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Controlling the sound of light: photoswitching optoacoustic imaging

Nature Methods (2024)Cite this article

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Abstract

Optoacoustic (photoacoustic) imaging advances allow high-resolution optical imaging much deeper than optical microscopy. However, while label-free optoacoustics have already entered clinical application, biological imaging is in need of ubiquitous optoacoustic labels for use in ways that are similar to how fluorescent proteins propelled optical microscopy. We review photoswitching advances that shine a new light or, in analogy, ‘bring a new sound’ to biological optoacoustic imaging. Based on engineered labels and novel devices, switching uses light or other energy forms and enables signal modulation and synchronous detection for maximizing contrast and detection sensitivity over other optoacoustic labels. Herein, we explain contrast enhancement in the spectral versus temporal domains and review labels and key concepts of switching and their properties to modulate optoacoustic signals. We further outline systems and applications and discuss how switching can enable optoacoustic imaging of cellular or molecular contrast at depths and resolutions beyond those of other optical methods.

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Fig. 1: Fundamental principles of psOptA.
Fig. 2: Illustration of different mechanisms of temporal control of the OptA signal.
Fig. 3: Imaging examples of psOptA, OptA with thermo-control and magneto-control of label states and other applications of photocontrollable agents in OptA.

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Acknowledgements

We thank E. Bonnin and S. Lee for their attentive reading and improvements of the manuscript. A.C.S. acknowledges funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 101002646 (‘Switch2See’) and the Deutsche Forschungsgemeinschaft (STI-656/5-1 and STI-656/6-1).

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Authors and Affiliations

  1. Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany

    Andre C. Stiel & Vasilis Ntziachristos

  2. Protein Engineering for Superresolution Microscopy Lab, University of Regensburg, Regensburg, Germany

    Andre C. Stiel

  3. Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health, Technical University of Munich, Munich, Germany

    Vasilis Ntziachristos

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V.N. is a founder and equity owner of Maurus OY, sThesis GmbH, iThera Medical GmbH, Spear UG and I3. A.C.S. declares no competing interests.

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Nature Methods thanks Junjie Yao, Jeesu Kim, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Rita Strack, in collaboration with the Nature Methods team.

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Stiel, A.C., Ntziachristos, V. Controlling the sound of light: photoswitching optoacoustic imaging. Nat Methods (2024). https://doi.org/10.1038/s41592-024-02396-2

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