Development and deployment of a histopathology-based deep learning algorithm for patient prescreening in a clinical trial.

Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients.

Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma.

To discover distinct immune responses promoting or inhibiting hepatocellular carcinoma (HCC), we perform a three-dimensional analysis of the immune cells, correlating immune cell types, interactions, and changes over time in an animal model displaying gender disparity in nonalcoholic fatty liver disease (NAFLD)-associated HCC. In response to a Western diet (WD), animals mount acute and chronic patterns of inflammatory cytokines, respectively. Tumor progression in males and females is associated with a predominant CD8 CD4, Th1 > Th17 > Th2, NKT > NK, M1 > M2 pattern in the liver.

A Machine Learning Approach to Liver Histological Evaluation Predicts Clinically Significant Portal Hypertension in NASH Cirrhosis.

Background And Aims: The hepatic venous pressure gradient (HVPG) is the standard for estimating portal pressure but requires expertise for interpretation. We hypothesized that HVPG could be extrapolated from liver histology using a machine learning (ML) algorithm.

Approach And Results: Patients with NASH with compensated cirrhosis from a phase 2b trial were included.

Controlling for Artifacts in Widefield Optical Coherence Tomography Angiography Measurements of Non-Perfusion Area.

The recent clinical adoption of optical coherence tomography (OCT) angiography (OCTA) has enabled non-invasive, volumetric visualization of ocular vasculature at micron-scale resolutions. Initially limited to 3 mm × 3 mm and 6 mm × 6 mm fields-of-view (FOV), commercial OCTA systems now offer 12 mm × 12 mm, or larger, imaging fields. While larger FOVs promise a more complete visualization of retinal disease, they also introduce new challenges to the accurate and reliable interpretation of OCTA data.

Four-Dimensional Microscope-Integrated Optical Coherence Tomography Guidance in a Model Eye Subretinal Surgery.

Purpose:: Subretinal delivery of stem cells and gene therapy vectors hold great promise in clinical care. Delivery techniques are evolving. We investigate the utility of 4-dimensional (volumes over time) microscope-integrated optical coherence tomography (4D-MIOCT) to guide such maneuvers.

Real-Time Volumetric Imaging of Vitreoretinal Surgery with a Prototype Microscope-Integrated Swept-Source OCT Device.

Purpose: To evaluate the images produced in an initial surgical series of intraoperative near-real-time volumetric swept-source (SS) OCT imaging.

Design: Prospective translational study.

Participants: Forty-one consecutive adult patients undergoing vitreoretinal surgery between July 22, 2014, and July 1, 2015, at the Duke University Eye Center who agreed to participate.

Comparing histologic evaluation of prostate tissue using nonlinear microscopy and paraffin H&E: a pilot study.

Rapid histological assessment of large areas of prostate tissue is required for many intraoperative consultation scenarios such as margin evaluation. Nonlinear microscopy (NLM) enables imaging of large (whole mount) specimens without freezing or cryotoming. This study demonstrates rapid histological imaging of unsectioned prostate cancer surgical specimens using nonlinear microscopy and compares features of prostate pathology to standard paraffin embedded H&E histology.

Constant linear velocity spiral scanning for near video rate 4D OCT ophthalmic and surgical imaging with isotropic transverse sampling.

Ultrahigh speed optical coherence tomography (OCT) systems with >100 kHz A-scan rates can generate volumes rapidly with minimal motion artifacts and are well suited for 4D imaging (volumes through time) applications such as intra-operative imaging. In such systems, high OCT data acquisition efficiency (defined as the fraction of usable A-scans generated during the total acquisition time) is desired to maximize the volumetric frame rate and sampling pitch. However, current methods for beam scanning using non-resonant and resonant mirror scanners can result in severe scan distortion and transverse oversampling as well as require acquisition dead times, which limit the acquisition efficiency and performance of ultrahigh speed 4D OCT.

Real-time visualization and interaction with static and live optical coherence tomography volumes in immersive virtual reality.

Virtual reality (VR) head-mounted displays are an attractive technology for viewing intrasurgical optical coherence tomography (OCT) volumes because they liberate surgeons from microscope oculars. We demonstrate real-time, interactive viewing of OCT volumes in a commercial HTC Vive immersive VR system using previously reported ray casting techniques. Furthermore, we show interactive manipulation and sectioning of volumes using handheld controllers and guidance of mock surgical procedures in porcine eyes exclusively within VR.

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography.

Purpose: We advance studies of subretinal treatments by developing a microscope-integrated optical coherence tomography (MIOCT) image-based method for measuring the volume of therapeutics delivered into the subretinal space.

Methods: A MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging an object of known size in model eyes. This method then was applied to subretinal blebs created by injection of diluted triamcinolone.

Characterization of Long Working Distance Optical Coherence Tomography for Imaging of Pediatric Retinal Pathology.

Purpose: We determined the feasibility of fovea and optic nerve head imaging with a long working distance (LWD) swept source optical coherence tomography (OCT) prototype in adults, teenagers, and young children.

Methods: A prototype swept source OCT system with a LWD (defined as distance from the last optical element of the imaging system to the eye) of 350 mm with custom fixation targets was developed to facilitate imaging of children. Imaging was performed in 49 participants from three age groups: 26 adults, 16 children 13 to 18 years old (teenagers), and seven children under 6 years old (young children) under an approved institutional review board protocol.

Intraocular Pressure and Big Bubble Diameter in Deep Anterior Lamellar Keratoplasty: An Ex-Vivo Microscope-Integrated OCT With Heads-Up Display Study.

Purpose: To investigate the relationship between intraocular pressure (IOP) and big bubble (BB) formation in a model of deep anterior lamellar keratoplasty (DALK).

Design: Ex-vivo.

Methods: Corneoscleral buttons from human donors were loaded onto an artificial anterior chamber connected to a column of balanced salt solution.

Review of intraoperative optical coherence tomography: technology and applications [Invited].

During microsurgery, imaging of the surgical field through the operating microscope limits the surgeon's depth perception and visualization of instruments and sub-surface anatomy. Surgical procedures outside microsurgery, such as breast tumor resections, may also benefit from visualization of the sub-surface tissue structures. The widespread clinical adoption of optical coherence tomography (OCT) in ophthalmology and its growing prominence in other fields, such as cancer imaging, has motivated the development of intraoperative OCT for real-time tomographic visualization of surgical interventions.

Microscope-Integrated Optical Coherence Tomography Angiography in the Operating Room in Young Children With Retinal Vascular Disease.

Importance: Intraoperative optical coherence tomography (OCT) has gained traction as an important adjunct for clinical decision making during vitreoretinal surgery, and OCT angiography (OCTA) has provided novel insights in clinical evaluation of retinal diseases. To date, these two technologies have not been applied in combination to evaluate retinal vascular disease in the operating suite.

Objective: To conduct microscope-integrated, swept-source OCTA (MIOCTA) in children with retinal vascular disease.

Four-dimensional microscope- integrated optical coherence tomography to enhance visualization in glaucoma surgeries.

We report the first use of swept-source microscope-integrated optical coherence tomography (SS-MIOCT) capable of live four-dimensional (4D) (three-dimensional across time) imaging intraoperatively to directly visualize tube shunt placement and trabeculectomy surgeries in two patients with severe open-angle glaucoma and elevated intraocular pressure (IOP) that was not adequately managed by medical intervention or prior surgery. We performed tube shunt placement and trabeculectomy surgery and used SS-MIOCT to visualize and record surgical steps that benefitted from the enhanced visualization. In the case of tube shunt placement, SS-MIOCT successfully visualized the scleral tunneling, tube shunt positioning in the anterior chamber, and tube shunt suturing.

Four-dimensional Microscope-Integrated Optical Coherence Tomography to Visualize Suture Depth in Strabismus Surgery.

The authors report the use of swept-source microscope-integrated optical coherence tomography (SS-MIOCT), capable of live four-dimensional (three-dimensional across time) intraoperative imaging, to directly visualize suture depth during lateral rectus resection. Key surgical steps visualized in this report included needle depth during partial and full-thickness muscle passes along with scleral passes. [J Pediatr Ophthalmol Strabismus.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions.

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric.

Long working distance OCT with a compact 2f retinal scanning configuration for pediatric imaging.

Young and/or autistic children cannot be imaged with tabletop or handheld optical coherence tomography (OCT) because of their lack of attention and fear of large objects close to their face. We demonstrate a prototype retinal swept-source OCT system with a long working distance (from the last optical element to the subject's eye) to facilitate pediatric imaging. To reduce the number of optical elements and axial length compared to the traditional 4f telescope, we employ a compact 2f retinal scanning configuration and achieve a working distance of 350 mm with a 16° OCT field of view.

Needle Depth and Big-Bubble Success in Deep Anterior Lamellar Keratoplasty: An Ex Vivo Microscope-Integrated OCT Study.

Purpose: To examine big-bubble (BB) formation success rates in deep anterior lamellar keratoplasty (DALK) at various corneal depths using real-time guidance from swept-source, microscope-integrated optical coherence tomography (SS-MIOCT).

Methods: The DALK procedure was performed ex vivo with 34 human donor corneoscleral buttons on pressurized artificial anterior chambers using the BB technique employed by Anwar and Teichmann. We inserted a needle under controlled ex vivo conditions to corneal depths ranging from 40% to ≥90% using real-time guidance from SS-MIOCT and injected air.

Intraoperative 4-Dimensional Microscope-Integrated Optical Coherence Tomography-Guided 27-Gauge Transvitreal Choroidal Biopsy for Choroidal Melanoma.

Purpose: We describe two cases of intraoperative 4D microscope–integrated swept source optical coherence tomography (4D MIOCT) guided 27-gauge transvitreal retinochoroidal biopsy for choroidal melanoma.

Methods: Two 68-year-old females with choroidal melanomas underwent a transvitreal 27-gauge vitrectomy assisted chorioretinal biopsy for histologic and cytogenetic testing during I-125 radioactive episcleral plaque placement. A 4D (volumetric imaging through time) MIOCT device was used to simultaneously enable OCT image acquisition with surgical maneuvers during entry of and engagement of the vitreous cutter in the choroidal lesion.

Pupil Tracking for Real-Time Motion Corrected Anterior Segment Optical Coherence Tomography.

Volumetric acquisition with anterior segment optical coherence tomography (ASOCT) is necessary to obtain accurate representations of the tissue structure and to account for asymmetries of the anterior eye anatomy. Additionally, recent interest in imaging of anterior segment vasculature and aqueous humor flow resulted in application of OCT angiography techniques to generate en face and 3D micro-vasculature maps of the anterior segment. Unfortunately, ASOCT structural and vasculature imaging systems do not capture volumes instantaneously and are subject to motion artifacts due to involuntary eye motion that may hinder their accuracy and repeatability.

Optical Coherence Tomography for Retinal Surgery: Perioperative Analysis to Real-Time Four-Dimensional Image-Guided Surgery.

Magnification of the surgical field using the operating microscope facilitated profound innovations in retinal surgery in the 1970s, such as pars plana vitrectomy. Although surgical instrumentation and illumination techniques are continually developing, the operating microscope for vitreoretinal procedures has remained essentially unchanged and currently limits the surgeon's depth perception and assessment of subtle microanatomy. Optical coherence tomography (OCT) has revolutionized clinical management of retinal pathology, and its introduction into the operating suite may have a similar impact on surgical visualization and treatment.

Impact of Microscope-Integrated OCT on Ophthalmology Resident Performance of Anterior Segment Surgical Maneuvers in Model Eyes.

Purpose: The integration of swept-source optical coherence tomography (SS-OCT) into the operating microscope enables real-time, tissue-level three-dimensional (3D) imaging to aid in ophthalmic microsurgery. In this prospective randomized controlled study, we evaluated the impact of SS microscope-integrated OCT (MI-OCT) on ophthalmology residents' performance of ophthalmic microsurgical maneuvers.

Methods: Fourteen ophthalmology residents from a single institution were stratified by year of training and randomized to perform four anterior segment surgical maneuvers on porcine eyes with (MI-OCT+) or without (MI-OCT-) direct intraoperative OCT guidance.