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Published November 3, 2021 | Published + Supplemental Material
Journal Article Open

Multiscale Photoacoustic Tomography of a Genetically Encoded Near‐Infrared FRET Biosensor


Photoacoustic tomography (PAT) with genetically encoded near-infrared probes enables visualization of specific cell populations in vivo at high resolution deeply in biological tissues. However, because of a lack of proper probes, PAT of cellular dynamics remains unexplored. Here, the authors report a near-infrared Forster resonance energy transfer (FRET) biosensor based on a miRFP670-iRFP720 pair of the near-infrared fluorescent proteins, which enables dynamic functional imaging of active biological processes in deep tissues. By photoacoustically detecting the changes in the optical absorption of the miRFP670 FRET-donor, they monitored cell apoptosis in deep tissue at high spatiotemporal resolution using PAT. Specifically, they detected apoptosis in single cells at a resolution of ≈3 µm in a mouse ear tumor, and in deep brain tumors (>3 mm beneath the scalp) of living mice at a spatial resolution of ≈150 µm with a 20 Hz frame rate. These results open the way for high-resolution photoacoustic imaging of dynamic biological processes in deep tissues using NIR biosensors and PAT.

Additional Information

© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Issue Online: 03 November 2021; Version of Record online: 17 September 2021; Manuscript revised: 17 August 2021; Manuscript received: 11 June 2021. The authors thank Olena Oliinyk (University of Helsinki) for help with fluorescence imaging of the caspase-3 biosensor. This work was supported by grants GM122567 (to V.V.V.), EY030705 (to D.M.S.), CA186567, NS102213, and NS099717 (all to L.V.W) from the US National Institutes of Health, 322226 from the Academy of Finland (to V.V.V.), and 21-64-00025 from the Russian Science Foundation (to V.V.V.). Conflict of Interest: L.V.W. has financial interests in Microphotoacoustics, Inc., CalPACT, LLC, and Union Photoacoustic Technologies, Ltd., which did not support this work. The other authors declare no competing interests. Author Contributions: L.L. and H. H. characterized the biosensor in photoacoustic experiments. D.M.S. developed the caspase-3 sensor and characterized it in mammalian cells using fluorescence. V.V.V., L.W., and D.M.S. directed the project. L.L. and D.M.S. wrote the manuscript with contributions from all authors. Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Attached Files

Published - advs.202102474.pdf

Supplemental Material - advs3046-sup-0001-suppmat.pdf


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August 22, 2023
October 23, 2023