(PQC4) Towards In Vivo, 3D Cytotyping By Stimulated Raman Spectroscopic Imaging-Ba

描述（由申请人提供）：在临床实践中迫切需要能够帮助病理学家做出准确、客观和自动化决策的技术，以改善癌症结局。虽然已知肿瘤微环境起着重要作用，但由于我们没有简便的3D原位细胞分型方法，因此无法评估其解决这一需求的潜力。当今癌症研究的一个主要障碍是无法完全理解或正常化肿瘤微环境的作用。该项目的主要目标是提供一种实用的成像仪器，供临床和研究使用，可由病理实验室中任何受过培训的人员操作。该仪器将以最佳和快速的方式提供所有细胞的3D位置和身份。该方法的基础上，首先，开发新的仪器和分析方法的受激拉曼散射（SRS）显微镜。该仪器呈现出与当前技术状态的背离，其使用间隔光学器件以允许非微扰成像和先进的控制算法。光谱分析算法的集成使分子病理学数据的生成变得容易-无需任何染料、染色剂或人工监督。所开发的仪器和算法进行了测试，对组织学标准和获得的性能的定量措施。与目前主要依赖上皮细胞的做法相反，该项目克服了无法对肿瘤微环境进行细胞分型的问题，有可能改变患者的决策，并改变研究中组织学评估的标准做法。

DESCRIPTION (provided by applicant): Technologies that can help make accurate, objective and automated decisions to aid the pathologist are sorely needed in clinical practice to improve cancer outcomes. While it is known that the tumor microenvironment plays a strong role, its potential to address this need cannot be assessed as we don't have facile methods for 3D, in situ cytotyping. A major stumbling block in cancer research today is not being able to fully appreciate or normalize for the role of the tumor microenvironment. The major goal of this project is to provide a practical imaging instrument for clinical and research use that can be operated by any trained person in pathology laboratories. The instrument will provide 3D location and identity of all cells in an optimal and fast manner. The approach is based; first, on developing novel instrumentation and analytical methods for stimulate Raman scattering (SRS) microscopy. The instrument presents a departure from the current state of the art using standoff optics to allow non-perturbative imaging and advanced control algorithms. The integration of spectral analysis algorithms makes generation of molecular pathology data facile - without any dyes, stains or human supervision. The developed instrument and algorithms are tested in against histologic standards and quantitative measures of performance obtained. As opposed to current practice that largely relies only on epithelial cells, overcoming the inability to cytotypethe tumor microenvironment with this project has the potential to transform decision-making for patients and alter the standard practice of histologic assessment in research.