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.

Department of Systems Pharmacology University of Tokyo Tokyo Japan Laboratory for Synthetic Biology RIKEN BDR Suita Japan

Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA

Institut de la Vision Sorbonne Université INSERM CNRS Paris France

Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge MA USA Picower Institute for Learning and Memory Massachusetts Institute of Technology Cambridge MA USA Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA USA Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge MA USA Eli and Edythe Broad Institute of MIT and Harvard Cambridge MA USA Center for NanoMedicine Institute for Basic Science Seoul Republic of Korea Graduate Program of Nano Biomedical Engineering Yonsei IBS Institute Yonsei University Seoul Republic of Korea

Institute for Stroke and Dementia Research Klinikum der Universität München Ludwig Maximilian University of Munich Munich Germany Institute of Tissue Engineering and Regenerative Medicine Helmholtz Zentrum München Neuherberg Germany Munich Cluster for Systems Neurology Munich Germany

Janelia Research Campus Howard Hughes Medical Institute Ashburn VA USA

Max Planck Institute of Molecular Cell Biology and Genetics Dresden Germany IT4Innovations Technical University of Ostrava Ostrava Czech Republic

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