Optical coherence tomography (OCT) is widely used for diagnosing and monitoring retinal diseases, such as age-related macular degeneration (AMD). The segmentation of biomarkers such as layers and lesions is essential for patient diagnosis and follow-up. Recently, semi-supervised learning has shown promise in improving retinal segmentation performance. However, existing methods often produce anatomically implausible segmentations, fail to effectively model layer-lesion interactions, and lack guarantees on topological correctness. To address these limitations, we propose a novel semi-supervised model that introduces a fully differentiable biomarker topology engine to enforce anatomically correct segmentation of lesions and layers. This enables joint learning with bidirectional influence between layers and lesions, leveraging unlabeled and diverse partially labeled datasets. Our model learns a disentangled representation, separating spatial and style factors. This approach enables more realistic layer segmentations and improves lesion segmentation, while strictly enforcing lesion location in their anatomically plausible positions relative to the segmented layers. We evaluate the proposed model on public and internal datasets of OCT scans and show that it outperforms the current state-of-the-art in both lesion and layer segmentation, while demonstrating the ability to generalize layer segmentation to pathological cases using partially annotated training data. Our results demonstrate the potential of using anatomical constraints in semi-supervised learning for accurate, robust, and trustworthy retinal biomarker segmentation.

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

The use of multimodal imaging has led to significant improvements in the diagnosis and treatment of many diseases. Similar to clinical practice, some works have demonstrated the benefits of multimodal fusion for automatic segmentation and classification using deep learning-based methods. However, current segmentation methods are limited to fusion of modalities with the same dimensionality (e.g., 3D + 3D, 2D + 2D), which is not always possible, and the fusion strategies implemented by classification methods are incompatible with localization tasks. In this work, we propose a novel deep learning-based framework for the fusion of multimodal data with heterogeneous dimensionality (e.g., 3D + 2D) that is compatible with localization tasks. The proposed framework extracts the features of the different modalities and projects them into the common feature subspace. The projected features are then fused and further processed to obtain the final prediction. The framework was validated on the following tasks: segmentation of geographic atrophy (GA), a late-stage manifestation of age-related macular degeneration, and segmentation of retinal blood vessels (RBV) in multimodal retinal imaging. Our results show that the proposed method outperforms the state-of-the-art monomodal methods on GA and RBV segmentation by up to 3.10% and 4.64% Dice, respectively.

The early detection of glaucoma is essential in preventing visual impairment. Artificial intelligence (AI) can be used to analyze color fundus photographs (CFPs) in a cost-effective manner, making glaucoma screening more accessible. While AI models for glaucoma screening from CFPs have shown promising results in laboratory settings, their performance decreases significantly in real-world scenarios due to the presence of out-of-distribution and low-quality images. To address this issue, we propose the Artificial Intelligence for Robust Glaucoma Screening (AIROGS) challenge. This challenge includes a large dataset of around 113,000 images from about 60,000 patients and 500 different screening centers, and encourages the development of algorithms that are robust to ungradable and unexpected input data. We evaluated solutions from 14 teams in this paper and found that the best teams performed similarly to a set of 20 expert ophthalmologists and optometrists. The highest-scoring team achieved an area under the receiver operating characteristic curve of 0.99 (95% CI: 0.98-0.99) for detecting ungradable images on-the-fly. Additionally, many of the algorithms showed robust performance when tested on three other publicly available datasets. These results demonstrate the feasibility of robust AI-enabled glaucoma screening.

Bruch's membrane (BM) segmentation on optical coherence tomography (OCT) is a pivotal step for the diagnosis and follow-up of age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world. Automated BM segmentation methods exist, but they usually do not account for the anatomical coherence of the results, neither provide feedback on the confidence of the prediction. These factors limit the applicability of these systems in real-world scenarios. With this in mind, we propose an end-to-end deep learning method for automated BM segmentation in AMD patients. An Attention U-Net is trained to output a probability density function of the BM position, while taking into account the natural curvature of the surface. Besides the surface position, the method also estimates an A-scan wise uncertainty measure of the segmentation output. Subsequently, the A-scans with high uncertainty are interpolated using thin plate splines (TPS). We tested our method with ablation studies on an internal dataset with 138 patients covering all three AMD stages, and achieved a mean absolute localization error of 4.10 μm. In addition, the proposed segmentation method was compared against the state-of-the-art methods and showed a superior performance on an external publicly available dataset from a different patient cohort and OCT device, demonstrating strong generalization ability.

Diabetic retinopathy (DR) grading is crucial in determining the adequate treatment and follow up of patient, but the screening process can be tiresome and prone to errors. Deep learning approaches have shown promising performance as computer-aided diagnosis (CAD) systems, but their black-box behaviour hinders clinical application. We propose DR|GRADUATE, a novel deep learning-based DR grading CAD system that supports its decision by providing a medically interpretable explanation and an estimation of how uncertain that prediction is, allowing the ophthalmologist to measure how much that decision should be trusted. We designed DR|GRADUATE taking into account the ordinal nature of the DR grading problem. A novel Gaussian-sampling approach built upon a Multiple Instance Learning framework allow DR|GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR|GRADUATE was trained on the Kaggle DR detection training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (κ) between 0.71 and 0.84 was achieved in five different datasets. We show that high κ values occur for images with low prediction uncertainty, thus indicating that this uncertainty is a valid measure of the predictions' quality. Further, bad quality images are generally associated with higher uncertainties, showing that images not suitable for diagnosis indeed lead to less trustworthy predictions. Additionally, tests on unfamiliar medical image data types suggest that DR|GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR|GRADUATE as a second-opinion system in DR severity grading.

Early diagnosis of lung cancer via computed tomography can significantly reduce the morbidity and mortality rates associated with the pathology. However, searching lung nodules is a high complexity task, which affects the success of screening programs. Whilst computer-aided detection systems can be used as second observers, they may bias radiologists and introduce significant time overheads. With this in mind, this study assesses the potential of using gaze information for integrating automatic detection systems in the clinical practice. For that purpose, 4 radiologists were asked to annotate 20 scans from a public dataset while being monitored by an eye tracker device, and an automatic lung nodule detection system was developed. Our results show that radiologists follow a similar search routine and tend to have lower fixation periods in regions where finding errors occur. The overall detection sensitivity of the specialists was 0.67±0.07, whereas the system achieved 0.69. Combining the annotations of one radiologist with the automatic system significantly improves the detection performance to similar levels of two annotators. Filtering automatic detection candidates only for low fixation regions still significantly improves the detection sensitivity without increasing the number of false-positives.

Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). BACH aimed at the classification and localization of clinically relevant histopathological classes in microscopy and whole-slide images from a large annotated dataset, specifically compiled and made publicly available for the challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. The submitted algorithms improved the state-of-the-art in automatic classification of breast cancer with microscopy images to an accuracy of 87%. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publicly available as to promote further improvements to the field of automatic classification in digital pathology.