DECTECTION OF EARLY CANCER USING FUNCTIONAL OPTICAL COHERENCE TOMOGRAPHY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肺癌是迄今为止美国男性和女性癌症死亡的主要原因（1-3）。肺癌的成功治疗需要早期诊断。 然而，绝大多数肺癌在晚期被诊断出来，此时生存率很低。 需要用于成像和诊断肺癌的改进的方法。 随着分辨率、对比度和探头的改进，光学相干断层扫描（OCT）提供了帮助实现这一目标的潜力。 我们建议，在未来的多模态光学成像，结合自发荧光，高分辨率OCT，和多光子/共焦内窥镜可能最终提供一个完全有效的方法来解决这个问题。 该提案涉及这一概念的初始阶段：开发和优化用于诊断早期气道癌的OCT。 我们建议，高分辨率，在体内胸腔镜三维（3-D）OCT可以帮助诊断恶性相关的表面和亚表面形态和结构的变化，以提高支气管镜下气道癌症的诊断能力。 拟议研究的目标是：1）开发实时高速柔性光纤和刚性内窥镜技术，用于气道和胸膜恶性病理生理变化的3维近组织学分辨率光学可视化，2）增强光学对比度以改善诊断成像辨别，3）在动物模型中转化和优化该技术，以及4）将内窥镜OCT技术应用于临床研究中的体内，以证明提高诊断和治疗支气管气道癌患者的灵敏度和特异性的可行性。 这项建议的具体目标是： 1. 开发、集成和利用i）基于MEMS的小直径柔性光纤3-D支气管镜，和ii）刚性内窥镜3-D OCT探头。 2. 开发和测试抗体导向的金纳米粒子脂质体OCT组织对比度增强方法。 使用OCT、增强组织造影剂OCT对正常和恶性切除动物模型组织进行成像，并将结构图像与组织学图像进行比较。 3. 在初始临床前动物研究中，使用口腔癌和胸膜肿瘤动物模型评价F-OCT内窥镜设计和对比度增强方法，以推进技术交付、对比度和分析方法，用于临床气道恶性肿瘤的后续应用， 4. 对具有以下表现类别的人体气道和胸膜标本进行成像：1-正常，2  化生，3  恶性肿瘤和4-良性“阴性对照”气道异常，包括肉芽肿、狭窄和肉芽组织，以确定3-D F-OCT诊断参数的分辨率、穿透深度和区分病理异常的能力。 5. 进行临床研究，以证明高分辨率内窥镜F-OCT用于早期支气管内膜癌检测的可行性，以及诊断支气管内膜癌的能力，与组织学相比，其特异性和灵敏度有所提高。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lung cancer is by far the leading cause of cancer death in both men and women in the United States (1-3). Successful treatment of lung cancer requires early diagnosis. However, the vast majority of lung cancer is diagnosed at late stage when survival is poor. Improved methods for imaging and diagnosing lung cancers are needed. With improvements in resolution, contrast and probes, optical coherence tomography (OCT) offers the potential to help achieve this objective. We propose that in the future multimodality optical imaging, combining autofluorescence, ultrahigh resolution OCT, and multi-photon/confocal endoscopy may ultimately provide a fully effective approach to this problem. This proposal addresses the initial phases of this concept: development and optimization of OCT for diagnosis of early airway cancer. We propose that high resolution, in-vivo thoracic endoscopic three dimensional (3-D) OCT can help diagnose malignancy-related surface and subsurface morphological and structural changes in order to advance bronchoscopic airway cancer diagnostic capabilities. The objectives of the proposed research are to: 1) develop real-time high speed flexible fiberoptic and rigid endoscopic techniques for 3-dimensional near histologic-resolution optical visualization of airway and pleural malignant pathophysiologic changes, 2) enhance optical contrast to improve diagnostic imaging discrimination, 3) translate and optimize this technology in animal models, and 4) apply endoscopic OCT technology in-vivo in clinical studies to demonstrate feasibility for improving sensitivity and specificity of diagnosis and treatment in patients with bronchogenic airway cancers. The specific aims of this proposal are to: 1. Develop, integrate, and utilize i) small diameter flexible fiberoptic 3-D bronchoscopic MEMS based, and ii) rigid endoscopic 3-D OCT probes. 2. Develop and test antibody directed gold nano-particle liposomal OCT tissue contrast enhancement methods. Image normal and malignant excised animal model tissue with OCT, enhanced tissue contrast agent OCT, and compare structural images to histology. 3. Evaluate F-OCT endoscopy designs and contrast enhancement methods using oral cancer and pleural tumor animal models in initial pre-clinical animal studies to advance technical delivery, contrast, and analytical methods for subsequent application to clinical airway malignancy, 4. Image human airway and pleural specimens with the following categories of presentations: 1- normals, 2  metaplasia, 3  malignant neoplasia, and 4- benign "negative control" airway abnormalities including granulomas, strictures, and granulation tissue to determine capabilities of 3-D F-OCT diagnostic parameters of resolution, depth of penetration, and ability to differentiate pathologic abnormalities. 5. Perform clinical investigations to demonstrate high resolution endoscopic F-OCT feasibility for early endobronchial cancer detection and the ability to diagnose endobronchial cancer with improved specificity and sensitivity compared to histology.