University of Cambridge, Department of Physics, JJ Thomson Avenue, Cambridge CB3 0HE, United KingdombUniversity of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
J Biomed Opt. 2016 Aug 1;21(8):84001. doi: 10.1117/1.JBO.21.8.084001.
Barrett’s esophagus is a known precursor lesion to esophageal adenocarcinoma. In these patients, early detection of premalignant disease, known as dysplasia, allows curative minimally invasive endoscopic therapy, but is confounded by a lack of contrast in white light endoscopy. Imaging fluorescently labeled lectins applied topically to the tissue has the potential to more accurately delineate dysplasia, but tissue autofluorescence limits both sensitivity and contrast when operating in the visible region. To overcome this challenge, we synthesized near-infrared (NIR) fluorescent wheat germ agglutinin (WGA-IR800CW) and constructed a clinically translatable bimodal NIR and white light endoscope. Images of NIR and white light with a field of view of 63 deg and an image resolution of 182 μm are coregistered and the honeycomb artifact arising from the fiber bundle is removed. A minimum detectable concentration of 110 nM was determined using a dilution series of WGA-IR800CW. We demonstrated ex vivo that this system can distinguish between gastric and squamous tissue types in mouse stomachs (p=0.0005) and accurately detect WGA-IR800CW fluorescence in human esophageal resections (compared with a gold standard imaging system, rs>0.90). Based on these findings, future work will optimize the bimodal endoscopic system for clinical trials in Barrett’s surveillance.
巴雷特食管是食管腺癌的已知前体病变。在这些患者中，早期检测癌前病变（称为异型增生），可以通过微创内窥镜治疗达到治愈效果，但由于白光内窥镜对比度不足而变得复杂。对组织进行荧光标记的凝集素的成像具有更准确地区分异型增生的潜力，但当在可见区域操作时，组织自发荧光会限制敏感性和对比度。为了克服这一挑战，我们合成了近红外（NIR）荧光麦胚凝集素（WGA-IR800CW），并构建了一种可临床转化的近红外和白光双模态内窥镜。视野为 63 度且图像分辨率为 182 μm 的近红外和白光图像进行了配准，并且消除了光纤束产生的蜂窝状伪影。使用 WGA-IR800CW 的稀释系列确定了最小可检测浓度为 110 nM。我们在离体实验中证明，该系统可以区分小鼠胃中的胃和鳞状组织类型（p=0.0005），并且可以准确检测人食管切除术中的 WGA-IR800CW 荧光（与金标准成像系统相比，rs>0.90）。基于这些发现，未来的工作将优化双模态内窥镜系统，以用于 Barrett 监测的临床试验。
