(PQ7) In Vivo Cellular Optical Imaging of Esophageal Tumors and Microenvironment

 描述(申请人提供)：在这项申请中，我们建议开发体内自然对比度内窥镜成像系统，该系统可以识别食道癌肿瘤的细胞成分及其微环境，以确定癌症治疗的最佳疗程。食道癌是最致命的癌症之一，总的五年生存率为14%。在可手术的癌症中，存活率为22%，如果在手术前使用化疗作为新的辅助治疗，存活率将增加到37%。目前，有几种FDA批准的化疗药物，可以以各种组合使用。这些药物中的每一种都针对特定类型的癌细胞。因为肿瘤几乎总是由几种类型的癌细胞组成，所以联合疗法是最有效的。现有唯一确定癌症细胞类型的方法是组织病理学，这种方法只对一小部分肿瘤进行采样，鉴于不同肿瘤区域之间的巨大异质性，很容易出现活检错误。此外，目前还没有很好的方法来确定癌症对化疗的反应性，这与组成肿瘤的细胞类型和肿瘤微环境密切相关。因此，确定食道癌治疗的最佳靶向治疗的最大障碍是缺乏能够识别癌细胞类型、肿瘤微环境并能够密切监测治疗进展的体内成像方法。由于其能够感知肿瘤的细胞组织和识别细胞类型，同时提供大体解剖成像，基于光散射光谱(LSS)的成像将被独特地配备来解决识别癌症肿瘤的细胞类型和细胞类型分布的问题。我们建议用漫反射光谱(DRS)信息来补充LSS信息，DRS信息对肿瘤的微环境敏感，如血管生成程度和结缔组织密度。因此，本项目的目的是扩展LSS和DRS技术，开发自主对比度实时双模式内窥镜光谱成像系统(DMESIS)，并通过与肿瘤活检组织病理学结果的比较，在临床实验中对可疑食管癌患者进行测试。

 DESCRIPTION (provided by applicant): In this application we propose to develop the in vivo native contrast endoscopic imaging system that can identify cellular composition of the esophageal cancer tumors and their microenvironment in order to determine the optimal course of cancer therapy. Esophageal cancer is one of the deadliest forms of cancers with an overall 14% five-year survival rate. The survival rate among operable cancers is 22%, which increases to 37% with the use of chemotherapy prior to surgery as a neoadjuvant therapy. Currently, there are several FDA-approved chemotherapy drugs, which can be used in various combinations. Each of these drugs targets particular cancer cell types. Because tumors are almost always composed of several cancer cell types, combinatorial therapies are most effective. The only existing way of determining the cell type of the cancer is histopathology, which samples a small proportion of the tumor and, given the large heterogeneity between different tumor areas, is prone to biopsy errors. Additionally, there is no good way of determining the cancer responsiveness to the chemotherapy, which is closely related to the types of cells composing the tumor and the tumor microenvironment. Thus, the largest impediment for determining optimal targeted therapies for esophageal cancer treatment is the absence of the in vivo imaging method that can identify cancer cell types, tumor microenvironment, and are able to closely monitor treatment progress. Due to its ability to sense cellular organization of tumors and identify cell types, while providing gross anatomical imaging, light scattering spectroscopy (LSS) based imaging would be uniquely equipped to address the problem of identifying the cytotypes and cytotype distributions of cancer tumors. We propose to complement LSS information with diffuse reflectance spectroscopy (DRS) information which is sensitive to the microenvironment of the tumor, such as degree of angiogenesis and connective tissue density. Therefore, the purpose of this program is to extend the LSS and DRS technologies and develop native contrast real time dual mode endoscopic spectral imaging system (DMESIS) and test it in clinical experiments in patients with suspected esophageal cancer by comparing to histopathology results from tumor biopsies.