慢性伤口光学仿体的多尺度多模态医学影像技术研究

发布时间：2018-05-15 07:40

本文选题：多模态影像 + 多视角影像　；参考：《中国科学技术大学》2016年博士论文

【摘要】：生物光学仿体的三维打印制备与表征系统整合了多模态光学影像、微纳加工和三维仿体打印等技术,能够为生物光学影像标准化的研究提供多模态可溯源仿体。生物光学仿体可以用来检验和校准临床影像系统,从而提高影像精度,减少测量误差,确保疾病诊治的准确性。系统中生物组织的检测和表征模块使用多模态光学影像技术,实现对生物体结构、功能和分子特性的实时检测,具有成本低体积小、速度快、非侵入以及无辐射等诸多优点。本文从宏观和微观两种尺度,针对慢性伤口这一类生物组织的表面形态、血氧分布及微血管表征,提出了两套多模态影像系统。对系统中运用的多模态影像技术,进行了系统性的研究,用实验验证了每套系统的功能并测量了关键参数。实现了伤口组织宏观三维血氧分布和微观血氧、血管三维信息重建。为生物光学仿体三维打印制备与表征系统中光学检测技术的集成提供了新的思路和参考,具有重要的研究价值。论文的主要研究内容如下：(1)搭建了一套多视角三维重建系统。提出了一种基于平面镜套筒的多视角三维重建方法。使用4面平面镜组成的平面镜套筒,仅使用1台相机完成对被测生物组织的多视角成像,通过计算机视觉中的相关理论,重建生物组织的外形信息。平面镜套筒可以将1台真实相机扩展为4台虚拟子相机和1台实体子相机。针对这个真实-虚拟相机系统,定量的完成了相机系统标定。(2)搭建了基于多视角成像和高光谱成像的宏观尺度多模态生物医学影像系统。该系统可以实现生物组织样品的表面三维重建、高光谱成像和组织血氧测量。该系统包含1台高分辨率的互补金属氧化物半导体(CMOS)数码单反相机,1个平面镜套筒,1台高灵敏度电荷耦合器件(CCD)相机,1台高光谱光源,以及环形光圈等器件,实现了能够同时获取生物组织结构和功能信息的影像平台。实验量化了基于多视角成像和高光谱成像的宏观多模态医学影像系统的性能。搭建了三维重建测试系统,通过实验定量的计算了三维重建系统的空间分辨率和重建精度,通过足部伤口模型验证了多视角系统对生物组织的重建能力。通过离体血液仿体实验和健康人手指的血流阻断-灌注实验检测了高光谱血氧成像的性能。该宏观多模态生物医学影像系统可以实现高精度的生物组织表面形貌信息和功能信息的重建。(3)搭建了微观尺度多模态生物医学影像系统。该系统包含结构光显微成像、荧光显微成像和高光谱显微成像三个模态。各个模态相互交叉集成可以实现生物组织在微观尺度上的结构和功能信息测量。该系统包含了1台高光谱光源,1台高灵敏度空气制冷相机,1片数字微镜器件(DMD)芯片及其控制模块,多组显微物镜和滤光片等原件。编写了微观尺度多模态影像系统的控制软件。该软件基于LabVIEW编程环境。可以实现采集图像的实时预览,高光谱光源输出光的波长和亮度控制,相机的曝光控制,电动载物台的移动控制,DMD芯片条纹的切换以及采集过程中各组件的有序全自动控制。(4)提出了显微高光谱结构光影像的图像采集方法。结构光影像通过对所采集到的条纹光照明图像进行光学层析图像处理,得到全视场大深度样品的清晰成像。但在高光谱影像中,层析图像的亮度信息并不能完全包含样品的反射光谱信息。因此,我们使用采集到的条纹光照明原始图片,生成了光学层析图片堆栈和明场照明堆栈,通过对层析图片堆栈的分析,获得明场照明图片堆栈中清晰对焦点的坐标,重建出样品全视场大深度清晰成像的高光谱数据。(5)实验验证了微观尺度多模态影像系统的性能指标。通过标准微球的表面重建实验,定量的验证了结构光表面重建可以实现较高精度的样品重建。布洛芬颗粒样品、硬币样品重建实验显示了结构光表面重建应用效果。通过吲哚菁绿(ICG)荧光微管道仿体验证了系统的荧光结构光显微成像模态。植物花蕊和花粉颗粒的显微结构光成像实验显示出了荧光影像模态的成像效果。通过血液微管道仿体血氧饱和度测量实验,检验了系统高光谱影像模态的性能,从仿体层面验证了系统对伤口组织微血管血氧测量的潜力。将多种模态相互组合可以实现全彩色生物样品表面重建、高光谱光学活检和生物组织三维血氧成像等扩展功能。
[Abstract]:The three-dimensional print preparation and characterization system of biological optical imitation integrates multi-modal optical images, micro nano processing and three-dimensional imitation printing, which can provide multi-modal traceability imitation for the study of biological optical image standardization. Biological optical imitation can be used to test and calibrate clinical imaging systems, thus improving image accuracy and reducing the accuracy of the image. Measurement error to ensure the accuracy of the diagnosis and treatment of disease. The detection and characterization module of biological tissues in the system uses multi-modal optical imaging technology to realize real-time detection of the structure, function and molecular characteristics of the organism. It has many advantages, such as low cost, low volume, fast speed, non invasion and no radiating. This paper from the macro and micro two scales, In view of the surface morphology, blood oxygen distribution and microvascular characterization of the chronic wound, two sets of multimodal image systems are proposed. The multi-modal imaging techniques used in the system are systematically studied. The functions of each system are verified by experiments and the key parameters are measured. The macroscopic three-dimensional blood oxygen of the wound tissue is realized. Distribution and microscopic blood oxygen and reconstruction of three-dimensional information of blood vessels provide new ideas and references for the integration of optical detection technology in the system of three-dimensional printing and characterization of biological optical imitation. The main research contents of this paper are as follows: (1) a set of multi angle three-dimensional reconstruction system is built. A kind of plane based on plane is proposed. The multi view three-dimensional reconstruction method of the mirror sleeve. Using a plane mirror sleeve composed of 4 plane mirrors, only 1 cameras are used to complete the multi view imaging of the measured biological tissue, and the shape information of the biological tissue is reconstructed by the related theory in the computer vision. The plane mirror sleeve can extend the 1 real cameras to 4 virtual subcameras and 1 sets. The solid subcamera. Aiming at this real virtual camera system, the calibration of the camera system has been completed quantitatively. (2) a multi-modal biomedical imaging system based on multi view imaging and hyperspectral imaging is built. This system can realize the three-dimensional reconstruction of the surface of biological tissue samples, hyperspectral imaging and tissue oxygen measurement. 1 high resolution complementary metal oxide semiconductor (CMOS) digital single mirror camera, 1 plane mirror sleeve, 1 highly sensitive charge coupled device (CCD) camera, 1 hyperspectral light source, and ring aperture are used to realize the image platform which can obtain the structure and function information of biological tissue simultaneously. The performance of the macroscopic multi-modal medical imaging system of angular imaging and hyperspectral imaging. A three-dimensional reconstruction test system was built. The spatial resolution and reconstruction accuracy of the 3D reconstruction system were calculated quantitatively. The reconstruction ability of the multiview system to the biologic fabric was verified by the foot wound model. The performance of hyperspectral blood oxygen imaging was detected by the blood flow blocking experiment of the fingers of healthy people. The macro multimodal biomedical imaging system could achieve the high precision of the reconstruction of the surface morphology information and functional information of biological tissues. (3) a microscale multi-modal biologic medical imaging system was built. The system contains structural light microscopy. Image, fluorescence microscopy and hyperspectral microimaging three modes. Each mode is intersecting with each other to measure the structure and function information of biological tissue at microscale. The system includes 1 hyperspectral light sources, 1 high sensitivity air cooling cameras, 1 chip digital micromirror devices (DMD) chips and their control modules. The control software of the microscale multi-modal image system is written. The software is based on the LabVIEW programming environment. The software can realize the real-time preview of the collection image, the wavelength and brightness control of the output light of the hyperspectral light source, the exposure control of the camera, the movement control of the electric carrier table, the switching of the stripe of the DMD chip and the acquisition. The sequential and automatic control of the components in the process. (4) the image acquisition method of the optical and shadow image of the microscopic hyperspectral structure is proposed. The optical image of the structured light and shadow image is processed by the optical image processing of the Striped light illumination image collected, and the clear imaging of the large depth samples of the full field of view is obtained. We can not completely contain the reflection spectrum information of the sample. Therefore, we use the collected striped light to illuminate the original picture, and generate the optical tomography stack and the bright field lighting stack. Through the analysis of the tomographic stack, we obtain the clear coordinates of the focus in the lighting stack of the bright field, and reconstruct the full and clear field of the whole field of view of the sample. Like hyperspectral data. (5) the performance of microscale multi-modal imaging system was verified by experiments. The surface reconstruction experiments of standard microspheres showed that the reconstruction of structural light surface could achieve high precision of sample reconstruction. Ibuprofen Granules samples, the rebuilt experiment of coin samples showed the application effect of structural light surface reconstruction. The fluorescence microscopic imaging modality of the system was verified by the fluorescence microchannel imitates of the indocyanine green (ICG). The microscopic imaging experiments of the plant stamens and pollen grains showed the imaging results of the fluorescence imaging modality. The performance of the hyperspectral imaging modality was tested through the measurement of the oxygen saturation of the blood micropipeline. The potential of the system for microvascular blood oxygen measurement in wound tissue is verified from the imitating level. Multiple modes can be combined to realize the surface reconstruction of full color biological samples, hyperspectral optical biopsies and three dimensional oxygen imaging of biological tissues.

【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TP391.41;R310

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