Xiyue Wang

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.

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.

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.

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.