Abstract
Although laser scanning microscopy is a pivotal imaging tool in biomedical research, optical scattering from tissue limits the depth of the imaging. To overcome this limitation, we propose a scheme called ultrasound-induced optical clearing microscopy, which makes use of temporary, localized optical clearing based on ultrasound-induced gas bubbles. In this method, bubbles are generated by high-intensity pulsed ultrasound at a desired depth and subsequently maintained by low-intensity continuous ultrasound during imaging. As a result, optical scattering and unwanted changes in the propagation direction of the incident photons are minimized in the bubble cloud, and thus the laser can be tightly focused at a deeper imaging plane. Through phantom and ex vivo experiments, we demonstrate that ultrasound-induced optical clearing microscopy is capable of increasing the imaging depth by a factor of six or more, while the resolution is similar to that of conventional laser scanning microscopy.
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Data availability
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
Code availability
The codes for the simulation are available from the corresponding authors upon reasonable request.
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Acknowledgements
This work was supported by the Samsung Research Funding Center of Samsung Electronics under project number SRFC-IT1702-03 (J.H.C. and J.Y.W.).
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J.H.C. conceived the idea, and J.H.C. and J.Y.H. developed the idea and designed the project. H.K., J.Y.H. and J.H.C. developed the experimental protocol. S.Y., J.K. and M.L. designed and built the US-OCM system. S.P. performed the ultrasound beam simulations and analysed the standing-wave properties. H.K. collected the experimental data, performed the Monte Carlo simulations and wrote the initial manuscript draft. J.H.C. and J.Y.H. revised the draft. All authors were involved in the analysis of the results and revision of the manuscript.
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Supplementary description of the developed system, simulation and experimental results, discussion and Figs. 1–15.
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Kim, H., Youn, S., Kim, J. et al. Deep laser microscopy using optical clearing by ultrasound-induced gas bubbles. Nat. Photon. 16, 762–768 (2022). https://doi.org/10.1038/s41566-022-01068-x
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DOI: https://doi.org/10.1038/s41566-022-01068-x
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