Joseph A. Izatt

Adaptive optics scanning light ophthalmoscopy (AOSLO) reveals individual retinal cells and their function, microvasculature, and micropathologies in vivo. As compared to the single-channel offset pinhole and two-channel split-detector nonconfocal AOSLO designs, by providing multidirectional imaging capabilities, a recent generation of multidetector and (multi-)offset aperture AOSLO modalities has been demonstrated to provide critical information about retinal microstructures. However, increasing detection channels requires expensive optical components and/or critically increases imaging time. To address this issue, we present an innovative combination of machine learning and optics as an integrated technology to compressively capture 12 nonconfocal channel AOSLO images simultaneously. Imaging of healthy participants and diseased subjects using the proposed deep compressed multichannel AOSLO showed enhanced visualization of rods, cones, and mural cells with over an order-of-magnitude improvement in imaging speed as compared to conventional offset aperture imaging. To facilitate the adaptation and integration with other in vivo microscopy systems, we made optical design, acquisition, and computational reconstruction codes open source.

We describe a fiber-based coherent receiver topology which utilizes intrinsic phase shifts from fiber couplers to enable instantaneous quadrature projection with shot-noise limited signal-to-noise ratio (SNR). Fused 3x3 fiber couplers generate 3 phase-shifted signals simultaneously that can be combined with quadrature projection methods to detect magnitude and phase unambiguously. We present a novel differential detection topology which utilizes a combination of 3x3 and 2x2 couplers to enable quadrature projection with fully differential detection. We present a mathematical analysis of this 3x3 differential detection topology, extended methods for signal calibration, and SNR analysis. We characterize the SNR advantage of this approach and demonstrate a sample application illustrating simultaneous magnitude and phase imaging of a chrome-on-glass test chart.

We describe a fiber-based coherent receiver topology which utilizes intrinsic phase shifts from fiber couplers to enable instantaneous quadrature projection with shot-noise limited signal-to-noise ratio (SNR). Fused 3x3 fiber couplers generate 3 phase-shifted signals simultaneously that can be combined with quadrature projection methods to detect magnitude and phase unambiguously. We present a novel differential detection topology which utilizes a combination of 3x3 and 2x2 couplers to enable quadrature projection with fully differential detection. We present a mathematical analysis of this 3x3 differential detection topology, extended methods for signal calibration, and SNR analysis. We characterize the SNR advantage of this approach and demonstrate a sample application illustrating simultaneous magnitude and phase imaging of a chrome-on-glass test chart.

Ophthalmic microsurgery is traditionally performed using stereomicroscopes and requires visualization and manipulation of sub-millimeter tissue structures with limited contrast. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide high-resolution, depth-resolved cross sections, and has become a valuable tool in clinical practice in ophthalmology. While there has been substantial progress in both research and commercialization efforts to bring OCT imaging into live surgery, its use is still somewhat limited due to factors such as low imaging speed, limited scan configurations, and suboptimal data visualization. In this paper we describe, to the best of our knowledge, the translation of the fastest swept-source intraoperative OCT system with real-time volumetric imaging with stereoscopic data visualization provided via a heads-up display into the operating room. Results from a sampling of human anterior segment and retinal surgeries chosen from 93 human surgeries using the system are shown and the benefits that this mode of intrasurgical OCT imaging provides are discussed.

Optical coherence tomography (OCT) has seen widespread success as an in vivo clinical diagnostic 3D imaging modality, impacting areas including ophthalmology, cardiology, and gastroenterology. Despite its many advantages, such as high sensitivity, speed, and depth penetration, OCT suffers from several shortcomings that ultimately limit its utility as a 3D microscopy tool, such as its pervasive coherent speckle noise and poor lateral resolution required to maintain millimeter-scale imaging depths. Here, we present 3D optical coherence refraction tomography (OCRT), a computational extension of OCT that synthesizes an incoherent contrast mechanism by combining multiple OCT volumes, acquired across two rotation axes, to form a resolution-enhanced, speckle-reduced, refraction-corrected 3D reconstruction. Our label-free computational 3D microscope features a novel optical design incorporating a parabolic mirror to enable the capture of 5D plenoptic datasets, consisting of millimetric 3D fields of view over up to ± 75 ∘ without moving the sample. We demonstrate that 3D OCRT reveals 3D features unobserved by conventional OCT in fruit fly, zebrafish, and mouse samples.

Frequency-modulated continuous wave (FMCW) light detection and ranging (LiDAR) is an emerging 3D ranging technology that offers high sensitivity and ranging precision. Due to the limited bandwidth of digitizers and the speed limitations of beam steering using mechanical scanners, meter-scale FMCW LiDAR systems typically suffer from a low 3D frame rate, which greatly restricts their applications in real-time imaging of dynamic scenes. In this work, we report a high-speed FMCW based 3D imaging system, combining a grating for beam steering with a compressed time-frequency analysis approach for depth retrieval. We thoroughly investigate the localization accuracy and precision of our system both theoretically and experimentally. Finally, we demonstrate 3D imaging results of multiple static and moving objects, including a flexing human hand. The demonstrated technique achieves submillimeter localization accuracy over a tens-of-centimeter imaging range with an overall depth voxel acquisition rate of 7.6 MHz, enabling densely sampled 3D imaging at video rate.

Purpose: To report macular neurovascular abnormalities in a child with incontinentia pigmenti using handheld optical coherence tomography (OCT) and OCT angiography (OCT-A). Methods: An eye of a child with incontinentia pigmenti enrolled in BabySTEPS was imaged using an investigational noncontact, handheld swept-source OCT device during examination under anesthesia. Custom MATLAB scripts were used to generate depth-resolved vascular slabs, B-scans with flow overlay, and retinal thickness maps. Results: Depth-resolved OCT and OCT-A imaging demonstrated focal areas of decreased capillary flow that corresponded to areas of both inner retinal and outer retinal thinning on retinal thickness maps. Atypical diving of superficial retinal vessels occurred as they traversed from thin retina to normal-thickness retina. Conclusion: Depth-resolved OCT and OCT-A identified retinal vascular abnormalities that were not evident on fundus photography or fluorescein angiography. This case depicted concurrent, localized abnormalities in retinal thickness and microvasculature in an eye with incontinentia pigmenti.

Deep anterior lamellar keratoplasty (DALK) is a technique for cornea transplantation which is associated with reduced patient morbidity. DALK has been explored as a potential application of robot microsurgery because the small scales, fine control requirements, and difficulty of visualization make it very challenging for human surgeons to perform. We address the problem of modelling the small scale interactions between the surgical tool and the cornea tissue to improve the accuracy of needle insertion, since accurate placement within 5% of target depth has been associated with more reliable clinical outcomes. We develop a data-driven autoregressive dynamic model of the tool-tissue interaction and a model predictive controller to guide robot needle insertion. In an ex vivo model, our controller significantly improves the accuracy of needle positioning by more than 40% compared to prior methods.

Optical coherence tomography (OCT) has revolutionized diagnostics in ophthalmology. However, OCT requires a trained operator and patient cooperation to carefully align a scanner with the subject’s eye and orient it in such a way that it images a desired region of interest at the retina. With the goal of automating this process of orienting and aligning the scanner, we developed a robot-mounted OCT scanner that automatically aligned with the pupil while matching its optical axis with the target region of interest at the retina. The system used two 3D cameras for face tracking and three high-resolution 2D cameras for pupil and gaze tracking. The tracking software identified 5 degrees of freedom for robot alignment and ray aiming through the ocular pupil: 3 degrees of translation (x, y, z) and 2 degrees of orientation (yaw, pitch). We evaluated the accuracy, precision, and range of our tracking system and demonstrated imaging performance on free-standing human subjects. Our results demonstrate that the system stabilized images and that the addition of gaze tracking and aiming allowed for region-of-interest specific alignment at any gaze orientation within a 28° range.

Purpose: To investigate the use of imaging modalities in the volumetric measurement of the subretinal space and examine the volume of subretinal blebs created by a subretinal drug delivery device utilizing microscope-integrated optical coherence tomography (MIOCT). Methods: An MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging ceramic spheres of known size that were surgically implanted into ex vivo porcine eyes. This method was then used to measure subretinal blebs created in 10 porcine eyes by injection of balanced salt solution utilizing a subretinal delivery device via a suprachoroidal cannula. Bleb volumes obtained from MIOCT were compared to the intended injection volume. Results: Validation of image-based volume measurements of ceramic spheres showed accuracy to ±0.029 µL (5.6%) for objects imaged over the posterior pole and ±0.025 µL (4.8%) over peripheral retina. The mean expected injection volume from extraocular tests of the suprachoroidal cannula was 66.44 µL (σ = 2.4 µL). The mean injection volume as measured by the MIOCT imaging method was 54.8 µL (σ = 12.3 µL), or 82.48% of expected injection volume. Conclusions: MIOCT can measure the volume of subretinal blebs with accuracy and precision. The novel suprachoroidal approach using a subretinal delivery device was able to deliver greater than 80% of expected injection volume into the subretinal space, as assessed by MIOCT. Translational Relevance: MIOCT provides a method for visualization, and analysis of images enables surgeons to quantify and evaluate the success of subretinal drug delivery via a suprachoroidal approach.