Segmentation of Bruch's Membrane in retinal OCT with AMD using anatomical priors and uncertainty quantification

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 um. 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.

SD-LayerNet: Semi-supervised retinal layer segmentation in OCT using disentangled representation with anatomical priors

Optical coherence tomography (OCT) is a non-invasive 3D modality widely used in ophthalmology for imaging the retina. Achieving automated, anatomically coherent retinal layer segmentation on OCT is important for the detection and monitoring of different retinal diseases, like Age-related Macular Disease (AMD) or Diabetic Retinopathy. However, the majority of state-of-the-art layer segmentation methods are based on purely supervised deep-learning, requiring a large amount of pixel-level annotated data that is expensive and hard to obtain. With this in mind, we introduce a semi-supervised paradigm into the retinal layer segmentation task that makes use of the information present in large-scale unlabeled datasets as well as anatomical priors. In particular, a novel fully differentiable approach is used for converting surface position regression into a pixel-wise structured segmentation, allowing to use both 1D surface and 2D layer representations in a coupled fashion to train the model. In particular, these 2D segmentations are used as anatomical factors that, together with learned style factors, compose disentangled representations used for reconstructing the input image. In parallel, we propose a set of anatomical priors to improve network training when a limited amount of labeled data is available. We demonstrate on the real-world dataset of scans with intermediate and wet-AMD that our method outperforms state-of-the-art when using our full training set, but more importantly largely exceeds state-of-the-art when it is trained with a fraction of the labeled data.

Deep Dirichlet uncertainty for unsupervised out-of-distribution detection of eye fundus photographs in glaucoma screening

The development of automatic tools for early glaucoma diagnosis with color fundus photographs can significantly reduce the impact of this disease. However, current state-of-the-art solutions are not robust to real-world scenarios, providing over-confident predictions for out-of-distribution cases. With this in mind, we propose a model based on the Dirichlet distribution that allows to obtain class-wise probabilities together with an uncertainty estimation without exposure to out-of-distribution cases. We demonstrate our approach on the AIROGS challenge. At the start of the final test phase (8 Feb. 2022), our method had the highest average score among all submissions.

HEROHE Challenge: assessing HER2 status in breast cancer without immunohistochemistry or in situ hybridization

Breast cancer is the most common malignancy in women, being responsible for more than half a million deaths every year. As such, early and accurate diagnosis is of paramount importance. Human expertise is required to diagnose and correctly classify breast cancer and define appropriate therapy, which depends on the evaluation of the expression of different biomarkers such as the transmembrane protein receptor HER2. This evaluation requires several steps, including special techniques such as immunohistochemistry or in situ hybridization to assess HER2 status. With the goal of reducing the number of steps and human bias in diagnosis, the HEROHE Challenge was organized, as a parallel event of the 16th European Congress on Digital Pathology, aiming to automate the assessment of the HER2 status based only on hematoxylin and eosin stained tissue sample of invasive breast cancer. Methods to assess HER2 status were presented by 21 teams worldwide and the results achieved by some of the proposed methods open potential perspectives to advance the state-of-the-art.

LNDb: A Lung Nodule Database on Computed Tomography

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly, time-consuming and prone to variability. This has fueled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules but its application to clinical routine is challenging. In this study, a new database for the development and testing of pulmonary nodule computer-aided strategies is presented which intends to complement current databases by giving additional focus to radiologist variability and local clinical reality. State-of-the-art nodule detection, segmentation and characterization methods are tested and compared to manual annotations as well as collaborative strategies combining multiple radiologists and radiologists and computer-aided systems. It is shown that state-of-the-art methodologies can determine a patient's follow-up recommendation as accurately as a radiologist, though the nodule detection method used shows decreased performance in this database.

DR$\vert$GRADUATE: uncertainty-aware deep learning-based diabetic retinopathy grading in eye fundus images

Diabetic retinopathy (DR) grading is crucial in determining the patients' adequate treatment and follow up, 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 the clinical application. We propose DR$\vert$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$\vert$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$\vert$GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR$\vert$GRADUATE was trained on the Kaggle training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (QWK) between 0.71 and 0.84 was achieved in five different datasets. We show that high QWK 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$\vert$GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR$\vert$GRADUATE as a second-opinion system in DR severity grading.

Did you miss it? Automatic lung nodule detection combined with gaze information improves radiologists' screening performance

Early diagnosis of lung cancer via computed tomography can significantly reduce the morbidity and mortality rates associated with the pathology. However, search 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$\pm$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. Likewise, combining the findings of radiologist with the detection algorithm only for low fixation regions still significantly improves the detection sensitivity without increasing the number of false-positives. The combination of the automatic system with the gaze information allows to mitigate possible errors of the radiologist without some of the issues usually associated with automatic detection system.