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

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

GAN-Based Super-Resolution And Segmentation Of Retinal Layers In Optical Coherence Tomography Scans

Optical Coherence Tomography (OCT) has been identified as a noninvasive and cost-effective imaging modality for identifying potential biomarkers for Alzheimer\u27s diagnosis and progress detection. Current hypotheses indicate that retinal layer thickness, which can be assessed via OCT scans, is an efficient biomarker for identifying Alzheimer\u27s disease. Due to factors such as speckle noise, a small target region, and unfavorable imaging conditions manual segmentation of retina layers is a challenging task. Therefore, as a reasonable first step, this study focuses on automatically segmenting retinal layers to separate them for subsequent investigations. Another important challenge commonly faced is the lack of clarity of the layer boundaries in retina OCT scans, which compels the research of super-resolving the images for improved clarity. Deep learning pipelines have stimulated substantial progress for the segmentation tasks. Generative adversarial networks (GANs) are a prominent field of deep learning which achieved astonishing performance in semantic segmentation. Conditional adversarial networks as a general-purpose solution to image-to-image translation problems not only learn the mapping from the input image to the output image but also learn a loss function to train this mapping. We propose a GAN-based segmentation model and evaluate incorporating popular networks, namely, U-Net and ResNet, in the GAN architecture with additional blocks of transposed convolution and sub-pixel convolution for the task of upscaling OCT images from low to high resolution by a factor of four. We also incorporate the Dice loss as an additional reconstruction loss term to improve the performance of this joint optimization task. Our best model configuration empirically achieved the Dice coefficient of 0.867 and mIOU of 0.765

RetiFluidNet: A Self-Adaptive and Multi-Attention Deep Convolutional Network for Retinal OCT Fluid Segmentation

Optical coherence tomography (OCT) helps ophthalmologists assess macular edema, accumulation of fluids, and lesions at microscopic resolution. Quantification of retinal fluids is necessary for OCT-guided treatment management, which relies on a precise image segmentation step. As manual analysis of retinal fluids is a time-consuming, subjective, and error-prone task, there is increasing demand for fast and robust automatic solutions. In this study, a new convolutional neural architecture named RetiFluidNet is proposed for multi-class retinal fluid segmentation. The model benefits from hierarchical representation learning of textural, contextual, and edge features using a new self-adaptive dual-attention (SDA) module, multiple self-adaptive attention-based skip connections (SASC), and a novel multi-scale deep self supervision learning (DSL) scheme. The attention mechanism in the proposed SDA module enables the model to automatically extract deformation-aware representations at different levels, and the introduced SASC paths further consider spatial-channel interdependencies for concatenation of counterpart encoder and decoder units, which improve representational capability. RetiFluidNet is also optimized using a joint loss function comprising a weighted version of dice overlap and edge-preserved connectivity-based losses, where several hierarchical stages of multi-scale local losses are integrated into the optimization process. The model is validated based on three publicly available datasets: RETOUCH, OPTIMA, and DUKE, with comparisons against several baselines. Experimental results on the datasets prove the effectiveness of the proposed model in retinal OCT fluid segmentation and reveal that the suggested method is more effective than existing state-of-the-art fluid segmentation algorithms in adapting to retinal OCT scans recorded by various image scanning instruments.Comment: 11 pages, Early Access Version, IEEE Transactions on Medical Imagin

A new convolutional neural network based on combination of circlets and wavelets for macular OCT classification

Artificial intelligence (AI) algorithms, encompassing machine learning and deep learning, can assist ophthalmologists in early detection of various ocular abnormalities through the analysis of retinal optical coherence tomography (OCT) images. Despite considerable progress in these algorithms, several limitations persist in medical imaging fields, where a lack of data is a common issue. Accordingly, specific image processing techniques, such as time–frequency transforms, can be employed in conjunction with AI algorithms to enhance diagnostic accuracy. This research investigates the influence of non-data-adaptive time–frequency transforms, specifically X-lets, on the classification of OCT B-scans. For this purpose, each B-scan was transformed using every considered X-let individually, and all the sub-bands were utilized as the input for a designed 2D Convolutional Neural Network (CNN) to extract optimal features, which were subsequently fed to the classifiers. Evaluating per-class accuracy shows that the use of the 2D Discrete Wavelet Transform (2D-DWT) yields superior outcomes for normal cases, whereas the circlet transform outperforms other X-lets for abnormal cases characterized by circles in their retinal structure (due to the accumulation of fluid). As a result, we propose a novel transform named CircWave by concatenating all sub-bands from the 2D-DWT and the circlet transform. The objective is to enhance the per-class accuracy of both normal and abnormal cases simultaneously. Our findings show that classification results based on the CircWave transform outperform those derived from original images or any individual transform. Furthermore, Grad-CAM class activation visualization for B-scans reconstructed from CircWave sub-bands highlights a greater emphasis on circular formations in abnormal cases and straight lines in normal cases, in contrast to the focus on irrelevant regions in original B-scans. To assess the generalizability of our method, we applied it to another dataset obtained from a different imaging system. We achieved promising accuracies of 94.5% and 90% for the first and second datasets, respectively, which are comparable with results from previous studies. The proposed CNN based on CircWave sub-bands (i.e. CircWaveNet) not only produces superior outcomes but also offers more interpretable results with a heightened focus on features crucial for ophthalmologists

Going Deep in Medical Image Analysis: Concepts, Methods, Challenges and Future Directions

Medical Image Analysis is currently experiencing a paradigm shift due to Deep Learning. This technology has recently attracted so much interest of the Medical Imaging community that it led to a specialized conference in `Medical Imaging with Deep Learning' in the year 2018. This article surveys the recent developments in this direction, and provides a critical review of the related major aspects. We organize the reviewed literature according to the underlying Pattern Recognition tasks, and further sub-categorize it following a taxonomy based on human anatomy. This article does not assume prior knowledge of Deep Learning and makes a significant contribution in explaining the core Deep Learning concepts to the non-experts in the Medical community. Unique to this study is the Computer Vision/Machine Learning perspective taken on the advances of Deep Learning in Medical Imaging. This enables us to single out `lack of appropriately annotated large-scale datasets' as the core challenge (among other challenges) in this research direction. We draw on the insights from the sister research fields of Computer Vision, Pattern Recognition and Machine Learning etc.; where the techniques of dealing with such challenges have already matured, to provide promising directions for the Medical Imaging community to fully harness Deep Learning in the future

Semi-Weakly Supervised Learning for Label-efficient Semantic Segmentation in Expert-driven Domains

Unter Zuhilfenahme von Deep Learning haben semantische Segmentierungssysteme beeindruckende Ergebnisse erzielt, allerdings auf der Grundlage von überwachtem Lernen, das durch die Verfügbarkeit kostspieliger, pixelweise annotierter Bilder limitiert ist. Bei der Untersuchung der Performance dieser Segmentierungssysteme in Kontexten, in denen kaum Annotationen vorhanden sind, bleiben sie hinter den hohen Erwartungen, die durch die Performance in annotationsreichen Szenarien geschürt werden, zurück. Dieses Dilemma wiegt besonders schwer, wenn die Annotationen von lange geschultem Personal, z.B. Medizinern, Prozessexperten oder Wissenschaftlern, erstellt werden müssen. Um gut funktionierende Segmentierungsmodelle in diese annotationsarmen, Experten-angetriebenen Domänen zu bringen, sind neue Lösungen nötig. Zu diesem Zweck untersuchen wir zunächst, wie schlecht aktuelle Segmentierungsmodelle mit extrem annotationsarmen Szenarien in Experten-angetriebenen Bildgebungsdomänen zurechtkommen. Daran schließt sich direkt die Frage an, ob die kostspielige pixelweise Annotation, mit der Segmentierungsmodelle in der Regel trainiert werden, gänzlich umgangen werden kann, oder ob sie umgekehrt ein Kosten-effektiver Anstoß sein kann, um die Segmentierung in Gang zu bringen, wenn sie sparsam eingestetzt wird. Danach gehen wir auf die Frage ein, ob verschiedene Arten von Annotationen, schwache- und pixelweise Annotationen mit unterschiedlich hohen Kosten, gemeinsam genutzt werden können, um den Annotationsprozess flexibler zu gestalten. Experten-angetriebene Domänen haben oft nicht nur einen Annotationsmangel, sondern auch völlig andere Bildeigenschaften, beispielsweise volumetrische Bild-Daten. Der Übergang von der 2D- zur 3D-semantischen Segmentierung führt zu voxelweisen Annotationsprozessen, was den nötigen Zeitaufwand für die Annotierung mit der zusätzlichen Dimension multipliziert. Um zu einer handlicheren Annotation zu gelangen, untersuchen wir Trainingsstrategien für Segmentierungsmodelle, die nur preiswertere, partielle Annotationen oder rohe, nicht annotierte Volumina benötigen. Dieser Wechsel in der Art der Überwachung im Training macht die Anwendung der Volumensegmentierung in Experten-angetriebenen Domänen realistischer, da die Annotationskosten drastisch gesenkt werden und die Annotatoren von Volumina-Annotationen befreit werden, welche naturgemäß auch eine Menge visuell redundanter Regionen enthalten würden. Schließlich stellen wir die Frage, ob es möglich ist, die Annotations-Experten von der strikten Anforderung zu befreien, einen einzigen, spezifischen Annotationstyp liefern zu müssen, und eine Trainingsstrategie zu entwickeln, die mit einer breiten Vielfalt semantischer Information funktioniert. Eine solche Methode wurde hierzu entwickelt und in unserer umfangreichen experimentellen Evaluierung kommen interessante Eigenschaften verschiedener Annotationstypen-Mixe in Bezug auf deren Segmentierungsperformance ans Licht. Unsere Untersuchungen führten zu neuen Forschungsrichtungen in der semi-weakly überwachten Segmentierung, zu neuartigen, annotationseffizienteren Methoden und Trainingsstrategien sowie zu experimentellen Erkenntnissen, zur Verbesserung von Annotationsprozessen, indem diese annotationseffizient, expertenzentriert und flexibel gestaltet werden

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally