IN VIVO MULTI-MODALITY IMAGING IN THE ORAL CAVITY (OCT AND MPT)

口腔体内多模态成像（OCT 和 MPT）

• 批准号: 7954829
• 负责人: ZHONGPING CHEN
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954829
• 关键词: Animals; Basement membrane; Benchmarking; Biological Markers; Biotechnology; Blood Vessels; Blood flow; Cellular Structures; Cessation of life; Clinical; Collagen; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic Sensitivity; Dysplasia; Early Diagnosis; Ensure; Epithelial; Evaluation; Event; Extracellular Matrix; Exudate; Fiber; Fluorescence Microscopy; Funding; Gold; Grant; Histopathology; Hyperplasia; Image; Imaging Techniques; Immunohistochemistry; Institution; Lasers; Length; Location; Malignant - descriptor; Malignant Neoplasms; Maps; Monitor; Multimodal Imaging; Optical Coherence Tomography; Optics; Oral; Oral cavity; Patients; Plasminogen Activator Inhibitor 1; Population; Process; Quality of life; Research; Research Personnel; Resolution; Resources; Screening for cancer; Screening procedure; Sensitivity and Specificity; Source; Staging; Stratification; Technology; Testing; Time; Tissues; United States National Institutes of Health; Vascular Endothelial Growth Factors; Vascularization; Work; angiogenesis; base; carcinogenesis; density; high risk; human subject; imaging modality; improved; in vivo; innovation; keratinization; malignant mouth neoplasm; multi-photon; oral carcinogenesis; oral dysplasia; oral lesion; oral tissue; prevent; research clinical testing; second harmonic; tomography; treatment response

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. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually. Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. A highly sensitive, non-invasive capability for (1) early detection, diagnosis, and monitoring of oral dysplasia and malignancy; (2) screening high-risk populations; and (3) early evaluation of treatment response is urgently needed. The proposed work combines innovative optical in vivo technologies to image and characterize pathological oral changes at three levels: macroscopic, vascular, and cellular. Our multimodal approach will include Optical Coherence Tomography (OCT) multi-photon excited fluorescence microscopy and second harmonic generated imaging (MPM). Previous studies using this combined approach provide strong support for this approach, but lack of a combined in vivo probe has prevented comprehensive meaningful in vivo and clinical testing. Using animal oral carcinogenesis studies, multimodal imaging capability will be optimized and evaluated using the conventional histopathological gold standard, augmented by specific immunohistochemistry (IHC). We will use the micro-endoscopic OCT and muitiphoton tomography (MPT) developed in LAMMP to extend this studies in human subjects with leukoplakic and malignant oral lesions to define diagnostic capability. This work also will advance our understanding of the sequential and spatial processes involved in oral carcinogenesis. The specific hypotheses to be tested are: 1. High resolution in vivo F-OCT can map dysplasia-, malignancy-related epithelial, subepithelial, and vascular change. 2. In vivo MPT can image tissue extracellular matrix, cellular, vascular, and microtumor presence. 3. Improved diagnostic capability will be achieved by combining F-OCT and MPT data. 4. Specific biomarkers for angiogenesis and extracellular matrix remodeling (VEGF, HIF-1¿, uPA, PAI-1, MMP1,2,9) will target events detected by multimodal imaging during development of premalignancy and malignancy. To test these hypotheses, we proposed following specific aims: 1. F-OCT will be used to image and quantify specific epithelial, subepithelial and vascular changes that correspond with specific histopathological stages in the progression health-dysplasia-malignancy. Based on the techniques and diagnostic benchmarks for the imaging data established in animal studies, F-OCT's diagnostic sensitivity and specificity will be determined in 84 human subjects with healthy, leukoplakic, or malignant oral tissue. Diagnostic capability will be compared with conventional clinical and histopathological diagnosis. OCT-based evaluation of criteria such as epithelial keratinization, thickening, proliferation and invasion; rete pegs; epithelial stratification; basal hyperplasia; and presence of basement membrane will be benchmarked against specific stages of premalignancy and malignancy as defined by histopathology (existing gold standard), In addition, Doppler OCT based quantification of vessel density and blood flow at specific locations will identify the relationship between histopathological stages of dysplasia, malignancy vs. vascularization and blood flow. 2. MPT will be used to define specific events at a cellular level that correspond with specific histopathological stages in carcinogenesis. Based on the imaging techniques and diagnostic benchmarks established in animal studies, diagnostic sensitivity and specificity of MPT will be determined in 84 human subjects with healthy, leukoplakic, or malignant oral tissue. MPT's diagnostic capability will be compared with conventional clinical and histopathological diagnosis. Using MPT, changes in the extracellular matrix, specifically, collagen presence, fiber length/organization, matrix structure, cellular exudates, vascularization, and microtumors -- will be benchmarked against specific stages of premalignancy and malignancy, as defined by the histopathological gold standard. In addition, 3. F-OCT and MPT data will be combined to evaluate for improved diagnostic capability using this approach. 4. To advance our understanding at a macroscopic, vascular, and cellular level of the sequential and spatially-resolved processes involved in oral carcinogenesis, specific biomarker expression, combined with imaging data and histopathological staging, will provide a comprehensive, spatially-resolved, time- and sequence-sensitive map of specific components of the carcinogenesis process within the oral epithelial and subepithelial tissues.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 尽管治疗方面取得了重大进展，但口腔癌仍会每年导致10,000例美国死亡。早期发现癌症及其可治愈的前体仍然是确保患者生存和生活质量的最佳方法。 （1）早期检测，诊断和监测口腔发育不良和恶性肿瘤的高度敏感，无创的能力； （2）筛查高风险人群； （3）迫切需要对治疗反应的早期评估。拟议的工作结合了创新的光学体内技术，以形象和表征三个层次的病理口服变化：宏观，血管和细胞。我们的多模式方法将包括光学相干断层扫描（OCT）多光子激发荧光显微镜和第二次谐波产生的成像（MPM）。以前使用这种联合方法的研究为这种方法提供了强有力的支持，但是缺乏体内探针的组合可以阻止在体内和临床测试中具有全面有意义的有意义。使用动物口腔癌变研究，将使用常规的组织病理学金标准（IHC）增强多模式成像能力。我们将使用在LAMMP中开发的微观镜面OCT和Mutiphoton层析成像（MPT）来扩展具有白细胞和恶性口腔病变的人类受试者的研究，以定义诊断能力。这项工作还将促进我们对口服癌变涉及的顺序和空间过程的理解。要测试的具体假设是： 1。体内F-OCT的高分辨率可以映射异常增生，与恶性相关的上皮，下骨和血管变化。 2。体内MPT可以对组织细胞外基质，细胞，血管和微肿瘤的存在图像形象。 3。通过组合F-OCT和MPT数据来提高诊断能力。 4。用于血管生成和细胞外基质重塑的特定生物标志物（VEGF，HIF-1，UPA，PAI-1，MMP1,2,9）将靶向通过在预现象和恶性肿瘤发展过程中多模态成像检测到的事件。 为了检验这些假设，我们提出了以下特定目的： 1。F-OCT将用于图像和量化特定的上皮，下层和血管变化，这些变化与进展健康性增生性 - 超增长性癌变中的特定组织病理学阶段相对应。基于在动物研究中建立的成像数据的技术和诊断基准，F-OCT的诊断敏感性和特异性将在84位具有健康，白细胞培养基或恶性口腔组织的人类受试者中确定。将诊断能力与常规临床和组织病理学诊断进行比较。 基于OCT的标准评估，例如上皮角化，增厚，增殖和入侵；重钉;上皮分层；基本的增生；以及基于组织病理学（现有的金标准）定义的特定阶段和恶性阶段的特定阶段，地下膜的存在和存在，此外，基于多普勒OCT对特定位置的血管密度和血液流量的定量将确定性化症患者的组织病理学阶段之间的关系，恶性肿瘤，血管表现和血液流动。 2。MPT将用于定义与癌变中特定组织病理学阶段相对应的细胞水平上的特定事件。基于在动物研究中建立的成像技术和诊断基准，将在84名患有健康，白细胞增生或恶性口腔组织的人类受试者中确定MPT的诊断敏感性和特异性。 MPT的诊断能力将与常规的临床和组织病理学诊断进行比较。 使用MPT，细胞外基质的变化，具体来说，胶原蛋白的存在，纤维长度/组织，基质结构，细胞渗出液，血管化和微肿瘤 - 将根据组织性金标准定义的特定阶段和恶性肿瘤的特定阶段进行基准标记。此外， 3. F-OCT和MPT数据将合并以评估使用此方法提高诊断能力。 4。在宏观的，血管和细胞水平上提高我们的理解，以口服癌变涉及的顺序和空间分辨过程，特定的生物标志物表达，结合了成像数据和组织病理学的分期，将提供全面的，空间分辨的，时间和序列的典型和序列的概述，并构成了特定的综合术语，并构成了特定的典型典型的car词，并构成了car的典型典型的car词。组织。