Deep Learning Techniques for Automated Analysis and Processing of High Resolution Medical Imaging

Programa Oficial de Doutoramento en Computación . 5009V01[Abstract] Medical imaging plays a prominent role in modern clinical practice for numerous medical specialties. For instance, in ophthalmology, different imaging techniques are commonly used to visualize and study the eye fundus. In this context, automated image analysis methods are key towards facilitating the early diagnosis and adequate treatment of several diseases. Nowadays, deep learning algorithms have already demonstrated a remarkable performance for different image analysis tasks. However, these approaches typically require large amounts of annotated data for the training of deep neural networks. This complicates the adoption of deep learning approaches, especially in areas where large scale annotated datasets are harder to obtain, such as in medical imaging. This thesis aims to explore novel approaches for the automated analysis of medical images, particularly in ophthalmology. In this regard, the main focus is on the development of novel deep learning-based approaches that do not require large amounts of annotated training data and can be applied to high resolution images. For that purpose, we have presented a novel paradigm that allows to take advantage of unlabeled complementary image modalities for the training of deep neural networks. Additionally, we have also developed novel approaches for the detailed analysis of eye fundus images. In that regard, this thesis explores the analysis of relevant retinal structures as well as the diagnosis of different retinal diseases. In general, the developed algorithms provide satisfactory results for the analysis of the eye fundus, even when limited annotated training data is available.[Resumen] Las técnicas de imagen tienen un papel destacado en la práctica clínica moderna de numerosas especialidades médicas. Por ejemplo, en oftalmología es común el uso de diferentes técnicas de imagen para visualizar y estudiar el fondo de ojo. En este contexto, los métodos automáticos de análisis de imagen son clave para facilitar el diagnóstico precoz y el tratamiento adecuado de diversas enfermedades. En la actualidad, los algoritmos de aprendizaje profundo ya han demostrado un notable rendimiento en diferentes tareas de análisis de imagen. Sin embargo, estos métodos suelen necesitar grandes cantidades de datos etiquetados para el entrenamiento de las redes neuronales profundas. Esto complica la adopción de los métodos de aprendizaje profundo, especialmente en áreas donde los conjuntos masivos de datos etiquetados son más difíciles de obtener, como es el caso de la imagen médica. Esta tesis tiene como objetivo explorar nuevos métodos para el análisis automático de imagen médica, concretamente en oftalmología. En este sentido, el foco principal es el desarrollo de nuevos métodos basados en aprendizaje profundo que no requieran grandes cantidades de datos etiquetados para el entrenamiento y puedan aplicarse a imágenes de alta resolución. Para ello, hemos presentado un nuevo paradigma que permite aprovechar modalidades de imagen complementarias no etiquetadas para el entrenamiento de redes neuronales profundas. Además, también hemos desarrollado nuevos métodos para el análisis en detalle de las imágenes del fondo de ojo. En este sentido, esta tesis explora el análisis de estructuras retinianas relevantes, así como el diagnóstico de diferentes enfermedades de la retina. En general, los algoritmos desarrollados proporcionan resultados satisfactorios para el análisis de las imágenes de fondo de ojo, incluso cuando la disponibilidad de datos de entrenamiento etiquetados es limitada.[Resumo] As técnicas de imaxe teñen un papel destacado na práctica clínica moderna de numerosas especialidades médicas. Por exemplo, en oftalmoloxía é común o uso de diferentes técnicas de imaxe para visualizar e estudar o fondo de ollo. Neste contexto, os métodos automáticos de análises de imaxe son clave para facilitar o diagn ostico precoz e o tratamento adecuado de diversas enfermidades. Na actualidade, os algoritmos de aprendizaxe profunda xa demostraron un notable rendemento en diferentes tarefas de análises de imaxe. Con todo, estes métodos adoitan necesitar grandes cantidades de datos etiquetos para o adestramento das redes neuronais profundas. Isto complica a adopción dos métodos de aprendizaxe profunda, especialmente en áreas onde os conxuntos masivos de datos etiquetados son máis difíciles de obter, como é o caso da imaxe médica. Esta tese ten como obxectivo explorar novos métodos para a análise automática de imaxe médica, concretamente en oftalmoloxía. Neste sentido, o foco principal é o desenvolvemento de novos métodos baseados en aprendizaxe profunda que non requiran grandes cantidades de datos etiquetados para o adestramento e poidan aplicarse a imaxes de alta resolución. Para iso, presentamos un novo paradigma que permite aproveitar modalidades de imaxe complementarias non etiquetadas para o adestramento de redes neuronais profundas. Ademais, tamén desenvolvemos novos métodos para a análise en detalle das imaxes do fondo de ollo. Neste sentido, esta tese explora a análise de estruturas retinianas relevantes, así como o diagnóstico de diferentes enfermidades da retina. En xeral, os algoritmos desenvolvidos proporcionan resultados satisfactorios para a análise das imaxes de fondo de ollo, mesmo cando a dispoñibilidade de datos de adestramento etiquetados é limitada

Self-Supervised Multimodal Reconstruction of Retinal Images Over Paired Datasets

[Abstract] Data scarcity represents an important constraint for the training of deep neural networks in medical imaging. Medical image labeling, especially if pixel-level annotations are required, is an expensive task that needs expert intervention and usually results in a reduced number of annotated samples. In contrast, extensive amounts of unlabeled data are produced in the daily clinical practice, including paired multimodal images from patients that were subjected to multiple imaging tests. This work proposes a novel self-supervised multimodal reconstruction task that takes advantage of this unlabeled multimodal data for learning about the domain without human supervision. Paired multimodal data is a rich source of clinical information that can be naturally exploited by trying to estimate one image modality from others. This multimodal reconstruction requires the recognition of domain-specific patterns that can be used to complement the training of image analysis tasks in the same domain for which annotated data is scarce. In this work, a set of experiments is performed using a multimodal setting of retinography and fluorescein angiography pairs that offer complementary information about the eye fundus. The evaluations performed on different public datasets, which include pathological and healthy data samples, demonstrate that a network trained for self-supervised multimodal reconstruction of angiography from retinography achieves unsupervised recognition of important retinal structures. These results indicate that the proposed self-supervised task provides relevant cues for image analysis tasks in the same domain.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Economía, Industria y Competitividad, Government of Spain, through the DPI2015-69948-R research project. The authors of this work also receive financial support from the ERDF and Xunta de Galicia through Grupo de Referencia Competitiva, Ref. ED431C 2016-047, and from the European Social Fund (ESF) of the EU and Xunta de Galicia through the predoctoral grant contract Ref. ED481A-2017/328. CITIC, Centro de Investigación de Galicia Ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431C 2016-047Xunta de Galicia; ED481A-2017/328Xunta de Galicia; ED431G 2019/0

Color Fundus Image Registration Using a Learning-Based Domain-Specific Landmark Detection Methodology

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Medical imaging, and particularly retinal imaging, allows to accurately diagnose many eye pathologies as well as some systemic diseases such as hypertension or diabetes. Registering these images is crucial to correctly compare key structures, not only within patients, but also to contrast data with a model or among a population. Currently, this field is dominated by complex classical methods because the novel deep learning methods cannot compete yet in terms of results and commonly used methods are difficult to adapt to the retinal domain. In this work, we propose a novel method to register color fundus images based on previous works which employed classical approaches to detect domain-specific landmarks. Instead, we propose to use deep learning methods for the detection of these highly-specific domain-related landmarks. Our method uses a neural network to detect the bifurcations and crossovers of the retinal blood vessels, whose arrangement and location are unique to each eye and person. This proposal is the first deep learning feature-based registration method in fundus imaging. These keypoints are matched using a method based on RANSAC (Random Sample Consensus) without the requirement to calculate complex descriptors. Our method was tested using the public FIRE dataset, although the landmark detection network was trained using the DRIVE dataset. Our method provides accurate results, a registration score of 0.657 for the whole FIRE dataset (0.908 for category S, 0.293 for category P and 0.660 for category A). Therefore, our proposal can compete with complex classical methods and beat the deep learning methods in the state of the art.This research was funded by Instituto de Salud Carlos III, Government of Spain, DTS18/00 136 research project; Ministerio de Ciencia e Innovación y Universidades, Government of Spain, RTI2018-095 894-B-I00 research project; Consellería de Cultura, Educación e Universidade, Xunta de Galicia through the predoctoral grant contract ref. ED481A 2021/147 and Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%). The funding institutions had no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED481A 2021/147Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Deep multi-instance heatmap regression for the detection of retinal vessel crossings and bifurcations in eye fundus images

©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. This version of the article: Hervella, Á. S., Rouco, J., Novo, J., Penedo, M. G., & Ortega, M. (2020). “Deep multi-instance heatmap regression for the detection of retinal vessel crossings and bifurcations in eye fundus images” has been accepted for publication in Computer Methods and Programs in Biomedicine, 186(105201), 105201. The Version of Record is available online at: https://doi.org/10.1016/j.cmpb.2019.105201.[Abstract]: Background and objectives:The analysis of the retinal vasculature plays an important role in the diagnosis of many ocular and systemic diseases. In this context, the accurate detection of the vessel crossings and bifurcations is an important requirement for the automated extraction of relevant biomarkers. In that regard, we propose a novel approach that addresses the simultaneous detection of vessel crossings and bifurcations in eye fundus images. Method: We propose to formulate the detection of vessel crossings and bifurcations in eye fundus images as a multi-instance heatmap regression. In particular, a deep neural network is trained in the prediction of multi-instance heatmaps that model the likelihood of a pixel being a landmark location. This novel approach allows to make predictions using full images and integrates into a single step the detection and distinction of the vascular landmarks. Results: The proposed method is validated on two public datasets of reference that include detailed annotations for vessel crossings and bifurcations in eye fundus images. The conducted experiments evidence that the proposed method offers a satisfactory performance. In particular, the proposed method achieves 74.23% and 70.90% F-score for the detection of crossings and bifurcations, respectively, in color fundus images. Furthermore, the proposed method outperforms previous works by a significant margin. Conclusions: The proposed multi-instance heatmap regression allows to successfully exploit the potential of modern deep learning algorithms for the simultaneous detection of retinal vessel crossings and bifurcations. Consequently, this results in a significant improvement over previous methods, which will further facilitate the automated analysis of the retinal vasculature in many pathological conditions.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Ciencia, Innovación y Universidades, Government of Spain, through the DPI2015-69948-R and RTI2018-095894-B-I00 research projects. The authors of this work also receive financial support from the ERDF and European Social Fund (ESF) of the EU, and Xunta de Galicia through Centro Singular de Investigación de Galicia, accreditation 2016–2019, ref. ED431G/01, Grupo de Referencia Competitiva, ref. ED431C 2016-047, and the predoctoral grant contract ref. ED481A-2017/328.Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-047Xunta de Galicia; ED481A-2017/32

Learning the Retinal Anatomy From Scarce Annotated Data Using Self-Supervised Multimodal Reconstruction

[Abstract] Deep learning is becoming the reference paradigm for approaching many computer vision problems. Nevertheless, the training of deep neural networks typically requires a significantly large amount of annotated data, which is not always available. A proven approach to alleviate the scarcity of annotated data is transfer learning. However, in practice, the use of this technique typically relies on the availability of additional annotations, either from the same or natural domain. We propose a novel alternative that allows to apply transfer learning from unlabelled data of the same domain, which consists in the use of a multimodal reconstruction task. A neural network trained to generate one image modality from another must learn relevant patterns from the images to successfully solve the task. These learned patterns can then be used to solve additional tasks in the same domain, reducing the necessity of a large amount of annotated data. In this work, we apply the described idea to the localization and segmentation of the most important anatomical structures of the eye fundus in retinography. The objective is to reduce the amount of annotated data that is required to solve the different tasks using deep neural networks. For that purpose, a neural network is pre-trained using the self-supervised multimodal reconstruction of fluorescein angiography from retinography. Then, the network is fine-tuned on the different target tasks performed on the retinography. The obtained results demonstrate that the proposed self-supervised transfer learning strategy leads to state-of-the-art performance in all the studied tasks with a significant reduction of the required annotations.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Economía, Industria y Competitividad, Government of Spain, through the DPI2015-69948-R research project. The authors of this work also receive financial support from the ERDF and Xunta de Galicia (Spain) through Grupo de Referencia Competitiva, ref. ED431C 2016-047, and from the European Social Fund (ESF) of the EU and Xunta de Galicia (Spain) through the predoctoral grant contract ref. ED481A-2017/328. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (Spain) , through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431C 2016-047Xunta de Galicia ; ED481A-2017/328Xunta de Galicia; ED431G 2019/0

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

Review on retrospective procedures to correct retinal motion artefacts in OCT imaging

Motion artefacts from involuntary changes in eye fixation remain a major imaging issue in optical coherence tomography (OCT). This paper reviews the state-of-the-art of retrospective procedures to correct retinal motion and axial eye motion artefacts in OCT imaging. Following an overview of motion induced artefacts and correction strategies, a chronological survey of retrospective approaches since the introduction of OCT until the current days is presented. Pre-processing, registration, and validation techniques are described. The review finishes by discussing the limitations of the current techniques and the challenges to be tackled in future developments

MEMO: Dataset and Methods for Robust Multimodal Retinal Image Registration with Large or Small Vessel Density Differences

The measurement of retinal blood flow (RBF) in capillaries can provide a powerful biomarker for the early diagnosis and treatment of ocular diseases. However, no single modality can determine capillary flowrates with high precision. Combining erythrocyte-mediated angiography (EMA) with optical coherence tomography angiography (OCTA) has the potential to achieve this goal, as EMA can measure the absolute 2D RBF of retinal microvasculature and OCTA can provide the 3D structural images of capillaries. However, multimodal retinal image registration between these two modalities remains largely unexplored. To fill this gap, we establish MEMO, the first public multimodal EMA and OCTA retinal image dataset. A unique challenge in multimodal retinal image registration between these modalities is the relatively large difference in vessel density (VD). To address this challenge, we propose a segmentation-based deep-learning framework (VDD-Reg) and a new evaluation metric (MSD), which provide robust results despite differences in vessel density. VDD-Reg consists of a vessel segmentation module and a registration module. To train the vessel segmentation module, we further designed a two-stage semi-supervised learning framework (LVD-Seg) combining supervised and unsupervised losses. We demonstrate that VDD-Reg outperforms baseline methods quantitatively and qualitatively for cases of both small VD differences (using the CF-FA dataset) and large VD differences (using our MEMO dataset). Moreover, VDD-Reg requires as few as three annotated vessel segmentation masks to maintain its accuracy, demonstrating its feasibility.Comment: Submitted to IEEE JBH