用Transformer融合多染色病理图像,能处理缺失数据并预测动脉粥样硬化进展。
UNICORN: A Deep Learning Model for Integrating Multi-Stain Data in Histopathology
- 基于双阶段Transformer架构,分步提取和融合多染色特征。
- 在4000+张全切片图像上达到0.67分类准确率,优于现有模型。
- 适合需整合异质病理数据的医学研究者,尤其关注疾病进展建模。
背景:深度学习在数字病理学中整合多染色组织切片面临重大挑战,现有多模态方法难以应对数据异质性与缺失数据问题。本研究旨在开发一种新型Transformer模型,用于处理动脉粥样硬化严重程度分类的多染色图像集成,可有效应对训练和推理中的缺失数据。方法:提出UNICORN(UNiversal modality Integration Network for CORonary classificatioN),一种端到端可训练的多模态Transformer,通过两阶段设计实现特征提取与融合。第一阶段采用领域特定专家模块从各模态提取特征;第二阶段通过聚合专家模块学习不同模态间的交互关系。结果:在慕尼黑心血管研究生物样本库(MISSION)的多类动脉粥样硬化病变数据集上评估,包含170名逝者、4000余对多染色全切片图像(WSIs),覆盖冠状动脉7个预设节段,每段使用四种组织学染色协议。UNICORN在分类任务中取得0.67的准确率,优于其他先进模型,并能有效识别跨染色相关组织表型,隐式建模疾病进展。结论:所提出的多模态Transformer解决了医疗数据分析中的关键挑战,包括数据异质性和模态缺失问题,其可解释性及对动脉粥样硬化进展的预测能力,展现了在更广泛医学研究中的应用潜力。
原文摘要 · Abstract (English)
Background: The integration of multi-stain histopathology images through deep learning poses a significant challenge in digital histopathology. Current multi-modal approaches struggle with data heterogeneity and missing data. This study aims to overcome these limitations by developing a novel transformer model for multi-stain integration that can handle missing data during training as well as inference. Methods: We propose UNICORN (UNiversal modality Integration Network for CORonary classificatioN) a multi-modal transformer capable of processing multi-stain histopathology for atherosclerosis severity class prediction. The architecture comprises a two-stage, end-to-end trainable model with specialized modules utilizing transformer self-attention blocks. The initial stage employs domain-specific expert modules to extract features from each modality. In the subsequent stage, an aggregation expert module integrates these features by learning the interactions between the different data modalities. Results: Evaluation was performed using a multi-class dataset of atherosclerotic lesions from the Munich Cardiovascular Studies Biobank (MISSION), using over 4,000 paired multi-stain whole slide images (WSIs) from 170 deceased individuals on 7 prespecified segments of the coronary tree, each stained according to four histopathological protocols. UNICORN achieved a classification accuracy of 0.67, outperforming other state-of-the-art models. The model effectively identifies relevant tissue phenotypes across stainings and implicitly models disease progression. Conclusion: Our proposed multi-modal transformer model addresses key challenges in medical data analysis, including data heterogeneity and missing modalities. Explainability and the model's effectiveness in predicting atherosclerosis progression underscores its potential for broader applications in medical research.
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