Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

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

Automatic analysis of retinal images to aid in the diagnosis and grading of diabetic retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus and one of the leading causes of preventable blindness in the adult working population. Visual loss can be prevented from the early stages of DR, when the treatments are effective. Therefore, early diagnosis is paramount. However, DR may be clinically asymptomatic until the advanced stage, when vision is already affected and treatment may become difficult. For this reason, diabetic patients should undergo regular eye examinations through screening programs. Traditionally, DR screening programs are run by trained specialists through visual inspection of the retinal images. However, this manual analysis is time consuming and expensive. With the increasing incidence of diabetes and the limited number of clinicians and sanitary resources, the early detection of DR becomes non-viable. For this reason, computed-aided diagnosis (CAD) systems are required to assist specialists for a fast, reliable diagnosis, allowing to reduce the workload and the associated costs. We hypothesize that the application of novel, automatic algorithms for fundus image analysis could contribute to the early diagnosis of DR. Consequently, the main objective of the present Doctoral Thesis is to study, design and develop novel methods based on the automatic analysis of fundus images to aid in the screening, diagnosis, and treatment of DR. In order to achieve the main goal, we built a private database and used five retinal public databases: DRIMDB, DIARETDB1, DRIVE, Messidor and Kaggle. The stages of fundus image processing covered in this Thesis are: retinal image quality assessment (RIQA), the location of the optic disc (OD) and the fovea, the segmentation of RLs and EXs, and the DR severity grading. RIQA was studied with two different approaches. The first approach was based on the combination of novel, global features. Results achieved 91.46% accuracy, 92.04% sensitivity, and 87.92% specificity using the private database. We developed a second approach aimed at RIQA based on deep learning. We achieved 95.29% accuracy with the private database and 99.48% accuracy with the DRIMDB database. The location of the OD and the fovea was performed using a combination of saliency maps. The proposed methods were evaluated over the private database and the public databases DRIVE, DIARETDB1 and Messidor. For the OD, we achieved 100% accuracy for all databases except Messidor (99.50%). As for the fovea location, we also reached 100% accuracy for all databases except Messidor (99.67%). The joint segmentation of RLs and EXs was accomplished by decomposing the fundus image into layers. Results were computed per pixel and per image. Using the private database, 88.34% per-image accuracy (ACCi) was reached for the RL detection and 95.41% ACCi for EX detection. An additional method was proposed for the segmentation of RLs based on superpixels. Evaluating this method with the private database, we obtained 84.45% ACCi. Results were validated using the DIARETDB1 database. Finally, we proposed a deep learning framework for the automatic DR severity grading. The method was based on a novel attention mechanism which performs a separate attention of the dark and the bright structures of the retina. The Kaggle DR detection dataset was used for development and validation. The International Clinical DR Scale was considered, which is made up of 5 DR severity levels. Classification results for all classes achieved 83.70% accuracy and a Quadratic Weighted Kappa of 0.78. The methods proposed in this Doctoral Thesis form a complete, automatic DR screening system, contributing to aid in the early detection of DR. In this way, diabetic patients could receive better attention for their ocular health avoiding vision loss. In addition, the workload of specialists could be relieved while healthcare costs are reduced.La retinopatía diabética (RD) es la complicación más común de la diabetes mellitus y una de las principales causas de ceguera prevenible en la población activa adulta. El diagnóstico precoz es primordial para prevenir la pérdida visual. Sin embargo, la RD es clínicamente asintomática hasta etapas avanzadas, cuando la visión ya está afectada. Por eso, los pacientes diabéticos deben someterse a exámenes oftalmológicos periódicos a través de programas de cribado. Tradicionalmente, estos programas están a cargo de especialistas y se basan de la inspección visual de retinografías. Sin embargo, este análisis manual requiere mucho tiempo y es costoso. Con la creciente incidencia de la diabetes y la escasez de recursos sanitarios, la detección precoz de la RD se hace inviable. Por esta razón, se necesitan sistemas de diagnóstico asistido por ordenador (CAD) que ayuden a los especialistas a realizar un diagnóstico rápido y fiable, que permita reducir la carga de trabajo y los costes asociados. El objetivo principal de la presente Tesis Doctoral es estudiar, diseñar y desarrollar nuevos métodos basados en el análisis automático de retinografías para ayudar en el cribado, diagnóstico y tratamiento de la RD. Las etapas estudiadas fueron: la evaluación de la calidad de la imagen retiniana (RIQA), la localización del disco óptico (OD) y la fóvea, la segmentación de RL y EX y la graduación de la severidad de la RD. RIQA se estudió con dos enfoques diferentes. El primer enfoque se basó en la combinación de características globales. Los resultados lograron una precisión del 91,46% utilizando la base de datos privada. El segundo enfoque se basó en aprendizaje profundo. Logramos un 95,29% de precisión con la base de datos privada y un 99,48% con la base de datos DRIMDB. La localización del OD y la fóvea se realizó mediante una combinación de mapas de saliencia. Los métodos propuestos fueron evaluados sobre la base de datos privada y las bases de datos públicas DRIVE, DIARETDB1 y Messidor. Para el OD, logramos una precisión del 100% para todas las bases de datos excepto Messidor (99,50%). En cuanto a la ubicación de la fóvea, también alcanzamos un 100% de precisión para todas las bases de datos excepto Messidor (99,67%). La segmentación conjunta de RL y EX se logró descomponiendo la imagen del fondo de ojo en capas. Utilizando la base de datos privada, se alcanzó un 88,34% de precisión por imagen (ACCi) para la detección de RL y un 95,41% de ACCi para la detección de EX. Se propuso un método adicional para la segmentación de RL basado en superpíxeles. Evaluando este método con la base de datos privada, obtuvimos 84.45% ACCi. Los resultados se validaron utilizando la base de datos DIARETDB1. Finalmente, propusimos un método de aprendizaje profundo para la graduación automática de la gravedad de la DR. El método se basó en un mecanismo de atención. Se utilizó la base de datos Kaggle y la Escala Clínica Internacional de RD (5 niveles de severidad). Los resultados de clasificación para todas las clases alcanzaron una precisión del 83,70% y un Kappa ponderado cuadrático de 0,78. Los métodos propuestos en esta Tesis Doctoral forman un sistema completo y automático de cribado de RD, contribuyendo a ayudar en la detección precoz de la RD. De esta forma, los pacientes diabéticos podrían recibir una mejor atención para su salud ocular evitando la pérdida de visión. Además, se podría aliviar la carga de trabajo de los especialistas al mismo tiempo que se reducen los costes sanitarios.Escuela de DoctoradoDoctorado en Tecnologías de la Información y las Telecomunicacione

Human treelike tubular structure segmentation: A comprehensive review and future perspectives

Various structures in human physiology follow a treelike morphology, which often expresses complexity at very fine scales. Examples of such structures are intrathoracic airways, retinal blood vessels, and hepatic blood vessels. Large collections of 2D and 3D images have been made available by medical imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), Optical coherence tomography (OCT) and ultrasound in which the spatial arrangement can be observed. Segmentation of these structures in medical imaging is of great importance since the analysis of the structure provides insights into disease diagnosis, treatment planning, and prognosis. Manually labelling extensive data by radiologists is often time-consuming and error-prone. As a result, automated or semi-automated computational models have become a popular research field of medical imaging in the past two decades, and many have been developed to date. In this survey, we aim to provide a comprehensive review of currently publicly available datasets, segmentation algorithms, and evaluation metrics. In addition, current challenges and future research directions are discussed

A retinal vasculature tracking system guided by a deep architecture

Many diseases such as diabetic retinopathy (DR) and cardiovascular diseases show their early signs on retinal vasculature. Analysing the vasculature in fundus images may provide a tool for ophthalmologists to diagnose eye-related diseases and to monitor their progression. These analyses may also facilitate the discovery of new relations between changes on retinal vasculature and the existence or progression of related diseases or to validate present relations. In this thesis, a data driven method, namely a Translational Deep Belief Net (a TDBN), is adapted to vasculature segmentation. The segmentation performance of the TDBN on low resolution images was found to be comparable to that of the best-performing methods. Later, this network is used for the implementation of super-resolution for the segmentation of high resolution images. This approach provided an acceleration during segmentation, which relates to down-sampling ratio of an input fundus image. Finally, the TDBN is extended for the generation of probability maps for the existence of vessel parts, namely vessel interior, centreline, boundary and crossing/bifurcation patterns in centrelines. These probability maps are used to guide a probabilistic vasculature tracking system. Although segmentation can provide vasculature existence in a fundus image, it does not give quantifiable measures for vasculature. The latter has more practical value in medical clinics. In the second half of the thesis, a retinal vasculature tracking system is presented. This system uses Particle Filters to describe vessel morphology and topology. Apart from previous studies, the guidance for tracking is provided with the combination of probability maps generated by the TDBN. The experiments on a publicly available dataset, REVIEW, showed that the consistency of vessel widths predicted by the proposed method was better than that obtained from observers. Moreover, very noisy and low contrast vessel boundaries, which were hardly identifiable to the naked eye, were accurately estimated by the proposed tracking system. Also, bifurcation/crossing locations during the course of tracking were detected almost completely. Considering these promising initial results, future work involves analysing the performance of the tracking system on automatic detection of complete vessel networks in fundus images.Open Acces

Applications of interpretability in deep learning models for ophthalmology

PURPOSE OF REVIEW: In this article, we introduce the concept of model interpretability, review its applications in deep learning models for clinical ophthalmology, and discuss its role in the integration of artificial intelligence in healthcare. RECENT FINDINGS: The advent of deep learning in medicine has introduced models with remarkable accuracy. However, the inherent complexity of these models undermines its users' ability to understand, debug and ultimately trust them in clinical practice. Novel methods are being increasingly explored to improve models' 'interpretability' and draw clearer associations between their outputs and features in the input dataset. In the field of ophthalmology, interpretability methods have enabled users to make informed adjustments, identify clinically relevant imaging patterns, and predict outcomes in deep learning models. SUMMARY: Interpretability methods support the transparency necessary to implement, operate and modify complex deep learning models. These benefits are becoming increasingly demonstrated in models for clinical ophthalmology. As quality standards for deep learning models used in healthcare continue to evolve, interpretability methods may prove influential in their path to regulatory approval and acceptance in clinical practice

Pixel-level semantic understanding of ophthalmic images and beyond

Computer-assisted semantic image understanding constitutes the substrate of applications that range from biomarker detection to intraoperative guidance or street scene understanding for self-driving systems. This PhD thesis is on the development of deep learning-based, pixel-level, semantic segmentation methods for medical and natural images. For vessel segmentation in OCT-A, a method comprising iterative refinement of the extracted vessel maps and an auxiliary loss function that penalizes structural inaccuracies, is proposed and tested on data captured from real clinical conditions comprising various pathological cases. Ultimately, the presented method enables the extraction of a detailed vessel map of the retina with potential applications to diagnostics or intraoperative localization. Furthermore, for scene segmentation in cataract surgery, the major challenge of class imbalance is identified among several factors. Subsequently, a method addressing it is proposed, achieving state-of-the-art performance on a challenging public dataset. Accurate semantic segmentation in this domain can be used to monitor interactions between tools and anatomical parts for intraoperative guidance and safety. Finally, this thesis proposes a novel contrastive learning framework for supervised semantic segmentation, that aims to improve the discriminative power of features in deep neural networks. The proposed approach leverages contrastive loss function applied both at multiple model layers and across them. Importantly, the proposed framework is easy to combine with various model architectures and is experimentally shown to significantly improve performance on both natural and medical domain

Machine Learning Approaches for Automated Glaucoma Detection using Clinical Data and Optical Coherence Tomography Images

Glaucoma is a multi-factorial, progressive blinding optic-neuropathy. A variety of factors, including genetics, vasculature, anatomy, and immune factors, are involved. Worldwide more than 80 million people are affected by glaucoma, and around 300,000 in Australia, where 50% remain undiagnosed. Untreated glaucoma can lead to blindness. Early detection by Artificial intelligence (AI) is crucial to accelerate the diagnosis process and can prevent further vision loss. Many proposed AI systems have shown promising performance for automated glaucoma detection using two-dimensional (2D) data. However, only a few studies had optimistic outcomes for glaucoma detection and staging. Moreover, the automated AI system still faces challenges in diagnosing at the clinicians’ level due to the lack of interpretability of the ML algorithms and integration of multiple clinical data. AI technology would be welcomed by doctors and patients if the "black box" notion is overcome by developing an explainable, transparent AI system with similar pathological markers used by clinicians as the sign of early detection and progression of glaucomatous damage. Therefore, the thesis aimed to develop a comprehensive AI model to detect and stage glaucoma by incorporating a variety of clinical data and utilising advanced data analysis and machine learning (ML) techniques. The research first focuses on optimising glaucoma diagnostic features by combining structural, functional, demographic, risk factor, and optical coherence tomography (OCT) features. The significant features were evaluated using statistical analysis and trained in ML algorithms to observe the detection performance. Three crucial structural ONH OCT features: cross-sectional 2D radial B-scan, 3D vascular angiography and temporal-superior-nasal-inferior-temporal (TSNIT) B-scan, were analysed and trained in explainable deep learning (DL) models for automated glaucoma prediction. The explanation behind the decision making of DL models were successfully demonstrated using the feature visualisation. The structural features or distinguished affected regions of TSNIT OCT scans were precisely localised for glaucoma patients. This is consistent with the concept of explainable DL, which refers to the idea of making the decision-making processes of DL models transparent and interpretable to humans. However, artifacts and speckle noise often result in misinterpretation of the TSNIT OCT scans. This research also developed an automated DL model to remove the artifacts and noise from the OCT scans, facilitating error-free retinal layers segmentation, accurate tissue thickness estimation and image interpretation. Moreover, to monitor and grade glaucoma severity, the visual field (VF) test is commonly followed by clinicians for treatment and management. Therefore, this research uses the functional features extracted from VF images to train ML algorithms for staging glaucoma from early to advanced/severe stages. Finally, the selected significant features were used to design and develop a comprehensive AI model to detect and grade glaucoma stages based on the data quantity and availability. In the first stage, a DL model was trained with TSNIT OCT scans, and its output was combined with significant structural and functional features and trained in ML models. The best-performed ML model achieved an area under the curve (AUC): 0.98, an accuracy of 97.2%, a sensitivity of 97.9%, and a specificity of 96.4% for detecting glaucoma. The model achieved an overall accuracy of 90.7% and an F1 score of 84.0% for classifying normal, early, moderate, and advanced-stage glaucoma. In conclusion, this thesis developed and proposed a comprehensive, evidence-based AI model that will solve the screening problem for large populations and relieve experts from manually analysing a slew of patient data and associated misinterpretation problems. Moreover, this thesis demonstrated three structural OCT features that could be added as excellent diagnostic markers for precise glaucoma diagnosis