光学相干层析视网膜成像系统研究
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摘要
光学相干层析成像(Optical Coherence Tomograpby,OCT)技术将低相干干涉仪和共焦扫描显微术结合在一起,利用外差探测技术提高信噪比获取生物组织断层图像,其成像深度达mm量级,空间分辨率保持在μm量级,并且横向分辨率和纵向分辨率相互独立。因此,OCT技术一经问世就成为生物医学成像研究的热点。
OCT最显著的医学贡献在眼科领域,其能够提供其他无损诊断技术不能提供的视网膜结构和功能图像。研发高性能的实用OCT视网膜成像系统一直是人们追求的目标。本论文针对OCT视网膜成像系统研发中存在的困难和国内对OCT眼科成像系统研究还很不成熟的状况,以发展具有自主知识产权,提高OCT分辨率和信噪比性能为目标,对OCT视网膜成像系统原理、设计与研制、性能优化和关于血氧饱和度测量的功能扩展等多个方面进行了深入研究。
本课题的具体研究内容及取得的创新性研究成果有:
1.针对OCT外差探测位相调制和纵向扫描的需求,提出一种快速扫描延迟线(RapidScanning Optical Delay Line,RSOD)优化设计方案。该优化设计方案既保证了外差探测正确解调的要求,也兼顾了系统纵向扫描速度和扫描范围的要求,同时可以实现色散调节,优化系统纵向分辨率。
2.针对平衡探测系统透射式延迟线的需求,提出一种新型的透射式快速扫描延迟线(RSOD)设计方案,采用直角棱镜作双通反射式光束平移器,具有光耦合效率高,结构简单紧凑、安装调试方便,成本节约的优点;该透射式RSOD保留了双通反射式RSOD的所有优点,并且具有极强的移植性,既可用于时域OCT系统,也可用于频域OCT系统实现平衡探测提高信噪比和动态范围。
3.针对OCT系统横向分辨率和纵向成像范围间的矛盾,提出一种基于液晶菲涅耳波带透镜的OCT动态聚焦方法。根据扭曲相液晶空间光调制器(Twisted Nematic LiquidCrystal Spatial light Modulator,TN-LCSLM)的光学特性,设计了适用于OCT动态聚焦的菲涅耳波带透镜。利用设计的菲涅耳波带透镜进行了变焦控制实验,焦距实测结果与设计值比较吻合。
4.利用提出的RSOD优化设计方案,研制了一套基于RSOD位相调制的光纤型OCT视网膜成像系统,结果表明:系统的纵向分辨率为6.7μm,接近理论分辨率,纵向成像范围高达2.5mm;入射到样品的光功率低于500μW,系统信噪比高于88dB。最后进行了动物视网膜的离体和在体实验研究,以及人眼视网膜标本的成像研究。并开展了基于双波长光学低相干干涉术(Optical Coherence Interferometry,OCI)的血氧饱和度测量方法的前期研究。
5.在关于内窥OCT成像的研究工作中,提出了一种基于波长编码的扫频OCT内窥成像方法,详细分析了该方法的工作原理,从理论分析上证明了其可行性。从系统时间脉冲响应和传递函数推导出系统干涉信号的数学表达式;模拟了简单样品的干涉信号,并给出Morlet小波分析的解码结果;讨论了系统的一些关键性能参数,如横向成像点数、成像分辨率、成像范围、成像速度等,指出系统横向分辨率和纵向分辨率相互制约,提高扫频光源的扫频范围是优化系统分辨率的有效方法。
Optical coherence tomography (OCT) based on low coherence interferometer and confocal scanning microscopy combining with heterodyne detection for high signal-to-noise ratio, provides non-invasive cross-sectional image with micrometer resolution and millimeter imaging depth in real time. What's more, depth and transverse resolutions are decoupled. OCT has been the research focus of biomedical imaging since it was first introduced.
OCT has made its most significant clinical contribution in the field of ophthalmology, which provides images of retinal structure that cannot be obtained by any other noninvasive diagnostic technique. Many groups are doing research for high performance economical OCT retinal imaging system. In order to overcome some existing challenges of OCT retinal imaging system and meet the requirements of native development of OCT, the theory, design, alignment, performance optimization and functional detection about oxygen saturation of OCT retinal imaging system are studied to finally improve the resolution and signal-to-noise-ratio (SNR) of OCT and generate our own intellectual properties.
The main work and innovations in the dissertation are summarized as following:
1. To meet the demands of heterodyne detection and depth scanning in OCT, investigation on parameter optimization of the rapid scanning optical delay line (RSOD) as phase modulator and depth scanner is conducted. The optimized design of RSOD ensures the high carrier frequency of heterodyne detection required for accurate envelope demodulation, and meets the demands of range and rate of depth scanning. The dispersion of the system can also be matched simultaneously by RSOD for high depth resolution.
2. A novel design of transmissive RSOD is proposed for balanced detection. In our design, a right angle prism is used for double-pass reflecting and exit displacement shifting of the beam. The design of transmissive RSOD is characterized as high beam coupling efficiency, convenience for fixing and adjusting, and cost economy. The transmissive RSOD possesses all the merits of double-pass reflective RSOD, and can be suit for time-domain OCT and Fourier-domain OCT for balanced detection to achieve high SNR and dynamic range.
3. To resolve the conflict between the transverse resolution and depth imaging range, an approach to realize dynamic focusing in OCT using liquid crystal Fresnel zone lens is proposed . Fresnel zone lens suitable for dynamic focusing in OCT is designed based on optical characteristics of twisted nematic liquid crystal spatial light modulator (TN-LCSLM). Experiments on dynamic focusing control of the designed Fresnel zone lens are conducted. Measured focal lengths are in good agreement with the designed ones.
4. The single-mode fiber-designed OCT retinal imaging system based on the optimized RSOD as phase modulator is developed. The experiment results indicate an axial resolution of 6.7μm, approaching the ideal resolution. The depth imaging range is about 2.5mm in the sample. Although less than 500μW optical power is incident on the sample, the system SNR is above 88dB. In addition, the animal retinal imaging experiments are conducted both ex vivo and in vivo, and the specimens of human retinal are also imaged by our system. Dual-wavelength optical coherent interferometry (OCI) is also proposed to measure the oxygen saturation in human retinal blood vessel and proved in theory.
5. A scheme for swept-source optical coherence tomography (SS-OCT) based on wavelength-encoded endoscopic imaging is presented. The working principle is analysed in detail, and the feasibility of endoscopic imaing is proved in theory. The mathematical analysis of the interference signal pattern in terms of 'temporal impulse response' and 'spectral response' is conducted. The simulated interferograms of simple samples and the decode results by Morlet wavelet are presented. The system key parameters such as transverse imaging resolvable points, imaging range, resolutions are detailed discussed. It is found that the transverse resolution and depth resolution are affected by each other, and an effective method to improve the system resolutions is to enlarge the swept range of the swept source.
OCT最显著的医学贡献在眼科领域,其能够提供其他无损诊断技术不能提供的视网膜结构和功能图像。研发高性能的实用OCT视网膜成像系统一直是人们追求的目标。本论文针对OCT视网膜成像系统研发中存在的困难和国内对OCT眼科成像系统研究还很不成熟的状况,以发展具有自主知识产权,提高OCT分辨率和信噪比性能为目标,对OCT视网膜成像系统原理、设计与研制、性能优化和关于血氧饱和度测量的功能扩展等多个方面进行了深入研究。
本课题的具体研究内容及取得的创新性研究成果有:
1.针对OCT外差探测位相调制和纵向扫描的需求,提出一种快速扫描延迟线(RapidScanning Optical Delay Line,RSOD)优化设计方案。该优化设计方案既保证了外差探测正确解调的要求,也兼顾了系统纵向扫描速度和扫描范围的要求,同时可以实现色散调节,优化系统纵向分辨率。
2.针对平衡探测系统透射式延迟线的需求,提出一种新型的透射式快速扫描延迟线(RSOD)设计方案,采用直角棱镜作双通反射式光束平移器,具有光耦合效率高,结构简单紧凑、安装调试方便,成本节约的优点;该透射式RSOD保留了双通反射式RSOD的所有优点,并且具有极强的移植性,既可用于时域OCT系统,也可用于频域OCT系统实现平衡探测提高信噪比和动态范围。
3.针对OCT系统横向分辨率和纵向成像范围间的矛盾,提出一种基于液晶菲涅耳波带透镜的OCT动态聚焦方法。根据扭曲相液晶空间光调制器(Twisted Nematic LiquidCrystal Spatial light Modulator,TN-LCSLM)的光学特性,设计了适用于OCT动态聚焦的菲涅耳波带透镜。利用设计的菲涅耳波带透镜进行了变焦控制实验,焦距实测结果与设计值比较吻合。
4.利用提出的RSOD优化设计方案,研制了一套基于RSOD位相调制的光纤型OCT视网膜成像系统,结果表明:系统的纵向分辨率为6.7μm,接近理论分辨率,纵向成像范围高达2.5mm;入射到样品的光功率低于500μW,系统信噪比高于88dB。最后进行了动物视网膜的离体和在体实验研究,以及人眼视网膜标本的成像研究。并开展了基于双波长光学低相干干涉术(Optical Coherence Interferometry,OCI)的血氧饱和度测量方法的前期研究。
5.在关于内窥OCT成像的研究工作中,提出了一种基于波长编码的扫频OCT内窥成像方法,详细分析了该方法的工作原理,从理论分析上证明了其可行性。从系统时间脉冲响应和传递函数推导出系统干涉信号的数学表达式;模拟了简单样品的干涉信号,并给出Morlet小波分析的解码结果;讨论了系统的一些关键性能参数,如横向成像点数、成像分辨率、成像范围、成像速度等,指出系统横向分辨率和纵向分辨率相互制约,提高扫频光源的扫频范围是优化系统分辨率的有效方法。
Optical coherence tomography (OCT) based on low coherence interferometer and confocal scanning microscopy combining with heterodyne detection for high signal-to-noise ratio, provides non-invasive cross-sectional image with micrometer resolution and millimeter imaging depth in real time. What's more, depth and transverse resolutions are decoupled. OCT has been the research focus of biomedical imaging since it was first introduced.
OCT has made its most significant clinical contribution in the field of ophthalmology, which provides images of retinal structure that cannot be obtained by any other noninvasive diagnostic technique. Many groups are doing research for high performance economical OCT retinal imaging system. In order to overcome some existing challenges of OCT retinal imaging system and meet the requirements of native development of OCT, the theory, design, alignment, performance optimization and functional detection about oxygen saturation of OCT retinal imaging system are studied to finally improve the resolution and signal-to-noise-ratio (SNR) of OCT and generate our own intellectual properties.
The main work and innovations in the dissertation are summarized as following:
1. To meet the demands of heterodyne detection and depth scanning in OCT, investigation on parameter optimization of the rapid scanning optical delay line (RSOD) as phase modulator and depth scanner is conducted. The optimized design of RSOD ensures the high carrier frequency of heterodyne detection required for accurate envelope demodulation, and meets the demands of range and rate of depth scanning. The dispersion of the system can also be matched simultaneously by RSOD for high depth resolution.
2. A novel design of transmissive RSOD is proposed for balanced detection. In our design, a right angle prism is used for double-pass reflecting and exit displacement shifting of the beam. The design of transmissive RSOD is characterized as high beam coupling efficiency, convenience for fixing and adjusting, and cost economy. The transmissive RSOD possesses all the merits of double-pass reflective RSOD, and can be suit for time-domain OCT and Fourier-domain OCT for balanced detection to achieve high SNR and dynamic range.
3. To resolve the conflict between the transverse resolution and depth imaging range, an approach to realize dynamic focusing in OCT using liquid crystal Fresnel zone lens is proposed . Fresnel zone lens suitable for dynamic focusing in OCT is designed based on optical characteristics of twisted nematic liquid crystal spatial light modulator (TN-LCSLM). Experiments on dynamic focusing control of the designed Fresnel zone lens are conducted. Measured focal lengths are in good agreement with the designed ones.
4. The single-mode fiber-designed OCT retinal imaging system based on the optimized RSOD as phase modulator is developed. The experiment results indicate an axial resolution of 6.7μm, approaching the ideal resolution. The depth imaging range is about 2.5mm in the sample. Although less than 500μW optical power is incident on the sample, the system SNR is above 88dB. In addition, the animal retinal imaging experiments are conducted both ex vivo and in vivo, and the specimens of human retinal are also imaged by our system. Dual-wavelength optical coherent interferometry (OCI) is also proposed to measure the oxygen saturation in human retinal blood vessel and proved in theory.
5. A scheme for swept-source optical coherence tomography (SS-OCT) based on wavelength-encoded endoscopic imaging is presented. The working principle is analysed in detail, and the feasibility of endoscopic imaing is proved in theory. The mathematical analysis of the interference signal pattern in terms of 'temporal impulse response' and 'spectral response' is conducted. The simulated interferograms of simple samples and the decode results by Morlet wavelet are presented. The system key parameters such as transverse imaging resolvable points, imaging range, resolutions are detailed discussed. It is found that the transverse resolution and depth resolution are affected by each other, and an effective method to improve the system resolutions is to enlarge the swept range of the swept source.
引文
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