Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging.

A new formulation of the lateral imaging process of point-scanning optical coherence tomography (OCT) and a new differential contrast method designed by using this formulation are presented. The formulation is based on a mathematical sample model called the dispersed scatterer model (DSM), in which the sample is represented as a material with a spatially slowly varying refractive index and randomly distributed scatterers embedded in the material. It is shown that the formulation represents a meaningful OCT image and speckle as two independent mathematical quantities. The new differential contrast method is based on complex signal processing of OCT images, and the physical and numerical imaging processes of this method are jointly formulated using the same theoretical strategy as in the case of OCT. The formula shows that the method provides a spatially differential image of the sample structure. This differential imaging method is validated by measuring in vivo and in vitro samples.

Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography.

An organoid is a three-dimensional (3D) in vitro cell culture emulating human organs. We applied 3D dynamic optical coherence tomography (DOCT) to visualize the intratissue and intracellular activities of human induced pluripotent stem cells (hiPSCs)-derived alveolar organoids in normal and fibrosis models. 3D DOCT data were acquired with an 840-nm spectral domain optical coherence tomography with axial and lateral resolutions of 3.8 µm (in tissue) and 4.9 µm, respectively. The DOCT images were obtained by the logarithmic-intensity-variance (LIV) algorithm, which is sensitive to the signal fluctuation magnitude. The LIV images revealed cystic structures surrounded by high-LIV borders and mesh-like structures with low LIV. The former may be alveoli with a highly dynamics epithelium, while the latter may be fibroblasts. The LIV images also demonstrated the abnormal repair of the alveolar epithelium.

Non-destructive characterization of adult zebrafish models using Jones matrix optical coherence tomography.

The zebrafish is a valuable vertebrate animal model in pre-clinical cancer research. A Jones matrix optical coherence tomography (JM-OCT) prototype operating at 1310 nm and an intensity-based spectral-domain OCT setup at 840 nm were utilized to investigate adult wildtype and a tumor-developing zebrafish model. Various anatomical features were characterized based on their inherent scattering and polarization signature. A motorized translation stage in combination with the JM-OCT prototype enabled large field-of-view imaging to investigate adult zebrafish in a non-destructive way. The diseased animals exhibited tumor-related abnormalities in the brain and near the eye region. The scatter intensity, the attenuation coefficients and local polarization parameters such as the birefringence and the degree of polarization uniformity were analyzed to quantify differences in tumor versus control regions. The proof-of-concept study in a limited number of animals revealed a significant decrease in birefringence in tumors found in the brain and near the eye compared to control regions. The presented work showed the potential of OCT and JM-OCT as non-destructive, high-resolution, and real-time imaging modalities for pre-clinical research based on zebrafish.

Computational multi-directional optical coherence tomography for visualizing the microstructural directionality of the tissue.

We demonstrate computational multi-directional optical coherence tomography (OCT) to assess the directional property of tissue microstructure. This method is the combination of phase-sensitive volumetric OCT imaging and post-signal processing. The latter comprises of two steps. The first step is an intensity-directional analysis, which determines the dominant en face fiber orientations. The second step is the phase-directional imaging, which reveals the sub-resolution depth-orientation of the microstructure. The feasibility of the method was tested by assessing muscle and tendon samples. Stripe patterns with several sizes were visualized in the phase-directional images. In order to interpret these images, the muscle and tendon structures were numerically modeled, and the phase-directional images were generated from the numerical model. The similarity of the experimental and numerical results suggested that the stripe patterns correspond to the muscle fiber bundle and its crimping.