A Spatially-Aware Multiple Instance Learning Framework for Digital Pathology

Multiple instance learning (MIL) is a promising approach for weakly supervised classification in pathology using whole slide images (WSIs). However, conventional MIL methods such as Attention-Based Deep Multiple Instance Learning (ABMIL) typically disregard spatial interactions among patches that are crucial to pathological diagnosis. Recent advancements, such as Transformer based MIL (TransMIL), have incorporated spatial context and inter-patch relationships. However, it remains unclear whether explicitly modeling patch relationships yields similar performance gains in ABMIL, which relies solely on Multi-Layer Perceptrons (MLPs). In contrast, TransMIL employs Transformer-based layers, introducing a fundamental architectural shift at the cost of substantially increased computational complexity. In this work, we enhance the ABMIL framework by integrating interaction-aware representations to address this question. Our proposed model, Global ABMIL (GABMIL), explicitly captures inter-instance dependencies while preserving computational efficiency. Experimental results on two publicly available datasets for tumor subtyping in breast and lung cancers demonstrate that GABMIL achieves up to a 7 percentage point improvement in AUPRC and a 5 percentage point increase in the Kappa score over ABMIL, with minimal or no additional computational overhead. These findings underscore the importance of incorporating patch interactions within MIL frameworks.

Adaptive Prototype Learning for Multimodal Cancer Survival Analysis

Leveraging multimodal data, particularly the integration of whole-slide histology images (WSIs) and transcriptomic profiles, holds great promise for improving cancer survival prediction. However, excessive redundancy in multimodal data can degrade model performance. In this paper, we propose Adaptive Prototype Learning (APL), a novel and effective approach for multimodal cancer survival analysis. APL adaptively learns representative prototypes in a data-driven manner, reducing redundancy while preserving critical information. Our method employs two sets of learnable query vectors that serve as a bridge between high-dimensional representations and survival prediction, capturing task-relevant features. Additionally, we introduce a multimodal mixed self-attention mechanism to enable cross-modal interactions, further enhancing information fusion. Extensive experiments on five benchmark cancer datasets demonstrate the superiority of our approach over existing methods. The code is available at https://github.com/HongLiuuuuu/APL.

PathoPainter: Augmenting Histopathology Segmentation via Tumor-aware Inpainting

Tumor segmentation plays a critical role in histopathology, but it requires costly, fine-grained image-mask pairs annotated by pathologists. Thus, synthesizing histopathology data to expand the dataset is highly desirable. Previous works suffer from inaccuracies and limited diversity in image-mask pairs, both of which affect training segmentation, particularly in small-scale datasets and the inherently complex nature of histopathology images. To address this challenge, we propose PathoPainter, which reformulates image-mask pair generation as a tumor inpainting task. Specifically, our approach preserves the background while inpainting the tumor region, ensuring precise alignment between the generated image and its corresponding mask. To enhance dataset diversity while maintaining biological plausibility, we incorporate a sampling mechanism that conditions tumor inpainting on regional embeddings from a different image. Additionally, we introduce a filtering strategy to exclude uncertain synthetic regions, further improving the quality of the generated data. Our comprehensive evaluation spans multiple datasets featuring diverse tumor types and various training data scales. As a result, segmentation improved significantly with our synthetic data, surpassing existing segmentation data synthesis approaches, e.g., 75.69% -> 77.69% on CAMELYON16. The code is available at https://github.com/HongLiuuuuu/PathoPainter.

Scaling up self-supervised learning for improved surgical foundation models

Foundation models have revolutionized computer vision by achieving vastly superior performance across diverse tasks through large-scale pretraining on extensive datasets. However, their application in surgical computer vision has been limited. This study addresses this gap by introducing SurgeNetXL, a novel surgical foundation model that sets a new benchmark in surgical computer vision. Trained on the largest reported surgical dataset to date, comprising over 4.7 million video frames, SurgeNetXL achieves consistent top-tier performance across six datasets spanning four surgical procedures and three tasks, including semantic segmentation, phase recognition, and critical view of safety (CVS) classification. Compared with the best-performing surgical foundation models, SurgeNetXL shows mean improvements of 2.4, 9.0, and 12.6 percent for semantic segmentation, phase recognition, and CVS classification, respectively. Additionally, SurgeNetXL outperforms the best-performing ImageNet-based variants by 14.4, 4.0, and 1.6 percent in the respective tasks. In addition to advancing model performance, this study provides key insights into scaling pretraining datasets, extending training durations, and optimizing model architectures specifically for surgical computer vision. These findings pave the way for improved generalizability and robustness in data-scarce scenarios, offering a comprehensive framework for future research in this domain. All models and a subset of the SurgeNetXL dataset, including over 2 million video frames, are publicly available at: https://github.com/TimJaspers0801/SurgeNet.

Enhancing Reconstruction-Based Out-of-Distribution Detection in Brain MRI with Model and Metric Ensembles

Out-of-distribution (OOD) detection is crucial for safely deploying automated medical image analysis systems, as abnormal patterns in images could hamper their performance. However, OOD detection in medical imaging remains an open challenge, and we address three gaps: the underexplored potential of a simple OOD detection model, the lack of optimization of deep learning strategies specifically for OOD detection, and the selection of appropriate reconstruction metrics. In this study, we investigated the effectiveness of a reconstruction-based autoencoder for unsupervised detection of synthetic artifacts in brain MRI. We evaluated the general reconstruction capability of the model, analyzed the impact of the selected training epoch and reconstruction metrics, assessed the potential of model and/or metric ensembles, and tested the model on a dataset containing a diverse range of artifacts. Among the metrics assessed, the contrast component of SSIM and LPIPS consistently outperformed others in detecting homogeneous circular anomalies. By combining two well-converged models and using LPIPS and contrast as reconstruction metrics, we achieved a pixel-level area under the Precision-Recall curve of 0.66. Furthermore, with the more realistic OOD dataset, we observed that the detection performance varied between artifact types; local artifacts were more difficult to detect, while global artifacts showed better detection results. These findings underscore the importance of carefully selecting metrics and model configurations, and highlight the need for tailored approaches, as standard deep learning approaches do not always align with the unique needs of OOD detection.

Dataset Distribution Impacts Model Fairness: Single vs. Multi-Task Learning

The influence of bias in datasets on the fairness of model predictions is a topic of ongoing research in various fields. We evaluate the performance of skin lesion classification using ResNet-based CNNs, focusing on patient sex variations in training data and three different learning strategies. We present a linear programming method for generating datasets with varying patient sex and class labels, taking into account the correlations between these variables. We evaluated the model performance using three different learning strategies: a single-task model, a reinforcing multi-task model, and an adversarial learning scheme. Our observations include: 1) sex-specific training data yields better results, 2) single-task models exhibit sex bias, 3) the reinforcement approach does not remove sex bias, 4) the adversarial model eliminates sex bias in cases involving only female patients, and 5) datasets that include male patients enhance model performance for the male subgroup, even when female patients are the majority. To generalise these findings, in future research, we will examine more demographic attributes, like age, and other possibly confounding factors, such as skin colour and artefacts in the skin lesions. We make all data and models available on GitHub.

WSI-SAM: Multi-resolution Segment Anything Model (SAM) for histopathology whole-slide images

The Segment Anything Model (SAM) marks a significant advancement in segmentation models, offering robust zero-shot abilities and dynamic prompting. However, existing medical SAMs are not suitable for the multi-scale nature of whole-slide images (WSIs), restricting their effectiveness. To resolve this drawback, we present WSI-SAM, enhancing SAM with precise object segmentation capabilities for histopathology images using multi-resolution patches, while preserving its efficient, prompt-driven design, and zero-shot abilities. To fully exploit pretrained knowledge while minimizing training overhead, we keep SAM frozen, introducing only minimal extra parameters and computational overhead. In particular, we introduce High-Resolution (HR) token, Low-Resolution (LR) token and dual mask decoder. This decoder integrates the original SAM mask decoder with a lightweight fusion module that integrates features at multiple scales. Instead of predicting a mask independently, we integrate HR and LR token at intermediate layer to jointly learn features of the same object across multiple resolutions. Experiments show that our WSI-SAM outperforms state-of-the-art SAM and its variants. In particular, our model outperforms SAM by 4.1 and 2.5 percent points on a ductal carcinoma in situ (DCIS) segmentation tasks and breast cancer metastasis segmentation task (CAMELYON16 dataset). The code will be available at https://github.com/HongLiuuuuu/WSI-SAM.

Histogram- and Diffusion-Based Medical Out-of-Distribution Detection

Out-of-distribution (OOD) detection is crucial for the safety and reliability of artificial intelligence algorithms, especially in the medical domain. In the context of the Medical OOD (MOOD) detection challenge 2023, we propose a pipeline that combines a histogram-based method and a diffusion-based method. The histogram-based method is designed to accurately detect homogeneous anomalies in the toy examples of the challenge, such as blobs with constant intensity values. The diffusion-based method is based on one of the latest methods for unsupervised anomaly detection, called DDPM-OOD. We explore this method and propose extensive post-processing steps for pixel-level and sample-level anomaly detection on brain MRI and abdominal CT data provided by the challenge. Our results show that the proposed DDPM method is sensitive to blur and bias field samples, but faces challenges with anatomical deformation, black slice, and swapped patches. These findings suggest that further research is needed to improve the performance of DDPM for OOD detection in medical images.

Effect of latent space distribution on the segmentation of images with multiple annotations

We propose the Generalized Probabilistic U-Net, which extends the Probabilistic U-Net by allowing more general forms of the Gaussian distribution as the latent space distribution that can better approximate the uncertainty in the reference segmentations. We study the effect the choice of latent space distribution has on capturing the variation in the reference segmentations for lung tumors and white matter hyperintensities in the brain. We show that the choice of distribution affects the sample diversity of the predictions and their overlap with respect to the reference segmentations. We have made our implementation available at https://github.com/ishaanb92/GeneralizedProbabilisticUNet

LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.