Multimodality Microendoscope for Metastatic Ovarian Cancer Detection & Treatment

描述(申请人提供)：卵巢上皮癌是美国女性癌症死亡的第五大原因，也是所有妇科癌症中死亡率与病例比最高的。卵巢癌尤其危险，因为它有快速转移的倾向，因为这种疾病通过从原始肿瘤上剥离来侵袭整个腹部的组织。所有卵巢癌死亡的90%来自这种隐蔽的转移性疾病，这种疾病通常由大量极难发现的微转移组成。虽然已经使用了白光和荧光内窥镜，但它们的选择性和灵敏度太有限，无法在没有高假阳性和假阴性率的情况下准确地检测出微小的、致命的转移瘤。由于没有能力检测这种亚临床疾病状态，许多妇女错过了替代化疗或放射治疗可能挽救生命的关键时期。这个项目的长期目标是通过建立、测试和部署一种灵敏的微转移检测新范式来提高卵巢癌惨淡的存活率(30%)。在第一个目标中，该方案将可疑肿瘤的原位荧光可视化与结构敏感的光学相干断层成像(OCT)成像技术相结合，为卵巢癌的诊断提供了一种选择性、灵敏和全定量的显微成像探针。通过利用荧光检测进行快速检查和OCT进行三维结构成像，这种原位探针不仅可以显示肿瘤，还可以显示其潜在的组织结构、大小和血管系统。这种方法将被实现为由数万个单独的图像元素组成的显微内窥镜，这些图像元素被近端扫描，以确保用于微创成像的小的远端形状因数。在第二个具体目标中，将使用三维肿瘤模型和体外组织进行广泛的表征和编目，以便多模式对比可以用于任何组织中隐匿性转移疾病的原位诊断。这些实验将立即用于第三个目标，即使用显微内窥镜原位评估两种治疗方案的播散性卵巢癌小鼠模型的微转移治疗效果。其中一个实验将研究化疗药物阿霉素的有效性，而第二个方法将使用光动力疗法，即光敏剂被用来产生细胞毒物质来摧毁肿瘤。 公共卫生相关性：该项目建议构建一种新的显微纤维探头，用于选择性检测致命的卵巢癌转移肿瘤。通过检测这些转移，这项研究旨在极大地改进卵巢癌的检测和后续治疗，以挽救患有这种疾病的妇女的生命。

DESCRIPTION (provided by applicant): Ovarian epithelial cancer is the fifth leading cause of cancer death among women in the US, and has the highest fatality-to-case ratio of all gynecological cancers. Ovarian cancer is especially dangerous due to its propensity to rapidly metastasize, as the disease invades tissues throughout the abdomen by exfoliating from the original tumor. 90% of all ovarian cancer fatalities arise from this occult metastatic disease, which often is composed of a multitude of micrometastases that are exceedingly difficult to detect. While white-light and fluorescence endoscopy have been used, their selectivity and sensitivity have been too limited to accurately detect the microscopic, deadly metastases without high false-positive and false-negative rates. Without the ability to detect this sub-clinical disease state, many women miss a critical period where alternative chemotherapy or radiation treatment might be lifesaving. It is the long-term goal of this project to improve the dismal survival rates (<30%) of ovarian cancer by building, testing, and deploying a sensitive new paradigm for micrometastases detection. In the first aim, this proposal combines the visualization of suspect tumors in situ by fluorescence with the structurally sensitive optical coherence tomography (OCT) imaging technology to provide a selective, sensitive, and fully quantitative microscopic imaging probe for ovarian cancer diagnostics. By utilizing the fluorescence detection for rapid examination and OCT for 3D structural imaging, this in situ probe will not only visualize a tumor, but also render its underlying tissue structure, size, and vasculature. This approach will be realized as a microendoscope composed of tens of thousands of individual image elements that are scanned proximally to ensure a small distal form factor for minimally invasive imaging. In the second specific aim, three-dimensional tumor models and ex vivo tissues will be used for extensive characterization and cataloging so that the multimodal contrast can be used for in situ diagnosis of occult metastatic disease in any tissue. These experiments will find immediate use in the third aim, where the microendoscope will be used in situ to assess micrometastases treatment effectiveness in a mouse model of disseminated ovarian cancer for two treatment regimens. One experiment will study the effectiveness of the chemotherapy Adriamycin, while a second approach will use photodynamic therapy, where photosensitizers are used to generate cytotoxic species for tumor destruction. PUBLIC HEALTH RELEVANCE: This project proposes the construction of a new microscopic fiber probe for the selective detection of deadly ovarian cancer metastatic tumors. By detecting these metastases, this research aims to vastly improve the detection and subsequent treatment of ovarian cancer to save the lives of women with this disease.