Volume 16 Issue 5
Sep.  2023
Turn off MathJax
Article Contents
FU Qiang, ZHANG Zhi-miao, ZHAO Shang-nan, LIU Yang, DONG Yang. Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique[J]. Chinese Optics, 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007
Citation: FU Qiang, ZHANG Zhi-miao, ZHAO Shang-nan, LIU Yang, DONG Yang. Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique[J]. Chinese Optics, 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007

Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique

doi: 10.37188/CO.2023-0007
Funds:  Supported by National Natural Science Foundation of China (No. 62005271); Youth Innovation Promotion Association, CAS (No. 2021221); Youth growth technology program of Jilin province science and technology development plan (No. 20210508054RQ).
More Information
  • Corresponding author: fuqianghit@163.com
  • Received Date: 10 Jan 2023
  • Rev Recd Date: 05 Feb 2023
  • Accepted Date: 24 Mar 2023
  • Available Online: 05 May 2023
  • Miniature head-mounted single-photon fluorescence microscopy is a breakthrough approach for neuroscience research that has emerged in recent years. It can image the neural activity of freely moving vivo animals in real time, providing an unprecedented way to access neural signals and rapidly enhancing the understanding of how the brain works. Driven by the needs of brain science research, there have been many types of miniature head-mounted single-photon fluorescence microscopes, such as high-resolution imaging, wireless recording, 3D imaging, two-region imaging and two-color imaging. In order to have a more comprehensive understanding of this new optical neuroimaging technology, we classify its technologies according to the imaging field of view, introduce the characteristics of different types of micro-head-mounted single-photon fluorescence microscopes reported so far, and focus on the optical system scheme and optical performance parameters used. The advantages and disadvantages of different schemes are analyzed and compared and the future direction of development is described to provide reference for the practical application of brain science researchers.


  • loading
  • [1]
    CHEN SH Y, WANG Z CH, ZHANG D, et al. Miniature fluorescence microscopy for imaging brain activity in freely-behaving animals[J]. Neuroscience Bulletin, 2020, 36(10): 1182-1190. doi: 10.1007/s12264-020-00561-z
    GRIENBERGER C, KONNERTH A. Imaging calcium in neurons[J]. Neuron, 2012, 73(5): 862-885. doi: 10.1016/j.neuron.2012.02.011
    王义强, 林方睿, 胡睿, 等. 大视场光学显微成像技术[J]. 中国光学(中英文),2022,15(6):1194-1210.

    WANG Y Q, LIN F R, HU R, et al. Large field-of-view optical microscopic imaging technology[J]. Chinese Optics, 2022, 15(6): 1194-1210. (in Chinese)
    陈帅, 任林, 周镇乔, 等. 在体跨尺度双光子显微成像技术[J]. 中国光学(中英文),2022,15(6):1167-1181.

    CHEN SH, REN L, ZHOU ZH Q, et al. In-vivo across-scales two-photon microscopic imaging technique[J]. Chinese Optics, 2022, 15(6): 1167-1181. (in Chinese)
    王鹏, 周瑶, 赵宇轩, 等. 用于多尺度高分辨率三维成像的双环光片荧光显微技术[J]. 中国光学(中英文),2022,15(6):1321-1331.

    WANG P, ZHOU Y, ZHAO Y X, et al. Double-ring-modulated light sheet fluorescence microscopic technique for multi-scale high-resolution 3D imaging[J]. Chinese Optics, 2022, 15(6): 1321-1331. (in Chinese)
    YU H, SENARATHNA J, TYLER B M, et al. Miniaturized optical neuroimaging in unrestrained animals[J]. NeuroImage, 2015, 113: 397-406. doi: 10.1016/j.neuroimage.2015.02.070
    AHARONI D, KHAKH B S, SILVA A J, et al. All the light that we can see: a new era in miniaturized microscopy[J]. Nature Methods, 2019, 16(1): 11-13. doi: 10.1038/s41592-018-0266-x
    ZONG W J, WU R L, LI M L, et al. Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice[J]. Nature Methods, 2017, 14(7): 713-719. doi: 10.1038/nmeth.4305
    GHOSH K K, BURNS L D, COCKER E D, et al. Miniaturized integration of a fluorescence microscope[J]. Nature Methods, 2011, 8(10): 871-878. doi: 10.1038/nmeth.1694
    CAI D J, AHARONI D, SHUMAN T, et al. A shared neural ensemble links distinct contextual memories encoded close in time[J]. Nature, 2016, 534(7605): 115-118. doi: 10.1038/nature17955
    CAMPOS P, WALKER J J, MOLLARD P. Diving into the brain: deep-brain imaging techniques in conscious animals[J]. Journal of Endocrinology, 2020, 246(2): R33-R50. doi: 10.1530/JOE-20-0028
    BARBERA G, LIANG B, ZHANG L F, et al. Spatially compact neural clusters in the dorsal striatum encode locomotion relevant information[J]. Neuron, 2016, 92(1): 202-213. doi: 10.1016/j.neuron.2016.08.037
    ZHANG L F, LIANG B, BARBERA G, et al. Miniscope GRIN lens system for calcium imaging of neuronal activity from deep brain structures in behaving animals[J]. Current Protocols in Neuroscience, 2019, 86(1): e56. doi: 10.1002/cpns.56
    LIANG B, ZHANG L F, BARBERA G, et al. Distinct and dynamic ON and OFF neural ensembles in the prefrontal cortex code social exploration[J]. Neuron, 2018, 100(3): 700-714.e9. doi: 10.1016/j.neuron.2018.08.043
    JACOB A D, RAMSARAN A I, MOCLE A J, et al. A compact head-mounted endoscope for in vivo calcium imaging in freely behaving mice[J]. Current Protocols in Neuroscience, 2018, 84(1): e51. doi: 10.1002/cpns.51
    BAGRAMYAN A. Lightweight 1-photon miniscope for imaging in freely behaving animals at subcellular resolution[J]. IEEE Photonics Technology Letters, 2020, 32(15): 909-912. doi: 10.1109/LPT.2020.3004283
    LIBERTI III W A, MARKOWITZ J E, PERKINS L N, et al. Unstable neurons underlie a stable learned behavior[J]. Nature Neuroscience, 2016, 19(12): 1665-1671. doi: 10.1038/nn.4405
    COHEN Y, SHEN J, SEMU D, et al. Hidden neural states underlie canary song syntax[J]. Nature, 2020, 582(7813): 539-544. doi: 10.1038/s41586-020-2397-3
    LIBERTI III W A, PERKINS L N, LEMAN D P, et al. An open source, wireless capable miniature microscope system[J]. Journal of Neural Engineering, 2017, 14(4): 045001. doi: 10.1088/1741-2552/aa6806
    Alvarado J S, Goffinet J, Michael V, et al. Neural dynamics underlying birdsong practice and performance[J]. Nature, 2021, 599(7886): 635-639.
    SHUMAN T, AHARONI D, CAI D J, et al. Breakdown of spatial coding and interneuron synchronization in epileptic mice[J]. Nature Neuroscience, 2020, 23(2): 229-238. doi: 10.1038/s41593-019-0559-0
    BARBERA G, LIANG B, ZHANG L F, et al. A wireless miniScope for deep brain imaging in freely moving mice[J]. Journal of Neuroscience Methods, 2019, 323: 56-60. doi: 10.1016/j.jneumeth.2019.05.008
    WANG Y ZH, MA ZH T, LI W ZH, et al.. Cable-free brain imaging with miniature wireless microscopes[J]. Journal of Biomedical Optics, 2023, 28(2): 026503.
    SKOCEK O, NÖBAUER T, WEILGUNY L, et al. High-speed volumetric imaging of neuronal activity in freely moving rodents[J]. Nature Methods, 2018, 15(6): 429-432. doi: 10.1038/s41592-018-0008-0
    PREVEDEL R, YOON Y G, HOFFMANN M, et al. Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy[J]. Nature Methods, 2014, 11(7): 727-730. doi: 10.1038/nmeth.2964
    NÖBAUER T, SKOCEK O, PERNÍA-ANDRADE A J, et al. Video rate volumetric Ca2+ imaging across cortex using seeded iterative demixing (SID) microscopy[J]. Nature Methods, 2017, 14(8): 811-818. doi: 10.1038/nmeth.4341
    YANNY K, ANTIPA N, LIBERTI W, et al. Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy[J]. Light:Science &Applications, 2020, 9: 171.
    BAGRAMYAN A, TABOURIN L, RASTQAR A, et al. Focus-tunable microscope for imaging small neuronal processes in freely moving animals[J]. Photonics Research, 2021, 9(7): 1300-1309. doi: 10.1364/PRJ.418154
    SUPEKAR O D, SIAS A, HANSEN S R, et al. Miniature structured illumination microscope for in vivo 3D imaging of brain structures with optical sectioning[J]. Biomedical Optics Express, 2022, 13(4): 2530-2541. doi: 10.1364/BOE.449533
    GONZALEZ W G, ZHANG H W, HARUTYUNYAN A, et al. Persistence of neuronal representations through time and damage in the hippocampus[J]. Science, 2019, 365(6455): 821-825. doi: 10.1126/science.aav9199
    DE GROOT A, VAN DEN BOOM B J G, VAN GENDEREN R M, et al. NINscope, a versatile miniscope for multi-region circuit investigations[J]. eLife, 2020, 9: e49987. doi: 10.7554/eLife.49987
    Silva A J. Miniaturized two-photon microscope: seeing clearer and deeper into the brain[J]. Light,science &applications, 2017, 6(8): e17104.
    WIRTSHAFTER H S, DISTERHOFT J F. In vivo multi-day calcium imaging of CA1 hippocampus in freely moving rats reveals a high preponderance of place cells with consistent place fields[J]. Journal of Neuroscience, 2022, 42(22): 4538-4554. doi: 10.1523/JNEUROSCI.1750-21.2022
    AHARONI D, HOOGLAND T M. Circuit investigations with open-source miniaturized microscopes: past, present and future[J]. Frontiers in Cellular Neuroscience, 2019, 13: 141. doi: 10.3389/fncel.2019.00141
    蓝凯秋, 杨西斌, 徐宝腾, 等. 双色荧光成像在体微型显微镜[J]. 光子学报,2022,51(6):0618001. doi: 10.3788/gzxb20225106.0618001

    LAN K Q, YANG X B, XU B T, et al. In vivo, dual-color fluorescent imaging miniature microscope[J]. Acta Photonica Sinica, 2022, 51(6): 0618001. (in Chinese) doi: 10.3788/gzxb20225106.0618001
    SCOTT B B, THIBERGE S Y, GUO C Y, et al. Imaging cortical dynamics in GCaMP transgenic rats with a head-mounted widefield macroscope[J]. Neuron, 2018, 100(5): 1045-1058.e5. doi: 10.1016/j.neuron.2018.09.050
    XUE Y J, DAVISON I G, BOAS D A, et al. Single-shot 3D wide-field fluorescence imaging with a Computational Miniature Mesoscope[J]. Science Advances, 2020, 6(43): eabb7508. doi: 10.1126/sciadv.abb7508
    STERN A, JAVIDI B. Three-dimensional image sensing, visualization, and processing using integral imaging[J]. Proceedings of the IEEE, 2006, 94(3): 591-607. doi: 10.1109/JPROC.2006.870696
    邓慧, 吕国皎, 杨梅, 等. 基于掩膜板阵列的消串扰集成成像3D显示方法[J]. 液晶与显示,2022,37(5):592-597. doi: 10.37188/CJLCD.2022-0027

    DENG H, LYU G J, YANG M, et al. Crosstalk-free integral imaging 3D display method based on a mask array[J]. Chinese Journal of Liquid Crystals and Displays, 2022, 37(5): 592-597. (in Chinese) doi: 10.37188/CJLCD.2022-0027
    CONG L, WANG Z G, CHAI Y M, et al. Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (Danio rerio)[J]. eLife, 2017, 6: e28158. doi: 10.7554/eLife.28158
    徐斌, 于迅博, 高鑫, 等. 一种视点均匀分布的桌面式光场显示系统[J]. 液晶与显示,2022,37(5):573-580. doi: 10.37188/CJLCD.2022-0041

    XU B, YU X B, GAO X, et al. Tabletop light field display system with uniform distribution of viewpoints[J]. Chinese Journal of Liquid Crystals and Displays, 2022, 37(5): 573-580. (in Chinese) doi: 10.37188/CJLCD.2022-0041
    于迅博, 李涵宇, 高鑫, 等. 基于预处理卷积神经网络提升3D光场显示视觉分辨率的方法[J]. 液晶与显示,2022,37(5):549-554. doi: 10.37188/CJLCD.2022-0044

    YU X B, LI H Y, GAO X, et al. 3D light field display with improved visual resolution based on pre-processing convolutional neural network[J]. Chinese Journal of Liquid Crystals and Displays, 2022, 37(5): 549-554. (in Chinese) doi: 10.37188/CJLCD.2022-0044
    TANIDA J, KUMAGAI T, YAMADA K, et al. Thin observation module by bound optics (TOMBO): concept and experimental verification[J]. Applied Optics, 2001, 40(11): 1806-1813. doi: 10.1364/AO.40.001806
    MCCALL B, OLSEN R J, NELLES N J, et al. Evaluation of a miniature microscope objective designed for fluorescence array microscopy detection of Mycobacterium tuberculosis[J]. Archives of Pathology &Laboratory Medicine, 2014, 138(3): 379-389.
    ANTIPA N, KUO G, HECKEL R, et al. DiffuserCam: lensless single-exposure 3D imaging[J]. Optica, 2018, 5(1): 1-9. doi: 10.1364/OPTICA.5.000001
    RYNES M L, SURINACH D A, LINN S, et al. Miniaturized head-mounted microscope for whole-cortex mesoscale imaging in freely behaving mice[J]. Nature Methods, 2021, 18(4): 417-425. doi: 10.1038/s41592-021-01104-8
    WU J M, GUO Y D, DENG CH, et al. An integrated imaging sensor for aberration-corrected 3D photography[J]. Nature, 2022, 612(7938): 62-71. doi: 10.1038/s41586-022-05306-8
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(7)

    Article views(536) PDF downloads(235) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint