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Chemical Processing of Brain Tissues for Large-Volume, High-Resolution Optical Imaging

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Advanced Optical Methods for Brain Imaging

Part of the book series: Progress in Optical Science and Photonics ((POSP,volume 5))

Abstract

Imaging the brain circuitry in intact, three-dimensional context has been challenging due to the physical constraints including light scattering and slow molecular diffusion inside biological tissues. Over the past few years, advanced clearing and labeling methods—broadly defined as ‘chemical processing’ of brain tissues—have emerged as promising strategies for multiplexed, large-scale imaging of brains. Tissue clearing techniques improve the accessibility of light and molecular probes, allowing for volumetric imaging without sectioning. Multiplexed labeling and signal amplification strategies enable precise detection, localization, and sometimes quantification of various biomolecules (e.g., RNA, protein) within a single tissue. The newly emerging, size-modulating clearing techniques increase imaging speed (via size reduction) or effective imaging resolution (via expansion) while rendering the samples transparent. Here we review the recent progress in the chemical techniques for brain tissue processing and overview the underlying principles for each technique. We further discuss important challenges and suggest directions for the future chemical tissue-processing techniques for high-resolution, large-scale brain imaging.

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  1. Department of Chemistry, Interdisciplinary Program in Neuroscience, Institute of Molecular Biology and Genetics, Seoul National University, Bldg 105 Rm 209, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea

    Jinyoung Seo, Dong-Jun Koo & Sung-Yon Kim

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Editors and Affiliations

  1. Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan

    Fu-Jen Kao

  2. Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts, USA

    Gerd Keiser

  3. Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan

    Ankur Gogoi

Glossary of Acronyms Used in Clearing and Labeling Techniques for Large Brain Tissues

Glossary of Acronyms Used in Clearing and Labeling Techniques for Large Brain Tissues

3DISCO, 3D Imaging of Solvent-Cleared Organs; AAV, Adeno-Associated Virus; Ab, Antibody; ACT-PRESTO, Active Clarity Technique–Pressure Related Efficient and Stable Transfer of macromolecules into Organs; AcX, Acryloyl-X; A4P0, 4% Acrylamide; A4P4B0.05, 4% Acrylamide-4% PFA-0.05%; APS, Ammonium persulfate; BABB, Benzyl Alcohol–Benzyl Benzoate; BABB-D, mixture of DPE and BABB; Bisacrylamide; BIS, N,N′-methylenebis(acrylamide); CLARITY, Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel; COLM, Clarity Optimized Light-sheet Microscopy; CUBIC, Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis; DBE, dibenzyl ether; DCM, dichloromethane; DHEBA, N,N’-(1,2-dihydroxyethylene)bisacrylamide; DIG, digoxigenin; DPE, diphenyl ether; DMSO, dimethyl sulfoxide; EDC, 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide; ePACT, expansion-PACT; ExM, Expansion Microscopy; ExFISH, Expansion Fluorescent In Situ Hybridization; FP, Fluorescent Protein; GA, Glutaraldehyde; G1P4, 1% Glutaraldehyde-4% PFA; HCR, Hybridization Chain Reaction; hp-iExM, High pH iExM; iDISCO, Immunolabeling-enabled 3D Imaging of Solvent-Cleared Organs; iExM, Iterative Expansion Microscopy; IF staining, Immunofluorescence staining; ISH, In Situ Hybridization; IHC, Immunohistochemistry; LNA, Locked Nucleic Acid; LSFM, Light Sheet Fluorescence Microscopy; LSTM, Light Sheet Theta Microscopy; MAP, Magnified Analysis of the Proteome; MA-NHS, methacrylic acid-N-hydroxysuccinimide ester; MBAA, N,N′-methylenebisacrylamide; MERFISH, Multiplexed error-robust FISH; PACT, Passive CLARITY Technique; PAINT, Point Accumulation for Imaging in Nanoscale Topography; PARS, Perfusion-assisted Agent Release in Situ; PEG, Polyethylene Glycol; PFA, Paraformaldehyde; poly-dT, a short sequence of deoxy-thymidine nucleotides; proExM, Protein retention ExM; Pro-K, Proteinase K; PRISM, Probe-based Imaging for Sequential Multiplexing; RI, Refractive Index; RIMS, Refractive Index Matching Solution; RT, room temperature; SDS, Sodium Dodecyl Sulfate; SE-CLARITY, Stochastic Electrotransport-CLARITY; SeeDB, See Deep Brain; SeeDB2G, G for glycerol-immersion lens; SeeDB2S, S for super-resolution; SeqFISH, sequential FISH; smFISH, Single-Molecule Fluorescent In Situ Hybridization; SPED, SPherical aberration assisted Extended depth-of-field; SWITCH, System-Wide control of Interaction Time and kinetics of CHemicals; TDE, 2,2′-thiodiethanol; TEMED, tetramethylethylenediamine; THF, Tetrahydrofuran; Triethanolamine, TEA; TX-100, Triton X-100; uDISCO, Ultimate DISCO

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Seo, J., Koo, DJ., Kim, SY. (2019). Chemical Processing of Brain Tissues for Large-Volume, High-Resolution Optical Imaging. In: Kao, FJ., Keiser, G., Gogoi, A. (eds) Advanced Optical Methods for Brain Imaging. Progress in Optical Science and Photonics, vol 5. Springer, Singapore. https://doi.org/10.1007/978-981-10-9020-2_15

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