Multiphoton Detection of Cancer

描述（由申请人提供）：该项目的目标是表征和实现多光子激发荧光和非线性散射的独特性质，用于癌症的体内检测和癌症生物学的新颖体内研究。该提案的工程目标是构建功能齐全的激光扫描多光子内窥镜，能够主要使用具有当前可获得的分辨率和质量的内在荧光团和胶原二次谐波信号来生成活组织图像；配备最先进的多光子显微镜。 为了适应这一多学科提案的气息，涉及三个实验室和一家生物医学仪器公司（Optiscan Imaging Ltd），其综合专业知识涵盖了成功完成该项目所需的所有科学和技术。该项目的领导中心是康奈尔大学应用​​与工程物理系的 NIH/NIBIB 生物物理成像和光电子学开发资源 (DRBIO)。 这三个具体目标是：1）将多光子成像和内在组织信号的光谱参数与标准组织学技术进行直接比较，重点是发现新的癌症诊断标准。 2）构建用于组织中多光子发射成像的光栅扫描光纤内窥镜。 3）优化用于癌症小鼠模型成像的多光子显微镜，并探索大视场（~1cm2）多光子成像作为临床诊断工具的潜力。 该计划的总体目标是开发一个新的、强大的基础设施，用于癌前病变和癌症的非侵入性显微医学检测和诊断。我们预计所建立的方法对于表征其他癌症模型中的致癌作用以及最终在人类临床应用中具有普遍价值。

DESCRIPTION (provided by applicant): The goal of this project is to characterize and implement the unique properties of multiphoton excited fluorescence and nonlinear scattering for in vivo detection of cancer and novel in vivo studies in cancer biology. An engineering goal of this proposal is to construct a fully functional laser-scanning multiphoton endoscope capable of producing images of living tissue using primarily intrinsic fluorophores and collagen second harmonic signals that are of the resolution and quality currently obtainable; with a state-of-the-art multiphoton microscope. To accommodate the breath of this multidisciplinary proposal, there are three laboratories and a biomedical instrument company (Optiscan Imaging Ltd) involved, whose combined expertise encompasses all of the science and technologies required to successfully complete the project. The project leadership is centered at the NIH/NIBIB Developmental Resource for Biophysical Imaging and Opto-electronics (DRBIO) at Cornell University in the department of Applied and Engineering Physics. The three specific aims are: 1) A direct comparison of multiphoton imaging and spectroscopic parameters of intrinsic tissue signals with standard histological techniques, focusing on the discovery of new diagnostic criteria for cancer. 2) Construction of a raster-scanning fiber endoscope for multiphoton emission imaging in tissue. 3) Optimization of multiphoton microscopy for imaging mouse models of cancer, and an exploration of the potential of large field-of-view (~ 1cm2) multiphoton imaging as a diagnostic tool for clinical use. The overall goal of this program is to develop a new and powerful infrastructure for noninvasive, microscopic medical detection and diagnosis of premalignancy and cancer. We anticipate that methods established will be of general value for characterizing of carcinogenesis in other cancer models, and ultimately in human clinical applications.