Theranostics 2021; 11(7):3035-3051. doi:10.7150/thno.53979


Optical Tissue Clearing: Illuminating Brain Function and Dysfunction

Xiaohan Liang1,2, Haiming Luo1,2✉

1. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
2. MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China

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Liang X, Luo H. Optical Tissue Clearing: Illuminating Brain Function and Dysfunction. Theranostics 2021; 11(7):3035-3051. doi:10.7150/thno.53979. Available from

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Tissue optical clearing technology has been developing rapidly in the past decade due to advances in microscopy equipment and various labeling techniques. Consistent modification of primary methods for optical tissue transparency has allowed observation of the whole mouse body at single-cell resolution or thick tissue slices at the nanoscale level, with the final aim to make intact primate and human brains or thick human brain tissues optically transparent. Optical clearance combined with flexible large-volume tissue labeling technology can not only preserve the anatomical structure but also visualize multiple molecular information from intact samples in situ. It also provides a new strategy for studying complex tissues, which is of great significance for deciphering the functional structure of healthy brains and the mechanisms of neurological pathologies. In this review, we briefly introduce the existing optical clearing technology and discuss its application in deciphering connection and structure, brain development, and brain diseases. Besides, we discuss the standard computational analysis tools for large-scale imaging dataset processing and information extraction. In general, we hope that this review will provide a valuable reference for researchers who intend to use optical clearing technology in studying the brain.

Keywords: Optical tissue clearing, Neural circuits, Brain atlas, Brain diseases, Neurodevelopment, Image analysis tools