Integrated Imaging Methodology Detects Claudin-1 Expression in Premalignant Nonpolypoid and Polypoid Colonic Epithelium in Mice.

Autor:	Wang F; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Duan X; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Chen J; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Gao Z; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Zhou J; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Wu X; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Chang TS; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Lee M; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Li G; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Nusrat A; Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA., Kuick R; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA., Appelman HD; Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA., Wang TD; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk:	angličtina
Zdroj:	Clinical and translational gastroenterology [Clin Transl Gastroenterol] 2020 Jan; Vol. 11 (1), pp. e00089.
DOI:	10.14309/ctg.0000000000000089
Abstrakt:	Objectives: Conventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa. Methods: A peptide specific for claudin-1 is labeled with Cy5.5 and administrated intravenously in genetically engineered mice that develop adenomas spontaneously in the distal colon. Wide-field endoscopy is used to identify the presence of nonpolypoid and polypoid adenomas. Anatomic landmarks are used to guide placement of a confocal endomicroscope with side-view optics to visualize claudin-1 expression patterns with subcellular resolution. Results: Wide-field fluorescence images show peak uptake in colon adenoma at ∼1 hour after systemic peptide administration, and lesion margins are clearly defined. Further examination of the lesion using a confocal endomicroscope shows dysplastic crypts with large size, elongated shape, distorted architecture, and variable dimension compared with normal. The mean fluorescence intensity is significantly higher for dysplasia than normal. Increased claudin-1 expression in dysplasia vs normal is confirmed ex vivo, and the binding pattern is consistent with the in vivo imaging results. Discussion: Wide-field endoscopy can visualize molecular expression of claudin-1 in vivo to localize premalignant colonic mucosa, and confocal endomicroscopy can identify subcellular feature to distinguish dysplasia from normal.
Databáze:	MEDLINE
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