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.

中文翻译：

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综合成像方法检测小鼠癌前非息肉和息肉结肠上皮中 Claudin-1 的表达。

目标 传统的白光结肠镜检查仅根据结构变化检测结肠腺瘤，并且受到高漏诊率的限制。我们的目标是展示一种集成的成像策略，该策略结合了广域内窥镜检查和共聚焦内窥镜检查，以可视化体内分子表达模式，以检测癌前结肠黏膜。方法 claudin-1 特异性肽用 Cy5.5 标记，并在远端结肠自发形成腺瘤的基因工程小鼠中静脉内给药。广角内窥镜检查用于识别非息肉样和息肉样腺瘤的存在。解剖标志用于指导放置带有侧视光学器件的共聚焦内窥镜，以亚细胞分辨率可视化 claudin-1 表达模式。结果 宽视场荧光图像显示在全身肽给药后约 1 小时结肠腺瘤的吸收峰值，并且病灶边缘清晰。使用共聚焦内窥镜进一步检查病变显示发育不良的隐窝，与正常相比具有大尺寸、细长形状、扭曲结构和可变尺寸。发育异常的平均荧光强度显着高于正常值。离体证实异型增生与正常情况下 claudin-1 表达增加，结合模式与体内成像结果一致。讨论 大视野内镜可以观察体内 claudin-1 的分子表达以定位癌前结肠黏膜，共聚焦内镜可以识别亚细胞特征以区分发育异常和正常。