Xiyue Wang

Haolu Liu, Xiyue Wang, Xuanting Xie et al.

Standard IMVC evaluation retrains separate models for different missing-data configurations. We show that this paradigm obscures a fundamental vulnerability: missing rate alone is insufficient to characterize data incompleteness. Specifically, we show that protocols with identical nominal missing rates can differ by up to $50\times$ in their proportion of fully observed samples, inducing drastically different learning regimes. We formalize this phenomenon as incompleteness divergence, providing measures that capture structural disparities across missing-data protocols. We further prove that for a broad class of reconstruction-based objectives, learning becomes structurally ill-posed when the proportion of complete samples falls below a critical threshold, leading to near-random performance. To bypass this theoretical bound, we propose CRAFT (Complete-data Robust Attention-masked Fusion Transformer). CRAFT shifts the burden of robustness from the loss function to the architecture via two key properties: (i) per-sample independence, which removes reliance on complete-sample co-occurrence, and (ii) mask-aware variable-length fusion, which aggregates only observed views through attention masking. This design allows a single model, trained once on complete data, to generalize to diverse missing patterns at inference time without retraining. Extensive experiments on seven benchmarks show that CRAFT matches or outperforms per-configuration baselines while reducing training overhead by $8.8\times$, demonstrating that robustness to missing data can be achieved as an inherent architectural property. Code (CRAFT) and our imvc-audit toolkit are available at https://anonymous.4open.science/r/CRAFT-BF80/ and https://anonymous.4open.science/r/imvc-audit-8263/.

Wenhua Zhang, Sen Yang, Meiwei Luo et al.

Accurate segmentation and classification of nuclei in histology images is critical but challenging due to nuclei heterogeneity, staining variations, and tissue complexity. Existing methods often struggle with limited dataset variability, with patches extracted from similar whole slide images (WSI), making models prone to falling into local optima. Here we propose a new framework to address this limitation and enable robust nuclear analysis. Our method leverages dual-level ensemble modeling to overcome issues stemming from limited dataset variation. Intra-ensembling applies diverse transformations to individual samples, while inter-ensembling combines networks of different scales. We also introduce enhancements to the HoVer-Net architecture, including updated encoders, nested dense decoding and model regularization strategy. We achieve state-of-the-art results on public benchmarks, including 1st place for nuclear composition prediction and 3rd place for segmentation/classification in the 2022 Colon Nuclei Identification and Counting (CoNIC) Challenge. This success validates our approach for accurate histological nuclei analysis. Extensive experiments and ablation studies provide insights into optimal network design choices and training techniques. In conclusion, this work proposes an improved framework advancing the state-of-the-art in nuclei analysis. We release our code and models (https://github.com/WinnieLaugh/CONIC_Pathology_AI) to serve as a toolkit for the community.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

Marc Aubreville, Nikolas Stathonikos, Christof A. Bertram et al.

The density of mitotic figures within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of mitotic figures by pathologists is known to be subject to a strong inter-rater bias, which limits the prognostic value. State-of-the-art deep learning methods can support the expert in this assessment but are known to strongly deteriorate when applied in a different clinical environment than was used for training. One decisive component in the underlying domain shift has been identified as the variability caused by using different whole slide scanners. The goal of the MICCAI MIDOG 2021 challenge has been to propose and evaluate methods that counter this domain shift and derive scanner-agnostic mitosis detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As a test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were given. The best approaches performed on an expert level, with the winning algorithm yielding an F_1 score of 0.748 (CI95: 0.704-0.781). In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance.

Simon Graham, Quoc Dang Vu, Mostafa Jahanifar et al.

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

Marc Aubreville, Nikolas Stathonikos, Taryn A. Donovan et al.

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an $F_1$ score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.

Siteng Chen, Jinxi Xiang, Xiyue Wang et al.

Tumor mutational burden (TMB) is a potential genomic biomarker of immunotherapy. However, TMB detected through whole exome sequencing lacks clinical penetration in low-resource settings. In this study, we proposed a multi-scale deep learning framework to address the detection of TMB status from routinely used whole slide images for a multiple cancer TMB prediction model (MC- TMB). The MC-TMB achieved a mean area under the curve (AUC) of 0.818 (0.804-0.831) in the cross-validation cohort, which showed superior performance to each single-scale model. The improvements of MC-TMB over the single-tumor models were also confirmed by the ablation tests on x10 magnification, and the highly concerned regions typically correspond to dense lymphocytic infiltration and heteromorphic tumor cells. MC-TMB algorithm also exhibited good generalization on the external validation cohort with an AUC of 0.732 (0.683-0.761), and better performance when compared to other methods. In conclusion, we proposed a deep learning-based approach to reveal tumor mutational burden status from routinely used pathological slides across multiple cancer types.

Fei Kong, Xiyue Wang, Jinxi Xiang et al.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Zihan Niu, Wenping Hu, Junmin Chen et al.

Effective and controllable data selection is critical for LLM instruction tuning, especially with massive open-source datasets. Existing approaches primarily rely on instance-level quality scores, or diversity metrics based on embedding clusters or semantic tags. However, constrained by the flatness of embedding spaces or the coarseness of tags, these approaches overlook fine-grained knowledge and its intrinsic hierarchical dependencies, consequently hindering precise data valuation and knowledge-aligned sampling. To address this challenge, we propose Tree-aware Aligned Global Sampling (TAGS), a unified framework that leverages a knowledge tree built from fine-grained tags, thereby enabling joint control of global quality, diversity, and target alignment. Using an LLM-based tagger, we extract atomic knowledge concepts, which are organized into a global tree through bottom-up hierarchical clustering. By grounding data instances onto this tree, a tree-aware metric then quantifies data quality and diversity, facilitating effective sampling. Our controllable sampling strategy maximizes tree-level information gain and enforces leaf-level alignment via KL-divergence for specific domains. Extensive experiments demonstrate that TAGS significantly outperforms state-of-the-art baselines. Notably, it surpasses the full-dataset model by \textbf{+5.84\%} using only \textbf{5\%} of the data, while our aligned sampling strategy further boosts average performance by \textbf{+4.24\%}.

Yuci Liang, Xinheng Lyu, Wenting Chen et al.

Recent advancements in computational pathology have produced patch-level Multi-modal Large Language Models (MLLMs), but these models are limited by their inability to analyze whole slide images (WSIs) comprehensively and their tendency to bypass crucial morphological features that pathologists rely on for diagnosis. To address these challenges, we first introduce WSI-Bench, a large-scale morphology-aware benchmark containing 180k VQA pairs from 9,850 WSIs across 30 cancer types, designed to evaluate MLLMs' understanding of morphological characteristics crucial for accurate diagnosis. Building upon this benchmark, we present WSI-LLaVA, a novel framework for gigapixel WSI understanding that employs a three-stage training approach: WSI-text alignment, feature space alignment, and task-specific instruction tuning. To better assess model performance in pathological contexts, we develop two specialized WSI metrics: WSI-Precision and WSI-Relevance. Experimental results demonstrate that WSI-LLaVA outperforms existing models across all capability dimensions, with a significant improvement in morphological analysis, establishing a clear correlation between morphological understanding and diagnostic accuracy.

Xiangde Luo, Xiyue Wang, Feyisope Eweje et al.

Histopathology is essential for disease diagnosis and treatment decision-making. Recent advances in artificial intelligence (AI) have enabled the development of pathology foundation models that learn rich visual representations from large-scale whole-slide images (WSIs). However, existing models are often trained on disparate datasets using varying strategies, leading to inconsistent performance and limited generalizability. Here, we introduce ELF (Ensemble Learning of Foundation models), a novel framework that integrates five state-of-the-art pathology foundation models to generate unified slide-level representations. Trained on 53,699 WSIs spanning 20 anatomical sites, ELF leverages ensemble learning to capture complementary information from diverse models while maintaining high data efficiency. Unlike traditional tile-level models, ELF's slide-level architecture is particularly advantageous in clinical contexts where data are limited, such as therapeutic response prediction. We evaluated ELF across a wide range of clinical applications, including disease classification, biomarker detection, and response prediction to major anticancer therapies, cytotoxic chemotherapy, targeted therapy, and immunotherapy, across multiple cancer types. ELF consistently outperformed all constituent foundation models and existing slide-level models, demonstrating superior accuracy and robustness. Our results highlight the power of ensemble learning for pathology foundation models and suggest ELF as a scalable and generalizable solution for advancing AI-assisted precision oncology.

Yuanfeng Ji, Dan Lin, Xiyue Wang et al.

The scarcity of well-annotated diverse medical images is a major hurdle for developing reliable AI models in healthcare. Substantial technical advances have been made in generative foundation models for natural images. Here we develop `ChexGen', a generative vision-language foundation model that introduces a unified framework for text-, mask-, and bounding box-guided synthesis of chest radiographs. Built upon the latent diffusion transformer architecture, ChexGen was pretrained on the largest curated chest X-ray dataset to date, consisting of 960,000 radiograph-report pairs. ChexGen achieves accurate synthesis of radiographs through expert evaluations and quantitative metrics. We demonstrate the utility of ChexGen for training data augmentation and supervised pretraining, which led to performance improvements across disease classification, detection, and segmentation tasks using a small fraction of training data. Further, our model enables the creation of diverse patient cohorts that enhance model fairness by detecting and mitigating demographic biases. Our study supports the transformative role of generative foundation models in building more accurate, data-efficient, and equitable medical AI systems.

Liang Qiu, Wenhao Chi, Xiaohan Xing et al.

Precision therapy for liver cancer necessitates accurately delineating liver sub-regions to protect healthy tissue while targeting tumors, which is essential for reducing recurrence and improving survival rates. However, the segmentation of hepatic segments, known as Couinaud segmentation, is challenging due to indistinct sub-region boundaries and the need for extensive annotated datasets. This study introduces LiverFormer, a novel Couinaud segmentation model that effectively integrates global context with low-level local features based on a 3D hybrid CNN-Transformer architecture. Additionally, a registration-based data augmentation strategy is equipped to enhance the segmentation performance with limited labeled data. Evaluated on CT images from 123 patients, LiverFormer demonstrated high accuracy and strong concordance with expert annotations across various metrics, allowing for enhanced treatment planning for surgery and radiation therapy. It has great potential to reduces complications and minimizes potential damages to surrounding tissue, leading to improved outcomes for patients undergoing complex liver cancer treatments.

Sen Yang, Feng Luo, Jun Zhang et al.

Mitotic count is the most important morphological feature of breast cancer grading. Many deep learning-based methods have been proposed but suffer from domain shift. In this work, we construct a Fourier-based segmentation model for mitosis detection to address the problem. Swapping the low-frequency spectrum of source and target images is shown effective to alleviate the discrepancy between different scanners. Our Fourier-based segmentation method can achieve F1 with 0.7456 on the preliminary test set.

Alain Lalande, Zhihao Chen, Thibaut Pommier et al.

A key factor for assessing the state of the heart after myocardial infarction (MI) is to measure whether the myocardium segment is viable after reperfusion or revascularization therapy. Delayed enhancement-MRI or DE-MRI, which is performed several minutes after injection of the contrast agent, provides high contrast between viable and nonviable myocardium and is therefore a method of choice to evaluate the extent of MI. To automatically assess myocardial status, the results of the EMIDEC challenge that focused on this task are presented in this paper. The challenge's main objectives were twofold. First, to evaluate if deep learning methods can distinguish between normal and pathological cases. Second, to automatically calculate the extent of myocardial infarction. The publicly available database consists of 150 exams divided into 50 cases with normal MRI after injection of a contrast agent and 100 cases with myocardial infarction (and then with a hyperenhanced area on DE-MRI), whatever their inclusion in the cardiac emergency department. Along with MRI, clinical characteristics are also provided. The obtained results issued from several works show that the automatic classification of an exam is a reachable task (the best method providing an accuracy of 0.92), and the automatic segmentation of the myocardium is possible. However, the segmentation of the diseased area needs to be improved, mainly due to the small size of these areas and the lack of contrast with the surrounding structures.