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Harmonic optical tomography of nonlinear structures

Nature Photonics volume 14, pages 564–569 (2020)Cite this article

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Abstract

Second-harmonic generation microscopy is a valuable label-free modality for imaging non-centrosymmetric structures and has important biomedical applications from live-cell imaging to cancer diagnosis. Conventional second-harmonic generation microscopy measures intensity signals that originate from tightly focused laser beams, preventing researchers from solving the scattering inverse problem for second-order nonlinear materials. Here, we present harmonic optical tomography (HOT) as a novel modality for imaging microscopic, nonlinear and inhomogeneous objects. The HOT principle of operation relies on interferometrically measuring the complex harmonic field and using a scattering inverse model to reconstruct the three-dimensional distribution of harmonophores. HOT enables strong axial sectioning via the momentum conservation of spatially and temporally broadband fields. We illustrate the HOT operation with experiments and reconstructions on a beta-barium borate crystal and various biological specimens. Although our results involve second-order nonlinear materials, we show that this approach applies to any coherent nonlinear process.

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Fig. 1: A schematic of HOT and the procedure of complex field retrieval.
Fig. 2: The second-harmonic scattering.
Fig. 3: The normalized transfer function under different NAc values.
Fig. 4: HOT of an inhomogeneous nonlinear crystal.
Fig. 5: HOT of murine skeletal muscle slice.

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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 MATLAB code used for HOT reconstruction is available from the corresponding authors upon reasonable request.

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Acknowledgements

This work is supported in part by the National Science Foundation (0939511, 1450962, 1353368) and the National Institutes of Health (R01CA238191, R01GM129709, R21EB025389 and R21MH117786).

Author information

Author notes

  1. These authors contributed equally: Chenfei Hu, Jeffrey J. Field.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Chenfei Hu, Varun Kelkar, Benny Chiang & Gabriel Popescu

  2. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Chenfei Hu, Benny Chiang & Gabriel Popescu

  3. Microscope Imaging Network Core Facility, Colorado State University, Fort Collins, CO, USA

    Jeffrey J. Field

  4. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA

    Jeffrey J. Field

  5. Department of Electrical and Computer Engineering, Colorado State University, Fort Collins, CO, USA

    Jeffrey J. Field, Keith Wernsing & Randy A. Bartels

  6. School of Engineering, Brown University, Providence, RI, USA

    Kimani C. Toussaint

  7. School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA

    Randy A. Bartels

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Contributions

C.H., V.K. and G.P. developed the theoretical model, with input from R.A.B. and K.C.T. K.W. built the fibre laser system, J.J.F. built the microscope system and collected experimental data. C.H. developed the numerical reconstruction. C.H. and B.C. rendered figures and Supplememtary videos. R.A.B. supervised the experimental work. G.P. supervised the theoretical work. C.H. and G.P. wrote the manuscript with input from all authors.

Corresponding authors

Correspondence to Randy A. Bartels or Gabriel Popescu.

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Competing interests

G.P. has financial interest in Phi Optics, a company developing quantitative phase imaging technology for materials and life science applications, which, however, did not sponsor the research. The authors disclosed this invention to the UIUC Office of Technology management.

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Supplementary information

Supplementary Information

Supplementary Fig. 1 and discussion.

Supplementary Video 1

A 3D rendering of an inhomogeneous nonlinear crystal.

Supplementary Video 2

A 3D rendering of murine skeletal muscle.

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Hu, C., Field, J.J., Kelkar, V. et al. Harmonic optical tomography of nonlinear structures. Nat. Photonics 14, 564–569 (2020). https://doi.org/10.1038/s41566-020-0638-5

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