无标记显微成像技术的研究进展
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摘要
无标记显微成像技术包括光学相干层析、光声成像、非线性成像和微球透镜成像等技术。概述了目前常用的无标记显微成像技术,并对各种传统和先进的成像原理进行了总结。详细介绍了各种无标记成像技术的优缺点和最新研究进展,以及此类成像技术在各领域的应用,并对基于无标记显微技术的多模态成像技术的未来发展进行了展望。
Label-free microscopic imaging technology includes the optical coherence tomography,photoacoustic imaging,nonlinear imaging,and microsphere lens imaging technology.The commonly used label-free imaging techniques are introduced,and the traditional and advanced imaging principles are summarized.The advantages and disadvantages of such various of label-free imaging technologies and the latest research progress are introduced in detail,including the applications of such imaging technology in various fields.Finally,the future development of multi-modal imaging technology based on unmarked microscopy technology is prospected.
Label-free microscopic imaging technology includes the optical coherence tomography,photoacoustic imaging,nonlinear imaging,and microsphere lens imaging technology.The commonly used label-free imaging techniques are introduced,and the traditional and advanced imaging principles are summarized.The advantages and disadvantages of such various of label-free imaging technologies and the latest research progress are introduced in detail,including the applications of such imaging technology in various fields.Finally,the future development of multi-modal imaging technology based on unmarked microscopy technology is prospected.
引文
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[8]Jia Y L,Tan O,Tokayer J,et al.Split-spectrum amplitude-decorrelation angiography with optical coherence tomography[J].Optics Express,2012,20(4):4710-4725.
[9]Zhang Q Q,Huang Y P,Zhang T,et al.Wide-field imaging of retinal vasculature using optical coherence tomography-based microangiography provided by motion tracking[J].Journal of Biomedical Optics,2015,20(6):066008.
[10]Tearney G J,Bouma B E.Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis[J].Optics Letters,2002,27(7):533-535.
[11]Motaghian N S M,Joo C,Tearney G J,et al.Application of maximum likelihood estimator in nanoscale optical path length measurement using spectraldomain optical coherence phase microscopy[J].Optics Express,2008,16(22):17186-17195.
[12]D′amico A V,Weinstein M,Li X D,et al.Optical coherence tomography as a method for identifying benign and malignant microscopic structures in the prostate gland[J].Urology,2000,55(5):783-787.
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[16]Liu G J,Chen Z P.Advances in Doppler OCT[J].Chinese Optics Letters,2013,11(1):011702.
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[18]Maslov K,Stoica G,Wang L V.In vivo dark-field reflection-mode photoacoustic microscopy[J].Optics Letters,2005,30(6):625-627.
[19]Maslov K,Zhang H F,Hu S,et al.Opticalresolution photoacoustic microscopy for in vivo imaging of single capillaries[J].Optics Letters,2008,33(9):929-931.
[20]Song L,Maslov K,Wang L V.Multifocal opticalresolution photoacoustic microscopy in vivo[J].Optics Letters,2011,36(7):1236-1238.
[21]Aguirre J,Schwarz M,Soliman D,et al.Broadband mesoscopic optoacoustic tomography reveals skin layers[J].Optics Letters,2014,39(21):6297-6300.
[22]Wang X D,Pang Y J,Ku G,et al.Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain[J].Nature Biotechnology,2003,21(7):803-806.
[23]Lin H C A,Chekkoury A,Omar M,et al.Selective plane illumination optical and optoacoustic microscopy for postembryonic imaging[J].Laser&Photonics Reviews,2015,9(5):L29-L34.
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[26]Chu S W,Chen S Y,Tsai T H,et al.In vivo developmental biology study using noninvasive multiharmonic generation microscopy[J].Optics Express,2003,11(23):3093-3099.
[27]Fine S,Hansen W P.Optical second harmonic generation in biological systems[J].Applied Optics,1971,10(10):2350-2353.
[28]Bancelin S,AiméC,Gusachenko I,et al.Determination of collagen fibril size via absolute measurements of second-harmonic generation signals[J].Nature Communications,2014,5:4920.
[29]Small D M,Jones J S,Tendler I I,et al.Label-free imaging of atherosclerotic plaques using thirdharmonic generation microscopy[J].Biomedical Optics Express,2018,9(1):214-229.
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[31]Mahou P,Olivier N,Labroille G,et al.Combined third-harmonic generation and four-wave mixing microscopy of tissues and embryos[J].Biomedical Optics Express,2011,2(10):2837-2849.
[32]Segawa H,Okuno M,Kano H,et al.Label-free tetra-modal molecular imaging of living cells with CARS,SHG,THG and TSFG(coherent anti-Stokes Raman scattering,second harmonic generation,third harmonic generation and third-order sum frequency generation)[J].Optics Express,2012,20(9):9551-9557.
[33]Nan X L,Potma E O,Xie X S.Nonperturbative chemical imaging of organelle transport in living cells with coherent anti-Stokes Raman scattering microscopy[J].Biophysical Journal,2006,91(2):728-735.
[34]Eckhardt G,Hellwarth R W,McClung F J,et al.Stimulated Raman scattering from organic liquids[J].Physical Review Letters,1962,9(11):455-458.
[35]Lee J Y,Hong B H,Kim W Y,et al.Near-field focusing and magnification through self-assembled nanoscale spherical lenses[J].Nature,2009,460(7254):498-501.
[36]Wang Z B,Guo W,Li L,et al.Optical virtual imaging at 50nm lateral resolution with a white-light nanoscope[J].Nature Communications,2011,2:218-224.
[37]Li L,Guo W,Yan Y Z,et al.Label-free superresolution imaging of adenoviruses by submerged microsphere optical nanoscopy[J].Light:Science&Applications,2013,2(9):e104.
[38]Huszka G,Yang H,Gijs M A M.Microspherebased super-resolution scanning optical microscope[J].Optics Express,2017,25(13):15079-15092.
[39]Hong G S,Lee J C,Robinson J T,et al.Multifunctional in vivo vascular imaging using nearinfrared II fluorescence[J].Nature Medicine,2012,18(12):1841-1846.
[40]Yang V X D,Gordon M L,Seng-Yue E,et al.High speed,wide velocity dynamic range Doppler optical coherence tomography(Part II):imaging in vivo cardiac dynamics of xenopus laevis[J].Optics Express,2003,11(14):1650-1658.
[41]Sudheendran N,Syed S H,Dickinson M E,et al.Speckle variance OCT imaging of the vasculature in live mammalian embryos[J].Laser Physics Letters,2011,8(3):247-252.
[42]Peterson L M,Jenkins M W,Gu S,et al.4Dshear stress maps of the developing heart using Doppler optical coherence tomography[J].Biomedical Optics Express,2012,3(11):3022-3032.
[43]Wang S,Lopez A L,Larina I V.Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis[J].Proceedings of SPIE,2018,10493:104930C.
[44]Kruger R A,Lam R B,Reinecke D R,et al.Photoacoustic angiography of the breast[J].Medical Physics,2010,37(11):6096-6100.
[45]Ku G,Fornage B D,Jin X,et al.Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging[J].Technology in Cancer Research&Treatment,2005,4(5):559-566.
[46]Matsumoto Y,Asao Y,Yoshikawa A,et al.Labelfree photoacoustic imaging of human palmar vessels:a structural morphological analysis[J].Scientific Reports,2018,8:786.
[47]Ferrari M.Cancer nanotechnology:opportunities and challenges[J].Nature Reviews Cancer,2005,5(3):161-171.
[48]Yao J J,Wang L H V.Photoacoustic brain imaging:from microscopic to macroscopic scales[J].Neurophotonics,2014,1(1):011003.
[49]Lui H,Zhao J,McLean D,et al.Real-time Raman spectroscopy for in vivo skin cancer diagnosis[J].Cancer Research,2012,72(10):2491-2500.
[50]He J P,Wang N,Tsurui H,et al.Noninvasive,label-free,three-dimensional imaging of melanoma with confocal photothermal microscopy:differentiate malignant melanoma from benign tumor tissue[J].Scientific Reports,2016,6:30209.
[51]Stummer W.5-aminolevulinic acid-derived tumor fluorescence:the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging[J].Neurosurgery,2015,76(2):230-231.
[52]Kut C,Chaichana K L,Xi J F,et al.Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography[J].Science Translational Medicine,2015,7(292):292ra100.
[53]Ji M B,Orringer D A,Freudiger C W,et al.Rapid,label-free detection of brain tumors with stimulated Raman scattering microscopy[J].Science Translational Medicine,2013,5(201):201ra119.
[54]Jermyn M,Mok K,Mercier J,et al.Intraoperative brain cancer detection with Raman spectroscopy in humans[J].Science Translational Medicine,2015,7(274):274ra19.
[55]Kuzmin N V,Wesseling P,de Witt Hamer P C,et al.Third harmonic generation imaging for fast,labelfree pathology of human brain tumors[J].Biomedical Optics Express,2016,7(5):1889-1904.
[56]Losick R,Desplan C.Stochasticity and cell fate[J].Science,2008,320(5872):65-68.
[57]Muzzey D,van Oudenaarden A.Quantitative timelapse fluorescence microscopy in single cells[J].Annual Review of Cell and Developmental Biology,2009,25(1):301-327.
[58]Wang L D,Maslov K,Wang L H V.Single-cell label-free photoacoustic flowoxigraphy in vivo[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(15):5759-5764.
[59]He G,Xu D,Qin H,et al.In vivo cell characteristic extraction and identification by photoacoustic flow cytography[J].Biomedical Optics Express,2015,6(10):3748-3756.
[60]Zhao Y,Yang S H,Chen C G,et al.Simultaneous optical absorption and viscoelasticity imaging based on photoacoustic lock-in measurement[J].Optics Letters,2014,39(9):2565-2568.
[61]Marrison J,Rty L,Marriott P,et al.Ptychography-a label free,high-contrast imaging technique for live cells using quantitative phase information[J].Scientific Reports,2013,3:2369.
[62]Lim H,Sharoukhov D,Kassim I,et al.Label-free imaging of Schwann cell myelination by third harmonic generation microscopy[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(50):18025-18030.
[63]Jüngst C,Klein M,Zumbusch A.Long-term live cell microscopy studies of lipid droplet fusion dynamics in adipocytes[J].Journal of Lipid Research,2013,54(12):3419-3429.
[64]Kim G,Lee S,Shin S,et al.Three-dimensional label-free imaging and analysis of pinus pollen grains using optical diffraction tomography[J].Scientific Reports,2018,8:1782.
[65]Liu X W,Kuang C F,Hao X,et al.Fluorescent nanowire ring illumination for wide-field far-field subdiffraction imaging[J].Physical Review Letters,2017,118(7):076101.
[66]Chen Z J,Yang S H,Xing D.Optically integrated trimodality imaging system:combined all-optical photoacoustic microscopy,optical coherence tomography,and fluorescence imaging[J].Optics Letters,2016,41(7):1636-1639.
[67]Meng X Q,Yang Y T,Zhou L H,et al.Dualresponsive molecular probe for tumor targeted imaging and photodynamic therapy[J].Theranostics,2017,7(7):1781-1794.
[2]Betzig E,Patterson G H,Sougrat R,et al.Imaging intracellular fluorescent proteins at nanometer resolution[J].Science,2006,313(5793):1642-1645.
[3]Nakayama Y,Pauzauskie P J,Radenovic A,et al.Tunable nanowire nonlinear optical probe[J].Nature,2007,447(7148):1098-1101.
[4]Yao J J,Wang L D,Li C Y,et al.Photoimprint photoacoustic microscopy for three-dimensional labelfree subdiffraction imaging[J].Physical Review Letters,2014,112(1):014302.
[5]Huang D,Swanson E A,Lin C P,et al.Optical coherence tomography[J].Science,1991,254(5035):1178-1181.
[6]Raghunathan R,Singh M,Dickinson M,et al.Optical coherence tomography for embryonic imaging:a review[J].Journal of Biomedical Optics,2016,21(5):050902.
[7]Aydin A,Wollstein G,Price L L,et al.Optical coherence tomography assessment of retinal nerve fiber layer thickness changes after glaucoma surgery[J].Ophthalmology,2003,110(8):1506-1511.
[8]Jia Y L,Tan O,Tokayer J,et al.Split-spectrum amplitude-decorrelation angiography with optical coherence tomography[J].Optics Express,2012,20(4):4710-4725.
[9]Zhang Q Q,Huang Y P,Zhang T,et al.Wide-field imaging of retinal vasculature using optical coherence tomography-based microangiography provided by motion tracking[J].Journal of Biomedical Optics,2015,20(6):066008.
[10]Tearney G J,Bouma B E.Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis[J].Optics Letters,2002,27(7):533-535.
[11]Motaghian N S M,Joo C,Tearney G J,et al.Application of maximum likelihood estimator in nanoscale optical path length measurement using spectraldomain optical coherence phase microscopy[J].Optics Express,2008,16(22):17186-17195.
[12]D′amico A V,Weinstein M,Li X D,et al.Optical coherence tomography as a method for identifying benign and malignant microscopic structures in the prostate gland[J].Urology,2000,55(5):783-787.
[13]Welzel J.Optical coherence tomography in dermatology:a review[J].Skin Research and Technology,2001,7(1):1-9.
[14]Baumgartner A,Dichtl S,Hitzenberger C K,et al.Polarization-sensitive optical coherence tomography of dental structures[J].Caries Research,2000,34(1):59-69.
[15]Leitgeb R A,Werkmeister R M,Blatter C,et al.Doppler optical coherence tomography[J].Progress in Retinal and Eye Research,2014,41:26-43.
[16]Liu G J,Chen Z P.Advances in Doppler OCT[J].Chinese Optics Letters,2013,11(1):011702.
[17]Diebold G J,Sun T,Khan M I.Photoacoustic monopole radiation in one,two,and three dimensions[J].Physical Review Letters,1991,67(24):3384-3387.
[18]Maslov K,Stoica G,Wang L V.In vivo dark-field reflection-mode photoacoustic microscopy[J].Optics Letters,2005,30(6):625-627.
[19]Maslov K,Zhang H F,Hu S,et al.Opticalresolution photoacoustic microscopy for in vivo imaging of single capillaries[J].Optics Letters,2008,33(9):929-931.
[20]Song L,Maslov K,Wang L V.Multifocal opticalresolution photoacoustic microscopy in vivo[J].Optics Letters,2011,36(7):1236-1238.
[21]Aguirre J,Schwarz M,Soliman D,et al.Broadband mesoscopic optoacoustic tomography reveals skin layers[J].Optics Letters,2014,39(21):6297-6300.
[22]Wang X D,Pang Y J,Ku G,et al.Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain[J].Nature Biotechnology,2003,21(7):803-806.
[23]Lin H C A,Chekkoury A,Omar M,et al.Selective plane illumination optical and optoacoustic microscopy for postembryonic imaging[J].Laser&Photonics Reviews,2015,9(5):L29-L34.
[24]Park K,Kim J Y,Lee C,et al.Handheld photoacoustic microscopy probe[J].Scientific Reports,2017,7:13359.
[25]Tian C,Zhang W,Mordovanakis A,et al.Noninvasive chorioretinal imaging in living rabbits using integrated photoacoustic microscopy and optical coherence tomography[J].Optics Express,2017,25(14):15947-15955.
[26]Chu S W,Chen S Y,Tsai T H,et al.In vivo developmental biology study using noninvasive multiharmonic generation microscopy[J].Optics Express,2003,11(23):3093-3099.
[27]Fine S,Hansen W P.Optical second harmonic generation in biological systems[J].Applied Optics,1971,10(10):2350-2353.
[28]Bancelin S,AiméC,Gusachenko I,et al.Determination of collagen fibril size via absolute measurements of second-harmonic generation signals[J].Nature Communications,2014,5:4920.
[29]Small D M,Jones J S,Tendler I I,et al.Label-free imaging of atherosclerotic plaques using thirdharmonic generation microscopy[J].Biomedical Optics Express,2018,9(1):214-229.
[30]Gauderon R,Lukins P B,Sheppard C J R.Simultaneous multichannel nonlinear imaging:combined two-photon excited fluorescence and second-harmonic generation microscopy[J].Micron,2001,32(7):685-689.
[31]Mahou P,Olivier N,Labroille G,et al.Combined third-harmonic generation and four-wave mixing microscopy of tissues and embryos[J].Biomedical Optics Express,2011,2(10):2837-2849.
[32]Segawa H,Okuno M,Kano H,et al.Label-free tetra-modal molecular imaging of living cells with CARS,SHG,THG and TSFG(coherent anti-Stokes Raman scattering,second harmonic generation,third harmonic generation and third-order sum frequency generation)[J].Optics Express,2012,20(9):9551-9557.
[33]Nan X L,Potma E O,Xie X S.Nonperturbative chemical imaging of organelle transport in living cells with coherent anti-Stokes Raman scattering microscopy[J].Biophysical Journal,2006,91(2):728-735.
[34]Eckhardt G,Hellwarth R W,McClung F J,et al.Stimulated Raman scattering from organic liquids[J].Physical Review Letters,1962,9(11):455-458.
[35]Lee J Y,Hong B H,Kim W Y,et al.Near-field focusing and magnification through self-assembled nanoscale spherical lenses[J].Nature,2009,460(7254):498-501.
[36]Wang Z B,Guo W,Li L,et al.Optical virtual imaging at 50nm lateral resolution with a white-light nanoscope[J].Nature Communications,2011,2:218-224.
[37]Li L,Guo W,Yan Y Z,et al.Label-free superresolution imaging of adenoviruses by submerged microsphere optical nanoscopy[J].Light:Science&Applications,2013,2(9):e104.
[38]Huszka G,Yang H,Gijs M A M.Microspherebased super-resolution scanning optical microscope[J].Optics Express,2017,25(13):15079-15092.
[39]Hong G S,Lee J C,Robinson J T,et al.Multifunctional in vivo vascular imaging using nearinfrared II fluorescence[J].Nature Medicine,2012,18(12):1841-1846.
[40]Yang V X D,Gordon M L,Seng-Yue E,et al.High speed,wide velocity dynamic range Doppler optical coherence tomography(Part II):imaging in vivo cardiac dynamics of xenopus laevis[J].Optics Express,2003,11(14):1650-1658.
[41]Sudheendran N,Syed S H,Dickinson M E,et al.Speckle variance OCT imaging of the vasculature in live mammalian embryos[J].Laser Physics Letters,2011,8(3):247-252.
[42]Peterson L M,Jenkins M W,Gu S,et al.4Dshear stress maps of the developing heart using Doppler optical coherence tomography[J].Biomedical Optics Express,2012,3(11):3022-3032.
[43]Wang S,Lopez A L,Larina I V.Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis[J].Proceedings of SPIE,2018,10493:104930C.
[44]Kruger R A,Lam R B,Reinecke D R,et al.Photoacoustic angiography of the breast[J].Medical Physics,2010,37(11):6096-6100.
[45]Ku G,Fornage B D,Jin X,et al.Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging[J].Technology in Cancer Research&Treatment,2005,4(5):559-566.
[46]Matsumoto Y,Asao Y,Yoshikawa A,et al.Labelfree photoacoustic imaging of human palmar vessels:a structural morphological analysis[J].Scientific Reports,2018,8:786.
[47]Ferrari M.Cancer nanotechnology:opportunities and challenges[J].Nature Reviews Cancer,2005,5(3):161-171.
[48]Yao J J,Wang L H V.Photoacoustic brain imaging:from microscopic to macroscopic scales[J].Neurophotonics,2014,1(1):011003.
[49]Lui H,Zhao J,McLean D,et al.Real-time Raman spectroscopy for in vivo skin cancer diagnosis[J].Cancer Research,2012,72(10):2491-2500.
[50]He J P,Wang N,Tsurui H,et al.Noninvasive,label-free,three-dimensional imaging of melanoma with confocal photothermal microscopy:differentiate malignant melanoma from benign tumor tissue[J].Scientific Reports,2016,6:30209.
[51]Stummer W.5-aminolevulinic acid-derived tumor fluorescence:the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging[J].Neurosurgery,2015,76(2):230-231.
[52]Kut C,Chaichana K L,Xi J F,et al.Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography[J].Science Translational Medicine,2015,7(292):292ra100.
[53]Ji M B,Orringer D A,Freudiger C W,et al.Rapid,label-free detection of brain tumors with stimulated Raman scattering microscopy[J].Science Translational Medicine,2013,5(201):201ra119.
[54]Jermyn M,Mok K,Mercier J,et al.Intraoperative brain cancer detection with Raman spectroscopy in humans[J].Science Translational Medicine,2015,7(274):274ra19.
[55]Kuzmin N V,Wesseling P,de Witt Hamer P C,et al.Third harmonic generation imaging for fast,labelfree pathology of human brain tumors[J].Biomedical Optics Express,2016,7(5):1889-1904.
[56]Losick R,Desplan C.Stochasticity and cell fate[J].Science,2008,320(5872):65-68.
[57]Muzzey D,van Oudenaarden A.Quantitative timelapse fluorescence microscopy in single cells[J].Annual Review of Cell and Developmental Biology,2009,25(1):301-327.
[58]Wang L D,Maslov K,Wang L H V.Single-cell label-free photoacoustic flowoxigraphy in vivo[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(15):5759-5764.
[59]He G,Xu D,Qin H,et al.In vivo cell characteristic extraction and identification by photoacoustic flow cytography[J].Biomedical Optics Express,2015,6(10):3748-3756.
[60]Zhao Y,Yang S H,Chen C G,et al.Simultaneous optical absorption and viscoelasticity imaging based on photoacoustic lock-in measurement[J].Optics Letters,2014,39(9):2565-2568.
[61]Marrison J,Rty L,Marriott P,et al.Ptychography-a label free,high-contrast imaging technique for live cells using quantitative phase information[J].Scientific Reports,2013,3:2369.
[62]Lim H,Sharoukhov D,Kassim I,et al.Label-free imaging of Schwann cell myelination by third harmonic generation microscopy[J].Proceedings of the National Academy of Sciences of the United States of America,2014,111(50):18025-18030.
[63]Jüngst C,Klein M,Zumbusch A.Long-term live cell microscopy studies of lipid droplet fusion dynamics in adipocytes[J].Journal of Lipid Research,2013,54(12):3419-3429.
[64]Kim G,Lee S,Shin S,et al.Three-dimensional label-free imaging and analysis of pinus pollen grains using optical diffraction tomography[J].Scientific Reports,2018,8:1782.
[65]Liu X W,Kuang C F,Hao X,et al.Fluorescent nanowire ring illumination for wide-field far-field subdiffraction imaging[J].Physical Review Letters,2017,118(7):076101.
[66]Chen Z J,Yang S H,Xing D.Optically integrated trimodality imaging system:combined all-optical photoacoustic microscopy,optical coherence tomography,and fluorescence imaging[J].Optics Letters,2016,41(7):1636-1639.
[67]Meng X Q,Yang Y T,Zhou L H,et al.Dualresponsive molecular probe for tumor targeted imaging and photodynamic therapy[J].Theranostics,2017,7(7):1781-1794.