Bidirectional in-silico clearing approach for deep refractive-index tomography using a sparsely sampled transmission matrix

Optical diffraction tomography (ODT) enables the label-free volumetric imaging of biological specimens by mapping their three-dimensional refractive index (RI) distribution. However, the depth of imaging achievable is restricted due to spatially inhomogeneous RI distributions that induce multiple scattering. In this study, we introduce a novel ODT technique named bidirectional in-silico clearing RI tomography. This method incorporates both forward and reversed in-silico clearing. For the reversed in-silico clearing, we have integrated an ODT reconstruction framework with a transmission matrix approach, which enables RI reconstruction and wave backpropagation from the illumination side without necessitating modifications to the conventional ODT setup. Furthermore, the framework employs a sparsely sampled transmission matrix, significantly reducing the requisite number of measurements and computational expenses. Employing this proposed technique, we successfully imaged a spheroid with a thickness of 263 µm, corresponding to 11.4 scattering mean free paths. This method was successfully applied to various biological specimens, including liver and colon spheroids, demonstrating consistent imaging performance across samples with varied morphologies.