(PQC2)High-content Pathology with Confocal Microscope Arrays

描述（由申请人提供）：头颈部癌症的手术切除对外科医生提出了挑战，因为他们寻求切除癌组织，保持正常组织和功能，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”的确定目前是基于传统的冷冻切片方法，常规检查不到0.2%的切除组织。拟议研究的目的是通过开发工具来改进肿瘤边缘的评估，这些工具可以有效地在时间和空间上使显微镜检查更接近患者，并为组织选择提供改进的指导。这将通过开发和部署小型化显微镜阵列来实现，这些显微镜以接近传统显微镜的分辨率显示组织病理，并提供大范围的组织样本和高速扫描。这些阵列可以作为快速筛选工具，并通过集成光学和光刻制造技术（如MOEMS（微光电机械系统））的发展，以及高分辨率，高速数字图像捕获和复杂的图像处理算法来加速获取和改善病理图像的质量。我们建议在外科病理套件的切割台上使用这些阵列，以增加大体病理分析的组织数量，将组织的宏观检查与微观检查联系起来，并比传统方法更快地提供更多信息。我们将构建双轴共聚焦（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，以实现对切除组织大面积的快速显微检查。排列的双轴共聚焦（ADAC）装置大约是手机大小，将提供1-5um分辨率的组织结构和分子特征的细胞水平图像，并将应用于肿瘤边缘的病理评估。虽然这项研究仅限于头颈部癌症，但ADAC的全部潜力是巨大的。在许多情况下，由于目前的采样方法效率低下，切除标本的边缘没有得到充分的采样。ADAC设备可以对整个乳房肿瘤切除标本进行全面的正面检查，并将在外科病理台上选择组织进行处理时发挥作用。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。

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.