谱域光学相干层析成像技术及其生物医学应用研究
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摘要
光学相干层析成像（Optical coherence tomography, OCT）技术是20世纪90年代发展起来的、利用相干特性来实现层析成像的新兴技术，通过探测干涉信号来获得组织内部的深度信息。OCT技术是由宽带光源照明的迈克尔逊干涉仪组成的。宽带光源的低相干特性实现了OCT技术的高分辨率、无创伤、非侵入等优点。OCT技术主要分为时间域OCT(时域OCT)和频率域OCT(频域OCT)。时域OCT是一种传统的OCT技术，通过改变参考臂的光程来实现样品的深度扫描，称之为点扫描方式。点扫描方式大大地降低了时域OCT技术的采集速度，影响了它的广泛应用。频域OCT是在时域OCT的基础上发展起来的新型的OCT技术。频域OCT主要分为谱域（Spectral domain）OCT和扫描光源（Swept source）OCT。谱域OCT是通过测量参考臂和样品臂的干涉光谱来实现样品的深度的采集，从而提高了OCT的采集速度；同时兼备了时域OCT技术的所有优点。因此，谱域OCT目前已经成为各个领域研究的热点。
本文首先介绍了OCT技术的基本理论，并在此基础上展开对谱域OCT的成像原理和实验系统的阐述。谱域OCT技术是利用光谱仪探测参考光和样品光的干涉光谱，然后对干涉光谱进行傅里叶变换，便可获得样品的深度信息，而无须参考臂的深度扫描。
与天津医科大学第二附属医院合作，对口腔组织——腮腺导管进行研究，通过谱域OCT技术对腮腺导管进行成像研究，可以诊断出疾病的位置和特征，并可以实时观测，对内窥式谱域OCT技术的研究具有重要的意义。与南开大学生命科学学院和医学院合作，利用谱域OCT技术研究紫外线对斑马鱼眼底的损伤，观测了斑马鱼眼底损伤的修复过程，并注射脂质体颗粒观测斑马鱼眼底延迟修复的过程，并与相对应的免疫组化结果进行比较，取得了理想的符合结果。同时利用谱域OCT实现了实时、活体的观测斑马鱼眼底的修复过程。对斑马鱼眼底的观测，对以后研究修复眼底损伤的药物研究就要重要的意义。
在传统的光学系统中，轴向分辨率和横向分辨率是相互制约、相互关联的，然而在OCT技术中二者是相互独立、互不影响的。在OCT系统中，轴向分辨率是由宽带光源的带宽决定的，并成反比关系；横向分辨率是由成像物镜的数值孔径（NA）成正比的。然而当利用普通的成像物镜时，横向分辨率和焦深是成反比关系的，NA越大焦深越短，从而影响测量样品的深度信息。针对横向分辨率与焦深的制约关系，研究并设计了一种微光学元件，命名为改进型分形波带片，通过光束整形的方法解决了这个问题并利用样品进行了实验验证。
针对癌症的特点，与天津市人民医院合作，对人体直肠癌进行研究并利用OCT图像获得了诊断癌症的量化参数——散射系数。谱域OCT通过探测样品的后向散射光来获得样品的深度信息，本文利用对采集的图像进行数据拟合的方式获得样品不同深度的散射系数，对组织的病变部位进行量化，通过数值判断出疾病的所在；并与目前临床医学上的诊断手段——病理切片进行比较，得到了很好的验证。
Optical Coherence Tomography is a new tomographic imaging technologydeveloped in1990s, which is obtaining the internal depth information of biologicaltissue through detecting the back scattering. OCT is composed by Michelsoninterferometer illuminated by broadband source. The low coherence of broadbandsource achieves the advantages of OCT, such as high resolution, non-contact,non-invasive, and so on. OCT is divided into time domain OCT (TDOCT) andfrequency domain OCT (FDOCT). Time domain OCT is a traditional OCTtechnology, which is through controlling the movement of reference mirror to realizethe axial scanning and obtain the depth information. Due to the scanning mode, thepicking rate of TDOCT is very slow, which is restricting the applications. Frequencydomain OCT is a new type OCT technology developing from TDOCT and is dividedinto spectral domain OCT (SDOCT) and swept source OCT (SSOCT). Spectraldomain OCT is detecting the interference spectrum of reference and sample light,which is realized the depth parallel sampling and improve the picking rate. Now,many fields are focus on the research of SDOCT.
In the beginning, the paper introduces the basic principle of OCT and theimaging principle of SDOCT including the experimental system. SDOCT uses thespectrometer to detect the interference spectrum, and then obtain the depthinformation through Fourier transformation of interference spectrum, which is noneed of axial scanning.
Allying with the2nd hospital of Tianjin medical university, we study the oraltissue (salivary glands) to detect the disease, which can be realized real-time imagingand is useful for the research of endoscope. Allying with Nankai university school ofmedicine and college of life science, we use SDOCT to study the zebrafish retinaldamage-regeneration caused by ultraviolet rays. Furthermore, the zebrafish areinjected with clodronate-liposome to study the regeneration process. In addition, weassess retinal light damage at various dpt (days post treatment) using immunohistochemistry in order to offer a solid criterion for an analytic result by OCT.The OCT results give a great agreement with the immunohistochemistry. Ascomparison, the SDOCT system is a real-time and non-invasive technology withoutfluorescence labeling and frozen cryosectioning. As a result, we observed the injuryand regeneration of the cone photoreceptors cells with SDOCT in live after UV lightillumination. The results demonstrate the SDOCT system for dynamic detection ofretina damage by UV illumination without requiring fluorescence labeling and frozencryosectioning, which gives a great value of the studying of the medicine of retinaldisease.
In traditional optical system, the axial and transverse resolution areinterdependent, however, in OCT system the resolutions are independent. In OCTsystem, the axial resolution is determined by the bandwidth of broadband source; thetransverse resolution is determined by the NA of objective lens. In the commonobjective lens system, the transverse resolution and depth of focus (DOF) arereciprocal. The larger the resolution is, the shorter the DOF. In the paper, we design amicro-element named modified fractal zone plate to resolve the problem and give theexperimental results.
To study the features of cancers, we extract the scattering coefficient of rectaltissue to quantify the disease from the OCT images allying with Nankai universityaffiliated hospital. In the paper, we use the data fitting method of OCT images toextract the scattering coefficient and confirm the disease. To give a criterion, wecompare the results with pathological sections which gives a perfect result.
本文首先介绍了OCT技术的基本理论，并在此基础上展开对谱域OCT的成像原理和实验系统的阐述。谱域OCT技术是利用光谱仪探测参考光和样品光的干涉光谱，然后对干涉光谱进行傅里叶变换，便可获得样品的深度信息，而无须参考臂的深度扫描。
与天津医科大学第二附属医院合作，对口腔组织——腮腺导管进行研究，通过谱域OCT技术对腮腺导管进行成像研究，可以诊断出疾病的位置和特征，并可以实时观测，对内窥式谱域OCT技术的研究具有重要的意义。与南开大学生命科学学院和医学院合作，利用谱域OCT技术研究紫外线对斑马鱼眼底的损伤，观测了斑马鱼眼底损伤的修复过程，并注射脂质体颗粒观测斑马鱼眼底延迟修复的过程，并与相对应的免疫组化结果进行比较，取得了理想的符合结果。同时利用谱域OCT实现了实时、活体的观测斑马鱼眼底的修复过程。对斑马鱼眼底的观测，对以后研究修复眼底损伤的药物研究就要重要的意义。
在传统的光学系统中，轴向分辨率和横向分辨率是相互制约、相互关联的，然而在OCT技术中二者是相互独立、互不影响的。在OCT系统中，轴向分辨率是由宽带光源的带宽决定的，并成反比关系；横向分辨率是由成像物镜的数值孔径（NA）成正比的。然而当利用普通的成像物镜时，横向分辨率和焦深是成反比关系的，NA越大焦深越短，从而影响测量样品的深度信息。针对横向分辨率与焦深的制约关系，研究并设计了一种微光学元件，命名为改进型分形波带片，通过光束整形的方法解决了这个问题并利用样品进行了实验验证。
针对癌症的特点，与天津市人民医院合作，对人体直肠癌进行研究并利用OCT图像获得了诊断癌症的量化参数——散射系数。谱域OCT通过探测样品的后向散射光来获得样品的深度信息，本文利用对采集的图像进行数据拟合的方式获得样品不同深度的散射系数，对组织的病变部位进行量化，通过数值判断出疾病的所在；并与目前临床医学上的诊断手段——病理切片进行比较，得到了很好的验证。
Optical Coherence Tomography is a new tomographic imaging technologydeveloped in1990s, which is obtaining the internal depth information of biologicaltissue through detecting the back scattering. OCT is composed by Michelsoninterferometer illuminated by broadband source. The low coherence of broadbandsource achieves the advantages of OCT, such as high resolution, non-contact,non-invasive, and so on. OCT is divided into time domain OCT (TDOCT) andfrequency domain OCT (FDOCT). Time domain OCT is a traditional OCTtechnology, which is through controlling the movement of reference mirror to realizethe axial scanning and obtain the depth information. Due to the scanning mode, thepicking rate of TDOCT is very slow, which is restricting the applications. Frequencydomain OCT is a new type OCT technology developing from TDOCT and is dividedinto spectral domain OCT (SDOCT) and swept source OCT (SSOCT). Spectraldomain OCT is detecting the interference spectrum of reference and sample light,which is realized the depth parallel sampling and improve the picking rate. Now,many fields are focus on the research of SDOCT.
In the beginning, the paper introduces the basic principle of OCT and theimaging principle of SDOCT including the experimental system. SDOCT uses thespectrometer to detect the interference spectrum, and then obtain the depthinformation through Fourier transformation of interference spectrum, which is noneed of axial scanning.
Allying with the2nd hospital of Tianjin medical university, we study the oraltissue (salivary glands) to detect the disease, which can be realized real-time imagingand is useful for the research of endoscope. Allying with Nankai university school ofmedicine and college of life science, we use SDOCT to study the zebrafish retinaldamage-regeneration caused by ultraviolet rays. Furthermore, the zebrafish areinjected with clodronate-liposome to study the regeneration process. In addition, weassess retinal light damage at various dpt (days post treatment) using immunohistochemistry in order to offer a solid criterion for an analytic result by OCT.The OCT results give a great agreement with the immunohistochemistry. Ascomparison, the SDOCT system is a real-time and non-invasive technology withoutfluorescence labeling and frozen cryosectioning. As a result, we observed the injuryand regeneration of the cone photoreceptors cells with SDOCT in live after UV lightillumination. The results demonstrate the SDOCT system for dynamic detection ofretina damage by UV illumination without requiring fluorescence labeling and frozencryosectioning, which gives a great value of the studying of the medicine of retinaldisease.
In traditional optical system, the axial and transverse resolution areinterdependent, however, in OCT system the resolutions are independent. In OCTsystem, the axial resolution is determined by the bandwidth of broadband source; thetransverse resolution is determined by the NA of objective lens. In the commonobjective lens system, the transverse resolution and depth of focus (DOF) arereciprocal. The larger the resolution is, the shorter the DOF. In the paper, we design amicro-element named modified fractal zone plate to resolve the problem and give theexperimental results.
To study the features of cancers, we extract the scattering coefficient of rectaltissue to quantify the disease from the OCT images allying with Nankai universityaffiliated hospital. In the paper, we use the data fitting method of OCT images toextract the scattering coefficient and confirm the disease. To give a criterion, wecompare the results with pathological sections which gives a perfect result.
引文
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