Functional optical detection based on pH dependent fluorescence lifetime
Functional optical detection based on pH dependent fluorescence lifetime
复制标题
DOI：
10.1002/lsm.20101
复制
发表时间：
2004-01-01
影响因子：
2.4
通讯作者：
Gandjbakhche, A
中科院分区：
文献类型：
--
作者：
Gannot, I;Ron, I;Gandjbakhche, A
背景和目的：检测生理参数（例如，pH和温度），由最初健康组织的恶性转化产生，可以是早期癌症检测的有力诊断工具。这种变化可以通过将这些参数与异常周围的健康组织的参数进行比较来观察。特异性靶向的荧光标记抗体的时间分辨光谱可以对这种变化敏感，并提供感兴趣区域的高分辨率功能图像。本研究的目标是建立一个前向实验装置，用于校准近红外荧光染料对生理参数的寿命依赖性，并开发分析解决方案，考虑到混浊介质中光传播的影响（例如，组织），这是能够提取一个原始的寿命荧光信号的飞行时间强度分布，在体内测量从一个深埋的活organ.Study设计/材料和方法：组织样phantom嵌入荧光染料和背景光学特性模拟那些活组织的设计和创建。测量不同荧光团位置和pH值的荧光衰减曲线。这些测量是与一个系统的基础上的时间相关的单光子计数（TCSPC）仪器和可调飞秒钛蓝宝石系统built by our group.Results：衰减曲线记录的荧光深度为5 mm和源探测器分离7 mm。它表明，一个前向模型，基于随机游走理论，充分描述了实验数据。测量的pH值的荧光寿命的依赖性，其特征在于为两个不同的dye.Conclusions：实验数据和理论模型的预测之间的良好相关性允许使用封闭形式的分析解决方案，以分离的光子时间延迟的影响，由于在组织中的多次散射从原来的强度荧光时间衰减曲线，确定由荧光团本身和它的周围环境。后一种依赖性在诊断上是重要的。实验获得的寿命和感兴趣的参数之间的缩放可以在体内使用，以获得生理参数变化的图，其可以用作体内特异性诊断系统的基础。
Background and Objectives: Detection of possible alterations of physiological parameters (e.g., pH and temperature), resulting from malignant transformation of initially healthy tissue, can be a powerful diagnostic tool for earlier cancer detection. Such variations can be observed by comparing these parameters with those of healthy tissue surrounding the abnormality. Time-resolved spectroscopy of specifically targeted fluorescent labeled antibodies can be sensitive to such variations and provide a high resolution functional image of the region of interest. The goal of this study was to establish a forward experimental setup for calibration of the lifetime dependencies of near-IR fluorescent dyes on physiological parameters, and to develop analytical solutions, taking into account the effects of light propagation in turbid media (e.g., tissue), that was able to extract an original lifetime fluorescence signal from time-of-flight intensity distributions, measured in vivo from a deeply embedded live organ for further analysis.Study Design/Materials - and Methods: Tissue-like phantoms with embedded fluorescent dyes and background optical properties simulating those of live tissues were designed and created. Fluorescence decay curves were measured for different fluorophore positions, and pH values. Those measurements were made with a system based on a time-correlated single photon counting (TCSPC) instrument and a tunable femtosecond Ti-Sapphire system built by our group.Results: Decay curves were recorded for fluorophore depths of up to 5 mm and source-detector separation of 7 mm. It was shown that a forward model, based on the random walk theory, adequately described the experimental data. Measured pH dependencies of the fluorescence lifetime were characterized for two different dyes.Conclusions: Good correlation between experimental data and predictions of the theoretical model allows the use of close-form analytical solutions to separate the effects of photon time delays due to multiple scattering in tissues from the original intensity fluorescence time decay curve, determined by the fluorophore itself and its immediate surroundings. It is the latter dependence that can be diagnostically important. Experimentally obtained scaling between lifetime and a parameter of interest can be used in vivo to obtain a map of physiological parameter changes which can serve as a base for an in vivo specific diagnostic system.