Donald T. Miller

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.

PhD Student Opening in Advanced Imaging at Indiana University

A PhD student position is available in Don Miller’s laboratory on advanced ophthalmic imaging at Indiana University (www.MillerImagingLab.org). The laboratory is looking for a highly motivated student in engineering, optical physics, or a related discipline with an interest to develop cutting-edge optical instrumentation to study noninvasively the retina at the cellular level. The laboratory’s primary focus is on the development and use of adaptive optics and optical coherence tomography, technologies the laboratory has been advancing for the past two decades. Some of our recent work can be found in PNAS: https://www.pnas.org/content/118/47/e2107444118, www.pnas.org/content/116/16/7951.short, andwww.pnas.org/content/114/48/12803.abstract. The student position is part of the IU Vision Science Graduate Program. The Program provides a vibrant and collegial environment and has existing strengths in visual optics, retinal Imaging, optical engineering, neur...

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...

Multi-reference global registration of individual A-lines in adaptive optics optical coherence tomography retinal images

, , , ,

Significance: Adaptive optics optical coherence tomography (AO-OCT) technology enables non-invasive, high-resolution three-dimensional (3D) imaging of the retina and promises earlier detection of ocular disease. However, AO-OCT data are corrupted by eye-movement artifacts that must be removed in post-processing, a process rendered time-consuming by the immense quantity of data. Aim: To efficiently remove eye-movement artifacts at the level of individual A-lines, including those present in any individual reference volume. Approach: We developed a registration method that cascades (1) a 3D B-scan registration algorithm with (2) a global A-line registration algorithm for correcting torsional eye movements and image scaling and generating global motion-free coordinates. The first algorithm corrects 3D translational eye movements to a single reference volume, accelerated using parallel computing. The second algorithm combines outputs of multiple runs of the first algorithm using differen...

Cellular Scale Imaging of Transparent Retinal Structures and Processes Using Adaptive Optics Optical Coherence Tomography

,

High-resolution retinal imaging is revolutionizing how scientists and clinicians study the retina on the cellular scale. Its exquisite sensitivity enables time-lapse optical biopsies that capture minute changes in the structure and physiological processes of cells in the living eye. This information is increasingly used to detect disease onset and monitor disease progression during early stages, raising the possibility of personalized eye care. Powerful high-resolution imaging tools have been in development for more than two decades; one that has garnered considerable interest in recent years is optical coherence tomography enhanced with adaptive optics. State-of-the-art adaptive optics optical coherence tomography (AO-OCT) makes it possible to visualize even highly transparent cells and measure some of their internal processes at all depths within the retina, permitting reconstruction of a 3D view of the living microscopic retina. In this review, we report current AO-OCT performanc...

PhD Opening at Indiana University

A PhD student position is available in Don Miller’s laboratory on advanced ophthalmic imaging at Indiana University (www.opt.indiana.edu/dtmiller/Index.aspx). The laboratory is looking for a highly motivated student in engineering, optical physics, or a related discipline with an interest to develop cutting-edge optical instrumentation to study noninvasively the retina at the cellular level. The laboratory’s primary focus is on the development and use of adaptive optics and optical coherence tomography, technologies the laboratory has been advancing for the past two decades. Some of our recent work can be found in PNAS: www.pnas.org/content/114/48/12803.abstract andwww.pnas.org/content/116/16/7951.short. The student position is part of the IU Vision Science Graduate Program. The Program includes a highly active group of multidisciplinary vision scientists, mostly from within the School of Optometry but also from Neuroscience, Psychology, Brain Science, Biology,...

Research Associate / Postdoctoral Fellow in Adaptive Optics and Optical Coherence Tomography at Indiana University

The Advanced Ophthalmic Imaging Laboratory at Indiana University is looking to fill a postdoctoral fellow or research associateposition. The successful candidate will join a team of scientists and engineers that are developing adaptive optics–optical coherence tomography (AO-OCT) for studying structure and function of the living human retina at the cellular level. The system is opening exciting new directions to study both normal and pathological vision. The laboratory (www.opt.indiana.edu/dtmiller/Index.aspx) is part of an active and well-funded community of vision scientists and engineers working in the areas of visual optics, retinal imaging, OCT, and adaptive optics. A major aim of the group is to create advanced optical instrumentation for eye research.  Indiana University is a major research university founded in 1820. It currently enrolls over 32,000 undergraduates and 7,500 graduate and professional students on the Bloomington campus with over 110,000 students in ...

Measuring polarization changes in the human outer retina with polarization‐sensitive optical coherence tomography

, , , ,

Morphological changes in the outer retina such as drusen are established biomarkers to diagnose age‐related macular degeneration. However, earlier diagnosis might be possible by taking advantage of more subtle changes that accompany tissues that bear polarization‐altering properties. To test this hypothesis, we developed a method based on polarization‐sensitive optical coherence tomography with which volumetric data sets of the macula were obtained from 10 young (<25 years) and 10 older (>54 years) subjects. All young subjects and 5 of the older subjects had retardance values induced by the retinal pigment epithelium and Bruch's membrane (RPE‐BM) complex that were just above the noise floor measurement (5°‐13° at 840 nm). In contrast, elevated retardance, up to 180°, was observed in the other 5 older subjects. Analysis of the degree of polarization uniformity (DOPU) demonstrates that reduced DOPU (<0.4) in the RPE is associated with elevated...

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...

Measuring polarization changes in the human outer retina with polarization-sensitive optical coherence tomography

, , , ,

Morphological changes in the outer retina such as drusen are established biomarkers to diagnose age-related macular degeneration. However earlier diagnosis might be possible by taking advantage of more subtle changes that accompany tissues that bear polarization-altering properties. To test this hypothesis, we developed a method based on polarization-sensitive optical coherence tomography with which volumetric data sets of the macula were obtained from 10 young (<25 yr) and 10 older (>54 yr) subjects. All young subjects and five of the older subjects had retardance values induced by the retinal pigment epithelium and Bruch's membrane (RPE-BM) complex that were just above the noise floor measurement (5°-13° at 840 nm). In contrast, elevated retardance, up to 180°, was observed in the other five older subjects. Analysis of the degree of polarization uniformity (DOPU) demonstrates that reduced DOPU (<0.4) in the RPE is associated with elevated double pass phase ret...

PhD Position in Advanced Ophthalmic Imaging at Indiana University

A PhD student position is available in Don Miller’s laboratory on advanced ophthalmic imaging at Indiana University (www.opt.indiana.edu/dtmiller/Index.aspx). The laboratory is looking for a highly motivated student in engineering, optical physics, or a related discipline with an interest  to develop cutting-edge optical instrumentation to study noninvasively the retina at the cellular level. The laboratory’s primary focus is on the development and use of adaptive optics and optical coherence tomography (AO-OCT) for high-resolution retinal imaging, technologies the laboratory has been advancing for almost two decades. Our most recent work can be found in PNAS: http://www.pnas.org/content/114/48/12803.abstract. The student position is part of the IU Vision Science Graduate Program. The Program includes a highly active group of multidisciplinary vision scientists, mostly from within the School of Optometry but also from Neuroscience, Psychology, Brain Science, Biology...

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...

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...

PhD Position is Available in Don Miller’s Laboratory on Advanced Ophthalmic Imaging at Indiana University

A PhD student position is available in Don Miller’s laboratory on advanced ophthalmic imaging at Indiana University (www.opt.indiana.edu/dtmiller/Index.aspx). The laboratory is looking for a highly motivated student in optics, bioengineering, physics, computer science, or a related discipline to develop cutting edge optical instrumentation and software to conduct vision research. The student could also have a background in biological or medical vision who wants to use the laboratory’s sophisticated optical systems to study anatomical structures and physiological processes associated with normal and pathological vision. The lab’s primary focus is on the development and use of optical coherence tomography (OCT) and adaptive optics for high-resolution retinal imaging. The student position is part of the IU Vision Science Graduate Program. The Program includes a highly active group of multidisciplinary vision scientists, mostly from within the School of Optometry but a...

Categories

Organizations in the News

OCT Companies in the News

Picture Gallery