Deep learning for diabetic retinopathy detection and classification based on fundus images: A review.

Diabetic Retinopathy is a retina disease caused by diabetes mellitus and it is the leading cause of blindness globally. Early detection and treatment are necessary in order to delay or avoid vision deterioration and vision loss. To that end, many artificial-intelligence-powered methods have been proposed by the research community for the detection and classification of diabetic retinopathy on fundus retina images. This review article provides a thorough analysis of the use of deep learning methods at the various steps of the diabetic retinopathy detection pipeline based on fundus images. We discuss several aspects of that pipeline, ranging from the datasets that are widely used by the research community, the preprocessing techniques employed and how these accelerate and improve the models' performance, to the development of such deep learning models for the diagnosis and grading of the disease as well as the localization of the disease's lesions. We also discuss certain models that have been applied in real clinical settings. Finally, we conclude with some important insights and provide future research directions

Advanced Representation Learning for Dense Prediction Tasks in Medical Image Analysis

Machine learning is a rapidly growing field of artificial intelligence that allows computers to learn and make predictions using human labels. However, traditional machine learning methods have many drawbacks, such as being time-consuming, inefficient, task-specific biased, and requiring a large amount of domain knowledge. A subfield of machine learning, representation learning, focuses on learning meaningful and useful features or representations from input data. It aims to automatically learn relevant features from raw data, saving time, increasing efficiency and generalization, and reducing reliance on expert knowledge. Recently, deep learning has further accelerated the development of representation learning. It leverages deep architectures to extract complex and abstract representations, resulting in significant outperformance in many areas. In the field of computer vision, deep learning has made remarkable progress, particularly in high-level and real-world computer vision tasks. Since deep learning methods do not require handcrafted features and have the ability to understand complex visual information, they facilitate researchers to design automated systems that make accurate diagnoses and interpretations, especially in the field of medical image analysis. Deep learning has achieved state-of-the-art performance in many medical image analysis tasks, such as medical image regression/classification, generation and segmentation tasks. Compared to regression/classification tasks, medical image generation and segmentation tasks are more complex dense prediction tasks that understand semantic representations and generate pixel-level predictions. This thesis focuses on designing representation learning methods to improve the performance of dense prediction tasks in the field of medical image analysis. With advances in imaging technology, more complex medical images become available for use in this field. In contrast to traditional machine learning algorithms, current deep learning-based representation learning methods provide an end-to-end approach to automatically extract representations without the need for manual feature engineering from the complex data. In the field of medical image analysis, there are three unique challenges requiring the design of advanced representation learning architectures, \ie, limited labeled medical images, overfitting with limited data, and lack of interpretability. To address these challenges, we aim to design robust representation learning architectures for the two main directions of dense prediction tasks, namely medical image generation and segmentation. For medical image generation, the specific topic that we focus on is chromosome straightening. This task involves generating a straightened chromosome image from a curved chromosome input. In addition, the challenges of this task include insufficient training images and corresponding ground truth, as well as the non-rigid nature of chromosomes, leading to distorted details and shapes after straightening. We first propose a study for the chromosome straightening task. We introduce a novel framework using image-to-image translation and demonstrate its efficacy and robustness in generating straightened chromosomes. The framework addresses the challenges of limited training data and outperforms existing studies. We then present a subsequent study to address the limitations of our previous framework, resulting in new state-of-the-art performance and better interpretability and generalization capability. We propose a new robust chromosome straightening framework, named Vit-Patch GAN, which instead learns the motion representation of chromosomes for straightening while retaining more details of shape and banding patterns. For medical image segmentation, we focus on the fovea localization task, which is transferred from localization to small region segmentation. Accurate segmentation of the fovea region is crucial for monitoring and analyzing retinal diseases to prevent irreversible vision loss. This task also requires the incorporation of global features to effectively identify the fovea region and overcome hard cases associated with retinal diseases and non-standard fovea locations. We first propose a novel two-branch architecture, Bilateral-ViT, for fovea localization in retina image segmentation. This vision-transformer-based architecture incorporates global image context and blood vessel structure. It surpasses existing methods and achieves state-of-the-art results on two public datasets. We then propose a subsequent method to further improve the performance of fovea localization. We design a novel dual-stream deep learning architecture called Bilateral-Fuser. In contrast to our previous Bilateral-ViT, Bilateral-Fuser globally incorporates long-range connections from multiple cues, including fundus and vessel distribution. Moreover, with the newly designed Bilateral Token Incorporation module, Bilateral-Fuser learns anatomical-aware tokens, significantly reducing computational costs while achieving new state-of-the-art performance. Our comprehensive experiments also demonstrate that Bilateral-Fuser achieves better accuracy and robustness on both normal and diseased retina images, with excellent generalization capability

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

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Spatial and temporal features of neutrophils in homeostasis from the perspective of computational biology

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 22-07-2022Neutrophils are myeloid cells that originate in the Bone Marrow and enter circulation to patrol for infectious agents. An important part of the “nonspecific” immune system consists on Neutrophils infiltrating challenged tissues, and the established belief was that they stay away from steady-state organs to avoid the risk of exposing them to their cytotoxic content. In the papers presented in this thesis, we show that neutrophils can in fact be found in almost all tissues under homeostasis. We further present proof that they undergo shifts in DNA accessibility, RNA expression and protein content in the infiltrated tissues. Using functional annotation we predict distinct roles depending on the tissue. While in hematopoietic organs the transcriptomic signatures of neutrophils align with canonical functions like immune response and migration, in other tissues such as the skin we find non-canonical functions i.e, epithelial and connective tissue growth or pro-angiogenic roles in the gut and the lung. This predicted pro-angiogenic role was indeed confirmed for the lung. We finally describe that infiltration in tissues follows circadian dynamics, and that once it has occurred, neutrophils experience changes in transcription depending on the time of the day. The analyses of circadian rhythms on mammalian models are often hindered by the inherent difficulty of performing exhaustive sampling (i.e.: every hour for at least 48h). Hence, I implemented CircaN as an R package, which outperforms existing tools in most scenarios. To provide the most complete analysis possible, we provide a full mode analysis option, in which we run CircaN and the two most used algorithms and provide integrated results. We present proof-of-concept results showing that combining various tools yields the best true positive to false positive ratio for most purposesEsta Tesis ha sido financiada por el Ministerio de Ciencia, Innovación y Universidades (MICINN

Boosted Exudate Segmentation in Retinal Images using Residual Nets

Exudates in retinal images are one of the early signs of the vision-threatening diabetic retinopathy and diabetic macular edema. Early diagnosis is very helpful in preventing the progression of the disease. In this work, we propose a fully automatic exudate segmentation method based on the state-of-the-art residual learning framework. With our proposed end-to-end architecture the training is done on small patches, but at the test time, the full sized segmentation is obtained at once. The small number of exudates in the training set and the presence of other bright regions are the limiting factors, which are tackled by our proposed importance sampling approach. This technique selects the misleading normal patches with a higher priority, and at the same time avoids the network to overfit to those samples. Thus, no additional post-processing is needed. The method was evaluated on three public datasets for both detecting and segmenting the exudates and outperformed the state-of-the-art techniques

Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts