【作者】 张丽敏；

【导师】 高峰；

【作者基本信息】 天津大学 ， 生物医学工程， 2009， 博士

【摘要】 由于近红外光在生物组织中具有相对较低的组织吸收,可达到数厘米的穿透深度,同时随着荧光分子探针技术在生物医学研究中的深入研究和广泛应用,荧光扩散光层析(FDOT)技术作为一种新颖的分子成像技术得到了不断发展。时域技术在测量荧光寿命上具有潜在的优势,且能够同时重建荧光产率和寿命以及进行多组分分析。本文主要探讨了时域FDOT的基本原理和实验方法,其内容包括基于时间相关单光子计数技术的多通道时间分辨系统测量、图像重建算法、数值模拟和实验验证三个主要环节。扩散方程为辐射传输方程的一阶球谐近似,可作为描述光在组织体中的传输模型。荧光检测量的数学表达式可由激发光和发射荧光之间的耦合扩散方程得到。文中提出了将广义脉冲谱技术(GPST)应用到时域FDOT的方法。此方法应用有限元方法求解拉普拉斯变换的时域耦合扩散方程正向模型,在逆向模型中,通过引入一对拉普拉斯变换因子和应用代数重建技术(ART)求解线性方程使得荧光产率和寿命图像同时重建。另外还应用了归一化玻恩比方法,此方法具有与光源强度无关、对系统误差具有较小敏感性、对背景光学特性的非均匀性不敏感等优点,与拉普拉斯变换相结合能够克服测量系统的零点校正问题。将提出的算法进行了数值模拟验证,在空间分辨率、定量重建性等方面进行了评估,且讨论了在噪声数据下变换因子的选择对图像重建的影响。全时间分辨方法(Full TR)包含了组织体内部光学参数和荧光参数最丰富的信息,成像质量高,因而可作为评估其它算法成像质量的标准。在此方法中,利用有限元-时域有限差分方法求解了时域耦合扩散方程的正向模型,在逆向模型中应用了Newtown-Raphson方法重建了荧光产率和寿命图像,另外对权重矩阵的计算、线性逆和正则化方法进行了说明。将提出的方法进行了二维模拟验证,并对其空间分辨率、重建定量性、重建目标尺寸、噪声鲁棒性等方面进行了评估,且与广义脉冲谱技术进行了比较。针对时间相关单光子计数系统,采用了基于时间分辨反射测量技术的混浊介质光学参数重构方法快速准确地测量了固态及液态仿体的光学参数。基于自行设计的多通道时间分辩FDOT实验系统,将测得的实验数据应用于图像重建,应用前述的广义脉冲谱技术重建了荧光产率和荧光寿命的全三维图像,图像重建结果与实际情况相符,且验证了模拟实验结果,并对实验结果进行了讨论。更多还原

【Abstract】 As near infrared light can travel several centimeters in tissue, fluorescence diffuse optical tomography(FDOT)with the aid of specific fluorescent probes promises to open new pathways for the characterization of biological processes in living animals at cellular and molecular levels. The time domain technique offers the potential advantages of directly measuring lifetime and has the favorite performances of simultaneously recovering of fluorescent yield and lifetime distributions, as well as resolving multiple components. The thesis focuses on the research of the imaging theory and method on time-domain FDOT, including measurement method based on the multichannel time-resolved system, the algorithm of image reconstruction, numerical simulation and experimental investigation.The diffusion equation (DE) is the P1 approximation of the Radiative Transfer Equation, and has been proved to be adequately accurate in case of thick tissue and mathematically tractable. The fluorescent light detection relies on a coupled DE that associates the excitation-light with the emission-one. We propose a generalized pulse spectrum technique (GPST) for time-domain FDOT. In this work, a finite element method solution to the Laplace transformed time-domain coupled diffusion equations is employed as the forward model, and the resultant linear inversions at two distinct transform-factors are solved with an algebraic reconstruction technique to separate fluorescent yield and lifetime images. The normalized Born ratio is used for its independence of the source intensity and less sensitivity to the systematic errors. In addition, it eliminates the requirement for accurate calibration of the temporal-origin in time-domain measurement and also exhibits a high robustness to the uncertainties of highly optically heterogeneous background. The algorithm is validated using simulated data, and the spatial resolution, noise-robustness and so on are assessed. The choice of appropriate transform factors is discussed.The full time-resolved mode possesses the richest information about the optical and fluorescent properties. Making full use of the time-resolved data would improve fidelity of the image reconstruction, and help set up the‘golden standard’for evaluating the performance of the other featured-data methodologies. In this work, a hybrid finite-element-finite-time-difference method for solving the TD coupled diffusion equations is developed to serve as the forward model. The Newtown-Raphson inverse model for simultaneous reconstruction of fluorescent yield and lifetime images is proposed, and some issues associated to its implementation, such as the computation of the weighting matrix, linear inversion and regularization strategy, are highlighted.The proposed algorithm is validated with simulated data for 2D phantom and its superiority in the improvement of image quality is demonstrated, in comparasion with the featured-data algorithm previously developed based on GPST.A method for determining the optical properties in turbid medium is developed based on time-resolved reflection measurement, and the optical properties of solid and liquid phantoms are measured. By use of multchannels time-resolved measurent system based on time-correlated single photon counting (TCSPC), we experimentally validate that the proposed GPST scheme can achieve simultaneous reconstruction of the fluorescent yield and lifetime distributions with a reasonable accuracy. The results demonstrate that the proposed methodology is suitable for further application into FDOT. Nevertheless, a lot of improvements on both the instrumentation and methodology are necessarily required prior to clinical applications.更多还原