Nonlinear Intrinsic Microspectroscopy of Cancer

描述（由申请人提供）： 这项研究的目的是利用 多光子荧光激发和非线性散射， 用于癌症的体内检测和癌症生物学的体内研究的方法。 拟议的研究和开发包括两个并行的研究 组件;第一个涉及多光子显微镜的应用， 明确定义的转基因癌症小鼠模型，以检查癌症进展 以及早期发现的可能性。第二个重点是仪器仪表 从组织发射中收集最多信息的发展， 构建体内多光子内窥镜所需的工程，最初用于 多光子光谱学，然后根据需要用于多光子显微术。到 为了适应这一应用，有四个实验室 他们的综合专业知识涵盖了所有的科学和 成功完成项目所需的技术。领导 将集中在NIH生物物理成像发展资源， 光电子（DRBIO）。5个具体目标是：1）直接比较 利用标准组织学的内在组织信号的多光子成像 技术，重点是发现新的诊断标准。2)测试 假设通过使用体内多光子显微镜， 可以追溯到从变异开始的时间，直到外观的 形态学上可识别的表型。3)检测的发展 专门针对体内多光子显微镜优化的仪器 在目标1和2中提出，并用于定义的原型多光子内窥镜 目标4和5。4)用于点或多点的纤维内窥镜的构造 点（纤维束）光谱学，其在近距离内使用多光子激发 红外和获得光谱和荧光寿命信息，从 组织. 5)光栅扫描光纤内窥镜原型的构建 多光子发射成像技术。这个项目的最终目标 是制定战略并确定信息基础设施， 非侵入性、显微医学检测和诊断癌前病变， 癌

DESCRIPTION (provided by applicant): The goal of this proposed research is to utilize the unique advantages of multiphoton fluorescence excitation and nonlinear scattering to develop methods for in vivo detection of cancer and in vivo studies in cancer biology. The proposed research and development consists of two concurrent research components; the first involves the application of multiphoton microscopy to well-defined transgenic mouse models of cancer to examine cancer progression and the potential for early detection. The second focus is on instrumentation development for gleaning the most information from tissue emission and on the engineering required to build an in vivo multiphoton endoscope, initially for multiphoton spectroscopy and then as required for multiphoton microscopy. To accommodate the breath of this application, there are four laboratories involved whose combined expertise encompasses all of the science and technologies required to successfully complete the project. The leadership will be centered at the NIH Developmental Resource for Biophysical Imaging and Opto-electronics (DRBIO). The 5 specific aims are: 1) A direct comparison of multiphoton imaging of intrinsic tissue signals with standard histological techniques, focusing on the discovery of new diagnostic criteria. 2) Testing the hypothesis that by using in vivo multiphoton microscopy, malignant cells can be traced from the time of mutancy initiation until appearance of the morphologically identifiable phenotype. 3) The development of detection instrumentation specifically optimized for the in vivo multiphoton microscopy proposed in Aims 1 and 2 and for the prototype multiphoton endoscopes defined in Aims 4 and 5. 4) Construction of a fiber endoscope for point or multiple point (fiber bundle) spectroscopy that uses multiphoton excitation in the near infrared and obtains spectral and fluorescence lifetime information from tissue. 5) Construction of a prototype raster-scanning fiber endoscope for multiphoton emission imaging in tissue. The ultimate objective of this program is to develop the strategy and determine the information infrastructure for noninvasive, microscopic medical detection and diagnosis of premalignancy and cancer.