  The measurement of three-dimensional (3D) images and the analysis of
subcellular organelles are crucial for the study of the pathophysiology of
cells and tissues. Optical diffraction tomography (ODT) facilitates label-free
and quantitative imaging of live cells by reconstructing 3D refractive index
(RI) distributions. In many cases, however, the contrast in RI distributions is
not strong enough to effectively distinguish subcellular organelles in live
cells. To realize label-free and quantitative imaging of subcellular organelles
in unlabeled live cells with enhanced contrasts, we present a computational
approach using ODT. We demonstrate that the contrast of ODT can be enhanced via
spatial high-pass filtering in a 3D spatial frequency domain, and that it
yields theoretically equivalent results to physical dark-field illumination.
Without changing the optical instruments used in ODT, subcellular organelles in
live cells are clearly distinguished by applying a simple but effective
computational approach that is validated by comparison with 3D epifluorescence
images. We expect that the proposed method will satisfy the demand for
label-free organelle observations, and will be extended to fully utilize
complex information in 3D RI distributions.
