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Published April 3, 2019 | Supplemental Material + Published
Journal Article Open

In vivo superresolution photoacoustic computed tomography by localization of single dyed droplets


Photoacoustic (PA) computed tomography (PACT) is a noninvasive hybrid imaging technique that combines optical excitation and acoustic detection to realize high contrast, high resolution, and deep penetration in biological tissues. However, the spatial resolution of PACT is limited by acoustic diffraction. Here, we report in vivo superresolution PACT, which breaks the acoustic diffraction limit by localizing the centers of single dyed droplets that are flowing in blood vessels. The droplets were prepared by dissolving hydrophobic absorbing dye in oil, followed by mixing with water. The dyed droplets generate much higher-amplitude PA signals than blood and can flow smoothly in vessels; thus, they are excellent tracers for localization-based superresolution imaging. The in vivo resolution enhancement was demonstrated by continuously imaging the cortical layer of a mouse brain during droplet injection. The droplets that were flowing in the vessels were localized, and their center positions were used to construct a superresolution image that exhibits sharper features and more finely resolved vascular details. An improvement in spatial resolution by a factor of 6 has been realized in vivo by the droplet localization technique.

Additional Information

© 2019 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 24 December 2018; Revised 21 March 2019; Accepted 22 March 2019. This work was sponsored by the NIH grants DP1 EB016986 (NIH Director's Pioneer Award), R01 CA186567 (NIH Director's Transformative Research Award), U01 NS090579 (BRAIN Initiative), and U01 NS099717 (BRAIN Initiative). Authors contributions: P. Z., L. Li, and L.V.W. conceived of and designed the study. P.Z., L. Li, and L. Lin performed the experiments. P.Z. and L. Li processed the data. J.S. constructed the control program. L.V.W. supervised the study. All authors contributed to the writing of the manuscript. P.Z. and L. Li contributed equally to this work. Conflict of interest: L.W. has a financial interest in Microphotoacoustics, Inc., CalPACT, LLC, and Union Photoacoustic Technologies, Ltd., which did not support this work. The other authors declare no conflicts of interest.

Attached Files

Published - s41377-019-0147-9.pdf

Supplemental Material - 41377_2019_147_MOESM1_ESM.docx

Supplemental Material - 41377_2019_147_MOESM2_ESM.mov

Supplemental Material - 41377_2019_147_MOESM3_ESM.mov

Supplemental Material - 41377_2019_147_MOESM4_ESM.mov

Supplemental Material - 41377_2019_147_MOESM5_ESM.mov


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