谱域光学相干层析成像方法与系统研究
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摘要
光学相干层析成像(Optical Coherence tomography, OCT)技术是一种非侵入、非接触微米级分辨率的成像技术,利用光学相干门来获得组织内部的层析结构。谱域OCT(Spectral domain OCT, SD-OCT)是第二代OCT技术,相比第一代时域OCT技术,在成像速度、信噪比和灵敏度等方面具有明显优势,在眼科成像、功能成像等领域发挥了重要作用。本课题对SD-OCT成像系统及技术进行了研究,具体的研究内容及取得的创新性研究成果有：
1.研制了由光纤型迈克尔逊干涉仪和基于线阵CCD的快速光谱仪组成的835nm波段的SD-OCT成像系统。其中快速光谱仪的光谱分辨率为0.0674nm,系统轴向扫描(A-scan)速度为29KHz,轴向分辨率为7.5μm,最大成像深度为2.56mm,最大信噪比为115dB,能够对生物组织和散射样品进行高分辨率的实时在体成像。
2.提出了不借助校正光源,直接基于SD-OCT系统本身对光谱仪进行波长标定的方法。通过获取反射镜样品两个不同位置处的干涉光谱,分别对两个干涉光谱作希尔伯特变换和相位去包裹运算提取光谱相位分布,依据光谱相位分布差和反射镜样品不同位置间的光程差标定波长相对分布。最后由特定像素对应的波长值,确定波长的绝对分布。此标定方法对系统色散不敏感。
3.分析了光谱仪中典型光谱的聚焦光斑尺寸和系统灵敏度下降之间的关系。通过Zemax模拟了光谱仪中各个光学元件,确定了线阵CCD上的光谱点列图。通过点列图,定性分析了在一定的线阵CCD像素尺寸情况下,典型光谱的聚焦光斑尺寸不同时的系统灵敏度下降曲线。当聚焦光斑尺寸与CCD像素尺寸相比拟时,系统的灵敏度随深度增加的下降趋势缓慢,在2mm的成像深度范围内下降16.1dB。
4.首次将非均匀傅里叶变换应用在SD-OCT系统进行图像重建。将光谱仪中线阵CCD采集到的光谱信号看做是在波数空间的非均匀采样,直接通过非均匀傅里叶变换重建图像,而不需要进行传统重建算法中的差值处理。人体手指的实时OCT成像结果表明相比传统图像重建方法,基于非均匀傅里叶变换的重建方法能有效抑制系统灵敏度随深度增加而下降的趋势,使样品深层的结构更加清晰。
5.首次提出了基于正弦空间相位调制的消除共轭镜像的方法,其中参考臂正弦相位调制和样品臂的横向扫描同步进行,即正弦B-M方法。对正弦相位调制后的干涉光谱进行谐波分析构造复干涉频谱,并有效抑制自相关项和直流项,实现全量程的SD-OCT成像。相比已有的线性B-M方法,正弦B-M方法不仅降低了对参考臂移相器件的要求,同时也避免了横向方向的灵敏度下降问题。对活虾的成像结果表明,正弦B-M的方法不仅实现了成像深度范围加倍,同时复共轭抑制率高达45dB。
6.提出了适用于SD-OCT系统的解卷积方法。在SD-OCT系统中,CCD采集到的干涉光谱信号是原始干涉光谱信号和光谱仪传递函数的卷积,导致了轴向点扩散函数随着成像深度的增加而下降。因此SD-OCT系统不具备空不变特性,无法直接应用于解卷积运算。我们首先通过标定轴向点扩散函数的调制函数,再经过数值补偿后在空间域采用Lucy-Richardson迭代算法解卷积。活虾的OCT图像在解卷积前和解卷积后的对比表明：解卷积算法不仅可以去除OCT图像的模糊,同时可以使样品深层的结构更加清晰。
Optical coherence tomography (OCT) is a non-invasive, non-contact imaging modality with micrometer resolution, which uses coherent gating to obtain cross-sectional images of tissue microstructure. As the second generation of OCT technology, spectral domain OCT (SD-OCT) offers significant advantages in imaging speed, detection sensitivity and signal noise ratio (SNR) in contrast to time domain OCT. Therefore, it plays an important role in the field of ophthalmology and functional imaging. This dissertation is mainly focused on SD-OCT technology, the main work and innovations are summarized as following:
1. The SD-OCT system at 835nm wavelength is developed, which is consisted of a fiber based Michelson interferometer and a line-scan CCD based high speed spectrometer. The spectral resolution of the spectrometer is about 0.0674nm, corresponding to an axial imaging range of 2.56mm. With the A-scan rate of 29 KHz, the axial resolution and maximum SNR of the system are 7.5μm and 115dB, respectively, which is capable for real time in vivo imaging of biomedical samples.
2. A spectral calibration method for spectrometer is proposed, which is directly based on the SD-OCT system itself without the utilization of additional calibration source. With two measurements of interference spectra from two reference mirror position, the corresponding phase differences can be calculated after Hilbert transform and phase unwrapping. Then, with the wavelength value of specific CCD pixel, the wavelength distribution on CCD plane can be determined. Furthermore, this method is not sensitive to system unmatched dispersion.
3. The relationship between system sensitivity fall-off and diffraction spot size is studied. According to the spot diagrams on CCD plane obtained by Zemax, system sensitivity fall-off with different spot size of typical spectral components is calculated. When the spot size of typical spectral components are comparable to the size of CCD pixel, improved depth dependent sensitivity fall-off can be achieved, and sensitivity drops by 16.1dB over 2mm imaging depth range.
4. Non-uniform discrete Fourier transform (NDFT) is introduced into SD-OCT system for image reconstruction. The spectral data is considered as irregular sampling in wavenumber space, then the depth information can be reconstructed by NDFT directly without interpolation. Real time in vivo imaging of human finger confirms that compared with conventional DFT and interpolation method, reconstruction method based on NDFT indeed improves sensitivity fall-off especially at larger depth.
5. A spatial sinusoidal phase modulation for the elimination of complex-conjugate artifact is proposed, where sinusoidal phase modulation of reference arm (M scan) and transverse scanning of sample arm (B scan) are performed simultaneously (sinusoidal B-M method). The complex interference spectra are reconstructed by harmonic analysis, its Fourier transform is free of mirror image and coherent noises. Compared with the linear B-M method, the proposed sinusoidal B-M method relaxes the requirements on the phase-shifting mechanical system and avoids sensitivity fall-off along the transverse direction. Double imaging depth range on shrimp with complex conjugate rejection ratio up to 45dB is achieved.
6. Deconvolution method in SD-OCT system is proposed. In SD-OCT system, the spectral data acquired by CCD is the convolution of the original interference spectral signal and the transfer function of spectrometer, which results in the degradation of axial point spread function (PSF) along the depth direction. Herein, the axial modulation function of the PSF is retrieved firstly. Then after compensating the A-scan signal with the modulation function, devolution method is performed in spatial domain by Lucy-Richardson algorithm. In vivo OCT imaging of a fresh shrimp demonstrates that compared with original image, image enhancement is achieved by the proposed deconvolution method.
1.研制了由光纤型迈克尔逊干涉仪和基于线阵CCD的快速光谱仪组成的835nm波段的SD-OCT成像系统。其中快速光谱仪的光谱分辨率为0.0674nm,系统轴向扫描(A-scan)速度为29KHz,轴向分辨率为7.5μm,最大成像深度为2.56mm,最大信噪比为115dB,能够对生物组织和散射样品进行高分辨率的实时在体成像。
2.提出了不借助校正光源,直接基于SD-OCT系统本身对光谱仪进行波长标定的方法。通过获取反射镜样品两个不同位置处的干涉光谱,分别对两个干涉光谱作希尔伯特变换和相位去包裹运算提取光谱相位分布,依据光谱相位分布差和反射镜样品不同位置间的光程差标定波长相对分布。最后由特定像素对应的波长值,确定波长的绝对分布。此标定方法对系统色散不敏感。
3.分析了光谱仪中典型光谱的聚焦光斑尺寸和系统灵敏度下降之间的关系。通过Zemax模拟了光谱仪中各个光学元件,确定了线阵CCD上的光谱点列图。通过点列图,定性分析了在一定的线阵CCD像素尺寸情况下,典型光谱的聚焦光斑尺寸不同时的系统灵敏度下降曲线。当聚焦光斑尺寸与CCD像素尺寸相比拟时,系统的灵敏度随深度增加的下降趋势缓慢,在2mm的成像深度范围内下降16.1dB。
4.首次将非均匀傅里叶变换应用在SD-OCT系统进行图像重建。将光谱仪中线阵CCD采集到的光谱信号看做是在波数空间的非均匀采样,直接通过非均匀傅里叶变换重建图像,而不需要进行传统重建算法中的差值处理。人体手指的实时OCT成像结果表明相比传统图像重建方法,基于非均匀傅里叶变换的重建方法能有效抑制系统灵敏度随深度增加而下降的趋势,使样品深层的结构更加清晰。
5.首次提出了基于正弦空间相位调制的消除共轭镜像的方法,其中参考臂正弦相位调制和样品臂的横向扫描同步进行,即正弦B-M方法。对正弦相位调制后的干涉光谱进行谐波分析构造复干涉频谱,并有效抑制自相关项和直流项,实现全量程的SD-OCT成像。相比已有的线性B-M方法,正弦B-M方法不仅降低了对参考臂移相器件的要求,同时也避免了横向方向的灵敏度下降问题。对活虾的成像结果表明,正弦B-M的方法不仅实现了成像深度范围加倍,同时复共轭抑制率高达45dB。
6.提出了适用于SD-OCT系统的解卷积方法。在SD-OCT系统中,CCD采集到的干涉光谱信号是原始干涉光谱信号和光谱仪传递函数的卷积,导致了轴向点扩散函数随着成像深度的增加而下降。因此SD-OCT系统不具备空不变特性,无法直接应用于解卷积运算。我们首先通过标定轴向点扩散函数的调制函数,再经过数值补偿后在空间域采用Lucy-Richardson迭代算法解卷积。活虾的OCT图像在解卷积前和解卷积后的对比表明：解卷积算法不仅可以去除OCT图像的模糊,同时可以使样品深层的结构更加清晰。
Optical coherence tomography (OCT) is a non-invasive, non-contact imaging modality with micrometer resolution, which uses coherent gating to obtain cross-sectional images of tissue microstructure. As the second generation of OCT technology, spectral domain OCT (SD-OCT) offers significant advantages in imaging speed, detection sensitivity and signal noise ratio (SNR) in contrast to time domain OCT. Therefore, it plays an important role in the field of ophthalmology and functional imaging. This dissertation is mainly focused on SD-OCT technology, the main work and innovations are summarized as following:
1. The SD-OCT system at 835nm wavelength is developed, which is consisted of a fiber based Michelson interferometer and a line-scan CCD based high speed spectrometer. The spectral resolution of the spectrometer is about 0.0674nm, corresponding to an axial imaging range of 2.56mm. With the A-scan rate of 29 KHz, the axial resolution and maximum SNR of the system are 7.5μm and 115dB, respectively, which is capable for real time in vivo imaging of biomedical samples.
2. A spectral calibration method for spectrometer is proposed, which is directly based on the SD-OCT system itself without the utilization of additional calibration source. With two measurements of interference spectra from two reference mirror position, the corresponding phase differences can be calculated after Hilbert transform and phase unwrapping. Then, with the wavelength value of specific CCD pixel, the wavelength distribution on CCD plane can be determined. Furthermore, this method is not sensitive to system unmatched dispersion.
3. The relationship between system sensitivity fall-off and diffraction spot size is studied. According to the spot diagrams on CCD plane obtained by Zemax, system sensitivity fall-off with different spot size of typical spectral components is calculated. When the spot size of typical spectral components are comparable to the size of CCD pixel, improved depth dependent sensitivity fall-off can be achieved, and sensitivity drops by 16.1dB over 2mm imaging depth range.
4. Non-uniform discrete Fourier transform (NDFT) is introduced into SD-OCT system for image reconstruction. The spectral data is considered as irregular sampling in wavenumber space, then the depth information can be reconstructed by NDFT directly without interpolation. Real time in vivo imaging of human finger confirms that compared with conventional DFT and interpolation method, reconstruction method based on NDFT indeed improves sensitivity fall-off especially at larger depth.
5. A spatial sinusoidal phase modulation for the elimination of complex-conjugate artifact is proposed, where sinusoidal phase modulation of reference arm (M scan) and transverse scanning of sample arm (B scan) are performed simultaneously (sinusoidal B-M method). The complex interference spectra are reconstructed by harmonic analysis, its Fourier transform is free of mirror image and coherent noises. Compared with the linear B-M method, the proposed sinusoidal B-M method relaxes the requirements on the phase-shifting mechanical system and avoids sensitivity fall-off along the transverse direction. Double imaging depth range on shrimp with complex conjugate rejection ratio up to 45dB is achieved.
6. Deconvolution method in SD-OCT system is proposed. In SD-OCT system, the spectral data acquired by CCD is the convolution of the original interference spectral signal and the transfer function of spectrometer, which results in the degradation of axial point spread function (PSF) along the depth direction. Herein, the axial modulation function of the PSF is retrieved firstly. Then after compensating the A-scan signal with the modulation function, devolution method is performed in spatial domain by Lucy-Richardson algorithm. In vivo OCT imaging of a fresh shrimp demonstrates that compared with original image, image enhancement is achieved by the proposed deconvolution method.
引文
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