Combined OCT/FLIM Biochemical and Anatomical Imaging for Early Cancer Diagnosis

描述(申请人提供)：早期发现口腔中的肿瘤性变化对提高存活率和幸存者的生活质量具有很大的希望。光学成像的高空间分辨率使肿瘤性病变的诊断成为可能，而肿瘤性病变的大小仍在亚毫米范围，且高度可治疗。从正常组织到肿瘤组织的转变伴随着生化和形态的变化。然而，迄今为止被研究为癌症的潜在筛查和诊断工具的光学技术主要集中于检测其中之一，主要是因为基本上缺乏容易提供这两种类型信息的光学成像模式。在这里，我们建议通过结合两种成熟的光学成像技术，光学相干层析成像(OCT)和荧光寿命成像(FLIM)来同时收集形态和生化信息。由于OCT和FLIM分别测量不同的组织特征(分别是结构和生化)，我们假设与各自独立应用的方法相比，它们的协同作用将提高检测早期上皮癌的敏感性和特异性。这项研究的最终目标是开发一种新的光学成像系统和相关算法，用于口腔癌的非侵入性光学活检。这样的系统可以作为诊断和监测工具、筛查工具、标准活检和外科干预指南以及治疗反应的定量评估工具。虽然这项提议的重点是口腔癌的早期检测，但我们相信所开发的系统和算法也将普遍适用于许多上皮癌。目标1：将OCT和FLIM技术相结合，开发一种新的光学多模成像系统，用于同时进行体内和体外组织的显微解剖和生化成像。目的2：建立金黄地鼠颊囊口腔癌变的OCT/Flim图像及相应的组织病理学数据库。目的：开发新的OCT/FLIM图像分析计算方法，评价所提出的多模式成像系统在口腔肿瘤早期诊断中的敏感性和特异性。这项工作的成功完成将展示OCT和FLIM相结合作为一种无创光学检测手段对口腔癌前病变和恶性病变进行检测的潜力。 公共卫生相关性：早期发现口腔上皮癌可以显著降低癌症发病率和死亡率。目前，口腔上皮癌的诊断是通过直接或内窥镜检查，然后进行活检。由于肉眼检查是主观的，而且早期癌前病变通常在肉眼检查下是无法发现的，因此必须进行多次活组织检查以增加发现癌症病变的可能性。因此，需要能够比目视检查更准确地诊断口腔上皮癌前病变和癌症的技术来指导组织活检。光学成像特别适合于对包括口腔在内的许多身体上皮组织进行成像。从正常组织到肿瘤组织的转变伴随着生化和形态的变化，但迄今为止被研究为癌症潜在筛查和诊断工具的光学技术主要集中在其中之一。在这里，我们建议通过结合两种成熟的光学成像技术，光学相干层析成像(OCT)和荧光寿命成像(FLIM)来同时收集形态和生化信息。这项研究的最终目标是开发一种新的光学成像系统和相关算法，使口腔癌的非侵入性光学活检成为可能。

DESCRIPTION (provided by applicant): Early detection of neoplastic changes in the oral cavity holds great promise for improving survival rates and the quality of life of survivors. The high spatial resolution of optical imaging could make possible the diagnosis of neoplastic lesions while they are still in the submillimeter range in size and highly treatable. Both biochemical and morphological changes accompany the transition from normal tissue to neoplastic tissue. Yet the optical techniques heretofore investigated as potential screening and diagnostic tools for cancer have largely concentrated on detecting one or the other, principally because of the fundamental lack of optical imaging modalities which readily provide both types of information. Here we propose to simultaneously collect morphological and biochemical information by combining two well developed optical imaging techniques, optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIM). Since OCT and FLIM measure different tissue characteristics (structural and biochemical, respectively), we hypothesize that their synergy will increase the sensitivity and specificity for detecting early epithelial cancer, compared to each modality applied independently. The ultimate goal of this line of research is to develop a novel optical imaging system and associated algorithms for noninvasive optical biopsy in oral cancer. Such a system may serve as a diagnostic and monitoring tool, a screening tool, a guide to standard biopsy and surgical intervention, and a tool for quantitative evaluation of therapeutic response. While this proposal is focused on the early detection of oral cancer we believe that the system and algorithms developed will also be generally applicable to many of the cancers of the epithelium. The following three specific aims will be addressed in this proposal: Aim 1: To develop a novel optical multimodality imaging system by combining OCT and FLIM technology for simultaneous micro-anatomical and biochemical imaging of tissue in vivo and ex vivo. Aim 2: To acquire a unique database of OCT/FLIM images and corresponding histopathology of the development of oral cancer in a hamster cheek pouch model. Aim 3: To develop new computational methods for OCT/FLIM image analysis and evaluate the sensitivity/specificity of the proposed multimodality imaging system for the early detection of oral neoplasia. The successful completion of this work will demonstrate the potential of combining OCT and FLIM as a means for non-invasive optical detection of oral pre-malignant and malignant lesions. PUBLIC HEALTH RELEVANCE: Early detection of epithelial oral cancer could significantly reduce cancer morbidity and mortality. Currently, the diagnosis of oral epithelial cancers is performed through direct or endoscopic visual inspection followed by biopsy. Since visual inspection is subjective and early pre-cancers are often not detectable under visual inspection, multiple biopsies have to be taken to increase the likelihood of finding a cancerous lesion. Therefore, techniques that can diagnose oral epithelial pre-cancer and cancer with higher accuracy than visual inspection alone are needed to guide tissue biopsy. Optical imaging is particularly well suited for imaging many of the epithelial tissues of the body including the oral cavity. Both biochemical and morphological changes accompany the transition from normal tissue to neoplastic tissue, yet the optical techniques heretofore investigated as potential screening and diagnostic tools for cancer have largely concentrated on one or the other. Here we propose to simultaneously collect both morphological and biochemical information by combining two well developed optical imaging techniques, optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIM). The ultimate goal of this line of research is to develop a novel optical imaging system and associated algorithms which will enable noninvasive optical biopsy in oral cancer.