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

描述(申请人提供)：肿瘤变化的早期检测在临床癌症诊断和治疗中仍然是一个关键的挑战。许多癌症起源于胃肠道等上皮层。白光内窥镜引导下的切除活检和组织病理学是目前诊断胃肠道癌症的金标准。然而，由于采样误差，它存在较高的假阴性率。此外，很大一部分(~10%-30%)的患者在接受内窥镜消融治疗后显示出新生上皮下的化生或异型增生，这与癌症发展的风险有关。目前的标准内窥镜技术无法检测到这些表面下的病变。因此，迫切需要开发新的诊断工具来评估跨粘膜深度的组织结构和分子信息，以改进对亚表面癌症的检测，并评估病变的侵袭深度。由于癌症的发展与形态和分子的改变都有关，因此能够对组织的形态和分子生物标记物进行定量成像并在体内实时评估病变的深度和范围而不需要切除组织的成像技术将是胃肠道癌症诊断和治疗的重大进步。这项应用的目标是开发新一代用于胃肠道癌症检测的多模式深度分辨成像技术。这一建议建立在我们的新型多模式光学成像平台上，该平台结合了高分辨率光学相干层析成像(OCT)和深度分辨高灵敏度荧光层流光学层析成像(FLOT)，用于同时进行结构和分子成像。我们在动物模型多模式成像方面的大量初步数据表明，同时定量成像结构和分子信息以实现更准确的诊断和预后是可行的。为了建立OCT/FLOT对GI癌的诊断能力，我们建议进行一项探索性/发展性研究(R21)，以追求三个特定的目标：1)应用OCT/FLOT建立GI癌动物模型，并获得相关的组织病理学诊断。2)从共同配准的OCT/FLOT图像中提取定量的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，并与单一模式相比，验证联合信息增强癌症检测的假说。如果成功，该项目将带来一种全新的非侵入性多模式成像技术，用于改进GI癌症检测，这种技术可以很容易地转化为GI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、诊断和特征产生重大影响。 公共卫生相关性：早期发现肿瘤变化，特别是表面下的肿瘤变化，仍然是临床癌症诊断和胃肠道(GI)治疗的关键挑战。这项应用的目标是开发新一代多模式深度分辨成像技术，用于增强GI癌症检测的深度分辨结构和分子成像。如果成功，该项目将产生一种新的非侵入性多模式成像技术，可以很容易地转化为胃肠道癌症以及广泛的上皮性癌症的内窥镜成像。

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.