Melis Erdal Cesur

Aniek Eijpe, Soufyan Lakbir, Melis Erdal Cesur et al.

While multimodal survival prediction models are increasingly more accurate, their complexity often reduces interpretability, limiting insight into how different data sources influence predictions. To address this, we introduce DIMAFx, an explainable multimodal framework for cancer survival prediction that produces disentangled, interpretable modality-specific and modality-shared representations from histopathology whole-slide images and transcriptomics data. Across multiple cancer cohorts, DIMAFx achieves state-of-the-art performance and improved representation disentanglement. Leveraging its interpretable design and SHapley Additive exPlanations, DIMAFx systematically reveals key multimodal interactions and the biological information encoded in the disentangled representations. In breast cancer survival prediction, the most predictive features contain modality-shared information, including one capturing solid tumor morphology contextualized primarily by late estrogen response, where higher-grade morphology aligned with pathway upregulation and increased risk, consistent with known breast cancer biology. Key modality-specific features capture microenvironmental signals from interacting adipose and stromal morphologies. These results show that multimodal models can overcome the traditional trade-off between performance and explainability, supporting their application in precision medicine.

Vivien van Veldhuizen, Vanessa Botha, Chunyao Lu et al.

Foundation models (FMs) are changing the way medical images are analyzed by learning from large collections of unlabeled data. Instead of relying on manually annotated examples, FMs are pre-trained to learn general-purpose visual features that can later be adapted to specific clinical tasks with little additional supervision. In this review, we examine how FMs are being developed and applied in pathology, radiology, and ophthalmology, drawing on evidence from over 150 studies. We explain the core components of FM pipelines, including model architectures, self-supervised learning methods, and strategies for downstream adaptation. We also review how FMs are being used in each imaging domain and compare design choices across applications. Finally, we discuss key challenges and open questions to guide future research.

Aniek Eijpe, Soufyan Lakbir, Melis Erdal Cesur et al.

To improve the prediction of cancer survival using whole-slide images and transcriptomics data, it is crucial to capture both modality-shared and modality-specific information. However, multimodal frameworks often entangle these representations, limiting interpretability and potentially suppressing discriminative features. To address this, we propose Disentangled and Interpretable Multimodal Attention Fusion (DIMAF), a multimodal framework that separates the intra- and inter-modal interactions within an attention-based fusion mechanism to learn distinct modality-specific and modality-shared representations. We introduce a loss based on Distance Correlation to promote disentanglement between these representations and integrate Shapley additive explanations to assess their relative contributions to survival prediction. We evaluate DIMAF on four public cancer survival datasets, achieving a relative average improvement of 1.85% in performance and 23.7% in disentanglement compared to current state-of-the-art multimodal models. Beyond improved performance, our interpretable framework enables a deeper exploration of the underlying interactions between and within modalities in cancer biology.

José Teixeira, Pascal Klöckner, Diana Montezuma et al.

In addition to evaluating tumor morphology using H&E staining, immunohistochemistry is used to assess the presence of specific proteins within the tissue. However, this is a costly and labor-intensive technique, for which virtual staining, as an image-to-image translation task, offers a promising alternative. Although recent, this is an emerging field of research with 64% of published studies just in 2024. Most studies use publicly available datasets of H&E-IHC pairs from consecutive tissue sections. Recognizing the training challenges, many authors develop complex virtual staining models based on conditional Generative Adversarial Networks, but ignore the impact of adversarial loss on the quality of virtual staining. Furthermore, overlooking the issues of model evaluation, they claim improved performance based on metrics such as SSIM and PSNR, which are not sufficiently robust to evaluate the quality of virtually stained images. In this paper, we developed CSSP2P GAN, which we demonstrate to achieve heightened pathological fidelity through a blind pathological expert evaluation. Furthermore, while iteratively developing our model, we study the impact of the adversarial loss and demonstrate its crucial role in the quality of virtually stained images. Finally, while comparing our model with reference works in the field, we underscore the limitations of the currently used evaluation metrics and demonstrate the superior performance of CSSP2P GAN.

Mikhail Karasikov, Joost van Doorn, Nicolas Känzig et al. · eth-zurich

The field of computational pathology has recently seen rapid advances driven by the development of modern vision foundation models (FMs), typically trained on vast collections of pathology images. Recent studies demonstrate that increasing the training data set and model size and integrating domain-specific image processing techniques can significantly enhance the model's performance on downstream tasks. Building on these insights, our work incorporates several recent modifications to the standard DINOv2 framework from the literature to optimize the training of pathology FMs. We also apply a post-training procedure for fine-tuning models on higher-resolution images to further enrich the information encoded in the embeddings. We present three novel pathology FMs trained on up to two orders of magnitude fewer WSIs than those used to train other state-of-the-art FMs while demonstrating a comparable or superior performance on downstream tasks. Even the model trained on TCGA alone (12k WSIs) outperforms most existing FMs and, on average, matches Virchow2, the second-best FM published to date. This suggests that there still remains a significant potential for further improving the models and algorithms used to train pathology FMs to take full advantage of the vast data collections.