Fluorescence imaging through dynamic scattering media with speckle-encoded ultrasound-modulated light correlation

Abstract

Fluorescence imaging is indispensable to biomedical research, and yet it remains challenging to image through dynamic scattering samples. Techniques that combine ultrasound and light as exemplified by ultrasound-assisted wavefront shaping have enabled fluorescence imaging through scattering media. However, the translation of these techniques into in vivo applications has been hindered by the lack of high-speed solutions to counter the fast speckle decorrelation of dynamic tissue. Here, we report an ultrasound-enabled optical imaging method that instead leverages the dynamic nature to perform imaging. The method utilizes the correlation between the dynamic speckle-encoded fluorescence and ultrasound-modulated light signal that originate from the same location within a sample. We image fluorescent targets with an improved resolution of ≤75 µm (versus a resolution of 1.3 mm with direct optical imaging) within a scattering medium with 17 ms decorrelation time. This new imaging modality paves the way for fluorescence imaging in highly scattering tissue in vivo.

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Fig. 1: Principle of FLUX.
Fig. 2: Imaging a fluorescent target inside a dynamic scattering sample and characterizing the system performance.
Fig. 3: Imaging multiple fluorescent targets inside a dynamic scattering sample with a speckle decorrelation time of 17 ms.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request.

Code availability

The code that supports the plots within this paper and other findings of this study is available from the corresponding authors upon reasonable request.

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Acknowledgements

This work was supported by the Kernel–Brain Research and Technologies fund (FS 13520230) and the Rosen Bioengineering Center Endowment Fund (9900050).

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H.R. conceived the idea. H.R., Y.L. and C.Y. developed the idea and designed the experiments. Y.L. and H.R. developed the experimental protocol and set-up. Y.L. constructed the samples and conducted the imaging experiments. H.R. and Y.L. analysed the data. C.Y., J.X., H.R., Y.L. and Y.H. conducted the theoretical analysis. All authors contributed to the preparation of the manuscript.

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Correspondence to Haowen Ruan or Yan Liu or Changhuei Yang.

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Supplementary Figs. 1–5 and Notes 1–4.

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Ruan, H., Liu, Y., Xu, J. et al. Fluorescence imaging through dynamic scattering media with speckle-encoded ultrasound-modulated light correlation. Nat. Photonics (2020). https://doi.org/10.1038/s41566-020-0630-0

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