SignificanceImaging deep structures with optical coherence tomography (OCT) is difficult in highly scattering biological tissue, such as the sclera. There is a need to visualize the suprachoroidal space and choroid through the sclera to study suprachoroidal drug delivery.AimWe aim to develop optical methods to image through the highly scattering sclera with a custom-built OCT system to visualize the suprachoroidal space and drug delivery within.ApproachWe developed a custom handheld OCT scanner to image the anterior segment and suprachoroidal space in ex vivo eye models. Tartrazine (Yellow 5) solution, which has been shown to optically clear biological tissue in the visible regime, was tested as a clearing agent to optimize near infrared OCT imaging through the sclera.ResultsTartrazine dramatically increased OCT signal return from the deeper sclera and choroid and thus enabled visualization of the suprachoroidal drug delivery after transscleral injection.ConclusionsWe demonstrated successful optical clearing of the thick, porcine sclera with a compact handheld OCT system to image the suprachoroidal space. We believe there is broader potential to use optical clearing with handheld OCT for a variety of previously inaccessible, highly scattering tissue samples.
In fields such as virtual/augmented reality, robotic vision, facial recognition, and biomedical imaging, the demand for accurate, fast coherent 3D surface imaging technology is increasing. However, current technologies like FMCW LiDAR have limitations in terms of low spectral bandwidth efficiency and high cost. We demonstrate a novel approach using synthetic wavelength phase unwrapping and line-scan off-axis holography. Our system achieved fast 3D surface imaging with a non-ambiguous depth range of 22.3mm. We validated system performance using a 3D-printed test target and a U.S. copper penny.
We demonstrate in vivo imaging with a robotically aligned OCT (RAOCT) platform that incorporates interchangeable imaging modules with integrated pupil tracking cameras. Our OCT imaging platform consisted of a fixed scan head mounted to a cooperative robot and interchangeable cornea and retinal imaging modules with their own integrated pupil cameras. We validated pupil tracking in both imaging modules (<11 µm accuracy, <±4.5 µm precision). We utilized this platform for in vivo imaging of multiple target tissues of interest in a single imaging session. This flexible design enables the ability to develop new imaging modules for new robotically aligned applications.
Extending OCT into meter-scale working distances has potential applications in robotic vision, surgical planning and assistance, and non-invasive medical imaging. However, long-range imaging significantly decreases the numerical aperture (NA) of the system unless a much larger aperture is used. This diminishes the signal and requires the use of Gaussian beam theory for accurate determination of the beam profile and focusing behavior. We demonstrate and experimentally validate theory for focusing a laser source to optimize both resolution and signal and discuss the impact of the “focal shift” effect in which the geometric focus of the objective and Gaussian beam waist diverge at low NA.
Microscope-integrated optical coherence tomography (MIOCT) is an emerging multimodal imaging technology in which live volumetric OCT (“4D-OCT”) is displayed simultaneous with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many visual cues not available in microscopy, but it cannot serve as a replacement due to lack of color features. In this work, we demonstrate progress toward a unified solution by fusion of data from both modalities, guided by segmented 3D features, yielding a more efficient visualization combining important cues from both modalities.
We present a flexible optical coherence tomography (OCT) imaging platform that allows for interchangeable imaging modules for specific target tissues of interest while meeting the requirements for robotically aligned OCT including integrated pupil tracking cameras. Our OCT imaging platform consisted of a fixed scan head (analogous to an SLR camera body) mounted to the robot and interchangeable anterior chamber (AC) and retinal imaging modules with their own integrated pupil cameras. We validated our system in both phantom and ex vivo porcine eyes. This flexible design enables the ability to develop new imaging modules for new robotically aligned applications.
Most point-scanning retinal imaging modalities use raster scan patterns, which can appear in the subject’s vision as a rapidly moving line and cause subject eye motion, resulting in motion artifacts that require a dedicated fixation target to mitigate. In our recent development of a spiral-scanning confocal scanning laser ophthalmoscope, we noticed that the spiral scan pattern is visible to the subject as a bullseye-like shape and hypothesized that it could function as a virtual fixation target. A pilot study confirms this hypothesis by showing that images acquired with spiral scan show less eye motion than images acquired with raster scan.
Adaptive optics optical coherence tomography (AO-OCT) has allowed for the reliable 3-D imaging of individual retinal cells. The current AO-OCT systems are limited to tabletop implementation due to their size and complexity. This work describes the design and implementation of the first dual modality handheld AO-OCT (HAOOCT) and scanning laser ophthalmoscope (SLO) probe to extend AO-OCT imaging to previously excluded patients. Simultaneous SLO imaging allows for tracking of imaging features for HAOOCT localization. Pilot experiments on stabilized and recumbent adults using HAOOCT, weighing only 665 grams, revealed the 3-D photoreceptor structure for the first time using a handheld AO-OCT/SLO device.
Optical coherence tomography (OCT) has wide application in medicine, particularly ophthalmology. In the anterior chamber of the eye, OCT can potentially image blood cells to monitor cellular response to injury or inflammation. However, low volumetric refresh rates limit OCT in applications that require the tracking of individual, moving cells. Therefore, we propose an efficient 3D cell tracking using adaptive scanning OCT. Adaptive scanning prioritizes capturing regions of interest that change from volume to volume. Using depth information from OCT A-scans, our cell tracking method successfully localized simulated cells across multiple OCT volumes.
Ophthalmic microsurgery involves the manipulation of thin, semi-transparent structures and has traditionally been performed using stereoscopic microscopes that provide an en face view of the surgical field. However, new therapeutic interventions such as subretinal injections require precise tool placement and dosing that are difficult to determine from the traditional microscope view. Optical coherence tomography (OCT) provides micron scale cross-sectional imaging and has become a gold standard in clinical ophthalmology settings, but its use in surgery has been more limited. The high-speed 400 kHz intraoperative system presented here provides valuable image guidance and quantitative metrics for a variety of human surgeries.
The incorporation of adaptive optics (AO) technology into ophthalmic imaging systems has enhanced the understanding of retinal structure and function and the progression of various retinal diseases in adults by allowing for the dynamic correction of ocular and/or system aberrations. However, the in vivo visualization of important human retinal microanatomy, including cone photoreceptors, has been largely limited to fully cooperative subjects who are able to fixate and/or sit upright for extended imaging sessions in large tabletop AO systems. Previously, we developed the first handheld AO scanning laser ophthalmoscope capable of 2-D imaging of cone photoreceptors in supine adults and infants. In this work, we present the design and fabrication of the first handheld AO optical coherence tomography (HAOOCT) probe capable of collecting high-resolution volumetric images of the human retina. We designed custom optomechanics to build a spectral domain OCT system with a compact form factor of 22 cm × 18 cm × 5.2 cm and a total weight of 630 grams. The OCT imaging channel has a theoretical lateral resolution of 2.26 μm over a 1.0° × 1.0° field of view and an axial resolution of 4.01 μm. Stabilized imaging of healthy human adult volunteers revealed the 3-D photoreceptor structure and retinal pigment epithelium cells. HAOOCT was then deployed in handheld operation to image photoreceptors in upright and recumbent adults, indicating its potential to extend AO-OCT to previously excluded patient populations.
We present a portable confocal scanning laser ophthalmoscope (cSLO) for high-resolution, widefield retinal imaging that uses a low-backreflection double-clad fiber for both illumination and collection to maintain robust alignment of confocal pinholes in a handheld form factor. The cSLO uses a new type of "hybrid spiral" scan pattern that is a hybridization of a constant angular velocity spiral with a constant linear velocity spiral. The hybrid spiral offers efficiency advantages over traditional raster scan patterns while serving as a natural fixation target. Feasibility of the system is demonstrated by imaging a human volunteer.
Microscope-integrated optical coherence tomography (MIOCT) is an emerging multimodal imaging technology in which live volumetric OCT (“4D-OCT”) is displayed simultaneously with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many visual cues not available in microscopy, but it cannot serve as a replacement due to lack of color features. In this work, we demonstrate progress toward a unified solution by fusion of data from both modalities, guided by segmented 3D features, yielding a more efficient visualization combining important cues from both modalities.
Well-known limitations of optical coherence tomography (OCT) include deleterious speckle noise and relatively poor lateral resolution (typically >10 μm) due the tradeoff between lateral resolution and depth of focus. To address these limitations, we present 3D optical coherence refraction tomography (OCRT), which computationally combines 3D volumes from two rotational axes to form a 3D reconstruction with substantially reduced speckle noise and enhanced lateral resolution. Our approach features a parabolic mirror as the objective, which enables multi-view OCT volume acquisition over up to ±75° without moving the sample. We demonstrate 3D OCRT on a phantom sample and several biological samples, revealing new structures that are missed in conventional OCT.
FMCW depth imaging is a coherent 3D imaging modality analogous to SS-OCT. Due to constraints of mechanical steering mirrors, meter-scale FMCW depth cameras typically suffer from low data rates (<1Hz 3D map rate). Here, we describe the design and construction of a high-speed FMCW depth camera that employs a grating for beam steering and a telescope for angular FOV magnification. Our camera produces 3D depth maps at 33Hz, each consisting of 475x500 pixels, spanning a depth range of 32.8cm with sub-millimeter depth localization accuracy. Our FMCW depth camera is suitable for room-scale real-time 3D imaging applications, particularly computer vision applications.
Microscope-integrated optical coherence tomography (MIOCT) systems allow for 4D visualization of thin,
semi-transparent structures during ophthalmic microsurgery. While these visualizations have greatly
increased the information available to surgeons, new surgical techniques, such as subretinal injections of
gene therapies, would benefit from quantitative measurements of structures imaged using OCT. Calibration
of true scan dimensions in OCT is complicated by inter-patient ocular variability as well as poor control of
scanner-patient alignment. We introduce novel measurement techniques for calibration and de-warping of
OCT imagery which allows for accurate measurement of intraocular structures including subretinal
microinjection bleb volumes in the ocular posterior segment.
Ophthalmic surgery is typically performed through an en-face only surgical microscope that provides limited depth information. This work introduces a high speed (400 kHz) microscope integrated optical coherence tomography (MIOCT) system which provides real time volumetric “4D” visualization via a heads-up stereoscopic display. The MIOCT system provides sub retinal visualization of tools and enables surgeons to perform delicate manipulation of retinal structures during mock surgical procedures. Following these mock surgical procedures in porcine eyes, this system will be readily translated into human ophthalmic microsurgery.
Optical coherence tomography (OCT) allows for non-contact, high resolution, volumetric imaging of biological tissue and has become an indispensable ophthalmic imaging technique. However, conventional, commercial OCT systems require a cooperative, sitting patient typically stabilized by a head and/or chin rests. Additionally, current clinical systems are designed for imaging either the anterior or posterior segment of the eye exclusively. While these limitations are not severe in the ophthalmic clinic, they do limit the use of OCT in other more challenging medical environments where novel “whole eye” imaging could provide value, such as in the military theater or emergency department (ED). One solution to eliminate the need for a patient to sit upright and be stabilized during imaging would be a hand-held probe positioned and stabilized by the photographer or physician. Here we describe a hand-held OCT probe for simultaneous imaging of the anterior chamber (13.3 mm diameter field-of-view) and posterior segment (40° as measured from the pupil nodal point) simultaneously. The use of polarization multiplexing allows for two independent imaging channels which enable a wide posterior segment field-of-view and the ability to control the posterior segment path length and focal depth independently from the anterior chamber channel. Additionally, the probe was designed for a relatively compact form factor.
Confocal scanning laser ophthalmoscopy (cSLO) enables high-resolution and high-contrast imaging of the retina by employing spatial filtering for scattered light rejection. However, to obtain optimized image quality, one must design the cSLO around scanner technology limitations and minimize the effects of ocular aberrations and imaging artifacts. We describe a cSLO design methodology resulting in a simple, relatively inexpensive, and compact lens-based cSLO design optimized to balance resolution and throughput for a 20-deg field of view (FOV) with minimal imaging artifacts. We tested the imaging capabilities of our cSLO design with an experimental setup from which we obtained fast and high signal-to-noise ratio (SNR) retinal images. At lower FOVs, we were able to visualize parafoveal cone photoreceptors and nerve fiber bundles even without the use of adaptive optics. Through an experiment comparing our optimized cSLO design to a commercial cSLO system, we show that our design demonstrates a significant improvement in both image quality and resolution.
We present a novel optical coherence tomography (OCT) system design that employs coherence revival-based
heterodyning and polarization encoding to simultaneously image the ocular anterior segment and the retina. Coherence
revival heterodyning allows for multiple depths within a sample to be simultaneously imaged and frequency encoded by
carefully controlling the optical pathlength of each sample path. A polarization-encoded sample arm was used to direct
orthogonal polarizations to the anterior segment and retina. This design is a significant step toward realizing whole-eye
OCT, which would enable customized ray-traced modeling of patient eyes to improve refractive surgical interventions,
as well as the elimination of optical artifacts in retinal OCT diagnostics. We demonstrated the feasibility of this system
by acquiring images of the anterior segments and retinas of healthy human volunteers.
KEYWORDS: Spectroscopy, Optical coherence tomography, Doppler effect, Doppler tomography, Data acquisition, Signal to noise ratio, Velocity measurements, Signal attenuation, Imaging systems, Data centers
Recent advances in Doppler and variance techniques have enabled high sensitivity imaging in regions of
biological flow to measure blood velocities and vascular perfusion. In recent years, the sensitivity and imaging speed
benefits of Fourier domain OCT have become apparent. Spectrometer-based and wavelength-swept implementations
have both undergone rapid development. Comparative analysis of the potential benefits and limitations for the various
configurations would be useful for matching technology capabilities to specific clinical problems. Here we take a first
step in such a comparative analysis by presenting theoretical predictions and experimental results characterizing the
lower and upper observable velocity limits in spectrometer-based versus swept-source Doppler OCT. Furthermore, we
characterize the washout limit, the velocity at which signal degradation results in loss of flow information. We present
comparative results from phantom flow data as well as retinal data obtained with a commercial spectrometer OCT
system and a custom high-speed swept-source retinal OCT system.
The recent advent of ultra high frame rate cameras gives rise to the possibility of constructing swept source full-field
OCT systems with achievable volume rates approaching 10Hz and net A-scan rates approaching 10MHz. Unfortunately,
when illuminated with partially coherent light, full-field OCT in turbid media suffers resolution and SNR degradation
from coherent multiple scattering, a phenomenon commonly referred to as crosstalk. As a result, most FFOCT systems
employ thermal sources, which provide spatially incoherent illumination to achieve crosstalk rejection. However, these
thermal sources preclude the use of swept source lasers. In this work, we demonstrate the use of a carefully configured
FFOCT system employing multimode fiber in the illumination arm to reduce the spatial coherence of a partially coherent
source. By reducing the coherence area below the system resolution, the illumination becomes effectively spatially
incoherent and crosstalk is largely rejected. We compare FFOCT images of a USAF test chart positioned beneath both
transparent and turbid phantoms using both illumination schemes.
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