Method for Quantitative Fluorescence Sensing in Tissue

描述（由申请人提供）： 荧光光谱和成像技术正被广泛应用于各种非侵入性生物医学研究，用于体外和体内诊断。组织荧光中的挑战之一是获得关于组织中的分子荧光团的定量信息，而不管由组织吸收和散射引起的检测到的信号可变性。该R21应用的总体目标是开发、优化和验证一种技术和方法，以快速、非侵入性和定量地检测组织中的内源性和外源性荧光团。该方法结合了实验和计算方法，并将采用新的计算代码来模拟复杂组织中的时间分辨激发和荧光传播，其速度比现有方法快约100倍。 为了说明该方法的广泛实用性，它将被应用到两个不同的生物医学问题。一个多学科的研究人员团队，在生物医学光学，胃肠内窥镜检查和组织工程的专业知识已经组装，以确保这些目标的实现。 具体目标是：（1）利用时间分辨激光光谱学和组织光学原理，开发一种在均匀组织中进行快速、定量、非侵入性分子传感的新技术和方法;（2）将目标1中开发的技术扩展到包括多层非均匀组织的应用，以开发和优化与临床内窥镜兼容的光纤探针;（3）将目标1中开发的技术扩展到每层具有多个荧光团的组织，使组织工程师能够定量和非侵入性地监测其构建体的组成、结构和功能。 这里开发和验证的技术和方法广泛适用于定量组织荧光光谱和成像中的各种应用。为了促进这种方法的普遍使用，计算代码可以通过PI网站上的下载链接或交互式界面有效地传播给科学界。

DESCRIPTION (provided by applicant): Fluorescence spectroscopy and imaging are being applied to a wide variety of noninvasive biomedical studies for in vitro and in vivo diagnostics. One of the challenges in tissue fluorescence is to obtain quantitative information on the molecular fluorophores in tissues despite the detected signal variability caused by tissue absorption and scattering. The overall goal of this R21 application is to develop, optimize, and validate a technology and method to rapidly, non-invasively, and quantitatively sense endogenous and exogenous fluorophores in tissues. The method combines both experimental and computational approaches, and will employ novel computational codes developed to model time-resolved excitation and fluorescent light propagation in complex tissues approximately 100 times faster than current methods. To illustrate the broad utility of the method, it will be applied to two distinct biomedical problems. A multidisciplinary team of researchers with expertise in biomedical optics, gastrointestinal endoscopy, and tissue engineering has been assembled to ensure that these goals are achieved. The specific aims are: (1) To develop a novel technology and method for rapid, quantitative, non-invasive molecular sensing in homogeneous tissues using time-resolved laser spectroscopy and the principles of tissue optics; (2) To extend the technology developed in Aim 1 to include application to inhomogeneous tissues with multiple layers, for the development and optimization of fiber-optic probes compatible with clinical endoscopy; (3) To extend the technology developed in Aim 1 to include application to tissues with multiple fluorophores per layer, to enable tissue engineers to quantitatively and noninvasively monitor the composition, structure, and function of their constructs. The technologies and methods developed and validated here are broadly applicable to a variety of applications in quantitative tissue fluorescence spectroscopy and imaging. To facilitate the generalized use of this approach, the computational codes can be efficiently disseminated to the scientific community via a download link or interactive interface on the Pl's web-site.