Pathologists review histology cut perpendicular to the tissue surface or in the vertical cross-section (XZ-plane) in order to visualize the normal or abnormal differentiation patterns. The epithelium of hollow organs, such as the colon, is the origin of many important forms of cancer. The vertical cross-section provides a comprehensive view of the epithelium which normally differentiates in the basilar to luminal direction. Real-time imaging in this orientation has not been fully explored in endomicroscopy because most instruments collect images in the horizontal cross-section (XY-plane). Imaging microstructures from the tissue surface to about half a millimeter deep can reveal early signs of disease. Furthermore, the use of molecular probes is an important, emerging direction in diagnostic imaging that improves specificity for disease detection and reveals biological function. Dysplasia is a pre-malignant condition in the colon that can progress into colorectal cancer. Peptides have demonstrated tremendous potential for in-vivo use to detect colonic dysplasia. Moreover, peptides can be labeled with NIR dyes for visualizing the full depth of the epithelium in small animals. This study aims to demonstrate large FOV multi-spectral targeted in-vivo vertical optical section with a dual axes confocal endomicroscope enabled by MEMS technology. The NIR multi-spectral fluorescence images demonstrate both histology-like morphology imaging and molecular imaging of specific peptide binding to dysplasia in the mouse colon. The specific aims of this study are: (1) to develop miniature vertical cross-sectional scan engine based on MEMS technology for imaging on XZ-plane; (2) to integrate micro-optics and develop multi-spectral dual axes confocal endomicroscope imaging system; (3) to perform in-vivo targeted vertical cross-sectional imaging with large FOV on colorectal cancer mouse model.
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