Nonlinear Intrinsic Microspectroscopy of Cancer

描述(由申请人提供)： 这项拟议的研究的目标是利用 多光子荧光激发和非线性散射的发展 癌症的体内检测方法和癌症生物学的体内研究。 拟议的研究和开发由两项同时进行的研究组成 组件；第一个涉及将多光子显微镜应用于 明确定义的癌症转基因小鼠模型以检查癌症进展 以及及早发现的可能性。第二个重点是仪表化 从组织发射中收集最多信息的研究进展 建造活体多光子内窥镜所需的工程，最初用于 多光子光谱学，然后根据多光子显微镜的要求。至 适应这一应用的呼吸，有四个实验室 其综合专业知识涵盖了所有的科学和 成功完成该项目所需的技术。领导层 将集中在NIH生物物理成像和开发资源 光电子(DRBIO)。5个具体目标是：1)直接比较 用标准组织学方法对固有组织信号进行多光子成像 技术，重点是发现新的诊断标准。2)测试 假设通过使用活体多光子显微镜，恶性细胞 可以追溯到开始突变的时间，直到出现 在形态上可辨认的表型。3)检测技术的发展 专为活体多光子显微镜而优化的仪器 在AIMS 1和2中提出，并为原型多光子内窥镜定义 在AIMS 4和5中)用于点或多点的光纤内窥镜的构造 近距离使用多光子激发的点(光纤束)光谱学 红外光谱和荧光寿命信息从 组织。5)光栅式光纤内窥镜样机的研制 组织中的多光子发射成像。该计划的最终目标是 是制定战略并确定信息基础设施 癌前和癌前病变的无创、显微医学检测和诊断 癌症。

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.