Chenfei Hu  1,2,8, Jeffrey J. Field  3,4,5,8, Varun Kelkar1 , Benny Chiang1,2, Keith Wernsing5 , Kimani C. Toussaint6, Randy A. Bartels  5,7 ✉ and Gabriel Popescu  1,2 ✉
Nature Photonics, 14, pages 564–569 2020


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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