Nonlinear Optical Imaging for Digital Pathology

该项目将开发一种新的方法来改善组织病理学，使用多种非线性光组织相互作用， 当使用强烈但非常短的激光脉冲（小于十亿分之一秒）时发生。这些相互作用 为显微镜中的图像对比度提供了新的机制， 使用常规显微镜和组织染色。此外，为了使这项技术最大限度地用于临床， 病理学家和生物医学研究人员，研究小组将开发一个独特的平台，将允许数字成像， 整个组织切片，而不是仅对小区域成像。 最近使用实验性小视场非线性显微镜，肺癌组织的新信息 生化和超微结构。胶原蛋白（一种重要的结构蛋白）的详细结构 在肺组织肿瘤中有明显改变。细胞核内的核仁也被成像， 为研究它们如何随着恶性肿瘤而改变提供了新的视角。这些和其他最近的观察与非线性 这项技术最初将扩展到其他几种癌症类型（乳腺癌、前列腺癌、胃肠道癌），以测试它们是否 癌症的通用生物标志物。 非线性全载玻片扫描仪将成为支持新癌症诊断开发的技术 程序，将刺激其他非线性光学生物标志物的发展，也将允许快速评估生物标志物。 组织结构而无需染色。扫描仪将生成数字图像，因此结果可以直接 集成到电子临床记录中。原型仪器将被放置在显微镜用户设施，并将 生物医学研究人员、临床病理学家和包括牙科在内的其他领域的研究人员广泛使用， 法医学、农业、地质学、人类学和生物工程学。

This project will develop a novel approach to improve histopathology, using multiple nonlinear light-tissue interactions that occur when intense but very short pulses of laser light (less than one billionth of a second) are used. These interactions provide novel mechanisms for image contrast in microscopy that complement and extend the information that are obtained using conventional microscopy with histological stains. Further, in order to make this technology maximally useful to clinical pathologists and biomedical researchers, the research team will develop a unique platform that will allow digital imaging of whole tissue slides, rather than imaging only small regions. Recently using an experimental small-field-of-view nonlinear microscopy, new information on lung cancer tissue biochemistry and ultrastructure has been obtained. The detailed structure of collagen (an important structural protein) has been found to be distinctly modified in tumor of lung tissue. The nucleoli within the cell nucleus have also been imaged, providing new insight into how they are altered with malignancy. These and other recent observations with nonlinear technique will be extended initially to several other cancer types (breast, prostate, gastrointestinal) to test if they are universal biomarkers of cancer. The nonlinear whole-slide scanner will be the enabling technology that will support development of new cancer diagnostics procedures, will stimulate other nonlinear optical biomarker development, and also will allow quick assessment of biological tissue structures without requiring staining. The scanner will generate digital images, and so the results can be directly integrated into electronic clinical records. The prototype instrument will be placed in a microscopy User Facility, and will be widely accessible to biomedical researchers, clinical pathologists, and researchers in other areas including dentistry, forensics, agriculture, geology, anthropology and bioengineering.