Tissue clearing and its applications in neuroscience

  • Nat Rev Neurosci. 2020 Feb;21(2):61-79. doi: 10.1038/s41583-019-0250-1.
Hiroki R Ueda  1  2 ,  Ali Ertürk  3  4  5 ,  Kwanghun Chung  6  7  8  9  10  11  12 ,  Viviana Gradinaru  13 ,  Alain Chédotal  14 ,  Pavel Tomancak  15  16 ,  Philipp J Keller  17
Affiliations
  • 1. Department of Systems Pharmacology, University of Tokyo, Tokyo, Japan. [email protected].
  • 2. Laboratory for Synthetic Biology, RIKEN BDR, Suita, Japan. [email protected].
  • 3. Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian University of Munich, Munich, Germany.
  • 4. Institute of Tissue Engineering and Regenerative Medicine, Helmholtz Zentrum München, Neuherberg, Germany.
  • 5. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
  • 6. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 7. Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 8. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 9. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 10. Eli & Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • 11. Center for NanoMedicine, Institute for Basic Science, Seoul, Republic of Korea.
  • 12. Graduate Program of Nano Biomedical Engineering, Yonsei-IBS Institute, Yonsei University, Seoul, Republic of Korea.
  • 13. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • 14. Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.
  • 15. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
  • 16. IT4Innovations, Technical University of Ostrava, Ostrava, Czech Republic.
  • 17. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
PMID: 31896771 DOI: 10.1038/s41583-019-0250-1
Abstract

State-of-the-art tissue-clearing methods provide subcellular-level optical access to intact tissues from individual organs and even to some entire mammals. When combined with light-sheet microscopy and automated approaches to image analysis, existing tissue-clearing methods can speed up and may reduce the cost of conventional histology by several orders of magnitude. In addition, tissue-clearing chemistry allows whole-organ antibody labelling, which can be applied even to thick human tissues. By combining the most powerful labelling, clearing, imaging and data-analysis tools, scientists are extracting structural and functional cellular and subcellular information on complex mammalian bodies and large human specimens at an accelerated pace. The rapid generation of terabyte-scale imaging data furthermore creates a high demand for efficient computational approaches that tackle challenges in large-scale data analysis and management. In this Review, we discuss how tissue-clearing methods could provide an unbiased, system-level view of mammalian bodies and human specimens and discuss future opportunities for the use of these methods in human neuroscience.