Rods contribute crucially to human vision and their dysfunction precedes cones' in several retinal diseases. Here we describe light-evoked, functional responses of human rods and cones, measured noninvasively using adaptive optics optical coherence tomography.
It has been recently demonstrated that structures corresponding to the cell bodies of highly transparent cells in the retinal ganglion cell layer could be visualized noninvasively in the living human eye by optical coherence tomography (OCT) via temporal averaging. Inspired by this development, we explored the application of volumetric temporal averaging in mice, which are important models for studying human retinal diseases and therapeutic interventions. A general framework of temporal speckle-averaging (TSA) of OCT and optical coherence tomography angiography (OCTA) is presented and applied to mouse retinal volumetric data. Based on the image analysis, the eyes of mice under anesthesia ...
We describe the details of a multimodal retinal imaging system which combines adaptive optics (AO) with an integrated scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT) imaging system. The OCT subsystem consisted of a swept-source, Fourier-domain mode-locked (FDML) laser, with a very high A-scan rate (1.6 MHz), whose beam was raster scanned on the retina by two scanners—one resonant scanner and one galvanometer. The high sweep rate of the FDML permitted the SLO and OCT to utilize the same scanners for in vivo retinal imaging and, unlike existing multimodal systems, concurrently acquired SLO frames and OCT volumes ...
Optical coherence tomography (OCT) is a powerful tool in ophthalmology that provides in vivo morphology of the retinal layers and their light scattering properties. The directional (angular) reflectivity of the retinal layers was investigated with focus on the scattering from retinal pigment epithelium (RPE). The directional scattering of the RPE was studied in three mice strains with three distinct melanin concentrations: albino (BALB/c), agouti (129S1/SvlmJ), and strongly pigmented (C57BL/6J). The backscattering signal strength was measured with a directional OCT system in which the pupil entry position of the narrow OCT beam can be varied across the dilated ...
Functional assessment of the retina is a critical part of both clinical ophthalmology and vision research. Several techniques exist for measuring retinal function, such as Visual acuity/contrast sensitivity tests, Psychophysics and ERG (Electroretinogram and multifocal Electroretinogram). However, these approaches have important limitations, poor spatial resolution, slightly invasive; long duration of tests. There is great excitement about emerging noninvasive approaches to measuring retinal function, both from clinical and basic scientific perspectives .With emerging approaches such as gene therapy, stem cell therapy, and transplantation, there is new hope for rescuing existing dysfunctional photoreceptors. A critical aspect of these therapeutic approaches is ...
Objective optical assessment of photoreceptor function may permit earlier diagnosis of retinal disease than current methods such as perimetry, electrophysiology, and clinical imaging. In this work, we describe an adaptive optics (AO) optical coherence tomography (OCT) system designed to measure functional responses of single cones to visible stimuli. The OCT subsystem consisted of a raster-scanning Fourier-domain mode-locked laser that acquires A scans at 1.64 MHz with a center wavelength of 1063 nm and an AO system operating in closed-loop. Analysis of serial volumetric images revealed phase changes of cone photoreceptors consistent with outer segment elongation and proportional to stimulus ...
Speckle is an inevitable consequence of the use of coherent light in imaging and acts as noise that corrupts image formation in most applications. Optical coherence tomographic imaging, as a technique employing coherence time gating, suffers from speckle. We present here a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) for confocal coherent imaging: modulation of the phase in the system pupil aperture with a segmented deformable mirror (DM) to introduce minor perturbations in the point spread function. This approach creates uncorrelated speckle patterns in a series of images, enabling averaging to suppress speckle noise while ...
Angiographic imaging of the human eye with optical coherence tomography (OCT) is becoming an increasingly important tool in the scientific investigation and clinical management of several blinding diseases, including age-related macular degeneration and diabetic retinopathy. We have observed that OCT angiography (OCTA) of the human choriocapillaris and choroid with a 1.64 MHz A-scan rate swept-source laser yields higher contrast images as compared to a slower rate system operating at 100 kHz. This result is unexpected because signal sensitivity is reduced when acquisition rates are increased, and the incident illumination power is kept constant. The contrast of angiography images generated ...
In retinal raster imaging modalities, fixational eye movements manifest as image warp, where the relative positions of the beam and retina change during the acquisition of single frames. To remove warp artifacts, strip-based registration methods–in which fast-axis strips from target images are registered to a reference frame–have been applied in adaptive optics (AO) scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT). This approach has enabled object tracking and frame averaging, and methods have been described to automatically select reference frames with minimal motion. However, inconspicuous motion artifacts may persist in reference frames and propagate themselves throughout the ...
Speckle is an inevitable consequence of the use of coherent light in optical coherence tomography (OCT), and often acts as noise that obscures micro-structures of biological tissue. We here present a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) in OCT system: by modulating the phase inside the imaging system pupil aperture with a segmented deformable mirror, thus producing minor perturbations in the point spread function (PSF) to create un-correlated speckle pattern between B-scans, and further averaging to wash out the speckle but maintain the structures. It is a well-controlled and universal method which can efficiently ...
bjective optical assessment of photoreceptor function may permit earlier diagnosis of retinal disease than current methods such as perimetry, electrophysiology, and clinical imaging. In this work, we describe an adaptive optics (AO) optical coherence tomography (OCT) system designed to measure functional responses of single cones to visible stimuli. The OCT subsystem consisted of a raster-scanning Fourier-domain mode-locked laser that acquires A-scans at 1.64MHz with a center wavelength of 1063nm, and an AO subsystem providing diffraction-limited imaging. Analysis of serial volumetric images revealed phase changes of cone photoreceptors consistent with outer segment elongation and proportional to stimulus intensity, as well ...
Changes in visibility of the Henle fiber layer and photoreceptor bands of the human retina with illumination directionality have been reported in OCT clinical imaging. These are a direct consequence of the changes in back scattering due to fibrous tissue orientation and to waveguiding properties of the photoreceptors respectively. Here we report the preliminary results of a study on the effects of retinal images acquired with OCT of illumination directionality in the mouse retina. The quantitative assessment of the reflectivity of retinal layers of a BALB/c and WT pigmented mice was performed in-vivo using a swept-source optical coherence tomography ...
Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are two state-of-the-art imaging technologies commonly used to study retina. Adaptive Optics (AO) methodologies enable high-fidelity correction of ocular aberrations, resulting in improved resolution and sensitivity for both SLO and OCT systems. Here we present work integrating OCT into a previously described mouse retinal AO-SLO system, allowing simultaneous reflectance and fluorescence imaging. The new system allows simultaneous data acquisition of AO-SLO and AO-OCT, facilitating registration and comparison of data from both modalities. The system has data acquisition speed of 200 kHz A-scans/pixel, and high volumetric resolution.
We have designed and implemented a dual-mode adaptive optics (AO) imaging system that combines spectral domain optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) for in vivo imaging of the human retina. The system simultaneously acquires SLO frames and OCT B-scans at 60 Hz with an OCT volume acquisition time of 4.2 s. Transverse eye motion measured from the SLO is used to register the OCT B-scans to generate three-dimensional (3-D) volumes. Key optical design considerations include: minimizing system aberrations through the use of off-axis relay telescopes, conjugate pupil plane requirements, and the use of dichroic beam splitters ...
Purpose : Optical coherence tomography's (OCT) third outer retinal band has been attributed to the zone of interdigitation between RPE cells and cone outer segments. The purpose of this paper is to investigate the structure of this band with adaptive optics (AO)-OCT. Methods : Using AO-OCT, images were obtained from two subjects. Axial structure was characterized by measuring band 3 thickness and separation between bands 2 and 3 in segmented cones. Lateral structure was characterized by correlation of band 3 with band 2 and comparison of their power spectra. Band thickness and separation were also measured in a clinical OCT ...
The light responses of rod and cone photoreceptors have been studied electrophysiologically for decades, largely with ex vivo approaches that disrupt the photoreceptors’ subretinal microenvironment. Here we report the use of optical coherence tomography (OCT) to measure light-driven signals of rod photoreceptors in vivo. Visible light stimulation over a 200-fold intensity range caused correlated rod outer segment (OS) elongation and increased light scattering in wild-type mice, but not in mice lacking the rod G-protein alpha subunit, transducin (Gα t ), revealing these responses to be triggered by phototransduction. For stimuli that photoactivated one rhodopsin per Gα t the rod OS swelling ...
Applications are invited for post-doctoral researcher position in the field of Biomedical Imaging at UC Davis EyePod Small Animal Imaging Laboratory. The broad interest of our research group focuses on development of new in vivo cellular resolution multimodal retinal imaging instruments as well as novel data processing and analysis tools. The ideal candidate should have previous experience with retinal/microscopic imaging systems, including one of the following: adaptive optics (AO), OCT, SLO, multispectral imaging, fluorescence, etc. Basic knowledge of a programming language (e.g. C++, LabView, Matlab or Python) for maintaining of image acquisition and processing software is essential. Prior ...
Purpose : Optical coherence tomography (OCT) has enabled “virtual biopsy” of the living human retina, revolutionizing both basic retina research and clinical practice over the past 25 years. For most of those years, in parallel, adaptive optics (AO) has been used to improve the transverse resolution of ophthalmoscopes to foster in vivo study of the retina at the microscopic level. Here, we review work done over the last 15 years to combine the microscopic transverse resolution of AO with the microscopic axial resolution of OCT, building AO-OCT systems with the highest three-dimensional resolution of any existing retinal imaging modality. Methods : We ...
Optical coherence tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. Although the axial resolution of OCT system, which is a function of the light source bandwidth, is sufficient to resolve retinal features at a micrometer scale, the lateral resolution is dependent on the delivery optics and is limited by ocular aberrations. Through the combination of wavefront sensorless adaptive optics and the use of dual deformable transmissive optical elements, we present a compact lens-based OCT system at an imaging wavelength of 1060 nm for high ...
This case report uses phase-variance optical coherence tomographic angiography to demonstrate transient inner choroidal flow changes associated with acute posterior multifocal placoid pigment epitheliopathy. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is characterized by bilateral multiple placoid white-gray lesions of the posterior pole at the level of the retinal pigment epithelium (RPE) and/or choriocapillaris, which self-resolve with recovery of vision. 1 , 2 The etiology is unknown, but APMPPE has been associated with viral prodromes and vasculitis. The placoid lesions are thought to represent focal RPE inflammation or choriocapillaris ischemia based on fluorescein angiogram findings of early hypofluorescence and late ...
Applications are invited for post-doctoral research associate position in the UC Davis EyePod Small Animal Imaging Laboratory in the Department of Cell Biology and Human Anatomy at the UC Davis Main Campus. The goal of our research is to develop and translate the next generation in vivo cellular resolution multimodal retinal imaging instruments and data analysis tools and to apply them to disease mechanisms and therapeutic interventions that can be investigated in the eye. The ideal candidate will have strong skills in some combination of retinal/microscopic imaging modalities, including but not limited to adaptive optics (AO), OCT, SLO, multispectral ...
We compared the performance of three OCT angiography (OCTA) methods: speckle variance, amplitude decorrelation and phase variance for imaging of the human retina and choroid. Two averaging methods, split spectrum and volume averaging, were compared to assess the quality of the OCTA vascular images. All data were acquired using a swept-source OCT system at 1040 nm central wavelength, operating at 100,000 A-scans/s. We performed a quantitative comparison using a contrast-to-noise (CNR) metric to assess the capability of the three methods to visualize the choriocapillaris layer. For evaluation of the static tissue noise suppression in OCTA images we proposed ...
Applications are invited for a post-doctoral research associate position in the UC Davis EyePod Small Animal Imaging Laboratory in the Department of Cell Biology and Human Anatomy at the UC Davis Main Campus. The goal of our research is to develop and translate the next generation in vivo cellular resolution multimodal retinal imaging instruments and data analysis tools and to apply them to disease mechanisms and therapeutic interventions that can be investigated in the eye. The ideal candidate will have strong skills in some combination of retinal/microscopic imaging modalities, including but not limited to adaptive optics (AO), OCT, SLO ...
Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) provide complementary views of the retina, with the former collecting fluorescence data with good lateral but relatively low-axial resolution, and the latter collecting label-free backscattering data with comparable lateral but much higher axial resolution. To take maximal advantage of the information of both modalities in mouse retinal imaging, we have constructed a compact, four-channel, wide-field ( ∼ 50 deg ) system that simultaneously acquires and automatically coregisters three channels of confocal SLO and Fourier domain OCT data. The scanner control system allows “zoomed” imaging of a region of interest identified in a wide-field image ...
