Endoscope development for the clinical use of near infrared fluorescence molecular probes in the GI tract

分子探测器正在推动微创光学成像的发展，这种分子探测器可以通过 荧光。在癌症成像中的应用非常广泛，从癌症的早期诊断到 介入治疗的指导，如活检。广域荧光成像提供的高灵敏度，使用 扫描激光就是为这些广泛的应用而开发的。平台技术是SFE- 扫描光纤内窥镜，它将一个小于1毫米的扫描仪放置在高度灵活的轴的顶端。因为 几种不同波长的激光可以混合并扫描在一起，全彩反射成像将 结合近红外(NIR)荧光成像的4通道多模式超临界流体萃取。这样做的目的是 项目是开发用于特定癌症成像的VerAvanti 4通道多模式SFE(MmSFE)原型 对食道癌的早期发现和内窥镜治疗有重大影响的应用。 VerAvanti是一家位于华盛顿州雷德蒙德的初创公司，成立时拥有工程技术人员 毕业于华盛顿大学(UW)，SFE是在那里发明的，并在试点临床中进行了测试 审判。VerAvanti拥有将用于医学成像的SFE技术商业化的独家许可证，并拥有3- 通道全色SFE(使用红色、绿色和蓝色反射率)已经在试生产和测试中。 该项目将迅速将4声道MMSFE技术转化为荧光灯的特定产品 指导胃肠道的内窥镜干预。此外，VerAvanti MmSFE将为 模块化形式的高效制造，减少了部件数量，预期成本更低。 这项应用是使用密歇根大学开发的近红外荧光分子探测器 (Um)与高级别异型增生(HGD)和食管腺癌(EAC)肿瘤细胞结合。这个 MMSFE产品通过传统内窥镜的工作通道引入，以识别 食道下段过度表达EGFR和ErbB2，这是一种跨膜酪氨酸激酶 刺激上皮细胞生长、增殖和分化的受体。这些靶标的过度表达 反映了生物侵袭性的增加和进展到巴雷特食道，HGD， 和EAC。MMSFE诊断算法的设计是基于荧光的高相关性 与UW和UM合作进行病变目标到背景的测量。其他MMSFE指导工具 将开发使用近红外荧光分子探针进行更准确的内窥镜干预。两者都有 软件和硬件将进行制造和测试，以开始使用MMSFE的多点临床试验。

Minimally-invasive optical imaging is being advanced by molecular probes that enhance contrast using fluorescence. The applications in cancer imaging are very broad, ranging from early diagnosis of cancer to the guiding of interventions, such as biopsy. The high-sensitivity afforded by wide-field fluorescence imaging using scanning laser light is being developed for these broad applications. The platform technology is the SFE – Scanning Fiber Endoscope, which places a sub-1-mm scanner at the tip of a highly flexible shaft. Because several different laser wavelengths can be mixed and scanned together, full-color reflectance imaging will be combined with near infrared (NIR) fluorescence imaging in a 4-channel multimodal SFE. The goal of this project is to develop a prototype VerAvanti 4-channel multimodal SFE (mmSFE) for a specific cancer imaging application that can have significant impact in early detection and endoscopic treatment of esophageal cancer. VerAvanti is a start-up company located in Redmond, Washington and is founded and staffed with engineering graduates from the University of Washington (UW), where the SFE was invented and tested in pilot clinical trials. VerAvanti has exclusive license to commercialize the SFE technology for medical imaging and a 3- channel full color SFE (using red, green, and blue reflectance) is already in pilot manufacturing and testing. This project will rapidly translate the 4-channel mmSFE technology into a specific product for fluorescently guiding endoscopic interventions in the GI tract. Furthermore, the VerAvanti mmSFE will be designed for efficient manufacturing in a modular format with reduced part numbers and expected lower cost. The application is using NIR fluorescence molecular probes that were developed at the University of Michigan (UM) that bind to high grade dysplasia (HGD) and neoplastic cells of esophageal adenocarcinoma (EAC). The mmSFE product is introduced through the working channel of a conventional endoscope to identify regions of the lower esophagus that are over-expressing EGFR and ErbB2, which are transmembrane tyrosine kinase receptors that stimulate epithelial cell growth, proliferation, and differentiation. Overexpression of these targets reflects an increase in biological aggressiveness and higher risk for progression to Barrett's esophagus, HGD, and EAC. The design of the mmSFE diagnostic algorithm is based on the high correlation of the fluorescence lesion target-to-background measurement in collaboration with UW and UM. Additional mmSFE guided tools will be developed for more accurate endoscopic interventions using NIR fluorescence molecular probes. Both software and hardware will be fabricated and tested for the start of a multisite clinical trial using the mmSFE.