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      Fast, 3D Isotropic Imaging of Whole Mouse Brain Using Multiangle‐Resolved Subvoxel SPIM

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          Abstract

          The recent integration of light‐sheet microscopy and tissue‐clearing has facilitated an important alternative to conventional histological imaging approaches. However, the in toto cellular mapping of neural circuits throughout an intact mouse brain remains highly challenging, requiring complicated mechanical stitching, and suffering from anisotropic resolution insufficient for high‐quality reconstruction in 3D. Here, the use of a multiangle‐resolved subvoxel selective plane illumination microscope (Mars‐SPIM) is proposed to achieve high‐throughput imaging of whole mouse brain at isotropic cellular resolution. This light‐sheet imaging technique can computationally improve the spatial resolution over six times under a large field of view, eliminating the use of slow tile stitching. Furthermore, it can recover complete structural information of the sample from images subject to thick‐tissue scattering/attenuation. With Mars‐SPIM, a digital atlas of a cleared whole mouse brain (≈7 mm × 9.5 mm × 5 mm) can readily be obtained with an isotropic resolution of ≈2 µm (1 µm voxel) and a short acquisition time of 30 min. It provides an efficient way to implement system‐level cellular analysis, such as the mapping of different neuron populations and tracing of long‐distance neural projections over the entire brain. Mars‐SPIM is thus well suited for high‐throughput cell‐profiling phenotyping of brain and other mammalian organs.

          Abstract

          The newly developed multiangle‐resolved subvoxel selective plane illumination microscope (Mars‐SPIM) can rapidly image whole mouse brain at isotropic single‐cell resolution, on a timescale of minutes. Through computationally restoring the degraded signals from deep tissue and improving the spatial resolution under a very large field of view, Mars‐SPIM shows great potential for high‐throughput, high‐resolution mapping of entire large organs/organisms.

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          Author and article information

          Contributors
          dawnzh@mail.hust.edu.cn
          feipeng@hust.edu.cn
          Journal
          Adv Sci (Weinh)
          Adv Sci (Weinh)
          10.1002/(ISSN)2198-3844
          ADVS
          Advanced Science
          John Wiley and Sons Inc. (Hoboken )
          2198-3844
          03 December 2019
          February 2020
          : 7
          : 3 ( doiID: 10.1002/advs.v7.3 )
          : 1901891
          Affiliations
          [ 1 ] School of Optical and Electronic Information‐Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074 China
          [ 2 ] Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074 China
          [ 3 ] MoE Key Laboratory for Biomedical Photonics Huazhong University of Science and Technology Wuhan 430074 China
          [ 4 ] Department of Anesthesiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China
          Author notes
          Author information
          https://orcid.org/0000-0003-3764-817X
          Article
          ADVS1442
          10.1002/advs.201901891
          7001627
          32042557
          e2c84bc9-bc2d-4e1f-a006-667fd80f155c
          © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

          This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

          History
          : 23 July 2019
          : 14 October 2019
          Page count
          Figures: 6, Tables: 0, Pages: 11, Words: 7217
          Funding
          Funded by: National Key Research and Development Program of China , open-funder-registry 10.13039/501100012166;
          Award ID: 2017YFA0700501
          Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
          Award ID: 61860206009
          Funded by: Key Technologies Research and Development Program , open-funder-registry 10.13039/501100012165;
          Award ID: 2017YFA0700501
          Categories
          Full Paper
          Full Papers
          Custom metadata
          2.0
          February 5, 2020
          Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:05.02.2020

          brain imaging,computational imaging,light‐sheet fluorescence microscopy,neuroscience,super resolution

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