RudolfV: A Foundation Model by Pathologists for Pathologists

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

DiffInfinite: Large Mask-Image Synthesis via Parallel Random Patch Diffusion in Histopathology

We present DiffInfinite, a hierarchical diffusion model that generates arbitrarily large histological images while preserving long-range correlation structural information. Our approach first generates synthetic segmentation masks, subsequently used as conditions for the high-fidelity generative diffusion process. The proposed sampling method can be scaled up to any desired image size while only requiring small patches for fast training. Moreover, it can be parallelized more efficiently than previous large-content generation methods while avoiding tiling artefacts. The training leverages classifier-free guidance to augment a small, sparsely annotated dataset with unlabelled data. Our method alleviates unique challenges in histopathological imaging practice: large-scale information, costly manual annotation, and protective data handling. The biological plausibility of DiffInfinite data is validated in a survey by ten experienced pathologists as well as a downstream segmentation task. Furthermore, the model scores strongly on anti-copying metrics which is beneficial for the protection of patient data.

Leveraging weak complementary labels to improve semantic segmentation of hepatocellular carcinoma and cholangiocarcinoma in H&E-stained slides

In this paper, we present a deep learning segmentation approach to classify and quantify the two most prevalent primary liver cancers - hepatocellular carcinoma and intrahepatic cholangiocarcinoma - from hematoxylin and eosin (H&E) stained whole slide images. While semantic segmentation of medical images typically requires costly pixel-level annotations by domain experts, there often exists additional information which is routinely obtained in clinical diagnostics but rarely utilized for model training. We propose to leverage such weak information from patient diagnoses by deriving complementary labels that indicate to which class a sample cannot belong to. To integrate these labels, we formulate a complementary loss for segmentation. Motivated by the medical application, we demonstrate for general segmentation tasks that including additional patches with solely weak complementary labels during model training can significantly improve the predictive performance and robustness of a model. On the task of diagnostic differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma, we achieve a balanced accuracy of 0.91 (CI 95%: 0.86 - 0.95) at case level for 165 hold-out patients. Furthermore, we also show that leveraging complementary labels improves the robustness of segmentation and increases performance at case level.

Exposing Outlier Exposure: What Can Be Learned From Few, One, and Zero Outlier Images

Traditionally anomaly detection (AD) is treated as an unsupervised problem utilizing only normal samples due to the intractability of characterizing everything that looks unlike the normal data. However, it has recently been found that unsupervised image anomaly detection can be drastically improved through the utilization of huge corpora of random images to represent anomalousness; a technique which is known as Outlier Exposure. In this paper we show that specialized AD learning methods seem actually superfluous and huge corpora of data expendable. For a common AD benchmark on ImageNet, standard classifiers and semi-supervised one-class methods trained to discern between normal samples and just a few random natural images are able to outperform the current state of the art in deep AD, and only one useful outlier sample is sufficient to perform competitively. We investigate this phenomenon and reveal that one-class methods are more robust towards the particular choice of training outliers. Furthermore, we find that a simple classifier based on representations from CLIP, a recent foundation model, achieves state-of-the-art results on CIFAR-10 and also outperforms all previous AD methods on ImageNet without any training samples (i.e., in a zero-shot setting).

Deep Anomaly Detection by Residual Adaptation

Deep anomaly detection is a difficult task since, in high dimensions, it is hard to completely characterize a notion of "differentness" when given only examples of normality. In this paper we propose a novel approach to deep anomaly detection based on augmenting large pretrained networks with residual corrections that adjusts them to the task of anomaly detection. Our method gives rise to a highly parameter-efficient learning mechanism, enhances disentanglement of representations in the pretrained model, and outperforms all existing anomaly detection methods including other baselines utilizing pretrained networks. On the CIFAR-10 one-versus-rest benchmark, for example, our technique raises the state of the art from 96.1 to 99.0 mean AUC.

Geometric Disentanglement by Random Convex Polytopes

Finding and analyzing meaningful representations of data is the purpose of machine learning. The idea of representation learning is to extract representations from the data itself, e.g., by utilizing deep neural networks. In this work, we examine representation learning from a geometric perspective. Especially, we focus on the convexity of classes and clusters as a natural and desirable representation property, for which robust and scalable measures are still lacking. To address this, we propose a new approach called Random Polytope Descriptor that allows a convex description of data points based on the construction of random convex polytopes. This ties in with current methods for statistical disentanglement. We demonstrate the use of our technique on well-known deep learning methods for representation learning. Specifically we find that popular regularization variants such as the Variational Autoencoder can destroy crucial information that is relevant for tasks such as out-of-distribution detection.

A Unifying Review of Deep and Shallow Anomaly Detection

Deep learning approaches to anomaly detection have recently improved the state of the art in detection performance on complex datasets such as large collections of images or text. These results have sparked a renewed interest in the anomaly detection problem and led to the introduction of a great variety of new methods. With the emergence of numerous such methods, including approaches based on generative models, one-class classification, and reconstruction, there is a growing need to bring methods of this field into a systematic and unified perspective. In this review we aim to identify the common underlying principles as well as the assumptions that are often made implicitly by various methods. In particular, we draw connections between classic 'shallow' and novel deep approaches and show how this relation might cross-fertilize or extend both directions. We further provide an empirical assessment of major existing methods that is enriched by the use of recent explainability techniques, and present specific worked-through examples together with practical advice. Finally, we outline critical open challenges and identify specific paths for future research in anomaly detection.

Explainable Deep One-Class Classification

Deep one-class classification variants for anomaly detection learn a mapping that concentrates nominal samples in feature space causing anomalies to be mapped away. Because this transformation is highly non-linear, finding interpretations poses a significant challenge. In this paper we present an explainable deep one-class classification method, Fully Convolutional Data Description (FCDD), where the mapped samples are themselves also an explanation heatmap. FCDD yields competitive detection performance and provides reasonable explanations on common anomaly detection benchmarks with CIFAR-10 and ImageNet. On MVTec-AD, a recent manufacturing dataset offering ground-truth anomaly maps, FCDD meets the state of the art in an unsupervised setting, and outperforms its competitors in a semi-supervised setting. Finally, using FCDD's explanations we demonstrate the vulnerability of deep one-class classification models to spurious image features such as image watermarks.

The Clever Hans Effect in Anomaly Detection

The 'Clever Hans' effect occurs when the learned model produces correct predictions based on the 'wrong' features. This effect which undermines the generalization capability of an ML model and goes undetected by standard validation techniques has been frequently observed for supervised learning where the training algorithm leverages spurious correlations in the data. The question whether Clever Hans also occurs in unsupervised learning, and in which form, has received so far almost no attention. Therefore, this paper will contribute an explainable AI (XAI) procedure that can highlight the relevant features used by popular anomaly detection models of different type. Our analysis reveals that the Clever Hans effect is widespread in anomaly detection and occurs in many (unexpected) forms. Interestingly, the observed Clever Hans effects are in this case not so much due to the data, but due to the anomaly detection models themselves whose structure makes them unable to detect the truly relevant features, even though vast amounts of data points are available. Overall, our work contributes a warning against an unrestrained use of existing anomaly detection models in practical applications, but it also points at a possible way out of the Clever Hans dilemma, specifically, by allowing multiple anomaly models to mutually cancel their individual structural weaknesses to jointly produce a better and more trustworthy anomaly detector.