KEYWORDS: Eye, Hemodynamics, Retina, Imaging systems, In vivo imaging, Cameras, Optical coherence tomography, Signal to noise ratio, Neurophotonics, Tunable filters
SignificanceMicrocirculation and neurovascular coupling are important parameters to study in neurological and neuro-ophthalmic conditions. As the retina shares many similarities with the cerebral cortex and is optically accessible, a special focus is directed to assessing the chorioretinal structure, microvasculature, and hemodynamics of mice, a vital animal model for vision and neuroscience research.AimWe aim to introduce an optical imaging tool enabling in vivo volumetric mouse retinal monitoring of vascular hemodynamics with high temporal resolution.ApproachWe translated the spatio-temporal optical coherence tomography (STOC-T) technique into the field of small animal imaging by designing a new optical system that could compensate for the mouse eye refractive error. We also developed post-processing algorithms, notably for the assessment of (i) localized hemodynamics from the analysis of pulse wave–induced Doppler artifact modulation and (ii) retinal tissue displacement from phase-sensitive measurements.ResultsWe acquired high-quality, in vivo volumetric mouse retina images at a rate of 113 Hz over a lateral field of view of ∼500 μm. We presented high-resolution en face images of the retinal and choroidal structure and microvasculature from various layers, after digital aberration correction. We were able to measure the pulse wave velocity in capillaries of the outer plexiform layer with a mean speed of 0.35 mm/s and identified venous and arterial pulsation frequency and phase delay. We quantified the modulation amplitudes of tissue displacement near major vessels (with peaks of 150 nm), potentially carrying information about the biomechanical properties of the retinal layers involved. Last, we identified the delays between retinal displacements due to the passing of venous and arterial pulse waves.ConclusionsThe developed STOC-T system provides insights into the hemodynamics of the mouse retina and choroid that could be beneficial in the study of neurovascular coupling and vasculature and flow speed anomalies in neurological and neuro-ophthalmic conditions.
We present a novel ultrafast imaging system using Spatio-Temporal Optical Coherence Tomography (STOC-T), capable of acquiring structural images of a mouse retina at a volumetric rate of 112 Hz, aided by a calibrated fundus camera for focal plane adjustment. We extract blood pulse traces from retinal and choroidal vessels using a structural-only OCT analysis, and pulse wave-induced retinal layer displacement from differential OCT phase analysis. With both analyses, we measure hemodynamic parameters, such as the delays between arterial and venous pulsation, to provide a comprehensive suite of potential biomarkers of retinal diseases.
We applied spatio-temporal optical coherence tomography (STOC-T) method, supported by computational aberration correction for high resolution in vivo imaging of the human retina. Here, we demonstrate a modified STOC-T experimental system, with an increased lateral resolution of ~3 µm, and optimized illumination to enable rendering of the retinal ganglion cells. We present high resolution en face images of the human retina NFL and GCL layers.
We report Spatio-Temporal Optical Coherence Tomography (STOC-T) for acquiring optoretinography-based comprehensive characterization of retinal tissue response to flickering light across a broad spectrum (5Hz to 45Hz). This approach involves the introduction of frequency chirp during stimulation, offering a more practical means of assessing the frequency traits of photoreceptors. Our technique unveiled notable variations in response amplitudes between two subjects, both in the context of diverse stimulus amplitudes and when comparing responses to both rectangular and sinusoidal stimuli. This innovative method establishes a path for the unbiased identification of temporal-contrast sensitivity functions, exclusively focused on photoreceptors.
The progress made in optical coherence tomography (OCT) has facilitated the noninvasive observation of biological structures. While Fourier-Domain Full-Field OCT (FD-FF-OCT) enables rapid collection of volumetric data, it encounters challenges arising from coherent noise. To tackle this issue, we introduced STOC-T ľ spatial-temporal optical coherence tomography, which utilizes spatial phase modulation alleviate crosstalk interference. This research thoroughly investigates the characteristics of optical fibers in the context of STOC-T, crafted for volumetric imaging and the mitigation of coherent crosstalk noise. We assess the effects of multimode fibers and execute a performance analysis employing a purpose-designed scattering phantom. Our presentation encompasses detailed insights into the experimental arrangement and outcomes, emphasizing noise reduction. We also explore hurdles like determining the ideal fiber length, analyzing speckle patterns, and ensuring signal quality. Through a meticulous selection process of multimode fibers, we amplify the potential of STOC-T for structural and functional retinal imaging.
We present a novel ultrafast imaging system using Spatio-Temporal Optical Coherence Tomography (STOC-T), capable of acquiring structural images of a mouse retina at a volumetric rate of 112 Hz. A calibrated fundus camera and white-light illumination aid the alignment of the mouse and the adjustment of the focal plane in the mouse retina for the STOC-T image. We extract pulsatile blood flow frequency and other hemodynamic parameters from multiple retinal and choroidal vessels from structural-only OCT images, highlighting the prospects of STOC-T for monitoring retinal hemodynamics in a simple way.
We present an optical imaging system, termed Spatio-Temporal Optical Coherence Tomography, for high-resolution and fast in vivo imaging of chorioretinal complex. The system utilizes a fast camera and a swept laser source for fast volumetric data acquisition. A multimode fiber is used to break the spatial coherence of the laser that reduces the crosstalk noise in the OCT images. We choose the fiber parameters such that it gives the most optimal images in terms of signal strength, resolution and crosstalk reduction. We also test combinations of the fiber with other optomechanical devices in the attempt to further improve the images.
We developed and applied Spatio-Temporal Optical Coherence Tomography (STOC-T), which supported by computational aberration correction enables high resolution imaging of the human and mouse retina in vivo.
Spatio-Temporal Optical Coherence Tomography (STOC-T) is a new imaging modality that uses light with controlled spatial and temporal coherence. The retinal images acquired with the STOC-T system maintain high resolution in all three dimensions, over the entire thickness of about 700 μm, without mechanical scanning. We have employed known data processing algorithms and developed new ones to handle and process the acquired data sets to produce highly corrected 3D data for retinas over large fields of view. The technology and algorithms used here enabled high transverse resolution imaging of the retina and the choroid at various depths, making the differentiation of morphology visible for the first time within the Sattler’s, Haller’s, and choriocapillaris layers. Visualization of choroidal layers was carried out by using the STOCT angio algorithm. We analyzed the acquired data quantitatively to identify an effective biomarker.
We use Spatio-Temporal Optical Coherence Tomography (STOC-T) to record flicker ORG signals. The chirped frequency stimulus (5 Hz to 45 Hz) provides a more convenient way of measuring photoreceptors' frequency characteristics. Our method detected significant differences in response amplitudes in two measured subjects when comparing responses to different stimulus amplitudes as well as when comparing responses to rectangular and sinusoidal stimulation.
We present a novel mouse eye imaging system based on the Spatio-Temporal Optical Coherence Tomography (STOC-T) technique capable of acquiring structural image of a mouse retina at a volumetric rate of 112 Hz. A fundus camera and white light illumination aid the alignment of the mouse and the adjustment of the focal plane in the mouse retina for the STOC-T image. The fundus camera is calibrated so that when the white-light image of the mouse eye fundus appears in focus after the appropriate gel thickness is selected for a given mouse and bi-concave lens, the corresponding near infrared STOC-T image of the photoreceptor layer is also in focus, albeit with minor shifts. We present images of retinal and choroidal tissue from a B6 albino wild type mouse after the focal plane adjustment with richness of details.
We present results from measurements of retina response to a chirped frequency flickering light. Such an approach facilitates faster characterization of photoreceptor response amplitude in the function of stimulus frequency in comparison to separate measurements at different frequencies. In our work, we compare responses to stimuli of various types (e.g., different flicker amplitudes) in the frequency range from 5 Hz to 45 Hz.
We report on a novel mice imaging system based on the Spatio-Temporal Optical Coherence Tomography (STOC-T)
technique. The contribution describes the translation of the STOC-T technique, initially developed for human eye imaging, into the field of experimental small animal imaging. We present images of retinal and choroidal tissue from a B6 albino wild type mouse acquired at a volumetric rate of 112 Hz.
Critical flicker frequency measurements are important in determining the spatial variation of flicker sensitivity in the human retina. An objective and localized measurement of the frequency response of photoreceptors could help elucidate the true physiological mechanisms responsible for such flicker sensitivity variations. Flicker optoretinography (ORG) may be a promising technique for this purpose. In this work, we use Spatio-Temporal Optical Coherence-Tomography to capture flicker optoretinograms to visible patterned light stimulation modulated in the range from few Hz to 30Hz over 5.7º x 2.8º of the retina, at several foveal eccentricities, highlighting the prospect for objective flicker perimetry with ORG.
We recently demonstrated high-speed, high-resolution structural imaging of the human eye in vivo by spatiotemporal optical coherence tomography (STOC-T). STOC-T extends the Fourier-Domain Full-Field Optical Coherence Tomography (FD-FF-OCT) by the spatial phase modulation to improve the imaging depth and suppress coherent noises.
Here, we show that the dataset produced by STOC-T can be processed differently to reveal blood flow in the superficial and deep retina layers. Our method, denoted as multiwavelength LDH (MLDH) enables noninvasive visualization and quantification of the blood flow deep into the human retina at high speeds and high transverse resolution in vivo.
In this contribution, we report on in vivo retinal and choroid tissue imaging with Spatio-Temporal Optical Coherence Tomography (STOC-T) with a large field of view (9 x 4.6 mm2). We present en-face images of the retina's microstructure and choroid of the human eye with resolution enabling observation of single photoreceptors and choriocapillaris.
Despite the rapid development of OCT, high-resolution in vivo imaging of human eye with penetration into deeper retinal layers and choroid is still a major challenge due to its sensitivity to coherent noise, such as speckle and crosstalk. To address that, we have developed a technique termed Spatio-Temporal Optical Coherence Tomography (STOC-T) that uses light with controlled spatial and temporal coherence to obtain high-contrasted coronal projection images of the choroid at various depths including that of choriocapillaris. It can also detect blood flow and reveal vascular networks in various chorioretinal layers that are otherwise invisible to OCT.
Photoreceptors are the primary sensing element of the human visual system. Traditionally, photoreceptors are imaged with hardware-based adaptive optics (AO), which compensate for eye aberrations. However, these systems can be challenging to maintain. Here, we demonstrate the spatiotemporal optical coherence tomography
(STOC-T) as the new modality for high-speed, cellular-level volumetric imaging of the human retina in vivo. The cellular features become visible after applying digital aberration corrections. We also show that STOC-T provides cross-sectional images (B-scans) and, concurrently, high-resolution wide-field en face images of the inner and outer human retina layers.
We report results from in-vivo measurements of a human retina photoreceptors layer response to a flicker stimulus. We performed our experiments with the Spatio-Temporal Optical Coherence-Tomography (STOC-T) setup. We show that the phase analysis facilitates spatially resolved detection of the retina's response to different stimulus frequencies.
Spatiotemporal optical coherence (STOC) manipulation is a new method for crosstalk-free, aberration-free, high-speed, high-resolution imaging of the human eye in vivo. Here, we apply STOC for deep blood flow imaging of the human retina in vivo.
KEYWORDS: Spatial coherence, Optical coherence tomography, Eye, Cameras, Retina, Data acquisition, Line scan cameras, In vivo imaging, Ultrafast imaging, Sensors
We characterize the engineering of spatial coherence for STOC-T. We present large field-of-view (9x4.6 mm) images of the retina's microstructure and choroid of the human eye with resolution enabling observation of single photoreceptors and choriocapillaries.
KEYWORDS: Optical coherence tomography, Retina, Data acquisition, In vivo imaging, Digital micromirror devices, Optical testing, Optical filters, Multimode fibers, Light emitting diodes, Imaging systems
In this paper, we present in vivo optoretinography using a Spatio-Temporal Optical Coherence Tomography STOC-T setup. With our system, we were able to detect both fast and slow responses to a light stimulus.
We present an optical imaging system, termed STOC-T, for retinal in vivo imaging that uses a multimode fiber for crosstalk noise reduction and a line camera for fast preview mode.
We apply spatiotemporal optical coherence (STOC) manipulation with digital aberration correction to achieve aberration-free, crosstalk-free, high-speed, high-resolution Fourier-domain full-field optical coherence tomography (FD-FF-OCT). We demonstrate structural imaging of the human retina and cornea, and the blood flow imaging of the human retina in vivo.
Spatiotemporal optical coherence (STOC) imaging is a novel technique for suppressing coherent cross-talk noise in full-field swept-source OCT (FF-SS-OCT). In STOC, we use time-varying phase masks to modulate light incident on the sample. The modulated signals are averaged incoherently or coherently to yield cross-talk-free 3D images of the sample. We show that coherent averaging is only possible under specific hardware configuration. We explain this theoretically and confirm experimentally by imaging USAF chart covered by diffusers and the rat skin ex vivo. Finally, we present human forearm skin imaging in vivo. In all cases, STOC imaging reveals otherwise invisible sample features.
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