Nadine S. Schaadt

Pratibha Kumari, Daniel Reisenbüchler, Lucas Luttner et al.

In recent years, there has been remarkable progress in the field of digital pathology, driven by the ability to model complex tissue patterns using advanced deep-learning algorithms. However, the robustness of these models is often severely compromised in the presence of data shifts (e.g., different stains, organs, centers, etc.). Alternatively, continual learning (CL) techniques aim to reduce the forgetting of past data when learning new data with distributional shift conditions. Specifically, rehearsal-based CL techniques, which store some past data in a buffer and then replay it with new data, have proven effective in medical image analysis tasks. However, privacy concerns arise as these approaches store past data, prompting the development of our novel Generative Latent Replay-based CL (GLRCL) approach. GLRCL captures the previous distribution through Gaussian Mixture Models instead of storing past samples, which are then utilized to generate features and perform latent replay with new data. We systematically evaluate our proposed framework under different shift conditions in histopathology data, including stain and organ shift. Our approach significantly outperforms popular buffer-free CL approaches and performs similarly to rehearsal-based CL approaches that require large buffers causing serious privacy violations.

Jan-Philipp Redlich, Friedrich Feuerhake, Stefan Nikolin et al.

Glioblastoma, IDH-wildtype (GBM-IDHwt) is the most common malignant brain tumor. Histomorphology is a crucial component of the integrated diagnosis of GBM-IDHwt. Artificial intelligence (AI) methods have shown promise to extract additional prognostic information from histological whole-slide images (WSI) of hematoxylin and eosin-stained glioblastoma tissue. Here, we present an explainable AI-based method to support systematic interpretation of histomorphological features associated with survival. It combines an explainable multiple instance learning (MIL) architecture with a sparse autoencoder (SAE) to relate human-interpretable visual patterns of tissue to survival. The MIL architecture directly identifies prognosis-relevant image tiles and the SAE maps these tiles post-hoc to visual patterns. The MIL method was trained and evaluated using a new real-world dataset that comprised 720 GBM-IDHwt cases from three hospitals and four cancer registries in Germany. The SAE was trained using 1878 WSIs of glioblastoma from five independent public data collections. Despite the many factors influencing survival time, our method showed some ability to discriminate between patients living less than 180 days or more than 360 days solely based on histomorphology (AUC: 0.67; 95% CI: 0.63-0.72). Cox proportional hazards regression confirmed a significant difference in survival time between the predicted groups after adjustment for established prognostic factors (hazard ratio: 1.47; 95% CI: 1.26-1.72). Our method identified multiple interpretable visual patterns associated with survival. Three neuropathologists separately found that 21 of the 24 most strongly associated patterns could be clearly attributed to seven histomorphological categories. Necrosis and hemorrhage appeared to be associated with shorter survival while highly cellular tumor areas were associated with longer survival.

Niklas Kormann, Masoud Ramuz, Zeeshan Nisar et al.

Graph Neural Networks (GNNs) have recently been found to excel in histopathology. However, an important histopathological task, where GNNs have not been extensively explored, is the classification of glomeruli health as an important indicator in nephropathology. This task presents unique difficulties, particularly for the graph construction, i.e., the identification of nodes, edges, and informative features. In this work, we propose a pipeline composed of different traditional and machine learning-based computer vision techniques to identify nodes, edges, and their corresponding features to form a heterogeneous graph. We then proceed to propose a novel heterogeneous GNN architecture for glomeruli classification, called HIEGNet, that integrates both glomeruli and their surrounding immune cells. Hence, HIEGNet is able to consider the immune environment of each glomerulus in its classification. Our HIEGNet was trained and tested on a dataset of Whole Slide Images from kidney transplant patients. Experimental results demonstrate that HIEGNet outperforms several baseline models and generalises best between patients among all baseline models. Our implementation is publicly available at https://github.com/nklsKrmnn/HIEGNet.git.

Daniel Reisenbüchler, Lucas Luttner, Nadine S. Schaadt et al.

In computational pathology, deep learning (DL) models for tasks such as segmentation or tissue classification are known to suffer from domain shifts due to different staining techniques. Stain adaptation aims to reduce the generalization error between different stains by training a model on source stains that generalizes to target stains. Despite the abundance of target stain data, a key challenge is the lack of annotations. To address this, we propose a joint training between artificially labeled and unlabeled data including all available stained images called Unsupervised Latent Stain Adaptation (ULSA). Our method uses stain translation to enrich labeled source images with synthetic target images in order to increase the supervised signals. Moreover, we leverage unlabeled target stain images using stain-invariant feature consistency learning. With ULSA we present a semi-supervised strategy for efficient stain adaptation without access to annotated target stain data. Remarkably, ULSA is task agnostic in patch-level analysis for whole slide images (WSIs). Through extensive evaluation on external datasets, we demonstrate that ULSA achieves state-of-the-art (SOTA) performance in kidney tissue segmentation and breast cancer classification across a spectrum of staining variations. Our findings suggest that ULSA is an important framework for stain adaptation in computational pathology.

Jan-Philipp Redlich, Friedrich Feuerhake, Joachim Weis et al.

In recent years, the diagnosis of gliomas has become increasingly complex. Analysis of glioma histopathology images using artificial intelligence (AI) offers new opportunities to support diagnosis and outcome prediction. To give an overview of the current state of research, this review examines 83 publicly available research studies that have proposed AI-based methods for whole-slide histopathology images of human gliomas, covering the diagnostic tasks of subtyping (23/83), grading (27/83), molecular marker prediction (20/83), and survival prediction (29/83). All studies were reviewed with regard to methodological aspects as well as clinical applicability. It was found that the focus of current research is the assessment of hematoxylin and eosin-stained tissue sections of adult-type diffuse gliomas. The majority of studies (52/83) are based on the publicly available glioblastoma and low-grade glioma datasets from The Cancer Genome Atlas (TCGA) and only a few studies employed other datasets in isolation (16/83) or in addition to the TCGA datasets (15/83). Current approaches mostly rely on convolutional neural networks (63/83) for analyzing tissue at 20x magnification (35/83). A new field of research is the integration of clinical data, omics data, or magnetic resonance imaging (29/83). So far, AI-based methods have achieved promising results, but are not yet used in real clinical settings. Future work should focus on the independent validation of methods on larger, multi-site datasets with high-quality and up-to-date clinical and molecular pathology annotations to demonstrate routine applicability.