数字全息技术在生物医学成像中的应用基础研究

发布时间：2018-03-14 16:12

本文选题：数字全息　切入点：生物医学成像　出处：《暨南大学》2014年博士论文　论文类型：学位论文

【摘要】：在人类疾病诊断和生物医学研究方面，生物医学成像已经成为一种广泛使用的方法之一。传统的成像仪器是光学显微镜，可以将肉眼无法直接看清楚的微小物体进行光学放大成像。但传统的光学显微镜只能探测光波的强度，获得物光波强度二维分布图像，难于给出被成像物体的空间三维信息，应用在日益发展的生物医学领域中存在一定的局限性。发展新的成像分析技术，对生物活体、细胞、亚细胞等样品实现无扰、动态、定量分析是目前生命科学研究的迫切需求。本文针对数字全息成像技术开展在生物医学中的应用基础研究。数字全息是基于传统的全息原理，不同的是利用电子成像器件（如CCD、CMOS相机等）记录全息图，记录的全息图由数据采集卡采集并进行模/数转换和量化，以数字矩阵的形式存入计算机，即数字全息图；再由计算机模拟光学全息的再现过程，通过数值计算，可以同时获得量化表示的物光波的强度图像和位相图像。与传统全息成像方法相比，数字全息技术的优点是：可连续记录运动物体的各个瞬间过程，实现连续实时在线记录；通过数字再现，可以定量分析其幅度和位相信息；可以方便地对所记录的数字全息图进行图像处理，减少或消除在全息图记录过程中的噪声、像差等因素的影响。基于这些独特优势，数字全息术被认为是定量分析、研究生物活体等位相型物体的一个强有力工具，近几年来已成为国际研究的热点。本论文首先从光学全息原理出发，介绍了数字全息技术的记录和再现过程。然后搭建透射型数字全息成像装置，对数字全息技术在生物活体动态成像中的应用进行了大量的基础实验研究，主要研究内容包括以下几个方面：（一）针对目前混浊介质成像困难、散射光对成像对象干扰大，尤其无法获得动态成像等问题，本文开展了数字全息技术对混浊介质中的动态生物活体进行成像的研究。文中首先介绍了光在混浊介质中的传播方式；针对动态物体引起物光的光场连续变化的特点，采用相干长度较长的连续激光器作为全息记录的记录光源；利用数字滤波技术提取数字全息图的一级傅立叶变换谱，既可对全息图进行数字再现，又可消去孪生像和直流背景影响，还可减弱散射光引起的噪声；利用数字对焦技术，可解决对混浊介质中生物活体无法直接对焦的问题；结合空间滤波技术可进一步消去散射噪声的影响；实验成功实现了基于数字全息的动态活体在混浊介质中的动态成像。该成像方法，有望在混浊生物体内的生物活体动态成像方面获得应用。（二）针对利用表面等离子体共振成像进行生物芯片高通量分析问题，开展了基于数字全息技术的表面等离子体共振成像生物芯片高通量分析研究。为了实现高通量分析，必须解决目前表面等离子体共振成像生化分析技术的探测范围窄等问题，本文提出一种基于数字全息术的同时获取强度图像和位相图像的表面等离子体共振成像（SPRI）技术，同时利用强度和位相信息，可以拓宽高灵敏度下的探测范围，从而提高分析的通量数。本文建立了一套同时利用强度和位相信息表征生物芯片的理论模型，建立了一套单波长同时获取强度图像和位相图像的SPRI实验系统。实验证明了该技术的可行性，，有望在表面等离子体共振成像高通量芯片分析技术中获得应用。（三）水是各种生命体的主要成分，液体存在于所有的生物体中，对液体的各种特性的了解，有利于探索各种与液体有关的生命过程。本文利用数字全息技术针对纯水液滴和生理盐水液滴的动态蒸发过程进行了三维定量可视化技术研究，该技术有望在研究各种生物表面的湿润、蒸发机理方面获得应用。（四）双波长复用数字全息成像技术可拓宽测量范围，本文提出了一种基于三棱镜分光原理的离轴双波长数字全息技术的简单实验装置，并利用该实验装置对1951美国分辨率板进行了双波长复用数字全息图的解复用数字再现，成功分离出了和单个波长对应的位相再现图，验证了该实验装置的可行性，为方便开展双波长复用数字全息成像技术在生物医学中的应用提供了技术支持。
[Abstract]:In terms of human disease diagnosis and biomedical research, biomedical imaging has become one of the widely used methods. Imaging instrument is the traditional optical microscope, can be directly to the naked eye can not see the tiny objects clearly optical amplification imaging. But the traditional optical microscope can detect light intensity, light intensity distribution of 2D image. It is difficult to give, three-dimensional information of imaging objects, the application has some limitations in the biomedical field. The development of new imaging technology for analysis, for in vivo, cells, subcellular samples to achieve interference free, dynamic, quantitative analysis is the urgent needs of life science research at present. This paper carried out the basic research on the application of in the biomedical field for digital holographic imaging technology.
Digital holography is based on the traditional holographic principle, the difference is the use of electronic imaging devices (such as CCD, CMOS camera) hologram recording hologram recorded by data acquisition card and analog / digital conversion and quantization, stored in a computer in digital matrix form, namely digital hologram reconstruction process by computer; simulation of optical holography, through numerical calculation, the intensity image and phase image can be obtained simultaneously quantified the object wave. Compared with the traditional holographic imaging method, the advantages of digital holography is the continuous process of recording each moment: moving objects, realize continuous real-time recording; through digital reconstruction, it can quantitatively analyze the amplitude and phase information; can be easily image processing of digital hologram recording, reduce or eliminate the noise in the hologram recording process, aberration and other factors. Based on these unique advantages, digital holography is considered as a powerful tool for quantitative analysis and research of biphasic objects such as living organisms. In recent years, digital holography has become a hot research topic in the world.
This paper firstly introduces the principle of optical holography, digital holographic recording and reconstruction process technology. Then build a transmission type digital holographic imaging device, the application of digital holography in in vivo in dynamic imaging was carried out a large number of experiments, the main research contents are as follows: (a) for the current haze medium imaging difficult, scattering light on the imaging object interference, especially to obtain dynamic imaging and other issues, this paper carried out the study of digital holography imaging of dynamic living in turbid media. This paper first introduces the mode of transmission of light in a turbid medium; according to the characteristics of dynamic objects caused by light field continuous change, by continuous laser coherence length long as recording light holographic recording; extracting a Ji Fu digital hologram using digital filtering technology Fourier transform spectrum, both on the hologram digital reconstruction, and can eliminate the twin image and DC background effects, can also weaken the light scattering noise caused by digital technology; focus on, can be solved in a turbid medium in vivo cannot directly focus problems; influence with the spatial filtering technology can further eliminate the scattering noise; the experiment successfully realized dynamic imaging in turbid medium in digital holography based on the imaging method, application is expected to in vivo dynamic imaging in turbid organisms. (two) analyze the problem of high-throughput biochip for using surface plasmon resonance imaging, to carry out research. Analysis of surface plasmon resonance imaging biochip high throughput technique based on Digital holography in order to achieve high throughput analysis, must solve the surface plasmon resonance imaging and biochemical analysis The detection technology of narrow range, in this paper, a method is proposed to obtain the intensity image and phase image of digital holography based on surface plasmon resonance imaging (SPRI) technology, and the intensity and phase information, can broaden the detection range, high sensitivity, and improve the number of flux analysis. This paper established a set of the the intensity and phase information characterization of biochip model, SPRI experimental system has established a set of single wavelength to obtain the intensity image and phase image at the same time. The experiment proves the feasibility of the technology, is expected to get application in the analysis of surface plasmon resonance imaging microarray. (three) water is the main component of all kinds of life. The liquid exists in all organisms, for the understanding of the various characteristics of the liquid, and the liquid is conducive to explore various life related process. In this paper, based on digital holography According to the dynamic evaporation process of water droplets and Saline droplets of 3D visualization on the quantitative, the technology is expected in the study of various biological wetting, obtained by evaporation mechanism. (four) dual wavelength multiplexing digital holographic imaging technology can expand the scope of measurement, this paper presents a simple experimental device of off axis dual wavelength digital holography based on the principle of three prisms, and the 1951 United States resolution board of the dual wavelength digital hologram multiplexing demultiplexing digital reconstruction by using the experimental device, isolated phase and single wavelength representation, verify the feasibility of the experiment device, which provides technical support for convenient carry out double wavelength multiplexing digital holographic imaging technology in biomedicine.

【学位授予单位】：暨南大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318.04

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