Zhuolin Liu

Ultrahigh-speed multimodal adaptive optics system for microscopic structural and functional imaging of the human retina

, , , ,

We describe the design and performance of a multimodal and multifunctional adaptive optics (AO) system that combines scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) for simultaneous retinal imaging at 13.4 Hz. The high-speed AO-OCT channel uses a 3.4 MHz Fourier-domain mode-locked (FDML) swept source. The system achieves exquisite resolution and sensitivity for pan-macular and transretinal visualization of retinal cells and structures while providing a functional assessment of the cone photoreceptors. The ultra-high speed also enables wide-field scans for clinical usability and angiography for vascular visualization. The FDA FDML-AO system is a powerful platform for studying various retinal and neurological diseases for vision science research, retina physiology investigation, and biomarker development

Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes

, , , , , , ,

Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes Objective quantification of photoreceptor cell morphology, such as cell diameter and outer segment length, is crucial for early, accurate, and sensitive diagnosis and prognosis of retinal neurodegenerative diseases. Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional (3-D) visualization of photoreceptor cells in the living human eye. The current gold standard for extracting cell morphology from AO-OCT images involves the tedious process of 2-D manual marking. To automate this process and extend to 3-D analysis of the volumetric data, we propose a comprehensive deep learning framework to segment individual cone cells in AO-OCT scans. Our automated method achieved human-level performance in assessing cone photoreceptors of healthy and diseased participants captured with three different AO-OCT systems representing two different types of point scanning OCT: spectral domain and swept source.

Weakly supervised individual ganglion cell segmentation from adaptive optics OCT images for glaucomatous damage assessment

, , , , , , ,

Cell-level quantitative features of retinal ganglion cells (GCs) are potentially important biomarkers for improved diagnosis and treatment monitoring of neurodegenerative diseases such as glaucoma, Parkinson’s disease, and Alzheimer’s disease. Yet, due to limited resolution, individual GCs cannot be visualized by commonly used ophthalmic imaging systems, including optical coherence tomography (OCT), and assessment is limited to gross layer thickness analysis. Adaptive optics OCT (AO-OCT) enables in vivo imaging of individual retinal GCs. We present an automated segmentation of GC layer (GCL) somas from AO-OCT volumes based on weakly supervised deep learning (named WeakGCSeg), which effectively utilizes weak annotations in the training process. Experimental results show that WeakGCSeg is on par with or superior to human experts and is superior to other state-of-the-art networks. The automated quantitative features of individual GCLs show an increase in structure–fun...

Integrating adaptive optics-SLO and OCT for multimodal visualization of the human retinal pigment epithelial mosaic

, , , , , , , , , , ,

In vivo imaging of human retinal pigment epithelial (RPE) cells has been demonstrated through multiple adaptive optics (AO)-based modalities. However, whether consistent and complete information regarding the cellular structure of the RPE mosaic is obtained across these modalities remains uncertain due to limited comparisons performed in the same eye. Here, an imaging platform combining multimodal AO-scanning light ophthalmoscopy (AO-SLO) with AO-optical coherence tomography (AO-OCT) is developed to make a side-by-side comparison of the same RPE cells imaged across four modalities: AO-darkfield, AO-enhanced indocyanine green (AO-ICG), AO-infrared autofluorescence (AO-IRAF), and AO-OCT. Co-registered images were acquired in five subjects, including one patient with choroideremia. Multimodal imaging provided multiple perspectives of the RPE mosaic that were used to explore variations in RPE cell contrast in a subject-, location-, and even cell-dependent manner. Estimated cell-to-cell ...

Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics

, , , ,

Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question. Here we examine key characteristics of retinal macrophage cells in live human eyes, both healthy and diseased, with the unique capabilities of our adaptive optics–optical coherence tomography approach and owing to their propitious location above the inner limiting membrane (ILM), allowing direct visualization of cells. Our findings indicate that human ILM macrophage cells may be distributed distinctly, age differently, and have different dynamic characteristics than microglia in other animals. For example, we observed a macular pattern that was sparse cent...

Post-doctoral Adaptive Optics Research Fellow at US Food and Drug Administration

Summary of information: Post-doctoral Adaptive Optics Research Fellow Seeking a highly motivated post-doctoral Adaptive Optics Research Fellow to work at the U.S. Food and Drug Administration, Center for Devices and Radiological Health. The candidate will work in the Division of Biomedical Physics under the direction of Drs. Zhuolin Liu and Daniel X. Hammer, and perform research with the FDA multimodal adaptive optics (mAO) imager. The FDA mAO imaging system has allowed visualization of different retinal cells, including the retinal ganglion cells. The candidate will be expected to: conduct human imaging in healthy and diseased eyes, perform data processing, analysis and presentation, upgrade of AO imagers, fabricate of AO model eyes, and assess imaging quality and performance of AO-enhanced ophthalmic devices. The ideal candidate will have a PhD in optics, biomedical engineering, or other engineering with strong knowledge and experience in vision science and ophthalmology. The well...

Direct laser writing of a titanium dioxide-laden retinal cone phantom for adaptive optics-optical coherence tomography

, , , , , ,

The spatial resolution of adaptive optics-optical coherence tomography (AO-OCT) enables visualization of retinal components ( e.g ., photoreceptors), which can advance clinical diagnosis of ocular diseases. Currently, however, variability in AO-OCT system performance suggests a need for standardized physical models, or “phantoms”, that replicate the opto-structural properties of retinal components. Here we employ direct laser writing – a two-photon polymerization-based additive manufacturing technology – using a light scattering titanium (IV) dioxide nanoparticle-laden photomaterial to create novel retinal cone outer segment (OS) phantoms. Fabrication results demonstrate effective mimicry of cone OS diameter and spacing at four retinal eccentricities, while AO-OCT experiments demonstrate cone spacings >4 µ m can be resolved. These results suggest a promising methodology for biomimetic photoreceptor phantom development for AO-OCT. ( Read Full Arti...

Post-doctoral Adaptive Optics Research Fellow at U.S. Food and Drug Administration

Seeking a highly motivated post-doctoral Adaptive Optics Research Fellow to work at the U.S. Food and Drug Administration, Center for Devices and Radiological Health. The candidate will work in the Division of Biomedical Physics under the direction of Drs. Zhuolin Liu and Daniel X. Hammer and perform research with the FDA multimodal adaptive optics (mAO) imager. The FDA mAO imaging system allows visualization of different retinal cells, including ganglion cells, retinal pigment epithelial cells, and photoreceptors. The candidate will be expected to: conduct human imaging in healthy and diseased eyes, perform data processing, analysis and presentation, develop new and upgrade existing AO imagers, fabricate AO model eyes, and assess imaging quality and performance of AO-enhanced ophthalmic devices. The ideal candidate will have a PhD in optics, biomedical engineering, or other engineering with strong knowledge and experience in vision science and ophthalmology. The well- equipped DBP ...

3-D printed photoreceptor phantoms for evaluating lateral resolution of adaptive optics imaging systems

, , , , ,

With adaptive optics (AO), optical coherence tomography and scanning laser ophthalmoscopy imaging systems can resolve individual photoreceptor cells in living eyes, due to enhanced lateral spatial resolution. However, no standard test method exists for experimentally quantifying this parameter in ophthalmic AO imagers. Here, we present three-dimensional (3-D) printed phantoms, which enable the measurement of lateral resolution in an anatomically relevant manner. We used two-photon polymerization to fabricate two phantoms, which mimic the mosaic of cone photoreceptor outer segments at multiple retinal eccentricities. With these phantoms, we demonstrated that the resolution of two multimodal AO systems is similar to theoretical predictions, with some intriguing speckle effects. ( Read Full Article )

Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

, , , ,

The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellula...

Imaging and quantifying ganglion cells and other transparent neurons in the living human retina [Engineering]

, , , ,

Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency. Failure of conventional imaging—using predominately singly scattered light—to reveal GCs has led to a focus on multiply-scattered, fluorescence, two-photon, and phase imaging techniques to enhance GC contrast. Here, we show that singly scattered light actually carries substantial information that reveals GC somas, axons, and other retinal neurons and permits their quantitative analysis. We perform morphometry on GC layer somas, including projection of GCs...

OPTICAL PROPERTIES OF PHOTORECEPTOR AND RETINAL PIGMENT EPITHELIUM CELLS INVESTIGATED WITH ADAPTIVE OPTICS OPTICAL COHERENCE TOMOGRAPHY (Thesis)

Human vision starts when photoreceptors collect and respond to light. Photoreceptors do not function in isolation though, but share close interdependence with neighboring photoreceptors and underlying retinal pigment epithelium (RPE) cells. These cellular interactions are essential for normal function of the photoreceptor-RPE complex, but methods to assess these in the living human eye are limited. One approach that has gained increased promise is highresolution retinal imaging that has undergone tremendous technological advances over the last two decades to probe the living retina at the cellular level. Pivotal in these advances has been adaptive optics (AO) and optical coherence tomography (OCT) that together allow unprecedented spatial resolution of retinal structures in all three dimensions. Using these highresolution systems, cone photoreceptor are now routinely imaged in healthy and diseased retina enabling fundamental structural properties of cones to be studied such as cell ...

Tracking dynamics of photoreceptor disc shedding with adaptive optics-optical coherence tomography

, , ,

Absorption of light by photoreceptors initiates vision, but also leads to accumulation of toxic photo-oxidative compounds in the photoreceptor outer segment (OS). To prevent this buildup, small packets of OS discs are periodically pruned from the distal end of the OS, a process called disc shedding. Unfortunately dysfunction in any part of the shedding event can lead to photoreceptor and RPE dystrophy, and has been implicated in numerous retinal diseases, including age related macular degeneration and retinitis pigmentosa. While much is known about the complex molecular and signaling pathways that underpin shedding, all of these advancements have occurred in animal models using postmortem eyes. How these translate to the living retina and to humans remain major obstacles. To that end, we have recently discovered the optical signature of cone OS disc shedding in the living human retina, measured noninvasively using optical coherence tomography equipped with adaptive optics in conjunc...

Adaptive optics optical coherence tomography angiography for morphometric analysis of choriocapillaris [Invited]

, ,

Histological studies have shown that morphometric changes at the microscopic level of choriocapillaris (CC) occur with aging and disease onset, and therefore may be sensitive biomarkers of outer retinal health. However, visualizing CC at this level in the living human eye is challenging because its microvascular is tightly interconnected and weakly reflecting. In this study, we address these challenges by developing and validating a method based on adaptive optics optical coherence tomography with angiography (AO-OCTA) that provides the necessary 3D resolution and image contrast to visualize and quantify these microscopic details. The complex network of anastomotic CC capillaries was successfully imaged in nine healthy subjects (26 to 68 years of age) and at seven retinal eccentricities across the macula. Using these images, four fundamental morphometric parameters of CC were characterized: retinal pigment epithelium-to-CC depth separation (17.5 ± 2.1 µm), capillary dia...

Photoreceptor disc shedding in the living human eye

, , , , ,

Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of she...

Categories

Organizations in the News

OCT Companies in the News

Picture Gallery