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

EDDense-Net: Fully Dense Encoder Decoder Network for Joint Segmentation of Optic Cup and Disc

Glaucoma is an eye disease that causes damage to the optic nerve, which can lead to visual loss and permanent blindness. Early glaucoma detection is therefore critical in order to avoid permanent blindness. The estimation of the cup-to-disc ratio (CDR) during an examination of the optical disc (OD) is used for the diagnosis of glaucoma. In this paper, we present the EDDense-Net segmentation network for the joint segmentation of OC and OD. The encoder and decoder in this network are made up of dense blocks with a grouped convolutional layer in each block, allowing the network to acquire and convey spatial information from the image while simultaneously reducing the network's complexity. To reduce spatial information loss, the optimal number of filters in all convolution layers were utilised. In semantic segmentation, dice pixel classification is employed in the decoder to alleviate the problem of class imbalance. The proposed network was evaluated on two publicly available datasets where it outperformed existing state-of-the-art methods in terms of accuracy and efficiency. For the diagnosis and analysis of glaucoma, this method can be used as a second opinion system to assist medical ophthalmologists

Machine Learning for Glaucoma Assessment using Fundus Images

[ES] Las imágenes de fondo de ojo son muy utilizadas por los oftalmólogos para la evaluación de la retina y la detección de glaucoma. Esta patología es la segunda causa de ceguera en el mundo, según estudios de la Organización Mundial de la Salud (OMS). En esta tesis doctoral, se estudian algoritmos de aprendizaje automático (machine learning) para la evaluación automática del glaucoma usando imágenes de fondo de ojo. En primer lugar, se proponen dos métodos para la segmentación automática. El primer método utiliza la transformación Watershed Estocástica para segmentar la copa óptica y posteriormente medir características clínicas como la relación Copa/Disco y la regla ISNT. El segundo método es una arquitectura U-Net que se usa específicamente para la segmentación del disco óptico y la copa óptica. A continuación, se presentan sistemas automáticos de evaluación del glaucoma basados en redes neuronales convolucionales (CNN por sus siglas en inglés). En este enfoque se utilizan diferentes modelos entrenados en ImageNet como clasificadores automáticos de glaucoma, usando fine-tuning. Esta nueva técnica permite detectar el glaucoma sin segmentación previa o extracción de características. Además, este enfoque presenta una mejora considerable del rendimiento comparado con otros trabajos del estado del arte. En tercer lugar, dada la dificultad de obtener grandes cantidades de imágenes etiquetadas (glaucoma/no glaucoma), esta tesis también aborda el problema de la síntesis de imágenes de la retina. En concreto se analizaron dos arquitecturas diferentes para la síntesis de imágenes, las arquitecturas Variational Autoencoder (VAE) y la Generative Adversarial Networks (GAN). Con estas arquitecturas se generaron imágenes sintéticas que se analizaron cualitativa y cuantitativamente, obteniendo un rendimiento similar a otros trabajos en la literatura. Finalmente, en esta tesis se plantea la utilización de un tipo de GAN (DCGAN) como alternativa a los sistemas automáticos de evaluación del glaucoma presentados anteriormente. Para alcanzar este objetivo se implementó un algoritmo de aprendizaje semi-supervisado.[CA] Les imatges de fons d'ull són molt utilitzades pels oftalmòlegs per a l'avaluació de la retina i la detecció de glaucoma. Aquesta patologia és la segona causa de ceguesa al món, segons estudis de l'Organització Mundial de la Salut (OMS). En aquesta tesi doctoral, s'estudien algoritmes d'aprenentatge automàtic (machine learning) per a l'avaluació automàtica del glaucoma usant imatges de fons d'ull. En primer lloc, es proposen dos mètodes per a la segmentació automàtica. El primer mètode utilitza la transformació Watershed Estocàstica per segmentar la copa òptica i després mesurar característiques clíniques com la relació Copa / Disc i la regla ISNT. El segon mètode és una arquitectura U-Net que s'usa específicament per a la segmentació del disc òptic i la copa òptica. A continuació, es presenten sistemes automàtics d'avaluació del glaucoma basats en xarxes neuronals convolucionals (CNN per les sigles en anglès). En aquest enfocament s'utilitzen diferents models entrenats en ImageNet com classificadors automàtics de glaucoma, usant fine-tuning. Aquesta nova tècnica permet detectar el glaucoma sense segmentació prèvia o extracció de característiques. A més, aquest enfocament presenta una millora considerable del rendiment comparat amb altres treballs de l'estat de l'art. En tercer lloc, donada la dificultat d'obtenir grans quantitats d'imatges etiquetades (glaucoma / no glaucoma), aquesta tesi també aborda el problema de la síntesi d'imatges de la retina. En concret es van analitzar dues arquitectures diferents per a la síntesi d'imatges, les arquitectures Variational Autoencoder (VAE) i la Generative adversarial Networks (GAN). Amb aquestes arquitectures es van generar imatges sintètiques que es van analitzar qualitativament i quantitativament, obtenint un rendiment similar a altres treballs a la literatura. Finalment, en aquesta tesi es planteja la utilització d'un tipus de GAN (DCGAN) com a alternativa als sistemes automàtics d'avaluació del glaucoma presentats anteriorment. Per assolir aquest objectiu es va implementar un algoritme d'aprenentatge semi-supervisat.[EN] Fundus images are widely used by ophthalmologists to assess the retina and detect glaucoma, which is, according to studies from the World Health Organization (WHO), the second cause of blindness worldwide. In this thesis, machine learning algorithms for automatic glaucoma assessment using fundus images are studied. First, two methods for automatic segmentation are proposed. The first method uses the Stochastic Watershed transformation to segment the optic cup and measures clinical features such as the Cup/Disc ratio and ISNT rule. The second method is a U-Net architecture focused on the optic disc and optic cup segmentation task. Secondly, automated glaucoma assessment systems using convolutional neural networks (CNNs) are presented. In this approach, different ImageNet-trained models are fine-tuned and used as automatic glaucoma classifiers. These new techniques allow detecting glaucoma without previous segmentation or feature extraction. Moreover, it improves the performance of other state-of-art works. Thirdly, given the difficulty of getting large amounts of glaucoma-labelled images, this thesis addresses the problem of retinal image synthesis. Two different architectures for image synthesis, the Variational Autoencoder (VAE) and Generative Adversarial Networks (GAN) architectures, were analysed. Using these models, synthetic images that were qualitative and quantitative analysed, reporting state-of-the-art performance, were generated. Finally, an adversarial model is used to create an alternative automatic glaucoma assessment system. In this part, a semi-supervised learning algorithm was implemented to reach this goal.The research derived from this doctoral thesis has been supported by the Generalitat Valenciana under the scholarship Santiago Grisolía [GRISOLIA/2015/027].Díaz Pinto, AY. (2019). Machine Learning for Glaucoma Assessment using Fundus Images [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124351TESI

NON-INVASIVE IMAGE DENOISING AND CONTRAST ENHANCEMENT TECHNIQUES FOR RETINAL FUNDUS IMAGES

The analysis of retinal vasculature in digital fundus images is important for diagnosing eye related diseases. However, digital colour fundus images suffer from low and varied contrast, and are also affected by noise, requiring the use of fundus angiogram modality. The Fundus Fluorescein Angiogram (FFA) modality gives 5 to 6 time’s higher contrast. However, FFA is an invasive method that requires contrast agents to be injected and this can lead other physiological problems. A reported digital image enhancement technique named RETICA that combines Retinex and ICA (Independent Component Analysis) techniques, reduces varied contrast, and enhances the low contrast blood vessels of model fundus images

Towards PACE-CAD Systems

Despite phenomenal advancements in the availability of medical image datasets and the development of modern classification algorithms, Computer-Aided Diagnosis (CAD) has had limited practical exposure in the real-world clinical workflow. This is primarily because of the inherently demanding and sensitive nature of medical diagnosis that can have far-reaching and serious repercussions in case of misdiagnosis. In this work, a paradigm called PACE (Pragmatic, Accurate, Confident, & Explainable) is presented as a set of some of must-have features for any CAD. Diagnosis of glaucoma using Retinal Fundus Images (RFIs) is taken as the primary use case for development of various methods that may enrich an ordinary CAD system with PACE. However, depending on specific requirements for different methods, other application areas in ophthalmology and dermatology have also been explored. Pragmatic CAD systems refer to a solution that can perform reliably in day-to-day clinical setup. In this research two, of possibly many, aspects of a pragmatic CAD are addressed. Firstly, observing that the existing medical image datasets are small and not representative of images taken in the real-world, a large RFI dataset for glaucoma detection is curated and published. Secondly, realising that a salient attribute of a reliable and pragmatic CAD is its ability to perform in a range of clinically relevant scenarios, classification of 622 unique cutaneous diseases in one of the largest publicly available datasets of skin lesions is successfully performed. Accuracy is one of the most essential metrics of any CAD system's performance. Domain knowledge relevant to three types of diseases, namely glaucoma, Diabetic Retinopathy (DR), and skin lesions, is industriously utilised in an attempt to improve the accuracy. For glaucoma, a two-stage framework for automatic Optic Disc (OD) localisation and glaucoma detection is developed, which marked new state-of-the-art for glaucoma detection and OD localisation. To identify DR, a model is proposed that combines coarse-grained classifiers with fine-grained classifiers and grades the disease in four stages with respect to severity. Lastly, different methods of modelling and incorporating metadata are also examined and their effect on a model's classification performance is studied. Confidence in diagnosing a disease is equally important as the diagnosis itself. One of the biggest reasons hampering the successful deployment of CAD in the real-world is that medical diagnosis cannot be readily decided based on an algorithm's output. Therefore, a hybrid CNN architecture is proposed with the convolutional feature extractor trained using point estimates and a dense classifier trained using Bayesian estimates. Evaluation on 13 publicly available datasets shows the superiority of this method in terms of classification accuracy and also provides an estimate of uncertainty for every prediction. Explainability of AI-driven algorithms has become a legal requirement after Europe’s General Data Protection Regulations came into effect. This research presents a framework for easy-to-understand textual explanations of skin lesion diagnosis. The framework is called ExAID (Explainable AI for Dermatology) and relies upon two fundamental modules. The first module uses any deep skin lesion classifier and performs detailed analysis on its latent space to map human-understandable disease-related concepts to the latent representation learnt by the deep model. The second module proposes Concept Localisation Maps, which extend Concept Activation Vectors by locating significant regions corresponding to a learned concept in the latent space of a trained image classifier. This thesis probes many viable solutions to equip a CAD system with PACE. However, it is noted that some of these methods require specific attributes in datasets and, therefore, not all methods may be applied on a single dataset. Regardless, this work anticipates that consolidating PACE into a CAD system can not only increase the confidence of medical practitioners in such tools but also serve as a stepping stone for the further development of AI-driven technologies in healthcare

Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography

Tesis por compendio[ES] Esta tesis presenta soluciones de vanguardia basadas en algoritmos de computer vision (CV) y machine learning (ML) para ayudar a los expertos en el diagnóstico clínico. Se centra en dos áreas relevantes en el campo de la imagen médica: la patología digital y la oftalmología. Este trabajo propone diferentes paradigmas de machine learning y deep learning para abordar diversos escenarios de supervisión en el estudio del cáncer de próstata, el cáncer de vejiga y el glaucoma. En particular, se consideran métodos supervisados convencionales para segmentar y clasificar estructuras específicas de la próstata en imágenes histológicas digitalizadas. Para el reconocimiento de patrones específicos de la vejiga, se llevan a cabo enfoques totalmente no supervisados basados en técnicas de deep-clustering. Con respecto a la detección del glaucoma, se aplican algoritmos de memoria a corto plazo (LSTMs) que permiten llevar a cabo un aprendizaje recurrente a partir de volúmenes de tomografía por coherencia óptica en el dominio espectral (SD-OCT). Finalmente, se propone el uso de redes neuronales prototípicas (PNN) en un marco de few-shot learning para determinar el nivel de gravedad del glaucoma a partir de imágenes OCT circumpapilares. Los métodos de inteligencia artificial (IA) que se detallan en esta tesis proporcionan una valiosa herramienta de ayuda al diagnóstico por imagen, ya sea para el diagnóstico histológico del cáncer de próstata y vejiga o para la evaluación del glaucoma a partir de datos de OCT.[CA] Aquesta tesi presenta solucions d'avantguarda basades en algorismes de *computer *vision (CV) i *machine *learning (ML) per a ajudar als experts en el diagnòstic clínic. Se centra en dues àrees rellevants en el camp de la imatge mèdica: la patologia digital i l'oftalmologia. Aquest treball proposa diferents paradigmes de *machine *learning i *deep *learning per a abordar diversos escenaris de supervisió en l'estudi del càncer de pròstata, el càncer de bufeta i el glaucoma. En particular, es consideren mètodes supervisats convencionals per a segmentar i classificar estructures específiques de la pròstata en imatges histològiques digitalitzades. Per al reconeixement de patrons específics de la bufeta, es duen a terme enfocaments totalment no supervisats basats en tècniques de *deep-*clustering. Respecte a la detecció del glaucoma, s'apliquen algorismes de memòria a curt termini (*LSTMs) que permeten dur a terme un aprenentatge recurrent a partir de volums de tomografia per coherència òptica en el domini espectral (SD-*OCT). Finalment, es proposa l'ús de xarxes neuronals *prototípicas (*PNN) en un marc de *few-*shot *learning per a determinar el nivell de gravetat del glaucoma a partir d'imatges *OCT *circumpapilares. Els mètodes d'intel·ligència artificial (*IA) que es detallen en aquesta tesi proporcionen una valuosa eina d'ajuda al diagnòstic per imatge, ja siga per al diagnòstic histològic del càncer de pròstata i bufeta o per a l'avaluació del glaucoma a partir de dades d'OCT.[EN] This thesis presents cutting-edge solutions based on computer vision (CV) and machine learning (ML) algorithms to assist experts in clinical diagnosis. It focuses on two relevant areas at the forefront of medical imaging: digital pathology and ophthalmology. This work proposes different machine learning and deep learning paradigms to address various supervisory scenarios in the study of prostate cancer, bladder cancer and glaucoma. In particular, conventional supervised methods are considered for segmenting and classifying prostate-specific structures in digitised histological images. For bladder-specific pattern recognition, fully unsupervised approaches based on deep-clustering techniques are carried out. Regarding glaucoma detection, long-short term memory algorithms (LSTMs) are applied to perform recurrent learning from spectral-domain optical coherence tomography (SD-OCT) volumes. Finally, the use of prototypical neural networks (PNNs) in a few-shot learning framework is proposed to determine the severity level of glaucoma from circumpapillary OCT images. The artificial intelligence (AI) methods detailed in this thesis provide a valuable tool to aid diagnostic imaging, whether for the histological diagnosis of prostate and bladder cancer or glaucoma assessment from OCT data.García Pardo, JG. (2022). Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182400Compendi