Amit Narawane

This work experimentally demonstrates automatic optical 3D tracking of target areas of interest within wide-field digital stereoscope imagery to guide high-resolution intraoperative optical coherence tomography (iOCT) acquisition in real time. Eye surgeries such as cataract surgery are among the most commonly performed surgeries in the world and require precise visualization, especially in the axial dimension. By enabling unparalleled axial sensitivity, iOCT has emerged as a leading modality to enhance surgical visualization of the eye. However, current iOCT visualization of ophthalmic surgeries is limited by the small field of view (FOV) of OCT relative to that of the surgical microscope, requiring extensive manual realignment by a trained operator. We have developed an iOCT computer vision system that utilizes the built-in stereo microscope video feed to automatically align the OCT volume with the surgeon’s tool tip in 3D, tracking over a wide FOV and without modifications to surgical tools. Furthermore, our system used a deep-learning detection model trained on a novel synthetic microscope image generation pipeline and annotated real images to create what is believed to be   a new 3D tracking system that is both fast and accurate. We integrated this tracking system into a high-speed iOCT stereo microscope to acquire 3D tool-tip-aligned OCT volumes in real time. We demonstrated successful tracking performance by consistently positioning the iOCT volume ( x =5mm, y =5mm, and z =7mm) at the tool tip ( x =0.72±0.44mm, y =0.78±0.47mm, and z =2.07±1.43mm error) in testing with a motorized three-axis stage and by simulating ex vivo porcine eye cataract maneuvers with real surgical instruments. Our synthetic eye dataset pipeline and iOCT tracking system pave the way for more effective and usable visualization in eye surgery.

In focused Gaussian beam imaging systems, the low-numerical aperture (NA) of the beam inherently degrades signal and resolution. We demonstrate and experimentally validate a theory for optimally focusing a Gaussian beam source with a low-NA lens to maximize imaging quality. Specifically, reflectance signal and lateral resolution were optimized over two system parameters: (1) the axial working distance to the sample, and (2) the geometric focal length of the lens. In the former, we find that placing the sample at the waist of the beam is optimal, as expected. More interestingly, in the latter, we find that a higher reflectance signal and better lateral resolution are obtained at a fixed working distance by choosing the lens focal length to be equal to the working distance, even though this does not place the beam waist on the sample due to the focal shift effect.

Background: Scattering of the sclera limits optical coherence tomography (OCT) imaging of deeper targets including lesions, malignancies, and other surgical targets. While existing applications of fluorescein dye are currently focused on fluorescence properties for tissue labeling, the absorption characteristics of the dye also hold potential for scleral tissue clearing. Methods: Fluorescein is investigated here to gauge the potential impact of its optical clearing on intrasurgical OCT guidance. Fluorescein was applied topically to ex vivo porcine and human eye models. OCT imaging was conducted over time to assess the increases in imaging depth due to fluorescein clearing. High-speed microscope-integrated OCT was used during pilot trabeculectomy surgery on cleared eye models to assess clearing applications in a surgical context. Results: The OCT depth of imaging increased with fluorescein concentration and application time. The effect saturates at a near-20% concentration with 50 min of application time, with a maximum signal increase of +15 dB. Reversal of the effect was observed following 10 min of rinsing. Conclusions: High-concentration fluorescein dye has novel applications as an optical clearing agent, increasing the OCT imaging depth through highly scattering biological tissue. These properties can be leveraged for improved image guidance in surgical contexts.

Optical coherence tomography (OCT) is a non-invasive, three-dimensional imaging modality demonstrated to yield a wealth of high-resolution structural and functional information in a variety of biomedical imaging applications. However, there is a significant limitation on the penetration depth of the modality in most tissues due to their high optical scattering, hindering imaging of more deeply embedded targets. In ophthalmic applications, this makes transscleral imaging of targets such as suprachoroidal injection volumes, lesions, and malignancies challenging. Here, we investigate the novel application of fluorescein, a commonly applied biomedical dye, as an optical clearing agent for increasing the depth of OCT imaging in scleral tissues. The effect is characterized in ex-vivo models including the sclera of porcine and human eyes, examining its time and concentration dependence, reversibility, and potential for application in the enhancement of intrasurgical trabeculectomy image guidance. We demonstrate that fluorescein can serve not only as a biomedical fluorophore, but also as an optical clearing agent capable of significantly increasing OCT imaging depth in tissue. As a common and accessible ophthalmic agent with a long history of clinical application, we believe that this new potential use could have substantial positive impact in the enhancement of biomedical imaging in scattering tissue.

Optical coherence tomography (OCT) has revolutionized diagnostics in retinal ophthalmology. Traditional OCT requires minimal relative motion between the subject and scanner, which is difficult to achieve with handheld devices and/or non-stabilized subjects. We recently introduced robotically-aligned OCT (RAOCT) as an alternative that promises to alleviate these minimal-movement requirements by tracking the subject and compensating for their motion with dynamic hardware components in real-time. However, hardware and image processing delays lead to residual motion artifacts even after automatic alignment and motion compensation. Here, we introduce a novel sensor-driven digital motion correction approach that overcomes these shortcomings. Our method leverages synchronized sensing of both the subject’s eye and the scanner hardware to continuously estimate the imaging system state during acquisition. The A-scans are then remapped using a ray-tracing model of the system at the precise moment of acquisition. We demonstrate that, in addition to motion compensation from RAOCT, our method further reduces residual artifacts by 88.3 %, 80.4 %, and 62.6 % across axial, lateral, and rotational motions, respectively. We also show our correction in human retinal OCT images where residual errors from acquisition were reduced down to 12.4 µm, 0.11°, and 0.39° for axial, lateral, and rotational motion, respectively.

Optical coherence tomography (OCT) systems utilize 2D scanning methods to acquire reflectance-based volumetric images of samples, such as the human retina, with micrometer-scale depth resolution. A common method for performing this scanning at high speeds is to use a pair of sequential, single-axis galvanometer scanners. An undesired effect of using separated scanners is the variation in the beam position at the pupil plane, a phenomenon known as beam wander or pupil wobble. This can lead to loss of signal and vignetting artifacts in the resulting images. To overcome these limitations, we propose a method to deterministically analyze the pupil wobble in a given retinal OCT system and to correct for the displacement using pupil tracking OCT with a 2D scanning mirror placed anti-conjugate to the pupil plane. We demonstrate that we can model the pattern of pupil wobble present in any OCT system both theoretically and empirically and then use a pupil tracking system to correct for the displacement of the beam to acquire OCT images without the imposed artifacts.

Optical coherence tomography (OCT) is an interferometric technique for micron-level imaging in biological and non-biological contexts. As a non-invasive, non-ionizing, and video-rate imaging modality, OCT is widely used in biomedical and clinical applications, especially ophthalmology, where it functions in many roles, including tissue mapping, disease diagnosis, and intrasurgical visualization. In recent years, the rapid growth of medical robotics has led to new applications for OCT, primarily for 3D free-space scanning, volumetric perception, and novel optical designs for specialized medical applications. This review paper surveys these recent developments at the intersection of OCT and robotics and organizes them by degree of integration and application, with a focus on biomedical and clinical topics. We conclude with perspectives on how these recent innovations may lead to further advances in imaging and medical technology.

Retinal diseases such as age-related macular degeneration, diabetic retinopathy, and uveitic macular edema are leading causes of visual impairment.^{1 – 3} Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents and/or steroids have been effective in controlling vascular leakage and often restoring visual acuity but require repeated injections. Novel treatments such as intravitreal reservoirs or subretinal injections of gene therapies can be effective over a longer period but may cause glaucoma and cataract (in the case of steroids) or incur the cost and complexity of delivery in a microsurgical setting (in the case of subretinal gene therapy).⁴ This has led to the development of ocular therapeutics that can be delivered by transscleral injection into the suprachoroidal space in an office-based procedure.⁵ Triamcinolone suspension via suprachoroidal injection was approved in 2021 by the U.S. Food and Drug Administration for the treatment of uveitic macular edema, and clinical trials are underway using this delivery route for other posterior segment diseases. A limitation of this procedure is that clinicians are unable to obtain real-time feedback on the location and spread of the delivered product; rather, heat map imaging is used to estimate this.⁵

Suprachoroidal injections are a relatively new method of drug delivery to treat retinal disease. At present, it is difficult to visualize the distribution of injection-delivered product beneath the sclera into the suprachoroidal space. Imaging the suprachoroidal space with OCT is hindered by scattering of light from densely packed collagen fibers of the sclera, limiting depth penetration of the OCT light. In this Letter, we demonstrate the first use of tartrazine (Yellow 5) as an optical clearing agent for suprachoroidal research imaging with OCT in an ex vivo eye model. Our results show that this clearing agent dramatically improves visualization of the choroid and suprachoroidal space with transscleral OCT and allows for improved imaging of the location and extent of delivered suprachoroidal fluid. We believe these methods will enable use of optical techniques such as OCT to image through a variety of previously optically inaccessible, highly scattering tissue samples.