Deep learning algorithms to isolate and quantify the structures of the anterior segment in optical coherence tomography images

Background/Aims Accurate isolation and quantification of intraocular dimensions in the anterior segment (AS) of the eye using optical coherence tomography (OCT) images is important in the diagnosis and treatment of many eye diseases, especially angle-closure glaucoma. Method In this study, we developed a deep convolutional neural network (DCNN) for the localisation of the scleral spur; moreover, we introduced an information-rich segmentation approach for this localisation problem. An ensemble of DCNNs for the segmentation of AS structures (iris, corneosclera shell adn anterior chamber) was developed. Based on the results of two previous processes, an algorithm to automatically quantify clinically important measurements were created. 200 images from 58 patients (100 eyes) were used for testing. Results With limited training data, the DCNN was able to detect the scleral spur on unseen anterior segment optical coherence tomography (ASOCT) images as accurately as an experienced ophthalmologist on the given test dataset and simultaneously isolated the AS structures with a Dice coefficient of 95.7%. We then automatically extracted eight clinically relevant ASOCT measurements and proposed an automated quality check process that asserts the reliability of these measurements. When combined with an OCT machine capable of imaging multiple radial sections, the algorithms can provide a more complete objective assessment. The total segmentation and measurement time for a single scan is less than 2 s. Conclusion This is an essential step towards providing a robust automated framework for reliable quantification of ASOCT scans, for applications in the diagnosis and management of angle-closure glaucoma

Deep learning for optical coherence tomography angiography: Quantifying microvascular changes in diabetic retinopathy

Optical Coherence Tomography Angiography (OCT-A) permits visualization of the changes to the retinal circulation due to diabetic retinopathy (DR), a microvascular complication of diabetes. Machine learning applications have directly benefited ophthalmology, leveraging large amounts of data to create frameworks to aid clinical decision-making. In this thesis, several techniques to quantify the retinal microvasculature are explored. First, high-quality, averaged, 6x6mm OCT-A enface images are used to produce manual segmentations for the corresponding lower-quality, single-frame images to produce more training data. Using transfer learning, the resulting convolutional neural network (CNN) segmented the superficial capillary plexus and deep vascular complex with performance exceeding inter-rater comparisons. Next, a federated learning framework was designed to allow for collaborative training by multiple participants on a de-centralized data corpus. When trained for microvasculature segmentation, the framework achieved comparable performance to a CNN trained on a fully-centralized dataset

Automating the eye examination using optical coherence tomography

Optical coherence tomography (OCT) devices are becoming ubiquitous in eye clinics worldwide to aid the diagnosis and monitoring of eye disease. Much of this uptake relates to the ability to non-invasively capture micron-resolution images, enabling objective and quantitative data to be obtained from ocular structures. Although safe and reasonably quick to perform, the costs involved with operating OCT devices are not trivial, and the requirement for OCT and other imaging in addition to other clinical measures is placing increasing demand on ophthalmology clinics, contributing to fragmented patient pathways and often extended waiting times. In this thesis, a novel “binocular optical coherence tomography” system that seeks to overcome some of the limitations of current commercial OCT systems, is clinically evaluated. This device incorporates many aspects of the eye examination into a single patient-operated instrument, and aims to improve the efficiency and quality of eye care while reducing the overall labour and equipment costs. A progressive framework of testing is followed that includes human factors and usability testing, followed by early stage diagnostic studies to assess the agreement, repeatability, and reproducibility of individual diagnostic features. Health economics analysis of the retinal therapy clinic is used to model cost effectiveness of current practice and with binocular OCT implementation. The binocular OCT and development of other low-cost OCT systems may improve accessibility, however there remains a relative shortage of experts to interpret the images. Artificial intelligence (AI) is likely to play a role in rapid and automated image classification. This thesis explores the application of AI within retinal therapy clinics to predict the onset of exudative age-related macular degeneration in fellow eyes of patients undergoing treatment in their first eye. Together with automated and simultaneous imaging of both eyes with binocular OCT and the potential for low-cost patient-facing systems, AI is likely to have a role in personalising management plans, especially in a future where preventive treatments are available

Quantifying ocular inflammation in uveitis using optical coherence tomography

Inflammation is the key underlying physiological process in uveitis. It drives the onset of acute flares, causes permanent structural damage and can result in sight-threatening complications. Being able to accurately detect and measure changes in inflammatory activity is crucial for managing uveitic flares and rationalising therapeutic decisions. Unfortunately, many of the current methods for quantifying inflammation are imperfect, due to the fact that they are based on subjective and unreliable clinician estimates. In this thesis, I evaluated the potential for imaging-based technologies such as optical coherence tomography (OCT) to measure key markers of intraocular inflammation in uveitis. Whilst several key markers of inflammation are recognised, this thesis focuses on those with an existing clinical standard, which can be used as a comparator or reference test (anterior chamber cells, anterior chamber flare and vitreous haze). I conducted a series of systematic reviews evaluating potential instrument-based techniques for measuring anterior chamber cells, anterior chamber flare and vitreous inflammation, respectively. These identified OCT and laser flare photometry as potential instruments for measuring anterior chamber cell and flare, and OCT and retinal photography for measuring vitreous inflammation. However, the interpretation of results in each review was limited by relatively few studies and the inclusion of highly heterogenous uveitic patient populations, varying severities of disease, and lack of a standardised image acquisition protocol. Second, in the prospective study, OCTAVE (OCT-assisted vitreous evaluation), I found that our custom OCT-based vitreous analysis technique (EQUIP) demonstrated good repeatability in healthy and uveitic eyes, was able to detect vitreous inflammation and was associated with the current clinical vitreous haze grading. The EQUIP measurement was able to predict visual acuity whereas the current standard method (clinician grading 3 using the National Eye Institutevitreous haze scale) could not. Whilst these results were encouraging, there remains substantial overlap in the OCT measurement between NEI vitreous haze grades. It is not clear whether this is due to poor signal-to-noise ratio of the OCT technique, or a sign of poor reliability of the comparator (clinician-based grading using the NEI vitreous haze scale). Further investigation through longitudinal studies may be able to answer this question. In summary, OCT has demonstrated potential for quantifying inflammation for multiple key measures in uveitis. However, a key limitation for the validation of all instrument-based measures has been the lack of a reliable reference test

Deep Representation Learning with Limited Data for Biomedical Image Synthesis, Segmentation, and Detection

Biomedical imaging requires accurate expert annotation and interpretation that can aid medical staff and clinicians in automating differential diagnosis and solving underlying health conditions. With the advent of Deep learning, it has become a standard for reaching expert-level performance in non-invasive biomedical imaging tasks by training with large image datasets. However, with the need for large publicly available datasets, training a deep learning model to learn intrinsic representations becomes harder. Representation learning with limited data has introduced new learning techniques, such as Generative Adversarial Networks, Semi-supervised Learning, and Self-supervised Learning, that can be applied to various biomedical applications. For example, ophthalmologists use color funduscopy (CF) and fluorescein angiography (FA) to diagnose retinal degenerative diseases. However, fluorescein angiography requires injecting a dye, which can create adverse reactions in the patients. So, to alleviate this, a non-invasive technique needs to be developed that can translate fluorescein angiography from fundus images. Similarly, color funduscopy and optical coherence tomography (OCT) are also utilized to semantically segment the vasculature and fluid build-up in spatial and volumetric retinal imaging, which can help with the future prognosis of diseases. Although many automated techniques have been proposed for medical image segmentation, the main drawback is the model's precision in pixel-wise predictions. Another critical challenge in the biomedical imaging field is accurately segmenting and quantifying dynamic behaviors of calcium signals in cells. Calcium imaging is a widely utilized approach to studying subcellular calcium activity and cell function; however, large datasets have yielded a profound need for fast, accurate, and standardized analyses of calcium signals. For example, image sequences from calcium signals in colonic pacemaker cells ICC (Interstitial cells of Cajal) suffer from motion artifacts and high periodic and sensor noise, making it difficult to accurately segment and quantify calcium signal events. Moreover, it is time-consuming and tedious to annotate such a large volume of calcium image stacks or videos and extract their associated spatiotemporal maps. To address these problems, we propose various deep representation learning architectures that utilize limited labels and annotations to address the critical challenges in these biomedical applications. To this end, we detail our proposed semi-supervised, generative adversarial networks and transformer-based architectures for individual learning tasks such as retinal image-to-image translation, vessel and fluid segmentation from fundus and OCT images, breast micro-mass segmentation, and sub-cellular calcium events tracking from videos and spatiotemporal map quantification. We also illustrate two multi-modal multi-task learning frameworks with applications that can be extended to other domains of biomedical applications. The main idea is to incorporate each of these as individual modules to our proposed multi-modal frameworks to solve the existing challenges with 1) Fluorescein angiography synthesis, 2) Retinal vessel and fluid segmentation, 3) Breast micro-mass segmentation, and 4) Dynamic quantification of calcium imaging datasets

A fully automated pipeline for a robust conjunctival hyperemia estimation

Purpose: Many semi-automated and fully-automated approaches have been proposed in literature to improve the objectivity of the estimation of conjunctival hyperemia, based on image processing analysis of eyes’ photographs. The purpose is to improve its evaluation using faster fully-automated systems and independent by the human subjectivity. Methods: In this work, we introduce a fully-automated analysis of the redness grading scales able to completely automatize the clinical procedure, starting from the acquired image to the redness estimation. In particular, we introduce a neural network model for the conjunctival segmentation followed by an image processing pipeline for the vessels network segmentation. From these steps, we extract some features already known in literature and whose correlation with the conjunctival redness has already been proved. Lastly, we implemented a predictive model for the conjunctival hyperemia using these features. Results: In this work, we used a dataset of images acquired during clinical practice.We trained a neural network model for the conjunctival segmentation, obtaining an average accuracy of 0.94 and a corresponding IoU score of 0.88 on a test set of images. The set of features extracted on these ROIs is able to correctly predict the Efron scale values with a Spearman’s correlation coefficient of 0.701 on a set of not previously used samples. Conclusions: The robustness of our pipeline confirms its possible usage in a clinical practice as a viable decision support system for the ophthalmologists

Optical coherence tomography angiography

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detailed far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid, and the requirement for understanding the origins of image artifacts. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole