(PQC2)High-content Pathology with Confocal Microscope Arrays

(PQC2)使用共焦显微镜阵列进行高内涵病理学

• 批准号: 8884395
• 负责人: CHRISTOPHER H CONTAG
• 金额: $ 62.73万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884395
• 关键词: Algorithms; Appearance; Architecture; Area; Automation; Biological Preservation; Cancerous; Cells; Cellular Phone; Clinical; Clinical Research; Computer software; Cost Savings; Development; Devices; Diagnosis; Diagnostic; Ensure; Evaluation; Event; Excision; Feedback; Freezing; Fresh Tissue; Frozen Sections; Future; Goals; Hand; Head and Neck Cancer; Head and neck structure; Healthcare Systems; Hematoxylin and Eosin Staining Method; Histologic; Histology; Histopathology; Image; Individual; Link; Malignant Neoplasms; Mechanics; Methodology; Methods; Microscope; Microscopic; Microscopy; Miniaturization; Modeling; Molecular; Molecular Profiling; Normal tissue morphology; Operative Surgical Procedures; Optics; Pathologic; Pathologist; Pathology; Patients; Performance; Price; Procedures; Process; Quality Control; Reporting; Resected; Resolution; Sampling; Savings; Scanning; Series; Specificity; Specimen; Speed; Staging; Staining method; Stains; Surface; Surgeon; Surgical Pathology; System; Techniques; Technology; Testing; Time; Tissue Sample; Tissues; Update; Visual; Writing; base; breast lumpectomy; cellular imaging; cost; data acquisition; design; detector; digital imaging; effective intervention; fluorophore; image processing; image reconstruction; improved; interest; miniaturize; operation; prevent; prospective; prototype; public health relevance; screening; software development; tissue processing; tool; tumor

DESCRIPTION (provided by applicant): Surgical removal of head and neck cancers presents challenges to the surgeon as they seek to remove cancerous tissue, preserve normal tissues and function, and prevent disfigurement. For this purpose, assessment of tissue status at the margins is critical for effective intervention. The pathologic examination of margins for tumors and the determination of "clean margins" is currently based on traditional frozen section methods that routinely examine less than 0.2% of the tissue removed. The aims of the proposed studies are to improve the assessment of tumor margins by developing tools that effectively move the microscopic examination closer to the patient in both time and space, and that provide improved guidance for tissue selection. This will be accomplished by developing, and deploying, arrays of miniaturized microscopes that reveal tissue histopathology at a resolution approaching that of conventional microscopes, and offer large coverage of tissue samples, and high speed scanning. These arrays serve as rapid screening tools, and are enabled by developments in integrated optics, and lithographic fabrication techniques such as MOEMS (micro-opto-electro-mechanical systems), and high- resolution, high-speed digital image capture and sophisticated image-processing algorithms to accelerate acquisition and refine quality of pathology images. We propose to use these arrays at the cutting bench in the surgical pathology suite to increase the amount of tissue analyzed in gross pathology, link macroscopic inspection of tissue to microscopic examination and provide more information, more rapidly, than conventional approaches. We will construct arrays of dual axis confocal (DAC) microscopes, advance rapid fluorescent surface staining, and develop image reconstruction software to enable rapid, microscopic inspection of large surface areas of resected tissue. The arrayed dual axis confocal (ADAC) device will be approximately the size of a cell phone and will provide cellular-level images of tissue architecture and molecular signatures at 1-5um resolution, and will be applied to the pathologic assessment of tumor margins. Although this study is limited to head and neck cancers, the full potential of ADAC is substantial. The margins of resection specimens are, in many cases, inadequately sampled due to the inefficiency of current sampling methods. The ADAC device could allow comprehensive en face examination of the entire lumpectomy specimen, and will have utility in selection of tissue for processing at the surgical pathology bench. As these tools advance, the histology lab could be circumvented for many specimens, which would provide a significant cost savings to the healthcare system, and increase the speed at which pathology could be reported.

描述（由申请人提供）：头颈癌的手术切除给外科医生带来了挑战，因为他们试图去除癌组织、保留正常组织和功能并防止毁容。为此，评估边缘组织状态对于有效干预至关重要。肿瘤边缘的病理检查和“干净边缘”的确定目前基于传统的冰冻切片方法，通常检查不到0.2%的切除组织。拟议研究的目的是通过开发有效地使显微镜检查在时间和空间上更接近患者的工具来改善肿瘤边缘的评估，并为组织选择提供更好的指导。这将通过开发和部署微型显微镜阵列来实现，这些微型显微镜阵列以接近传统显微镜的分辨率揭示组织病理学，并提供大范围的组织样本覆盖和高速扫描。这些阵列可作为快速筛选工具，并通过集成光学和光刻制造技术（例如 MOEMS（微光机电系统）以及高分辨率、高速数字图像捕获和复杂的图像采集技术）的发展来实现。处理算法以加速采集并改善病理图像的质量。我们建议在外科病理学套件的切割台上使用这些阵列，以增加大体病理学中分析的组织量，将组织的宏观检查与显微镜检查联系起来，并比传统方法更快地提供更多信息。我们将构建双轴共焦（DAC）显微镜阵列，推进快速荧光表面染色，并开发图像重建软件，以实现对切除组织的大表面区域的快速显微镜检查。阵列式双轴共焦 (ADAC) 设备大约有手机大小，将提供 1-5um 分辨率的组织结构和分子特征的细胞级图像，并将应用于肿瘤边缘的病理评估。尽管这项研究仅限于头颈癌，但 ADAC 的全部潜力是巨大的。在许多情况下，由于当前采样方法效率低下，切除标本的边缘采样不充分。 ADAC 设备可以对整个肿瘤切除标本进行全面的正面检查，并且可以用于选择在手术病理台上进行处理的组织。随着这些工具的进步，许多标本可以绕过组织学实验室，这将为医疗保健系统节省大量成本，并提高病理报告的速度。