Focused Active Learning for Histopathological Image Classification

Active Learning (AL) has the potential to solve a major problem of digital pathology: the efficient acquisition of labeled data for machine learning algorithms. However, existing AL methods often struggle in realistic settings with artifacts, ambiguities, and class imbalances, as commonly seen in the medical field. The lack of precise uncertainty estimations leads to the acquisition of images with a low informative value. To address these challenges, we propose Focused Active Learning (FocAL), which combines a Bayesian Neural Network with Out-of-Distribution detection to estimate different uncertainties for the acquisition function. Specifically, the weighted epistemic uncertainty accounts for the class imbalance, aleatoric uncertainty for ambiguous images, and an OoD score for artifacts. We perform extensive experiments to validate our method on MNIST and the real-world Panda dataset for the classification of prostate cancer. The results confirm that other AL methods are 'distracted' by ambiguities and artifacts which harm the performance. FocAL effectively focuses on the most informative images, avoiding ambiguities and artifacts during acquisition. For both experiments, FocAL outperforms existing AL approaches, reaching a Cohen's kappa of 0.764 with only 0.69% of the labeled Panda data.

Introducing instance label correlation in multiple instance learning. Application to cancer detection on histopathological images

In the last years, the weakly supervised paradigm of multiple instance learning (MIL) has become very popular in many different areas. A paradigmatic example is computational pathology, where the lack of patch-level labels for whole-slide images prevents the application of supervised models. Probabilistic MIL methods based on Gaussian Processes (GPs) have obtained promising results due to their excellent uncertainty estimation capabilities. However, these are general-purpose MIL methods that do not take into account one important fact: in (histopathological) images, the labels of neighboring patches are expected to be correlated. In this work, we extend a state-of-the-art GP-based MIL method, which is called VGPMIL-PR, to exploit such correlation. To do so, we develop a novel coupling term inspired by the statistical physics Ising model. We use variational inference to estimate all the model parameters. Interestingly, the VGPMIL-PR formulation is recovered when the weight that regulates the strength of the Ising term vanishes. The performance of the proposed method is assessed in two real-world problems of prostate cancer detection. We show that our model achieves better results than other state-of-the-art probabilistic MIL methods. We also provide different visualizations and analysis to gain insights into the influence of the novel Ising term. These insights are expected to facilitate the application of the proposed model to other research areas.

Probabilistic Modeling of Inter- and Intra-observer Variability in Medical Image Segmentation

Medical image segmentation is a challenging task, particularly due to inter- and intra-observer variability, even between medical experts. In this paper, we propose a novel model, called Probabilistic Inter-Observer and iNtra-Observer variation NetwOrk (Pionono). It captures the labeling behavior of each rater with a multidimensional probability distribution and integrates this information with the feature maps of the image to produce probabilistic segmentation predictions. The model is optimized by variational inference and can be trained end-to-end. It outperforms state-of-the-art models such as STAPLE, Probabilistic U-Net, and models based on confusion matrices. Additionally, Pionono predicts multiple coherent segmentation maps that mimic the rater's expert opinion, which provides additional valuable information for the diagnostic process. Experiments on real-world cancer segmentation datasets demonstrate the high accuracy and efficiency of Pionono, making it a powerful tool for medical image analysis.

Smooth Attention for Deep Multiple Instance Learning: Application to CT Intracranial Hemorrhage Detection

Multiple Instance Learning (MIL) has been widely applied to medical imaging diagnosis, where bag labels are known and instance labels inside bags are unknown. Traditional MIL assumes that instances in each bag are independent samples from a given distribution. However, instances are often spatially or sequentially ordered, and one would expect similar diagnostic importance for neighboring instances. To address this, in this study, we propose a smooth attention deep MIL (SA-DMIL) model. Smoothness is achieved by the introduction of first and second order constraints on the latent function encoding the attention paid to each instance in a bag. The method is applied to the detection of intracranial hemorrhage (ICH) on head CT scans. The results show that this novel SA-DMIL: (a) achieves better performance than the non-smooth attention MIL at both scan (bag) and slice (instance) levels; (b) learns spatial dependencies between slices; and (c) outperforms current state-of-the-art MIL methods on the same ICH test set.

Probabilistic Attention based on Gaussian Processes for Deep Multiple Instance Learning

Multiple Instance Learning (MIL) is a weakly supervised learning paradigm that is becoming increasingly popular because it requires less labeling effort than fully supervised methods. This is especially interesting for areas where the creation of large annotated datasets remains challenging, as in medicine. Although recent deep learning MIL approaches have obtained state-of-the-art results, they are fully deterministic and do not provide uncertainty estimations for the predictions. In this work, we introduce the Attention Gaussian Process (AGP) model, a novel probabilistic attention mechanism based on Gaussian Processes for deep MIL. AGP provides accurate bag-level predictions as well as instance-level explainability, and can be trained end-to-end. Moreover, its probabilistic nature guarantees robustness to overfitting on small datasets and uncertainty estimations for the predictions. The latter is especially important in medical applications, where decisions have a direct impact on the patient's health. The proposed model is validated experimentally as follows. First, its behavior is illustrated in two synthetic MIL experiments based on the well-known MNIST and CIFAR-10 datasets, respectively. Then, it is evaluated in three different real-world cancer detection experiments. AGP outperforms state-of-the-art MIL approaches, including deterministic deep learning ones. It shows a strong performance even on a small dataset with less than 100 labels and generalizes better than competing methods on an external test set. Moreover, we experimentally show that predictive uncertainty correlates with the risk of wrong predictions, and therefore it is a good indicator of reliability in practice. Our code is publicly available.

Deep Gaussian Processes for geophysical parameter retrieval

This paper introduces deep Gaussian processes (DGPs) for geophysical parameter retrieval. Unlike the standard full GP model, the DGP accounts for complicated (modular, hierarchical) processes, provides an efficient solution that scales well to large datasets, and improves prediction accuracy over standard full and sparse GP models. We give empirical evidence of performance for estimation of surface dew point temperature from infrared sounding data.

Scalable Variational Gaussian Processes for Crowdsourcing: Glitch Detection in LIGO

In the last years, crowdsourcing is transforming the way classification training sets are obtained. Instead of relying on a single expert annotator, crowdsourcing shares the labelling effort among a large number of collaborators. For instance, this is being applied to the data acquired by the laureate Laser Interferometer Gravitational Waves Observatory (LIGO), in order to detect glitches which might hinder the identification of true gravitational-waves. The crowdsourcing scenario poses new challenging difficulties, as it deals with different opinions from a heterogeneous group of annotators with unknown degrees of expertise. Probabilistic methods, such as Gaussian Processes (GP), have proven successful in modeling this setting. However, GPs do not scale well to large data sets, which hampers their broad adoption in real practice (in particular at LIGO). This has led to the recent introduction of deep learning based crowdsourcing methods, which have become the state-of-the-art. However, the accurate uncertainty quantification of GPs has been partially sacrificed. This is an important aspect for astrophysicists in LIGO, since a glitch detection system should provide very accurate probability distributions of its predictions. In this work, we leverage the most popular sparse GP approximation to develop a novel GP based crowdsourcing method that factorizes into mini-batches. This makes it able to cope with previously-prohibitive data sets. The approach, which we refer to as Scalable Variational Gaussian Processes for Crowdsourcing (SVGPCR), brings back GP-based methods to the state-of-the-art, and excels at uncertainty quantification. SVGPCR is shown to outperform deep learning based methods and previous probabilistic approaches when applied to the LIGO data. Moreover, its behavior and main properties are carefully analyzed in a controlled experiment based on the MNIST data set.