Scattering compensation by focus scanning holographic aberration probing (F-SHARP)

Abstract

A long-standing goal in biomedical imaging, the control of light inside turbid media, requires knowledge of how the phase and amplitude of an illuminating wavefront are transformed as the electric field propagates inside a scattering sample onto a target plane. So far, it has proved challenging to non-invasively characterize the scattered optical wavefront inside a disordered medium. Here, we present a non-invasive scattering compensation method, termed F-SHARP, which allows us to measure the scattered electric-field point spread function (E-field PSF) in three dimensions. Knowledge of the phase and amplitude of the E-field PSF makes it possible to optically cancel sample turbulence. We demonstrate the imaging capabilities of this technique on a variety of samples and notably through vertebrate brains and across thinned skull in vivo.

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Figure 1: Principle of F-SHARP microscopy.
Figure 2: F-SHARP microscopy of fluorescent beads through muscle tissue.
Figure 3: Characterization of E-field PSF estimation.
Figure 4: In vivo F-SHARP imaging of a transgenic zebrafish larval brain.
Figure 5: Aberration and scattering compensation inside living mouse brain.
Figure 6: Imaging through thinned mouse skull in vivo.

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Acknowledgements

The authors thank R. Horstmeyer for discussions and help with the manuscript and S. Smith, A. Packer, C. Rowlands, E. Bobrov and M. Hoffmann for critically reviewing the manuscript. The authors thank L. Schulze for help with the zebrafish larvae mounting protocol and N. Hakiy for zebrafish husbandry. The authors also thank C. Wyart and A. Prendergast for providing the NeuroD:GCaMP6f zebrafish line. This work was supported by the DFG (EXC 257 NeuroCure), the European Research Council (ERC-2015-CoG-682422, to J.F.A.P.) and the European Union (3x3Dimaging 323945, to J.F.A.P.). I.N.P. is a recipient of the Early-PostDoc mobility fellowship of the Swiss National Science Foundation.

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B.J. and I.N.P. conceived and developed the idea. I.N.P. designed experiments with help from B.J. I.N.P. built the set-up, collected and analysed data. J.-S.J. performed mouse procedures under supervision from J.F.A.P. I.N.P. and B.J. wrote the manuscript. B.J. supervised the project.

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Correspondence to Benjamin Judkewitz.

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I.N.P. and B.J. have submitted a patent application on part of the described work.

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Papadopoulos, I., Jouhanneau, J., Poulet, J. et al. Scattering compensation by focus scanning holographic aberration probing (F-SHARP). Nature Photon 11, 116–123 (2017). https://doi.org/10.1038/nphoton.2016.252

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