提高显微成像分辨率关键技术的研究
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摘要
自第一台显微镜诞生以来,显微成像技术已经广泛的应用于医学,生物,电子,军事,工业等各个它所涵盖的微观领域,各种新颖的显微成像技术伴随高科技的应用正在不断的涌现。随着信息技术的飞速发展,显微成像技术的研究已经成为一个十分重要的课题。本文以目前较为新型的两种显微成像技术:数字显微成像系统和光学相干层析成像系统(OCT)为研究对象,对于提高显微成像系统的横向分辨率和纵向分辨率的关键技术展开了深入的研究。
本文以显微成像技术的发展概况为先导,以该研究领域中的热点激光共焦三维扫描显微系统(CSOM)的基本原理为例给出了显微系统的横向分辨率和纵向分辨率的概念。在对如何提高显微系统的横向和纵向分辨率的关键技术深入理论分析的基础上,本文提出了利用干涉显微镜为核心并结合数字图像处理测量技术相结合的数字显微镜来提高显微成像系统的横向分辨率和利用自制凸轮纵向扫描机构的OCT系统来提高显微成像系统中纵向分辨率的两种方法,围绕以上两种方法,研制了一套数字显微镜系统,并以Microsoft Visual C++为开发平台编写了相应的图像处理软件,对菲涅尔微透镜阵列做了深入的实验研究并给出了提高横向分辨率的试验数据,同时还研制了一套以凸轮扫描机构为核心的OCT实验系统,对玻璃试样行了实验获得了10微米左右的分辨率,并取得了实用眼检OCT系统的实验数据作为对照。
本文就如何提高横向分辨率和纵向分辨率的关键技术做的相关研究对于显微成像领域的设备改进与广泛应用有着实际价值。
Since the birth of the first microscope, the microscopy imaging technology has been widely applied in the microcosmic field that it covered just like medicine, biology, electronic, military, industry and so on. A lot of novel microscopy imaging technology are coming forth continuously with the application of high-tech. For the fast development of information technology, the research on microscopic imaging has become the important topic all around the world. In this paper, we has completed the embedded research on key-technology to improving transverse resolution and longitudinal resolution of microscopy imaging system, which is oriented at the two kinds of new-style microscopy imaging technology that are digital microscope system and optical coherence tomography (OCT) as research objects.
The thesis brings out the conception of transverse and longitudinal resolution of microscope system, following the development survey of microscope imaging technology as the fore-guidance and with the baasis of the theory of confocal scanning optic microscopy as example which is the hot point of microscope field. Based on the deep theoretical research on how to improving transverse resolution and longitudinal resolution of microscopy imaging system,, two methods are given in this thesis, one is about how to improve transverse resolution based on the digital image processing and measurement technology which utilize interference microscope as core of the system, and another is about how to improve longitudinal resolution of OCT experimental system by using self-designed cam-driving longitudinal scanning wheel. The paper encloses the methods giving above and gives out a set of digital microscope system. The corresponding digital image processing software coded on Microsoft Visual C++ platform has been developed, then a deep research on the Fresnel microlens arrays by using the developed system is excuted and the experiment results of improving transverse resolution are achieved in this paper. A set of OCT experimental system which the cam-driving longitude scanning wheel is as the core
component is established, by this system, we obtain about 10 micron longitudinal resolution from experiments results on glass sample and so on, comparing with the experiment data from practical eyes-examine OCT system.
The research on key-technology about how to improve transverse and longitudinal resolution of this paper has practical value for equipments promotion and widely application in the microscopy field.
本文以显微成像技术的发展概况为先导,以该研究领域中的热点激光共焦三维扫描显微系统(CSOM)的基本原理为例给出了显微系统的横向分辨率和纵向分辨率的概念。在对如何提高显微系统的横向和纵向分辨率的关键技术深入理论分析的基础上,本文提出了利用干涉显微镜为核心并结合数字图像处理测量技术相结合的数字显微镜来提高显微成像系统的横向分辨率和利用自制凸轮纵向扫描机构的OCT系统来提高显微成像系统中纵向分辨率的两种方法,围绕以上两种方法,研制了一套数字显微镜系统,并以Microsoft Visual C++为开发平台编写了相应的图像处理软件,对菲涅尔微透镜阵列做了深入的实验研究并给出了提高横向分辨率的试验数据,同时还研制了一套以凸轮扫描机构为核心的OCT实验系统,对玻璃试样行了实验获得了10微米左右的分辨率,并取得了实用眼检OCT系统的实验数据作为对照。
本文就如何提高横向分辨率和纵向分辨率的关键技术做的相关研究对于显微成像领域的设备改进与广泛应用有着实际价值。
Since the birth of the first microscope, the microscopy imaging technology has been widely applied in the microcosmic field that it covered just like medicine, biology, electronic, military, industry and so on. A lot of novel microscopy imaging technology are coming forth continuously with the application of high-tech. For the fast development of information technology, the research on microscopic imaging has become the important topic all around the world. In this paper, we has completed the embedded research on key-technology to improving transverse resolution and longitudinal resolution of microscopy imaging system, which is oriented at the two kinds of new-style microscopy imaging technology that are digital microscope system and optical coherence tomography (OCT) as research objects.
The thesis brings out the conception of transverse and longitudinal resolution of microscope system, following the development survey of microscope imaging technology as the fore-guidance and with the baasis of the theory of confocal scanning optic microscopy as example which is the hot point of microscope field. Based on the deep theoretical research on how to improving transverse resolution and longitudinal resolution of microscopy imaging system,, two methods are given in this thesis, one is about how to improve transverse resolution based on the digital image processing and measurement technology which utilize interference microscope as core of the system, and another is about how to improve longitudinal resolution of OCT experimental system by using self-designed cam-driving longitudinal scanning wheel. The paper encloses the methods giving above and gives out a set of digital microscope system. The corresponding digital image processing software coded on Microsoft Visual C++ platform has been developed, then a deep research on the Fresnel microlens arrays by using the developed system is excuted and the experiment results of improving transverse resolution are achieved in this paper. A set of OCT experimental system which the cam-driving longitude scanning wheel is as the core
component is established, by this system, we obtain about 10 micron longitudinal resolution from experiments results on glass sample and so on, comparing with the experiment data from practical eyes-examine OCT system.
The research on key-technology about how to improve transverse and longitudinal resolution of this paper has practical value for equipments promotion and widely application in the microscopy field.
引文
杨莉松,王桂英,王建岗等. 共焦扫描成像研究. 中国激光,1999,26(10):931~934
江萍,徐晓冰,方 敏. 基于形态学骨架提取算法的研究及其实现. 计算机应用,2003,23(6):135~136
Huang D, SwansonEA, et al. Optical coherence tomography. Science, 1991, 254:1178~1181
金霞,刘铁根,李刚等. 一种高速的光学相干层析成像系统. 仪器仪表学报, 2002, 23(3):127~129
薛平,陈则名.光学相干断层层析扫描成像新技术OCT.物理与工程,2001,11(3):39~43
Yimin Wang, Yonghua Zhao, et al. Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber. Optics letters, 2003, 28(3): 182~184
Nan Guang Chen, Quing zhu. Rotary mirror array for high speed optical coherence tomography. Optical Letters, 2002, 27(8):607~609
Povazay B, Bizheva K, Unterhuber A, et al. Submicrometer axial resolution optical coherence tomography. Optical Letters, 2002, 27(20):1800~1802
Bizheva K, Povazay B, Hermann B. Compact, broad-bandwidth fiber laser for sub-2-μm axial resolution optical coherence tomography in the 1300-nm wavelength region. Optical Letters, 2003, 28(9):707~709
Povazay B, Bizheva K, Unterhuber A, et al. Submicrometer axial resolution optical coherence tomography. Optical Letters, 2002, 27(20):1800~1802
寥洪波,胡翔宇. 二维扫描共焦显微镜的研究. 光学仪器, 2003, 2
孔令彬, 易新建, 申毕红等. 微透镜及其应用简介. 红外技术, 2002, 3
向际鹰. 弱相干层析与三维显微成像技术[博士学位论文]. 保存地点:华中科技
大学图书馆,1999
刘尾,樊宽章,陈长忠. 光学相干层析成像技术以及在医学中的应用. 医疗卫生装备, 2002, 26(3):56~58
M.Glass and T.P.Dabbs. The experimental effect of detector in confocal imaging system. J.Microscopy, 1991, 1664:153~158
MinGu, et al. CLSFM with a finite-sized circular detector. J. Opt. Soc. Am. A., 1992, 9(1):151~153
MinGu, C,J,R, Sheppard.Optical sectioning in CSOM with an annular pupil. Optik, 1991, 86(5):169~172
李耀辉, 刘保军. 基于直方图均衡的图像增强. 华北科技学院学报, 2003, 5(2):65~67
杨博, 周孝宽. 基于低通滤波的彩色图像多模式自适应系统. 北京航空航天大学学报, 2002, 28(2):213~216
谢可夫, 黄建平, 许光平. 图像降噪组合滤波优化算法. 计算机工程与应用, 2003, 39(26):84~85,88
聂守平, 王鸣. 数字图像纯位相编码分析. 激光杂志, 2002, 23(5):35~36
Joseph M.Schmitt. Optical Coherence Tomography(OCT). A review:IEEE Journal of selected topics in quantum electronics, 1999, 5(4)
Zhoingping Chen,Thomas E.Milner,et al. Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography. Optics Express, 1997, 22(14): 1119~1121
Siavash Yazdanfar,Manish D.Kulkarni et al. High resolution imaging of in vivo cardiac dynamics using color Doppler optical coherence tomography. Optics Express, 1997, 1(13):424~428
J.A.Izatt, M.D.Kulkarni, S.Yazdanfar, et al. In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using OCT. Opt. Lett., 1997, 22: 1439~1441
J.A.Izatt, M.D. Kulkarni, H.-W.Wang,et al.OCT and microscopy in gastrointestinal
tissues. IEEE J.Sel. Top. Quantum Electron, 1996, 2:1017~1028
Tearney G J, Bouma B E, Boppart S A, et al. Rapid acquisition of in vivo biological images by use of optical coherence tomography. Optic letters, 1996, 21(17): 1408~1410
Ballif J, Gianotti R, Chavanne Ph, et al. Rapid and scalable scans at 21m.s in optical low-coherence reflectmetry. Optics letters, 1997, 22(11):757~759
A.M.Rollins, S.Yazdanfar et al .Real time Color Doppler Optical Coherence Tomography Using an Autocorrelation Technique. SPIE Proc.3598, Coherence Domain Optical methods in Biomedical Science and Clinical Applications, V.V.Tuchin and J.A.lzatt eds, Washington, 1999, pp.168~176.
A.Unterhuber, B.PovaZay, et al. Compact,Low-cost Ti: Al2O3 Laser For in vivo ultrahigh-resolution optical coherence tomography. Optics letters 2003, 28(11): 905~907
Manish D. Kulkami, Joscph A. lzatt et al. A Novel Tool for Micron-Resolution Biomedical Diagnostics, Proceedings-19th Intermqtional Conference IEEE/EMBS Oct. 30-NOV.2.1997 Chicago, IL, USA, 883~886
姜志国,韩冬兵,谢凤英等. 基于全自动显微镜的图像新技术研究. 中国体视学与图像分析, 2004, 9(1):31~36
张新明,沈兰荪,沈波等. 裂隙灯生物显微镜图像分析系统的研制. 中国医疗器械杂志, 2002, 26(1):10~13
黄河, 李思忠. 显微成像数字化及教学应用. 郑州航空工业管理学院学报(社会科学版), 2003, 22(4):13~14
An Y, Yao J Q,Wang R K.E1imination of image spoiling oscillationin optical coherence tomography system[R]. 2nd international symposium on instrumen-tation science and technology, 2002, 2:514~517.
杨尚明,宋东草,陈瑞平等. 医用OCT成像研究. 烟台大学学报自然科学与工程版,2003, 16(2):104~108
姜宇, 姚建铨, 王瑞康. 光学相干层析系统的建立与研究. 光学仪器, 2003,
25(2):33~37
王新宇, 张春平等. 光学相干层析技术及其在生物医学中的应用. 光机电信息, 2001, 9:27~31
骆清铭,张益哲. 光学弱相干层析成像进展. CT理论与应用研究. 2000, 9(4):1~6
曾志男, 明海. 光学相干层析成像技术. 光电子技术与信息. 1999, 12(1):1~8
张平,傅哲强,姜发纲. 眼检光学相干层析术. 华中科技大学学报自然科学版,2004,5(32):38~40
傅哲强,张平,姜发纲. 光学相干层析系统的纵向扫描方式的研究. 华中科技大学学报自然科学版,2004, 5(32):41~43
江萍,徐晓冰,方 敏. 基于形态学骨架提取算法的研究及其实现. 计算机应用,2003,23(6):135~136
Huang D, SwansonEA, et al. Optical coherence tomography. Science, 1991, 254:1178~1181
金霞,刘铁根,李刚等. 一种高速的光学相干层析成像系统. 仪器仪表学报, 2002, 23(3):127~129
薛平,陈则名.光学相干断层层析扫描成像新技术OCT.物理与工程,2001,11(3):39~43
Yimin Wang, Yonghua Zhao, et al. Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber. Optics letters, 2003, 28(3): 182~184
Nan Guang Chen, Quing zhu. Rotary mirror array for high speed optical coherence tomography. Optical Letters, 2002, 27(8):607~609
Povazay B, Bizheva K, Unterhuber A, et al. Submicrometer axial resolution optical coherence tomography. Optical Letters, 2002, 27(20):1800~1802
Bizheva K, Povazay B, Hermann B. Compact, broad-bandwidth fiber laser for sub-2-μm axial resolution optical coherence tomography in the 1300-nm wavelength region. Optical Letters, 2003, 28(9):707~709
Povazay B, Bizheva K, Unterhuber A, et al. Submicrometer axial resolution optical coherence tomography. Optical Letters, 2002, 27(20):1800~1802
寥洪波,胡翔宇. 二维扫描共焦显微镜的研究. 光学仪器, 2003, 2
孔令彬, 易新建, 申毕红等. 微透镜及其应用简介. 红外技术, 2002, 3
向际鹰. 弱相干层析与三维显微成像技术[博士学位论文]. 保存地点:华中科技
大学图书馆,1999
刘尾,樊宽章,陈长忠. 光学相干层析成像技术以及在医学中的应用. 医疗卫生装备, 2002, 26(3):56~58
M.Glass and T.P.Dabbs. The experimental effect of detector in confocal imaging system. J.Microscopy, 1991, 1664:153~158
MinGu, et al. CLSFM with a finite-sized circular detector. J. Opt. Soc. Am. A., 1992, 9(1):151~153
MinGu, C,J,R, Sheppard.Optical sectioning in CSOM with an annular pupil. Optik, 1991, 86(5):169~172
李耀辉, 刘保军. 基于直方图均衡的图像增强. 华北科技学院学报, 2003, 5(2):65~67
杨博, 周孝宽. 基于低通滤波的彩色图像多模式自适应系统. 北京航空航天大学学报, 2002, 28(2):213~216
谢可夫, 黄建平, 许光平. 图像降噪组合滤波优化算法. 计算机工程与应用, 2003, 39(26):84~85,88
聂守平, 王鸣. 数字图像纯位相编码分析. 激光杂志, 2002, 23(5):35~36
Joseph M.Schmitt. Optical Coherence Tomography(OCT). A review:IEEE Journal of selected topics in quantum electronics, 1999, 5(4)
Zhoingping Chen,Thomas E.Milner,et al. Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography. Optics Express, 1997, 22(14): 1119~1121
Siavash Yazdanfar,Manish D.Kulkarni et al. High resolution imaging of in vivo cardiac dynamics using color Doppler optical coherence tomography. Optics Express, 1997, 1(13):424~428
J.A.Izatt, M.D.Kulkarni, S.Yazdanfar, et al. In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using OCT. Opt. Lett., 1997, 22: 1439~1441
J.A.Izatt, M.D. Kulkarni, H.-W.Wang,et al.OCT and microscopy in gastrointestinal
tissues. IEEE J.Sel. Top. Quantum Electron, 1996, 2:1017~1028
Tearney G J, Bouma B E, Boppart S A, et al. Rapid acquisition of in vivo biological images by use of optical coherence tomography. Optic letters, 1996, 21(17): 1408~1410
Ballif J, Gianotti R, Chavanne Ph, et al. Rapid and scalable scans at 21m.s in optical low-coherence reflectmetry. Optics letters, 1997, 22(11):757~759
A.M.Rollins, S.Yazdanfar et al .Real time Color Doppler Optical Coherence Tomography Using an Autocorrelation Technique. SPIE Proc.3598, Coherence Domain Optical methods in Biomedical Science and Clinical Applications, V.V.Tuchin and J.A.lzatt eds, Washington, 1999, pp.168~176.
A.Unterhuber, B.PovaZay, et al. Compact,Low-cost Ti: Al2O3 Laser For in vivo ultrahigh-resolution optical coherence tomography. Optics letters 2003, 28(11): 905~907
Manish D. Kulkami, Joscph A. lzatt et al. A Novel Tool for Micron-Resolution Biomedical Diagnostics, Proceedings-19th Intermqtional Conference IEEE/EMBS Oct. 30-NOV.2.1997 Chicago, IL, USA, 883~886
姜志国,韩冬兵,谢凤英等. 基于全自动显微镜的图像新技术研究. 中国体视学与图像分析, 2004, 9(1):31~36
张新明,沈兰荪,沈波等. 裂隙灯生物显微镜图像分析系统的研制. 中国医疗器械杂志, 2002, 26(1):10~13
黄河, 李思忠. 显微成像数字化及教学应用. 郑州航空工业管理学院学报(社会科学版), 2003, 22(4):13~14
An Y, Yao J Q,Wang R K.E1imination of image spoiling oscillationin optical coherence tomography system[R]. 2nd international symposium on instrumen-tation science and technology, 2002, 2:514~517.
杨尚明,宋东草,陈瑞平等. 医用OCT成像研究. 烟台大学学报自然科学与工程版,2003, 16(2):104~108
姜宇, 姚建铨, 王瑞康. 光学相干层析系统的建立与研究. 光学仪器, 2003,
25(2):33~37
王新宇, 张春平等. 光学相干层析技术及其在生物医学中的应用. 光机电信息, 2001, 9:27~31
骆清铭,张益哲. 光学弱相干层析成像进展. CT理论与应用研究. 2000, 9(4):1~6
曾志男, 明海. 光学相干层析成像技术. 光电子技术与信息. 1999, 12(1):1~8
张平,傅哲强,姜发纲. 眼检光学相干层析术. 华中科技大学学报自然科学版,2004,5(32):38~40
傅哲强,张平,姜发纲. 光学相干层析系统的纵向扫描方式的研究. 华中科技大学学报自然科学版,2004, 5(32):41~43