Confocal laser endomicroscopy (CLE) is a novel tool in the endoscopist’s armamentarium. It allows on-site histological information. The ability of gastroenterologists to interpret such microscopic information has been demonstrated in multiple studies from the upper and lower gastrointestinal tract. Recently, the field of application has expanded to provide hepatobiliary and intra-abdominal CLE imaging. CLE allows “smart,” targeted biopsies and is able to guide endoscopic interventions. But CLE is also translational in its approach and permits functional imaging that significantly impacts on our understanding of gastrointestinal diseases. Molecular imaging with CLE allows detection and characterization of lesions and may even be used for prediction of response to targeted therapy. This paper provides a comprehensive review over current applications of CLE in clinical applications and translational science. 1. Introduction Confocal laser endomicroscopy (CLE) is a novel endoscopic method that permits on-site microscopy of the gastrointestinal mucosa after the application of a fluorescent agent. Since the first description in 2004 [1], the number of diseases studied with this technique has been steadily growing [2–9]. Trials with CLE have moved from feasibility studies in different parts of the endoscopically accessible areas of the gastrointestinal tract towards inflammatory and (pre-) neoplastic diseases that are often only incompletely appreciated by random biopsies. Here, CLE is the tool to enable “smart” biopsies, biopsies that are targeted to areas of interest by means of intravital microscopy. But indications have broadened from the upper and lower GI tract towards intravital microscopy of the biliary tract, the liver or pancreas. In addition, endoscopic disciplines outside the field of gastroenterology have evaluated CLE within their field. The option of intravital microscopy makes CLE an ideal tool to study pathophysiological events dynamically in their natural surroundings in patients. Labeling of molecular targets links clinical patient care to translational science. 2. Technique of Endomicroscopy and Staining Protocols 2.1. Technique of Confocal Endomicroscopy Light microscopy uses white light in the visible range and lens systems for magnification. This necessitates incident light shining through thin, translucent tissue section in bench top light microscopy. For endoscopy, ultrahigh magnification endoscopes have been developed (“Endocytoscopy”) that deliver high resolution images of the uppermost epithelial layer of the gastrointestinal tract.
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