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Readout of fluorescence functional signals through highly scattering tissue


Fluorescence is a powerful means to probe information processing in the mammalian brain1. However, neuronal tissues are highly heterogeneous and thus opaque to light. A wide set of non-invasive or invasive techniques for scattered light rejection, optical sectioning or localized excitation have been developed, but non-invasive optical recording of activity through a highly scattering layer beyond the ballistic regime is impossible as yet. Here, we show that functional signals from fluorescent time-varying sources located below a highly scattering bone tissue can be retrieved efficiently by exploiting matrix factorization algorithms to demix this information from temporal sequences of low-contrast fluorescence speckle patterns.

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Fig. 1: Schematic of hardware set-up and operation of the fluorescence activity recording through a highly scattering sample.
Fig. 2: Temporal activity recording.
Fig. 3: Multiple depth recording.

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Data availability

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

Code availability

Analysis scripts are available at Hardware control scripts are available at


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We thank L. Bourdieu for providing biological samples and for numerous discussions, and F. Niwa for the cultured neurons. We also thank A. Vaziri and T. Nöbauer for useful suggestions, S. Leedumrongwatthanakun, J. Dong and A. Boniface for constructive comments, and B. Rauer and F. Soldevila for comments on the manuscript. This work was funded by the European Research Council (ERC; H2020, SMARTIES-724473). S.G. is a member of the Institut Universitaire de France.

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C.M. performed the experiment and analysed the data. S.G. and C.M. conceived the project and wrote the manuscript. S.G. supervised the project.

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Correspondence to Sylvain Gigan.

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Supplementary methods and Figs. 1–13.

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Moretti, C., Gigan, S. Readout of fluorescence functional signals through highly scattering tissue. Nat. Photonics 14, 361–364 (2020).

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