光透明技术在生物光学成像深度拓展及对比增强中的应用研究

发布时间：2018-09-14 10:43

【摘要】：生物光学成像技术具有无创、高分辨,高对比度及快速等特点,可实现微米或亚微米量级高分辨的生物组织的微结构及功能成像,在疾病检测及临床应用研究中呈现出广阔的应用前景。然而,由于大多数生物组织所具有的浑浊、高散射特性,严重限制了光在组织中的穿透深度,使得多种光学成像技术无法实现对组织更深层的结构进行成像。因此,本文的研究目的是以谱域光学相干层析成像(Spectral-domain OCT,SD-OCT)及光声显微成像技术(Photoacoustic microscopy,PAM)为例,利用组织光透明技术(Tissue optical clearing,TOC),研究提高生物光学成像探测深度的方法,提升光学成像技术探测组织深层的形态结构与功能特征的能力,以提供更加丰富有价值的组织图像及参数信息用于对医学疾病的诊断与治疗。针对以上研究目的,本研究利用TOC技术及超声波与光学透明剂(Optical clearing agents,OCAs)相结合的方法,提升了两种光学成像方法的成像深度,实现更深层的高对比度的组织结构成像,并定性定量分析了由OCAs所引起的组织光学特性参数的变化,讨论了OCAs剂量对成像效果及光穿透深度的影响。本论文的主要研究内容和结果如下:首先,针对OCT在生物组织成像中,由于受到组织高散射的影响而导致成像深度浅、图像对比度低等问题,基于TOC技术,选取OCAs葡萄糖作用于人的离体的正常与结肠癌组织,成功实现OCT对葡萄糖在两种组织中的整个扩散过程实时动态监控。并深入分析了oct信号强度、葡萄糖渗透系数(permeabilitycoefficients,pc)、葡萄糖在两种组织内所引起光衰减系数(attenuationcoefficients,ac)等参数变化规律及测量结果。研究结果表明葡萄糖对提高oct在对正常和癌变的结肠组织成像中图像的对比度、成像深度有效性和实用性。同时,通过定性定量评价与分析,发现葡萄糖在癌变结肠组织中pc是正常结肠组织的1.65倍,光的ac最大值及最小值分别是正常结肠组织的2.44和1.18倍。进而提出通过计算与比较由ocas在不同组织中引起的组织特性参数的差异,可用来提高oct对正常和病变组织的识别能力,这对拓宽oct的应用具有重要的应用价值。其次,为了进一步提高ocas在组织中的渗透速率及光透明效果(opticalclearingeffects,oce),进而促使光在组织中的穿透更深,在上一研究基础上,提出采用超声波协同葡萄糖策略,加快葡萄糖在正常和癌变结肠组织中的渗透,并实现oct对葡萄糖在组织中整个渗透过程的实时动态监测。深入研究了由超声波导入所引起的葡萄糖pc、oce、oct信号强度及1/e光穿透深度等参数变化及计算结果。研究结果表明经超声协同,葡萄糖在两种组织中的pc分别被提高了约1.87和2.14倍,oct信号强度被提高了约12.5%和10.8%,1/e光穿透深度被提高了约1.28和1.27倍。并证明超声协同葡萄糖策略可作为一种促进ocas扩散,进一步增强光在组织中穿透深度的有效方法,为进一步拓展oct成像能力提供新的思路与和理论依据。最后,为了深入了解ocas浓度及作用时间对oce、pam信号幅值、图像对比度及光的穿透深度等特征的影响,利用覆盖于皮肤组织下的仿体诱发光声信号,实现了pam对经不同浓度甘油处理后的皮肤组织下仿体图像的变化进行了实时动态监控。定性定量评价与分析了浓度对OCE、成像质量及光声信号幅值等特征之间的影响与的变化规律。研究结果不仅表明甘油对增强PAM成像深度及信号强度有效性,还证明甘油浓度与增强OCE、提高PAM成像能力之间存在紧密的相关性,其中60%甘油OCE最好、40%次之、20%最差,但相对于后两组,60%甘油组取得最佳组织OCE所需的时间却最长,并发现组织OCE并非随甘油作用时间的延长而呈现线性增加的趋势。此研究结果对更有效的利用OCAs增加组织OCE,进而提高光学成像技术的成像能力具有重要的指导意义。本论文重点对TOC技术在OCT与PAM成像深度拓展及图像对比增强中的应用进行了深入的研究。并定性评价了TOC技术对提升此两种技术成像能力的有效性,定量分析了由OCAs引起的生物组织光学特性参数的变化规律,及OCAs浓度对增强组织OCE与成像深度及图像对比度之间的相关性。本论文的研究成果为TOC技术提升光学成像技术在生命科学与工程科学领域中的成像能力和应用范围,及完善TOC技术理论评价体系,提供重要的理论依据及实验参考。
[Abstract]:Bio-optical imaging technology is noninvasive, high-resolution, high-contrast and fast. It can realize high-resolution micro-or sub-micron-scale imaging of the microstructure and function of biological tissues. It has a broad application prospect in disease detection and clinical application. However, due to the turbidity and high scattering characteristics of most biological tissues. Therefore, the purpose of this paper is to take spectral-domain optical coherence tomography (SD-OCT) and photoacoustic microscopy (PAM) as examples, and to utilize groups. Tissue optical clearing (TOC) is a new technique to improve the detection depth of bio-optical imaging, and to enhance the ability of optical imaging to detect the morphological structure and functional characteristics of deep tissue in order to provide more valuable tissue images and parameter information for the diagnosis and treatment of medical diseases. Aim: In this study, TOC technology and the combination of ultrasonic and optical clearing agents (OCAs) were used to enhance the imaging depth of the two optical imaging methods, to achieve deeper high contrast tissue imaging, and qualitative and quantitative analysis of the changes of tissue optical properties caused by OCAs was discussed. The main contents and results of this paper are as follows: Firstly, for the problems of low contrast and shallow imaging depth caused by high tissue scattering, OCAs glucose was selected to act on human normal in vitro based on TOC technology. With colon cancer tissues, OCT can monitor the whole glucose diffusion process in both tissues in real time and dynamically. The changes of OCT signal intensity, permeability coefficients (pc) and attenuation coefficients (ac) induced by glucose in the two tissues were analyzed and measured. Results. The results showed that glucose could improve the contrast, depth efficiency and practicability of OCT in normal and cancerous colon tissue imaging. Meanwhile, through qualitative and quantitative evaluation and analysis, it was found that the PC of glucose in cancerous colon tissue was 1.65 times that of normal colon tissue, and the maximum and minimum AC of light were positive respectively. 2.44 and 1.18 times of normal colon tissue. It is suggested that the ability of OCT to recognize normal and pathological tissues can be improved by calculating and comparing the differences of tissue characteristic parameters caused by OCAs in different tissues, which is of great value in broadening the application of Oct. Secondly, the osmotic rate of OCAs in tissues can be further increased. Based on the previous study, the ultrasound-assisted glucose strategy was proposed to accelerate the permeation of glucose into normal and cancerous colon tissues and to realize the real-time and dynamic monitoring of glucose permeation in tissues by Oct. The changes of glucose pc, oce, OCT signal intensity and 1/e light penetration depth caused by ultrasound were studied. The results showed that the PC of glucose in the two tissues was increased about 1.87 and 2.14 times, the OCT signal intensity was increased about 12.5% and 10.8%, and the 1/e light penetration depth was increased by ultrasound. It is proved that the ultrasound-glucose coordination strategy can be used as an effective method to promote the diffusion of OCAs and further enhance the depth of light penetration in tissues. It provides a new idea and theoretical basis for further expanding the imaging ability of Oct. Finally, in order to further understand the amplitude of oce, PAM signal and image contrast of OCAs concentration and action time. The PAM was used to monitor the changes of the bionic images of skin tissue after glycerol treatment with different concentrations. The effects of concentration on OCE, imaging quality and photoacoustic signal amplitude were evaluated and analyzed qualitatively and quantitatively. The results not only show that glycerol is effective in enhancing the imaging depth and signal intensity of PAM, but also prove that there is a close correlation between glycerol concentration and enhancing OCE and improving the imaging ability of PAM. It is found that OCE does not increase linearly with the prolongation of glycerol exposure time. The results of this study have important guiding significance for more effective use of OCAs to increase tissue OCE and improve the imaging ability of optical imaging technology. The application of TOC technology in image contrast enhancement is studied in depth, and the effectiveness of TOC technology in enhancing the imaging ability of these two technologies is evaluated qualitatively. The variation law of optical characteristic parameters of biological tissues caused by OCAs is analyzed quantitatively, and the correlation between OCE concentration and imaging depth and image contrast is discussed. The research results of this paper provide important theoretical basis and experimental reference for TOC technology to enhance the imaging ability and application scope of optical imaging technology in the field of life science and engineering science, and to improve the TOC technology theoretical evaluation system.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R318.51

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