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Published May 31, 2017 | Published + Supplemental Material
Journal Article Open

Photoacoustic imaging of voltage responses beyond the optical diffusion limit


Non-invasive optical imaging of neuronal voltage response signals in live brains is constrained in depth by the optical diffusion limit, which is due primarily to optical scattering by brain tissues. Although photoacoustic tomography breaks this limit by exciting the targets with diffused photons and detecting the resulting acoustic responses, it has not been demonstrated as a modality for imaging voltage responses. In this communication, we report the first demonstration of photoacoustic voltage response imaging in both in vitro HEK-293 cell cultures and in vivo mouse brain surfaces. Using spectroscopic photoacoustic tomography at isosbestic wavelengths, we can separate voltage response signals and hemodynamic signals on live brain surfaces. By imaging HEK-293 cell clusters through 4.5 mm thick ex vivo rat brain tissue, we demonstrate photoacoustic tomography of cell membrane voltage responses beyond the optical diffusion limit. Although the current voltage dye does not immediately allow in vivo deep brain voltage response imaging, we believe our method opens up a feasible technical path for deep brain studies in the future.

Additional Information

© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 04 August 2016; Accepted: 12 April 2017; Published online: 31 May 2017. We appreciate Prof. James Ballard's help in editing the manuscript. This work was sponsored in part by National Institutes of Health grants U01 NS090579 (NIH Brain Initiative grant, PI: Lihong Wang), and 5K99AR062530 (NIH K99/R00 grant, PI: Bin Rao). Author Contributions: L.V. Wang initiated and supervised the project. B. Rao and R. Zhang designed all experiments, constructed the experimental setups, conducted the experiments, analyzed the experimental data, and wrote the manuscript. L. Li helped with the PACT experiment and image reconstruction. J. Shao contributed to cell culturing. All edited the manuscript. Competing Interests: L.W. has a financial interest in Microphotoacoustics, Inc., which, however, did not support this work. B.R., R.Z and L.W. have a patent application whose value may be affected by publication. L.L and J.S. have no competing financial interests.

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Published - art_3A10.1038_2Fs41598-017-02458-w.pdf

Supplemental Material - 41598_2017_2458_MOESM1_ESM.pdf


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