Browsing by Author "Izatt, Joseph A"
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Item Open Access 3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea.(Opt Express, 2010-04-26) Zhao, Mingtao; Kuo, Anthony N; Izatt, Joseph ACapable of three-dimensional imaging of the cornea with micrometer-scale resolution, spectral domain-optical coherence tomography (SDOCT) offers potential advantages over Placido ring and Scheimpflug photography based systems for accurate extraction of quantitative keratometric parameters. In this work, an SDOCT scanning protocol and motion correction algorithm were implemented to minimize the effects of patient motion during data acquisition. Procedures are described for correction of image data artifacts resulting from 3D refraction of SDOCT light in the cornea and from non-idealities of the scanning system geometry performed as a pre-requisite for accurate parameter extraction. Zernike polynomial 3D reconstruction and a recursive half searching algorithm (RHSA) were implemented to extract clinical keratometric parameters including anterior and posterior radii of curvature, central cornea optical power, central corneal thickness, and thickness maps of the cornea. Accuracy and repeatability of the extracted parameters obtained using a commercial 859nm SDOCT retinal imaging system with a corneal adapter were assessed using a rigid gas permeable (RGP) contact lens as a phantom target. Extraction of these parameters was performed in vivo in 3 patients and compared to commercial Placido topography and Scheimpflug photography systems. The repeatability of SDOCT central corneal power measured in vivo was 0.18 Diopters, and the difference observed between the systems averaged 0.1 Diopters between SDOCT and Scheimpflug photography, and 0.6 Diopters between SDOCT and Placido topography.Item Embargo Advancing Compact, Multiplexed, and Wavefront-Controlled Designs for Coherent Optical Systems(2023) Hagan, Kristen ElizabethThe development of non-invasive retinal imaging systems has revolutionized the care and treatment of patients in ophthalmology clinics. Using high-resolution modalities such as scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT), physicians and vision scientists are able detect previously unseen features on the subject retina which can 1) provide information for diagnosis, 2) identify disease biomarkers, 3) inform treatment or clinical trial regimens, and 4) improve understanding of underlying disease processes. Traditional SLO and OCT devices are designed as tabletop systems which are unable to accommodate vulnerable populations including intrasurgical patients and young children. Thus, the miniaturization of these systems into compact, handheld form factors is of great interest in both biomedical optics/imaging and medical research fields as they are essential to the proper care of patients. Previous studies have shown that handheld systems are instrumental in assessing overall health of young children and disease progressions in subjects of all ages. However, handheld systems are limited in optical performance as hardware selection is restricted to components of small size and low weight. Additionally, aberrations induced by both the system optics and the human eye degrade the resolution of the images. This work focuses on the integration of adaptive optics (AO) technology into handheld form factors to correct for aberrations and provide in vivo visualization of single cells such as cone photoreceptors and retinal pigment epithelium cells. We present two devices which demonstrate the first ever dual-modality AO-SLO and AO-OCT handheld imaging devices that push the limits of comprehensive, cellular-resolution retinal imaging. Finally, we investigate the use of 3x3 fused fiber couplers as a simple, compact coherent receiver design. Our novel balanced-detection topology achieves shot-noise limited performance in the presence of excess noise and shows improved SNR as compared to previous implementations. We detail its ability to enable instantaneous quadrature projection for applications in LiDAR, phase imaging, and optical communications.
Item Open Access Computational 3D Optical Imaging Using Wavevector Diversity(2021) Zhou, KevinThe explosion in the popularity and success of deep learning in the past decade has accelerated the development of computationally efficient, GPU-accelerated frameworks, such as TensorFlow and PyTorch, for rapid prototyping of neural networks. In this dissertation, we show that these deep learning tools are also well-suited for computational 3D imaging problems, specifically optical diffraction tomography (ODT), photogrammetry, and our newly proposed optical coherence refraction tomography (OCRT). Underlying these computational 3D imaging techniques is a physical model that demands multiple measurements taken with either angular diversity, wavelength diversity, or both. This requirement can be compactly summarized as wavevector (or k-vector) diversity, where the magnitude and direction of the wavevector correspond to the color and angle of the light, respectively.
To understand the importance of wavevector diversity for 3D imaging, this dissertation starts by advancing a unified k-space theory of optical coherence tomography (OCT), the most comprehensive and inclusive theoretical description of OCT to date that not only describes the transfer functions of all major forms of OCT and other coherent techniques (e.g., confocal microscopy, holography, ODT), but also includes the fundamental concepts of OCT, such as speckle, dispersion, aberration, and the tradeoff between lateral resolution and depth of focus (DOF).
Consistent with this unified theory, we implemented in TensorFlow a reconstruction algorithm for ODT, a technique that relies on illumination angular diversity to achieve 3D refractive index (RI) imaging. We propose a new method for filling the well-known “missing cone” of the ODT transfer function by reparameterizing the 3D sample as the output of an untrained neural network known as a deep image prior (DIP), which we show to outperform traditional regularization strategies.
Next, we introduce OCRT, a computational extension of OCT that incorporates extreme angular diversity over OCT's already high wavelength diversity to enable resolution-enhanced, speckle-reduced reconstructions that overcome the lateral-resolution-DOF tradeoff. OCRT also jointly reconstructs quantitative RI maps of the sample using a ray-based physical model implemented in TensorFlow. We also demonstrate spectroscopic OCRT (SOCRT), an extension of spectroscopic OCT (SOCT) that overcomes its tradeoff between spectral and axial resolution.
Motivated to make OCRT more widely applicable, we propose a new use of conic-section (e.g., parabolic, ellipsoidal) mirrors to allow fast multi-view imaging over very high angular ranges (up to 360°) using galvanometers without requiring sample rotation. We theoretically characterize the achievable fields of view (FOVs) as a function of many imaging system parameters (e.g., NA, wavelength, incidence angle, focal length, and telecentricity). Based on these predictions, we constructed a parabolic-mirror-based imaging system that facilitates multi-view OCT volume capture with millimetric FOVs over up to ±75°, which we combined to perform 3D OCRT reconstructions of zebrafish, fruitfly, and mouse tissue.
Finally, we adapted the OCRT reconstruction algorithm to photogrammetric 3D mesoscopic imaging with tens-of-micron accuracy, using a sequence of smartphone camera images taken at close range under freehand motion. 3D estimation was possible due to the angular diversity afforded by the nontelecentricity of smartphone cameras, using a similar ray-based model as for OCRT. We show that careful modeling of lens distortion and incorporation of a DIP are both pivotal for obtaining high 3D accuracy using devices not designed for close-range imaging.
Item Open Access Crosstalk rejection in full-field optical coherence tomography using spatially incoherent illumination with a partially coherent source(Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2010-05-03) Dhalla, Al-Hafeez; Migacz, Justin V; Izatt, Joseph AThe 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. © 2010 Copyright SPIE - The International Society for Optical Engineering.Item Open Access Development of Coherence-Gated and Resolution-Multiplexed Optical Imaging Systems(2010) Tao, Yuankai KennyOptical interrogation techniques are particularly well-suited for imaging tissue morphology, biological dynamics, and disease pathogenesis by providing noninvasive access to subcellular-resolution diagnostic information. State-of-the-art spectral domain optical coherence tomography (SDOCT) systems provide real-time optical biopsies of in vivo tissue, and have demonstrated clinical potential, particularly for applications in ophthalmology.
Recent advances in microscopy and endoscopy have led to improved resolution and compact optical designs, beyond those of conventional imaging systems. Application of encoded and multiplexed illumination and detection schemes may allow for the development of optical tools that surpass classical imaging limitations. Furthermore, complementary technologies can be combined to create multimodal optical imaging tools with advantages over current-generation systems.
In this dissertation, the development of coherence-gated and resolution-multiplexed technologies, aimed towards applications in human vitreoretinal imaging is described. Technology development in coherence-gated systems included increasing the imaging range of SDOCT by removing the complex conjugate artifact, improving acquisition speed using a scanning spectrometer design and a two-dimensional detector array, and hardware and algorithmic implementations that facilitated imaging of Doppler flow.
Structured illumination microscopy techniques were applied for resolution enhancement, and a spectrally encoded ophthalmic imaging system was developed for en face confocal fundus imaging through a single-mode fiber. These devices were resolution-multiplexed extensions of existing ophthalmic imaging devices, such as scanning laser ophthalmoscopes (SLO), which demonstrated improved resolution and more compact optical designs as compared to their conventional counterparts.
Finally, several multimodal ophthalmic diagnostic tools were developed that combined the advantages of OCT with existing imaging devices. These included a combined SLO-OCT system and a vitreoretinal surgical microscope combined with OCT. These devices allowed for concurrent ophthalmic imaging using complementary modalities for improved visualization and clinical utility.
Item Open Access Development of Extended-Depth Swept Source Optical Coherence Tomography for Applications in Ophthalmic Imaging of the Anterior and Posterior Eye(2012) Dhalla, AlHafeez ZahirOptical coherence tomography (OCT) is a non-invasive optical imaging modality that provides micron-scale resolution of tissue micro-structure over depth ranges of several millimeters. This imaging technique has had a profound effect on the field of ophthalmology, wherein it has become the standard of care for the diagnosis of many retinal pathologies. Applications of OCT in the anterior eye, as well as for imaging of coronary arteries and the gastro-intestinal tract, have also shown promise, but have not yet achieved widespread clinical use.
The usable imaging depth of OCT systems is most often limited by one of three factors: optical attenuation, inherent imaging range, or depth-of-focus. The first of these, optical attenuation, stems from the limitation that OCT only detects singly-scattered light. Thus, beyond a certain penetration depth into turbid media, essentially all of the incident light will have been multiply scattered, and can no longer be used for OCT imaging. For many applications (especially retinal imaging), optical attenuation is the most restrictive of the three imaging depth limitations. However, for some applications, especially anterior segment, cardiovascular (catheter-based) and GI (endoscopic) imaging, the usable imaging depth is often not limited by optical attenuation, but rather by the inherent imaging depth of the OCT systems. This inherent imaging depth, which is specific to only Fourier Domain OCT, arises due to two factors: sensitivity fall-off and the complex conjugate ambiguity. Finally, due to the trade-off between lateral resolution and axial depth-of-focus inherent in diffractive optical systems, additional depth limitations sometimes arises in either high lateral resolution or extended depth OCT imaging systems. The depth-of-focus limitation is most apparent in applications such as adaptive optics (AO-) OCT imaging of the retina, and extended depth imaging of the ocular anterior segment.
In this dissertation, techniques for extending the imaging range of OCT systems are developed. These techniques include the use of a high spectral purity swept source laser in a full-field OCT system, as well as the use of a peculiar phenomenon known as coherence revival to resolve the complex conjugate ambiguity in swept source OCT. In addition, a technique for extending the depth of focus of OCT systems by using a polarization-encoded, dual-focus sample arm is demonstrated. Along the way, other related advances are also presented, including the development of techniques to reduce crosstalk and speckle artifacts in full-field OCT, and the use of fast optical switches to increase the imaging speed of certain low-duty cycle swept source OCT systems. Finally, the clinical utility of these techniques is demonstrated by combining them to demonstrate high-speed, high resolution, extended-depth imaging of both the anterior and posterior eye simultaneously and in vivo.
Item Open Access Development of Fourier Domain Optical Coherence Tomography for Applications in Developmental Biology(2008-06-05) Davis, Anjul M.Developmental biology is a field in which explorations are made to answer how an organism transforms from a single cell to a complex system made up of trillions of highly organized and highly specified cells. This field, however, is not just for discovery, it is crucial for unlocking factors that lead to diseases, defects, or malformations. The one key ingredient that contributes to the success of studies in developmental biology is the technology that is available for use. Optical coherence tomography (OCT) is one such technology. OCT fills a niche between the high resolution of confocal microscopy and deep imaging penetration of ultrasound. Developmental studies of the chicken embryo heart are of great interest. Studies in mature hearts, zebrafish animal models, and to a more limited degree chicken embryos, indicate a relationship between blood flow and development. It is believed that at the earliest stages, when the heart is still a tube, the purpose of blood flow is not for convective transport of oxygen, nutrients and waster, bur rather to induce shear-related gene expressions to induce further development. Yet, to this date, the simple question of "what makes blood flow?" has not been answered. This is mainly due limited availability to adequate imaging and blood flow measurement tools. Earlier work has demonstrated the potential of OCT for use in studying chicken embryo heart development, however quantitative measurement techniques still needed to be developed. In this dissertation I present technological developments I have made towards building an OCT system to study chick embryo heart development. I will describe: 1) a swept-source OCT with extended imaging depth; 2) a spectral domain OCT system for non-invasive small animal imaging; 3) Doppler flow imaging and techniques for quantitative blood flow measurement in living chicken embryos; and 4) application of the OCT system that was developed in the Specific Aims 2-5 to test hypotheses generated by a finite element model which treats the embryonic chick heart tube as a modified peristaltic pump.
Item Open Access Development of Multi-modal and Super-resolved Retinal Imaging Systems(2016) LaRocca, FrancescoAdvancements in retinal imaging technologies have drastically improved the quality of eye care in the past couple decades. Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) are two examples of critical imaging modalities for the diagnosis of retinal pathologies. However current-generation SLO and OCT systems have limitations in diagnostic capability due to the following factors: the use of bulky tabletop systems, monochromatic imaging, and resolution degradation due to ocular aberrations and diffraction.
Bulky tabletop SLO and OCT systems are incapable of imaging patients that are supine, under anesthesia, or otherwise unable to maintain the required posture and fixation. Monochromatic SLO and OCT imaging prevents the identification of various color-specific diagnostic markers visible with color fundus photography like those of neovascular age-related macular degeneration. Resolution degradation due to ocular aberrations and diffraction has prevented the imaging of photoreceptors close to the fovea without the use of adaptive optics (AO), which require bulky and expensive components that limit the potential for widespread clinical use.
In this dissertation, techniques for extending the diagnostic capability of SLO and OCT systems are developed. These techniques include design strategies for miniaturizing and combining SLO and OCT to permit multi-modal, lightweight handheld probes to extend high quality retinal imaging to pediatric eye care. In addition, a method for extending true color retinal imaging to SLO to enable high-contrast, depth-resolved, high-fidelity color fundus imaging is demonstrated using a supercontinuum light source. Finally, the development and combination of SLO with a super-resolution confocal microscopy technique known as optical photon reassignment (OPRA) is demonstrated to enable high-resolution imaging of retinal photoreceptors without the use of adaptive optics.
Item Open Access Development of Novel Optical Design and Signal Processing Approaches in Optical Coherence Imaging(2020) Qian, RuobingOptical coherence tomography (OCT) is a non-invasive optical imaging modality which can provide high-resolution, cross-sectional images of retina and cornea. It has become a standard of care in ophthalmology for the diagnosis and monitoring of ocular diseases. However, current OCT systems face several major challenges, among which include: (1) difficult alignment and fixation in pediatric retinal imaging (2) limited cellular-level contrast for ophthalmic disease diagnosis and (3) expensive hardware and intensive computation requirements for real-time high-speed 3D imaging.
This dissertation describes the development of several novel optical design and signal processing approaches in OCT and optical coherence imaging technologies to address these limitations. We first describe a long working distance swept-source OCT system to facilitate retinal imaging in young children (chapter 2). The system incorporates two custom lenses and a novel compact 2f retinal scanning configuration to achieve a working distance of 350mm with a 16o OCT field of view. The system achieves high quality retinal imaging of children as young as 21 months old without sedation in the clinic. We then present a spectroscopic OCT technology that utilizes time-frequency analysis to obtain quantitative diagnostic information of cellular responses in the anterior chamber of the eye, which can indicate many ocular diseases such as hyphema and anterior uveitis. We demonstrate that this technology can differentiate and quantify the composition of anterior chamber blood cells such as red blood cells and subtypes of WBCs, including granulocytes, lymphocytes and monocytes (chapter 3 and 4). Finally, we describe a coherence-based 3D imaging technique that uses a grating for fast beam steering, a swept-source laser with long coherence length, and time-frequency analysis for depth retrieval (chapter 5). We demonstrate that the system can achieve high-speed 3D imaging with sub-millimeter axial resolution and tens of centimeters axial imaging ranging.
Item Open Access Development of Optical Coherence Tomography Systems for Intrasurgical and Pediatric Imaging(2018) Viehland, Christian BlakeOptical coherence tomography (OCT) is a non-contact imaging modality that provides micron scale resolution of in-vivo tissue. Due to these characteristics, OCT is the clinical standard of care in ophthalmology for the diagnosis and monitoring of ocular diseases. Despite its success in adult clinical ophthalmology, OCT has seen more limited use in other ophthalmic specialties including pediatrics and surgery. This is primarily due to the fact that most commercially available OCT systems are large, tabletop systems that require a compliant seated subject. This limits their utility in imaging non-cooperative, supine subjects such as patients undergoing surgery and infants in the nursery.
The works presented in this dissertation describe the development and translation of several OCT systems specialized for intrasurgical and pediatric imaging. The first system presented is a microscope integrated OCT system that provided, for the first time, ever live 4D (3D over time) imaging of retinal microsurgery. We present techniques for visualization of real-time intrasurgical OCT data (chapter 2) and summary imaging results from mock surgeries in the wet lab and over 150 surgeries in the human ophthalmic operating room (chapter 3). For pediatric imaging we present two novel handheld OCT systems for point of care imaging of infants in the nursery. The first is the lightest handheld OCT system ever reported. We show imaging results from the intensive care nursery that demonstrate the ability of this system to image pediatric pathology and retinal development (chapter 5). The second system is faster handheld OCT probe that features a novel optical and ergonomic design (chapter 6). We present initial results from the translation of this system into the nursery.
OCT angiography (OCTA) is an emerging functional extension of OCT that leverages the high speed of modern OCT systems to allow for non-invasive imaging of the retinal microvasculature. The final aim of this dissertation reports on the use of the microscope integrated OCT system and the high speed handheld OCT system for OCTA (chapters 4 and 6 respectively). To the best of knowledge the handheld OCTA images described in this manuscript are the first handheld OCTA images taken of an awake infant.
Item Open Access Development of Optical Coherence Tomography Systems for Ophthalmic Imaging and Intrasurgical Guidance(2017) Carrasco-Zevallos, Oscar M.Ophthalmic microsurgery is one of the most commonly performed surgical procedures in the world and it necessitates precise three-dimensional manipulation of tissue at sub-millimeter spatial scales. As a result, ophthalmic surgeons require an operating microscope to perform surgery and to asses alterations to the tissue. Unfortunately, modern operating microscopes provide a limited en face perspective of the three-dimensional surgical field, and surgeons must infer depth information using stereoscopy and cannot directly visualize sub-surface anatomy. These limitations may compromise the surgeon’s ability to maneuver instruments axially and to comprehensively evaluate the three-dimensional tissue structure.
Optical coherence tomography (OCT) is a non-contact volumetric imaging modality that is well suited to image the anterior and posterior human eye in vivo. The success of OCT in clinical ophthalmology motivated the development of intraoperative OCT to overcome the limitations of the operating microscope for ophthalmic surgery. However, current intraoperative OCT systems either require pauses in surgery for imaging or are restricted to cross-sectional imaging during surgery, thereby preventing OCT imaging of live surgery that extends over three-dimensional space.
This dissertation describes the design, development, and assessment of novel technologies for ophthalmic OCT imaging and intrasurgical guidance. These technologies seek to address challenges associated with translating a biomedical imaging device to the human operating suite and to improve upon current surgical visualization methods. We first describe eye tracking technologies designed to compensate for undesired subject motion during retinal and anterior eye OCT imaging. Next, we present a novel optical design for OCT retinal imaging, demonstrate its use for pediatric imaging, and discuss its advantages compared to conventional OCT retinal scanners. We then present the first 4D (volumetric imaging over time) intraoperative OCT system capable of imaging human ophthalmic surgery at up to 3 volumes/second. We report the results of a clinical study in which 4D intraoperative OCT was successfully used in >150 human eye surgeries. Next, we describe the optimization of an ultrahigh-speed OCT system using optical amplification and present a novel OCT scanning method designed for 4D imaging. Finally, we present the preliminary design of a second-generation 4D intraoperative OCT system capable of imaging surgical maneuvers at 15 volumes/second.
Item Open Access Development of Swept Source Optical Coherence Tomography and Adaptive Optics Scanning Laser Ophthalmoscopy: Improved Imaging Speed and Handheld Applications(2016) Nankivil, DerekOptical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications.
Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.
Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.
Item Open Access Enhanced Vasculature Imaging of the Retina Using Optical Coherence Tomography(2013) Hendargo, HansfordOptical coherence tomography (OCT) is a non-invasive imaging modality that uses low coherence interferometry to generate three-dimensional datasets of a sample's structure. OCT has found tremendous clinical applications in imaging the retina and has demonstrated great utility in the diagnosis of various retinal diseases. However, such diagnoses rely upon the ability to observe abnormalities in the structure of the retina caused by pathology. By the time an ocular disease has progressed to the point of affecting the morphology of the retina, irreversible vision loss in the eye may already occur. Changes in the functionality of the tissue often precede changes to the structure. Thus, if imaging methods are developed to provide additional functional information about the behavior and response of the retinal tissue and vasculature, earlier treatment for disease may be prescribed, thus preserving vision for the patient.
Within the last decade, significant technological advances in OCT systems have enabled high-speed and high sensitivity image acquisition using either spectral domain OCT (SDOCT) or swept-source OCT (SSOCT) configurations. Such systems use Fourier processing to extract structural information of a sample from interferometric principles. But such systems also have access to the optical phase information, which allows for functional analysis of sample dynamics. This dissertation details the development and application of methods using both intensity and phase information as a tool for studying interesting biological phenomena. The goal of this work is an extension of techniques to image the vasculature in the retina and enhance the clinical utility of OCT.
I first outline basic theory necessary for understanding the principles of OCT. I then describe OCT phase imaging in cellular applications as a demonstration of the ability of OCT to provide functional information on biological dynamics. Phase imaging methods suffer from an artifact known as phase wrapping, and I have developed a software technique to overcome this problem in OCT, thus extending its usefulness in providing quantitative information. I characterize the limitations in measuring moving scatterers with Doppler OCT in both SDOCT and SSOCT system. I also show the ability to image the vasculature in the retina using variance imaging with a high-speed retinal imaging system and software based methods to correct for patient motion and create a widefield mosaic in an automated manner. Finally, future directions for this work are discussed.
Item Open Access Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography(2016) Polans, James MatthewThe goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.
OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.
Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.
For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.
Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.
The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.
Item Open Access Functional Spectral Domain Optical Coherence Tomography Imaging(2009) Bower, Bradley A.Spectral Domain Optical Coherence Tomography (SDOCT) is a high-speed, high resolution imaging modality capable of structural and functional resolution of tissue microstructure. SDOCT fills a niche between histology and ultrasound imaging, providing non-contact, non-invasive backscattering amplitude and phase from a sample. Due to the translucent nature of the tissue, ophthalmic imaging is an ideal space for SDOCT imaging.
Structural imaging of the retina has provided new insights into ophthalmic disease. The phase component of SDOCT images remains largely underexplored, though. While Doppler SDOCT has been explored in a research setting, it remains to catch on in the clinic. Other, functional exploitations of the phase are possible and necessary to expand the utility of SDOCT. Spectral Domain Phase Microscopy (SDPM) is an extension of SDOCT that is capable of resolving sub-wavelength displacements within a focal volume. Application of sub-wavelength displacement measurement ophthalmic imaging could provide a new method for imaging of optophysiology.
This body of work encompasses both hardware and software design and development for implementation of SDOCT. Structural imaging was proven in both the lab and the clinic. Coarse phase changes associated with Doppler flow frequency shifts were recorded and a study was conducted to validate Doppler measurement. Fine phase changes were explored through SDPM applications. Preliminary optophysiology data was acquired to study the potential of sub-wavelength measurements in the retina. To remove the complexity associated with in-vivo human retinal imaging, a first principles approach using isolated nerve samples was applied using standard SDPM and a depth-encoded technique for measuring conduction velocity.
Results from amplitude as well as both coarse and fine phase processing are presented. In-vivo optophysiology using SDPM is a promising avenue for exploration, and projects furthering or extending this body of work are discussed.
Item Open Access Imaging at the Limits: Segmentation Error Bounds and High Resolution Retinal Imaging Systems(2018) DuBose, Theodore BThe human retina is essential to quality of life and therefore a topic of intense clinical and research interest. The combination of this interest with modern biophotonics has yielded a number of technological and medical developments now in various stages of adoption.
Optical coherence tomography (OCT) is a noninvasive optical imaging technique that utilizes coherent light to produce 3-D images with resolutions as fine as a micrometer. Since its invention in 1990, it has become part of the standard of care in opthalmology, shedding new light on the progression of diseases, therapeutic efficacy, childhood development, and real-time surgery in the retina. OCT has also found applications in microscopy, cardiology, pulmonology, and many other fields.
OCT has become valuable for the standard of care primarily due to its abilities to visualize the structural and functional layers of the retina. The thicknesses and volumes of certain can be used as diagnostic criteria and thus there is a high demand of OCT image assessment. In response, many researchers have developed software algorithms to automatically identify and mark, or segment, each layer.
Scanning light ophthalmoscopy or scanning laser ophthalmoscopy (SLO) is similar to OCT but uses confocal gating to produce high-contrast high-speed en face images of the retina. Although SLO has not become as prevalent as OCT in the clinic, it is frequently combined with adaptive optics (AO) to produce extremely high-resolution images of rod and cone photoreceptors, ganglion cells, and moving blood cells in the living retina.
AO is a technique to eliminate image blurring due to monochromatic aberrations in optical systems. By using a spatial light modulator, such as a deformable mirror or liquid crystal array, the wavefront of a beam sent into the eye can be engineered to compensate for the eye's aberrations. AO-SLO was initially developed in 2002 and has continued to be a field of research growth and interest. However, the majority of AOSLO systems require a dedicated room and staff, hindering their clinical adoption
The objective of the work presented herein was to explore the limits of the above imaging modalities. First, we explored the limits of OCT segmentation and demonstrated that the field of automated segmentation is far from its accuracy limit. Second, we explored the limits on SLO portability and developed both the world's smallest SLO probe and the first handheld AOSLO probe. Finally, we explored the limits of SLO resolution, developing the first super-resolution human retinal imaging system through the use of optical reassignment (OR) SLO.
Item Open Access Intraoperative spectral domain optical coherence tomography for vitreoretinal surgery.(Opt Lett, 2010-10-15) Tao, Yuankai K; Ehlers, Justis P; Toth, Cynthia A; Izatt, Joseph AWe demonstrate in vivo human retinal imaging using an intraoperative microscope-mounted optical coherence tomography system (MMOCT). Our optomechanical design adapts an Oculus Binocular Indirect Ophthalmo Microscope (BIOM3), suspended from a Leica ophthalmic surgical microscope, with spectral domain optical coherence tomography (SD-OCT) scanning and relay optics. The MMOCT enables wide-field noncontact real-time cross-sectional imaging of retinal structure, allowing for SD-OCT augmented intrasurgical microscopy for intraocular visualization. We experimentally quantify the axial and lateral resolution of the MMOCT and demonstrate fundus imaging at a 20Hz frame rate.Item Open Access Mesoscopic photogrammetry with an unstabilized phone camera(CVPR 2021, 2020-12-10) Zhou, Kevin C; Cooke, Colin; Park, Jaehee; Qian, Ruobing; Horstmeyer, Roarke; Izatt, Joseph A; Farsiu, SinaWe present a feature-free photogrammetric technique that enables quantitative 3D mesoscopic (mm-scale height variation) imaging with tens-of-micron accuracy from sequences of images acquired by a smartphone at close range (several cm) under freehand motion without additional hardware. Our end-to-end, pixel-intensity-based approach jointly registers and stitches all the images by estimating a coaligned height map, which acts as a pixel-wise radial deformation field that orthorectifies each camera image to allow homographic registration. The height maps themselves are reparameterized as the output of an untrained encoder-decoder convolutional neural network (CNN) with the raw camera images as the input, which effectively removes many reconstruction artifacts. Our method also jointly estimates both the camera's dynamic 6D pose and its distortion using a nonparametric model, the latter of which is especially important in mesoscopic applications when using cameras not designed for imaging at short working distances, such as smartphone cameras. We also propose strategies for reducing computation time and memory, applicable to other multi-frame registration problems. Finally, we demonstrate our method using sequences of multi-megapixel images captured by an unstabilized smartphone on a variety of samples (e.g., painting brushstrokes, circuit board, seeds).Item Open Access Qualitative, Quantitative, and Autonomous Optical Coherence Tomography Guided Ophthalmic Microsurgery(2018) Keller, BrentonOphthalmic microsurgery is a challenging subspecialty mainly due to the size of the operating environment. Tissues and distances are measured in micrometers and a surgical microscope is required to view the surgical field. Even with the microscope, surgeons have trouble visualizing all aspects of surgery because of the limited depth perception the microscope provides. Surgeons spend years developing the fine motor skills necessary to operate, but still encounter difficulty when performing certain procedures.
Recent developments in optical coherence tomography (OCT) have improved ophthalmic surgeons' capability to visualize surgery. OCT is a non-contact volumetric imaging modality capable of penetrating 1-2mm in tissue and is ideally suited for imaging the cornea and retina. Using OCT alongside the standard microscope view during surgery provides surgeons with more complete depth information. Despite improved visualization, movement and manipulation challenges in microsurgery persist, and surgeons have attempted to solve these problems through the use of robots. Robots offer improved accuracy and tremor reduction when positioning instruments and have been specifically developed for ophthalmic surgery.
This dissertation presents technologies to help aid surgeons in ophthalmic microsurgery. We begin by describing software capable of acquiring and processing real-time volumetric OCT to enhance the surgeon's view of the surgical field. Next, we report on methods for extracting quantitative information from OCT scans via retinal segmentation, corneal segmentation, and three-dimensional needle tracking. Finally, we combine OCT and robotics to make progress toward automating ophthalmic microsurgery. We use quantitative information from corneal segmentation and needle tracking together with reinforcement learning to enable a robot to teach itself to perform needle insertions in ex vivo tissue.
Item Open Access Quantitative Fourier Domain Optical Coherence Tomography Imaging of the Ocular Anterior Segment(2013) McNabb, Ryan PalmerClinical imaging within ophthalmology has had transformative effects on ocular health over the last century. Imaging has guided clinicians in their pharmaceutical and surgical treatments of macular degeneration, glaucoma, cataracts and numerous other pathologies. Many of the imaging techniques currently used are photography based and are limited to imaging the surface of ocular structures. This limitation forces clinicians to make assumptions about the underlying tissue which may reduce the efficacy of their diagnoses.
Optical coherence tomography (OCT) is a non-invasive, non-ionizing imaging modality that has been widely adopted within the field of ophthalmology in the last 15 years. As an optical imaging technique, OCT utilizes low-coherence interferometry to produce micron-scale three-dimensional datasets of a tissue's structure. Much of the human body consists of tissues that significantly scatter and attenuate optical signals limiting the imaging depth of OCT in those tissues to only 1-2mm. However, the ocular anterior segment is unique among human tissue in that it is primarily transparent or translucent. This allows for relatively deep imaging of tissue structure with OCT and is no longer limited by the optical scattering properties of the tissue.
This goal of this work is to develop methods utilizing OCT that offer the potential to reduce the assumptions made by clinicians in their evaluations of their patients' ocular anterior segments. We achieved this by first developing a method to reduce the effects of patient motion during OCT volume acquisitions allowing for accurate, three dimensional measurements of corneal shape. Having accurate corneal shape measurements then allowed us to determine corneal spherical and astigmatic refractive contribution in a given individual. This was then validated in a clinical study that showed OCT better measured refractive change due to surgery than other clinical devices. Additionally, a method was developed to combine the clinical evaluation of the iridocorneal angle through gonioscopy with OCT.