Second-harmonic optical diffraction tomography

TL;DR

This paper introduces a novel nonlinear optical tomography technique using second-harmonic generation to achieve label-free 3D imaging of biological samples, providing new contrast mechanisms and property visualization.

Contribution

It generalizes traditional linear optical diffraction tomography to the nonlinear regime using SHG, enabling 3D susceptibility retrieval and enhanced contrast.

Findings

Successfully demonstrated with simulated nanoparticle data

Validated with muscle tissue fiber experiments

Revealed properties inaccessible to linear methods

Abstract

Optical diffraction tomography (ODT) has emerged as an important label-free tool in biomedicine to measure the three-dimensional (3D) structure of a biological sample. In this paper, we describe ODT using second-harmonic generation (SHG) which is a coherent nonlinear optical process with a strict symmetry selectivity and has several advantages over traditional fluorescence methods. We report the tomographic retrieval of the 3D second-order nonlinear optical susceptibility using two-dimensional holographic measurements of the SHG fields at different illumination angles and polarization states. The method is a generalization of the conventional linear ODT to the nonlinear scenario. We demonstrate the method with a numerically simulated nanoparticle distribution and an experiment with muscle tissue fibers. Our results show that SHG ODT does not only provide an effective contrast mechanism for label-free imaging but also due to the symmetry requirement enables the visualization of properties that are not otherwise accessible.