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Optical coherence tomography (OCT) has seen widespread success as anin vivoclinical diagnostic 3D imaging modality, impacting areas including ophthalmology, cardiology, and gastroenterology. Despite its many advantages, such as high sensitivity, speed, and depth penetration, OCT suffers from several shortcomings that ultimately limit its utility as a 3D microscopy tool, such as its pervasive coherent speckle noise and poor lateral resolution required to maintain millimeter-scale imaging depths. Here, we present 3D optical coherence refraction tomography (OCRT), a computational extension of OCT that synthesizes an incoherent contrast mechanism by combining multiple OCT volumes, acquired across two rotation axes, to form a resolution-enhanced, speckle-reduced, refraction-corrected 3D reconstruction. Our label-free computational 3D microscope features a novel optical design incorporating a parabolic mirror to enable the capture of 5D plenoptic datasets, consisting of millimetric 3D fields of view over up to$\pm <\#comment/>{75}^{\circ <\#comment/>}$without moving the sample. We demonstrate that 3D OCRT reveals 3D features unobserved by conventional OCT in fruit fly, zebrafish, and mouse samples.

 

Frequency-modulated continuous wave (FMCW) light detection and ranging (LiDAR) is an emerging 3D ranging technology that offers high sensitivity and ranging precision. Due to the limited bandwidth of digitizers and the speed limitations of beam steering using mechanical scanners, meter-scale FMCW LiDAR systems typically suffer from a low 3D frame rate, which greatly restricts their applications in real-time imaging of dynamic scenes. In this work, we report a high-speed FMCW based 3D imaging system, combining a grating for beam steering with a compressed time-frequency analysis approach for depth retrieval. We thoroughly investigate the localization accuracy and precision of our system both theoretically and experimentally. Finally, we demonstrate 3D imaging results of multiple static and moving objects, including a flexing human hand. The demonstrated technique achieves submillimeter localization accuracy over a tens-of-centimeter imaging range with an overall depth voxel acquisition rate of 7.6 MHz, enabling densely sampled 3D imaging at video rate.

 

We present a real-time spectral-scanning frequency-modulated continuous wave (FMCW) 3D imaging and velocimetry system that can produce 3D depth maps at 33 Hz, with 48° × 68° field of view (FOV) and 32.8-cm depth range. Each depth map consists of 507 × 500 pixels, with 0.095° × 0.14° angular resolution and 2.82-mm depth resolution. The system employs a grating for beam steering and a telescope for angular FOV magnification. Quantitative depth, reflectivity, and axial velocity measurements of a static 3D printed depth variation target and a moving robotic arm are demonstrated. 

Illuminating or imaging samples from a broad angular range is essential in a wide variety of computational 3D imaging and resolution-enhancement techniques, such as optical projection tomography, optical diffraction tomography, synthetic aperture microscopy, Fourier ptychographic microscopy, structured illumination microscopy, photogrammetry, and optical coherence refraction tomography. The wider the angular coverage, the better the resolution enhancement or 3D-resolving capabilities. However, achieving such angular ranges is a practical challenge, especially when approaching$\pm <\#comment/>{90}^{\circ <\#comment/>}$or beyond. Often, researchers resort to expensive, proprietary high numerical aperture (NA) objectives or to rotating the sample or source-detector pair, which sacrifices temporal resolution or perturbs the sample. Here, we propose several new strategies for multiangle imaging approaching 4pi steradians using concave parabolic or ellipsoidal mirrors and fast, low rotational inertia scanners, such as galvanometers. We derive theoretically and empirically relations between a variety of system parameters (e.g.,  NA, wavelength, focal length, telecentricity) and achievable fields of view (FOVs) and importantly show that intrinsic tilt aberrations donotrestrict FOV for many multiview imaging applications, contrary to conventional wisdom. Finally, we present strategies for avoiding spherical aberrations at obliquely illuminated flat boundaries. Our simple designs allow for high-speed multiangle imaging for microscopic, mesoscopic, and macroscopic applications.

 

We present a general theory of optical coherence tomography (OCT), which synthesizes the fundamental concepts and implementations of OCT under a common 3D$k$-space framework. At the heart of this analysis is the Fourier diffraction theorem, which relates the coherent interaction between a sample and plane wave to the Ewald sphere in the 3D$k$-space representation of the sample. While only the axial dimension of OCT is typically analyzed in$k$-space, we show that embracing a fully 3D$k$-space formalism allows explanation of nearly every fundamental physical phenomenon or property of OCT, including contrast mechanism, resolution, dispersion, aberration, limited depth of focus, and speckle. The theory also unifies diffraction tomography, confocal microscopy, point-scanning OCT, line-field OCT, full-field OCT, Bessel beam OCT, transillumination OCT, interferometric synthetic aperture microscopy (ISAM), and optical coherence refraction tomography (OCRT), among others. Our unified theory not only enables clear understanding of existing techniques but also suggests new research directions to continue advancing the field of OCT.

 

Anterior uveitis is the most common form of intraocular inflammation, and one of its main signs is the presence of white blood cells (WBCs) in the anterior chamber (AC). Clinically, the true composition of cells can currently only be obtained using AC paracentesis, an invasive procedure to obtain AC fluid requiring needle insertion into the AC. We previously developed a spectroscopic optical coherence tomography (SOCT) analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, bothin vitroand in ACs of excised porcine eyes. We have shown that different types of WBCs have distinct characteristic size distributions, extracted from the backscattered reflectance spectrum of individual cells using Mie theory. Here, we further develop our method to estimate the composition of blood cell mixtures, bothin vitroandin vivo. To do so, we estimate the size distribution of unknown cell mixtures by fitting the distribution observed using SOCT with a weighted combination of reference size distributions of each WBC type calculated using kernel density estimation. We validate the accuracy of our estimation in anin vitrostudy, by comparing our results for a given WBC sample mixture with the cellular concentrations measured by a hemocytometer and SOCT images before mixing. We also conducted a smallin vivoquantitative cell mixture validation pilot study which demonstrates congruence between our method and AC paracentesis in two patients with uveitis. The SOCT based method appears promising to provide quantitative diagnostic information of cellular responses in the ACs of patients with uveitis.

 

In optical coherence tomography (OCT), the axial resolution is often superior to the lateral resolution, which is sacrificed for long imaging depths. To address this anisotropy, we previously developed optical coherence refraction tomography (OCRT), which uses images from multiple angles to computationally reconstruct an image with isotropic resolution, given by the OCT axial resolution. On the other hand, spectroscopic OCT (SOCT), an extension of OCT, trades axial resolution for spectral resolution and hence often has superior lateral resolution. Here, we present spectroscopic OCRT (SOCRT), which uses SOCT images from multiple angles to reconstruct a spectroscopic image with isotropic spatial resolution limited by the OCTlateralresolution. We experimentally show that SOCRT can estimate bead size based on Mie theory at simultaneously high spectral and isotropic spatial resolution. We also applied SOCRT to a biological sample, achieving axial resolution enhancement limited by the lateral resolution.