Depth-resolved Quantitative Multi-Modal Imaging for GI Cancer Detection

描述（由申请人提供）：早期发现肿瘤改变仍然是临床癌症诊断和治疗的关键挑战。许多癌症起源于上皮层，如胃肠道。白光内镜引导下的切除活检和组织病理学是目前胃肠道肿瘤诊断的金标准。然而，由于采样误差，该方法存在较高的假阴性率。此外，相当一部分（~10%- 30%）的患者在内镜下消融治疗后发现新上皮下存在化生或发育不良，这与癌症发展的风险有关。目前标准的内窥镜技术无法检测到这些表面下病变。因此，迫切需要开发新的诊断工具，以评估跨粘膜深度的组织结构和分子信息，以改进对表面下癌症的检测，并评估病变的浸润深度。由于癌症的发展与形态和分子改变有关，一种能够定量成像组织的形态和分子生物标志物，并在体内实时评估病变的深度和范围，而不需要组织切除的成像技术，将是胃肠道癌症诊断和治疗的重大进步。本应用程序的目的是开发用于胃肠道癌症检测的新一代多模态深度分辨率成像技术。该建议建立在我们的新型多模态光学成像平台上，该平台结合了高分辨率光学相干断层扫描（OCT）和深度分辨率高灵敏度荧光层流光学断层扫描（FLOT），可同时进行结构和分子成像。我们对动物模型的多模态成像的广泛初步数据表明，同时定量成像结构和分子信息的可行性，以更准确的诊断和预后。为了建立OCT/FLOT对胃肠道肿瘤的诊断能力，我们建议开展一项探索性/发展性研究（Exploratory/Developmental Research, R21），以实现以下三个具体目标：1)利用OCT/FLOT对胃肠道肿瘤动物模型进行成像，并获得相关的组织病理学诊断。2)从共配准OCT/FLOT图像中开发定量结构和分子成像参数，用于多参数分析。3)建立OCT/FLOT对胃肠道肿瘤检测的敏感性、特异性和诊断准确性，验证联合信息较单一模式增强肿瘤检测的假设。如果成功，该项目将产生一种全新的非侵入性多模态成像技术，用于改善胃肠道癌症检测，这可以很容易地转化为胃肠道诊所的内窥镜成像。预计它将对胃肠道癌症以及广泛的上皮性癌症的检测、诊断和表征产生重大影响。

DESCRIPTION (provided by applicant): Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. White-light endoscopy guided excisional biopsy and histopathology is currently the gold standard for GI cancer diagnosis. However, it suffers from high false negative rates due to the sampling errors. Furthermore, a significant portion (~10%- 30%) of patients after endoscopic ablative therapeutic treatment showed the presence of metaplasia or dysplasia buried underneath the neo-epithelium, which is associated with the risk of cancer development. Current standard endoscopic technology is unable to detect those subsurface lesions. Therefore, there is a critical need for developing new diagnostic tools which can assess tissue architectural and molecular information across the mucosal depth for improved detection of subsurface cancer, and evaluate the invasion depth of a lesion. Since cancer development is associated with in both morphological and molecular alterations, an imaging technology that can quantitative image tissue's morphological and molecular biomarkers and assess the depth- extent of a lesion in vivo and in real time, without the need for tissue excision, would be a major advance in GI cancer diagnostics and therapy. The objective of this application is to develop a new generation of multi-modal depth-resolved imaging technology for GI cancer detection. This proposal is built upon our novel multi-modal optical imaging platform combining high-resolution optical coherence tomography (OCT) and depth-resolved high-sensitivity fluorescence laminar optical tomography (FLOT) for simultaneous structural and molecular imaging. Our extensive preliminary data on multi-modal imaging of animal models demonstrates the feasibility for simultaneous quantitative imaging of structural and molecular information for more accurate diagnosis and prognosis. To establish the diagnostic ability of OCT/FLOT for GI cancer detection, we propose to pursue an Exploratory/Developmental Research (R21) to pursue three specific aims: 1) Image an animal model of GI cancer using OCT/FLOT and obtain the correlated histopathological diagnosis. 2) Develop quantitative structural and molecular imaging parameters from co-registered OCT/FLOT images for multi-parametric analysis. 3) Establish the sensitivity, specificity, and diagnostic accuracy of OCT/FLOT for GI cancer detection, and test the hypothesis of enhanced cancer detection using combined information compared to single modality alone. If successful, this project will result in a fundamentally new non-invasive multi-modal imaging technology for improved GI cancer detection, which can be readily translated into endoscopic imaging in the GI clinics. It is expected to have a major impact on detection, diagnosis, and characterization of GI cancers, as well as a wide range of epithelial cancers. PUBLIC HEALTH RELEVANCE: Early detection of neoplastic changes especially those buried underneath the surface remains a critical challenge in clinical cancer diagnosis and treatment of the gastrointestinal (GI) tract. The objective of this application is to develop a new generation of multi-modal depth-resolved imaging technology for depth- resolved structural and molecular imaging for enhanced GI cancer detection. If successful, this project will result in a new non-invasive multi-modal imaging technology that can be readily translated into endoscopic imaging of GI cancers, as well as a wide range of epithelial cancers.