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.

Healthcare is one of the foremost applications of machine learning (ML). Traditionally, ML models are trained by central servers, which aggregate data from various distributed devices to forecast the results for newly generated data. This is a major concern as models can access sensitive user information, which raises privacy concerns. A federated learning (FL) approach can help address this issue: A global model sends its copy to all clients who train these copies, and the clients send the updates (weights) back to it. Over time, the global model improves and becomes more accurate. Data privacy is protected during training, as it is conducted locally on the clients' devices. However, the global model is susceptible to data poisoning. We develop a privacy-preserving FL technique for a skin cancer dataset and show that the model is prone to data poisoning attacks. Ten clients train the model, but one of them intentionally introduces flipped labels as an attack. This reduces the accuracy of the global model. As the percentage of label flipping increases, there is a noticeable decrease in accuracy. We use a stochastic gradient descent optimization algorithm to find the most optimal accuracy for the model. Although FL can protect user privacy for healthcare diagnostics, it is also vulnerable to data poisoning, which must be addressed.

Convolutional neural networks excel in histopathological image classification, yet their pixel-level focus hampers explainability. Conversely, emerging graph convolutional networks spotlight cell-level features and medical implications. However, limited by their shallowness and suboptimal use of high-dimensional pixel data, GCNs underperform in multi-class histopathological image classification. To make full use of pixel-level and cell-level features dynamically, we propose an asymmetric co-training framework combining a deep graph convolutional network and a convolutional neural network for multi-class histopathological image classification. To improve the explainability of the entire framework by embedding morphological and topological distribution of cells, we build a 14-layer deep graph convolutional network to handle cell graph data. For the further utilization and dynamic interactions between pixel-level and cell-level information, we also design a co-training strategy to integrate the two asymmetric branches. Notably, we collect a private clinically acquired dataset termed LUAD7C, including seven subtypes of lung adenocarcinoma, which is rare and more challenging. We evaluated our approach on the private LUAD7C and public colorectal cancer datasets, showcasing its superior performance, explainability, and generalizability in multi-class histopathological image classification.

Whole Slide Image (WSI) analysis is a powerful method to facilitate the diagnosis of cancer in tissue samples. Automating this diagnosis poses various issues, most notably caused by the immense image resolution and limited annotations. WSIs commonly exhibit resolutions of 100Kx100K pixels. Annotating cancerous areas in WSIs on the pixel level is prohibitively labor-intensive and requires a high level of expert knowledge. Multiple instance learning (MIL) alleviates the need for expensive pixel-level annotations. In MIL, learning is performed on slide-level labels, in which a pathologist provides information about whether a slide includes cancerous tissue. Here, we propose Self-ViT-MIL, a novel approach for classifying and localizing cancerous areas based on slide-level annotations, eliminating the need for pixel-wise annotated training data. Self-ViT- MIL is pre-trained in a self-supervised setting to learn rich feature representation without relying on any labels. The recent Vision Transformer (ViT) architecture builds the feature extractor of Self-ViT-MIL. For localizing cancerous regions, a MIL aggregator with global attention is utilized. To the best of our knowledge, Self-ViT- MIL is the first approach to introduce self-supervised ViTs in MIL-based WSI analysis tasks. We showcase the effectiveness of our approach on the common Camelyon16 dataset. Self-ViT-MIL surpasses existing state-of-the-art MIL-based approaches in terms of accuracy and area under the curve (AUC).

Data imbalance is a major problem that affects several machine learning algorithms. Such problems are troublesome because most of the learning algorithms attempts to optimize a loss function based on error measures that do not take into account the data imbalance. Accordingly, the learning algorithm simply generates a trivial model that is biased toward predicting the most frequent class in the training data. Data augmentation techniques have been used to mitigate the data imbalance problem. However, in the case of histopathologic images (HIs), low-level as well as high-level data augmentation techniques still present performance issues when applied in the presence of inter-patient variability; whence the model tends to learn color representations, which are in fact related to the stain process. In this paper, we propose an approach capable of not only augmenting HIs database but also distributing the inter-patient variability by means of image blending using Gaussian-Laplacian pyramid. The proposed approach consists in finding the Gaussian pyramids of two images of different patients and finding the Laplacian pyramids thereof. Afterwards, the left half of one image and the right half of another are joined in each level of Laplacian pyramid, and from the joint pyramids, the original image is reconstructed. This composition, resulting from the blending process, combines stain variation of two patients, avoiding that color misleads the learning process. Experimental results on the BreakHis dataset have shown promising gains vis-\`a-vis the majority of traditional techniques presented in the literature.