaging modalities within the gastrointestinal tract.