The incorporation of adaptive optics (AO) technology into ophthalmic imaging systems has enhanced the understanding of retinal structure and function and the progression of various retinal diseases in adults by allowing for the dynamic correction of ocular and/or system aberrations. However, the in vivo visualization of important human retinal microanatomy, including cone photoreceptors, has been largely limited to fully cooperative subjects who are able to fixate and/or sit upright for extended imaging sessions in large tabletop AO systems. Previously, we developed the first handheld AO scanning laser ophthalmoscope capable of 2-D imaging of cone photoreceptors in supine adults and infants. In this work, we present the design and fabrication of the first handheld AO optical coherence tomography (HAOOCT) probe capable of collecting high-resolution volumetric images of the human retina. We designed custom optomechanics to build a spectral domain OCT system with a compact form factor of 22 cm × 18 cm × 5.2 cm and a total weight of 630 grams. The OCT imaging channel has a theoretical lateral resolution of 2.26 μm over a 1.0° × 1.0° field of view and an axial resolution of 4.01 μm. Stabilized imaging of healthy human adult volunteers revealed the 3-D photoreceptor structure and retinal pigment epithelium cells. HAOOCT was then deployed in handheld operation to image photoreceptors in upright and recumbent adults, indicating its potential to extend AO-OCT to previously excluded patient populations.

Non-confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) has enhanced the study of human retinal photoreceptors by providing complementary information to standard confocal AOSLO images. Previously we developed the first confocal handheld AOSLO (HAOSLO) capable of in vivo cone photoreceptor imaging in supine and non-cooperative patients. Here, we introduce the first multimodal (M-)HAOSLO for confocal and non-confocal split-detection (SD) imaging to allow for more comprehensive patient data collection. Aside from its unprecedented miniature size and weight, M-HAOSLO is also the first system to perform sensorless wavefront-corrected SD imaging of cone photoreceptors.

Adaptive optics scanning laser ophthalmoscopy (AOSLO) has advanced the study of retinal structure and function by enabling in vivo imaging of individual photoreceptors. Most implementations of AOSLOs are large, complex tabletop systems, thereby preventing high quality photoreceptor imaging of patients who are unable to sit upright and/or fixate for an imaging session. We have previously addressed this limitation in the clinical translation of AOSLO by developing the first confocal handheld AOSLO (HAOSLO) capable of cone photoreceptor visualization in adults and infants. However, confocal AOSLO images suffer from imaging artifacts and the inability to detect remnant cone structure, leading to ambiguous or potentially misleading results. Recently, it has been shown that non-confocal split-detection (SD) AOSLO images, created by the collection of multiply backscattered light, enables more reliable studies of retinal photoreceptors by providing images of the cone inner segment. In this paper, we detail the extension of our HAOSLO probe to enable multi-channel light collection resulting in the first ever multimodal handheld AOSLO (M-HAOSLO). Imaging sessions were conducted on two dilated, healthy human adult volunteers, and M-HAOSLO images taken in handheld operation mode reveal the cone photoreceptor mosaic. Aside from being the first miniaturized and portable implementation of a SD AOSLO system, M-HAOSLO relies on sensorless optimization of the wavefront to correct aberrations. Thus, we also show the first ever SD images collected after correction of the eye’s estimated wavefront.

Optical coherence tomography angiography (OCTA) is an extension of OCTA that allows for non-invasive imaging of the retinal microvasculature. OCTA imaging of adult retinal diseases is area of active research in ophthalmology as OCTA can provide insight into the pathogenesis of many retinal diseases. Like these adult diseases, pediatric diseases such as retinopathy of prematurity (ROP) have a primarily vascular pathogenesis. However, table top OCTA systems require compliant, seated subjects and cannot be used on infants and young children. In this manuscript we describe the development of a non-contact handheld OCTA (HH-OCTA) probe for imaging of young children and infants in the operating room. The probe utilizes a novel, diverging light on the scanner optical design that provides improved performance over a traditional OCT scanner design. While most handheld OCT probes are designed to be held by the side of the case or by a handle, our operators tend to prefer to grip probes by the tip of the probe for supine imagine. The ergonomics of the HH-OCTA probe were designed to match this grip. The HH-OCTA probe used a 200 kHz OCT engine, has a motorized stage that provides +10 to -10 D refractive error correction, and weighs 700g. Initial OCTA imaging was performed in 9 children or infants during exam under anesthesia. The HH-OCTA images provide visualization of the retinal microvasculature in both normal and pathological eyes.

OCT angiography is a functional extension of OCT that allows for non-invasive imaging of retinal microvasculature. However, most current OCT angiography systems are tabletop systems that are typically used for imaging compliant, seated subjects. These systems cannot be readily applied for imaging important patient populations such as bedridden patients, patients undergoing surgery in the operating room, young children in the clinic, and infants in the intensive care nursery. In this manuscript, we describe the design and development of a non-contact, handheld probe optimized for OCT angiography that features a novel diverging light on the scanner optical design that provides improved optical performance over traditional OCT scanner designs. Unlike most handheld OCT probes, which are designed to be held by the side of the case or by a handle, the new probe was optimized for ergonomics of supine imaging where imagers prefer to hold the probe by the lens tube. The probe's design also includes an adjustable brace that gives the operator a point of contact closer to the center of mass of the probe, reducing the moment of inertia around the operator's fingers, facilitating stabilization, and reducing operator fatigue. The probe supports high-speed imaging using a 200 kHz swept source OCT engine, has a motorized stage that provides + 10 to -10 D refractive error correction and weighs 700g. We present initial handheld OCT angiography images from healthy adult volunteers, young children during exams under anesthesia, and non-sedated infants in the intensive care nursery. To the best of our knowledge, this represents the first reported use of handheld OCT angiography in non-sedated infants, and the first handheld OCT angiography images which show the clear delineation of key features of the retinal capillary complex including the foveal avascular zone, peripapillary vasculature, the superficial vascular complex, and the deep vascular complex.

Optical coherence tomography (OCT) allows for non-contact, high resolution, volumetric imaging of biological tissue and has become an indispensable ophthalmic imaging technique. However, conventional, commercial OCT systems require a cooperative, sitting patient typically stabilized by a head and/or chin rests. Additionally, current clinical systems are designed for imaging either the anterior or posterior segment of the eye exclusively. While these limitations are not severe in the ophthalmic clinic, they do limit the use of OCT in other more challenging medical environments where novel “whole eye” imaging could provide value, such as in the military theater or emergency department (ED). One solution to eliminate the need for a patient to sit upright and be stabilized during imaging would be a hand-held probe positioned and stabilized by the photographer or physician. Here we describe a hand-held OCT probe for simultaneous imaging of the anterior chamber (13.3 mm diameter field-of-view) and posterior segment (40° as measured from the pupil nodal point) simultaneously. The use of polarization multiplexing allows for two independent imaging channels which enable a wide posterior segment field-of-view and the ability to control the posterior segment path length and focal depth independently from the anterior chamber channel. Additionally, the probe was designed for a relatively compact form factor.

Adaptive optics scanning laser ophthalmoscopy (AOSLO) has enabled in vivo visualization and enhanced understanding of retinal structure and function. Current generation AOSLOs have a large footprint and are mainly limited to imaging cooperative adult subjects. To extend the application of AOSLO to new patient populations, we have designed the first portable handheld AOSLO (HAOSLO) system. By incorporating a novel computational wavefront sensorless AO algorithm and custom optics, we have miniaturized our HAOSLO to weigh less than 200 grams. HAOSLO imaged the cones closest to the fovea with a handheld probe in adults and captured the first AO-enhanced image of cones in infants.

Purpose: Optical coherence tomography (OCT) is widely used in ophthalmology clinics and has potential for more general medical settings and remote diagnostics. In anticipation of remote applications, we developed wireless interactive control of an OCT system using mobile devices.Methods: A web-based user interface (WebUI) was developed to interact with a handheld OCT system. The WebUI consisted of key OCT displays and controls ported to a webpage using HTML and JavaScript. Client-server relationships were created between the WebUI and the OCT system computer. The WebUI was accessed on a cellular phone mounted to the handheld OCT probe to wirelessly control the OCT system. Twenty subjects were imaged using the WebUI to assess the system. System latency was measured using different connection types (wireless 802.11n only, wireless to remote virtual private network [VPN], and cellular).Results: Using a cellular phone, the WebUI was successfully used to capture posterior eye OCT images in all subjects. Simultaneous interactivity by a remote user on a laptop was also demonstrated. On average, use of the WebUI added only 58, 95, and 170 ms to the system latency using wireless only, wireless to VPN, and cellular connections, respectively. Qualitatively, operator usage was not affected.Conclusions: Using a WebUI, we demonstrated wireless and remote control of an OCT system with mobile devices.Translational Relevance: The web and open source software tools used in this project make it possible for any mobile device to potentially control an OCT system through a WebUI. This platform can be a basis for remote, teleophthalmology applications using OCT.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.

We describe the first handheld, swept source optical coherence tomography (SSOCT) system capable of imaging both the anterior and posterior segments of the eye in rapid succession. A single 2D microelectromechanical systems (MEMS) scanner was utilized for both imaging modes, and the optical paths for each imaging mode were optimized for their respective application using a combination of commercial and custom optics. The system has a working distance of 26.1 mm and a measured axial resolution of 8 μm (in air). In posterior segment mode, the design has a lateral resolution of 9 μm, 7.4 mm imaging depth range (in air), 4.9 mm 6dB fall-off range (in air), and peak sensitivity of 103 dB over a 22° field of view (FOV). In anterior segment mode, the design has a lateral resolution of 24 μm, imaging depth range of 7.4 mm (in air), 6dB fall-off range of 4.5 mm (in air), depth-of-focus of 3.6 mm, and a peak sensitivity of 99 dB over a 17.5 mm FOV. In addition, the probe includes a wide-field iris imaging system to simplify alignment. A fold mirror assembly actuated by a bi-stable rotary solenoid was used to switch between anterior and posterior segment imaging modes, and a miniature motorized translation stage was used to adjust the objective lens position to correct for patient refraction between -12.6 and + 9.9 D. The entire probe weighs less than 630 g with a form factor of 20.3 x 9.5 x 8.8 cm. Healthy volunteers were imaged to illustrate imaging performance.

Intra-operative optical coherence tomography (OCT) requires a display technology which allows surgeons to visualize OCT data without disrupting surgery. Previous research and commercial intrasurgical OCT systems have integrated heads-up display (HUD) systems into surgical microscopes to provide monoscopic viewing of OCT data through one microscope ocular. To take full advantage of our previously reported real-time volumetric microscope-integrated OCT (4D MIOCT) system, we describe a stereoscopic HUD which projects a stereo pair of OCT volume renderings into both oculars simultaneously. The stereoscopic HUD uses a novel optical design employing spatial multiplexing to project dual OCT volume renderings utilizing a single micro-display. The optical performance of the surgical microscope with the HUD was quantitatively characterized and the addition of the HUD was found not to substantially effect the resolution, field of view, or pincushion distortion of the operating microscope. In a pilot depth perception subject study, five ophthalmic surgeons completed a pre-set dexterity task with 50.0% (SD = 37.3%) higher success rate and in 35.0% (SD = 24.8%) less time on average with stereoscopic OCT vision compared to monoscopic OCT vision. Preliminary experience using the HUD in 40 vitreo-retinal human surgeries by five ophthalmic surgeons is reported, in which all surgeons reported that the HUD did not alter their normal view of surgery and that live surgical maneuvers were readily visible in displayed stereoscopic OCT volumes.

In the weeks following birth, both the brain and the vascular network that supplies it undergo dramatic alteration. While studies of the postnatal evolution of the pial vasculature and blood flow through its vessels have been previously done histologically or acutely, here we describe a neonatal reinforced thin-skull preparation for longitudinally imaging the development of the pial vasculature in mice using two-photon laser scanning microscopy. Starting with mice as young as postnatal day 2 (P2), we are able to chronically image cortical areas >1 mm(2), repeatedly for several consecutive days, allowing us to observe the remodeling of the pial arterial and venous networks. We used this method to measure blood velocity in individual vessels over multiple days, and show that blood flow through individual pial venules was correlated with subsequent diameter changes. This preparation allows the longitudinal imaging of the developing mammalian cerebral vascular network and its physiology.