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Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light

Ruan, Haowen and Brake, Joshua and Robinson, J. Elliott and Liu, Yan and Jang, Mooseok and Xiao, Cheng and Zhou, Chunyi and Gradinaru, Viviana and Yang, Changhuei (2017) Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light. Science Advances, 3 (12). Art. No. eaao5520. ISSN 2375-2548. PMCID PMC5722648. doi:10.1126/sciadv.aao5520.

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Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-μm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE focusing enabled precise control of neuron firing and increased the spatial resolution of neuronal excitation fourfold when compared to conventional lens focusing. This work is an important step in the application of TRUE focusing for practical biomedical uses.

Item Type:Article
Related URLs:
URLURL TypeDescription Materials CentralArticle
Ruan, Haowen0000-0002-4917-4509
Brake, Joshua0000-0002-5113-6886
Robinson, J. Elliott0000-0001-9417-3938
Liu, Yan0000-0002-5837-4908
Jang, Mooseok0000-0003-1977-9539
Xiao, Cheng0000-0001-9649-7450
Gradinaru, Viviana0000-0001-5868-348X
Yang, Changhuei0000-0001-8791-0354
Additional Information:© 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Submitted 2 August 2017; Accepted 8 November 2017; Published 8 December 2017. We would like to thank B. Yang, L. Bremner, A. Shibukawa, and H. Deng for their assistance and helpful discussions. Funding: We would like to acknowledge support from the NIH (DP2OD007307 to C.Y., U01NS090577 to C.Y. and V.G., and F31EB021153 to J.B.), the Gwangju Institute of Science and Technology–California Institute of Technology (Caltech) Collaborative Research Program (CG2012 to C.Y.), the Children’s Tumor Foundation (2016-01-006 to J.E.R.), the Donna and Benjamin M. Rosen Bioengineering Center (to J.B.), the Heritage Medical Research Institute (to V.G.), and the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech (to V.G.). Author contributions: H.R. and J.B. contributed equally to the work. H.R. designed the experimental setup. H.R., J.B., M.J., and Y.L. conducted the optical experiments. J.E.R., C.X., and C.Z. prepared the biological samples. J.E.R., J.B., C.X., and C.Z. conducted the electrophysiological recordings. H.R., J.B., Y.L., and J.E.R. analyzed the experimental data. V.G. and C.Y. supervised the project. All authors contributed to the manuscript preparation. Competing interests: C.Y. is an author on a patent related to this work (publication no. US9313423 B2, filed on 27 March 2013). The authors declare that they have no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.
Group:Heritage Medical Research Institute, Tianqiao and Chrissy Chen Institute for Neuroscience, Rosen Bioengineering Center
Funding AgencyGrant Number
NIH Predoctoral FellowshipF31EB021153
GIST-Caltech Research CollaborationCG2012
Children’s Tumor Foundation2016-01-006
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Tianqiao and Chrissy Chen Institute for NeuroscienceUNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC5722648
Record Number:CaltechAUTHORS:20171107-132336726
Persistent URL:
Official Citation:Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light BY HAOWEN RUAN, JOSHUA BRAKE, J. ELLIOTT ROBINSON, YAN LIU, MOOSEOK JANG, CHENG XIAO, CHUNYI ZHOU, VIVIANA GRADINARU, CHANGHUEI YANG SCIENCE ADVANCES 08 DEC 2017 : EAAO5520
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83033
Deposited By: George Porter
Deposited On:07 Nov 2017 21:27
Last Modified:18 Mar 2022 22:27

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