通过多尺度融合提升病理切片细胞分类精度,解决局部细节与整体环境的平衡问题。
Adaptive Multi-Scale Integration Unlocks Robust Cell Annotation in Histopathology Images
- 融合核形态与微环境信息,用可学习门控模块动态调整局部与全局特征权重。
- 在三个独立队列上最高达96%的F1分数,显著优于现有基线模型。
- 适合需要高精度细胞亚型注释的病理研究者,尤其关注空间转录组与模型可解释性。
在常规病理学中识别细胞类型和亚型对理解疾病至关重要。现有基于瓦片的模型虽能捕捉核细节,却忽略了影响细胞身份的更广泛组织背景。当前人工标注粒度粗且不一致,难以实现精细的亚型分类。本研究基于Xenium空间转录组构建了标记引导数据集,包含超过两百万个细胞的单细胞分辨率标签,覆盖八个器官、16个类别。依托该数据资源,我们提出NuClass框架,受病理科工作流启发,实现细胞级别的多尺度整合:通过局部路径(224×224像素核区域)与全局路径(1024×1024像素邻域)的可学习门控融合,结合不确定性引导目标,使全局路径聚焦局部预测不确定区域。同时提供校准置信度与Grad-CAM热力图以增强可解释性。在三个完全独立队列上评估,最佳类别的F1最高达96%,显著优于强基线模型。结果表明,多尺度、不确定性感知的融合方法可弥合全切片病理基础模型与可靠细胞表型预测之间的差距。
原文摘要 · Abstract (English)
Identifying cell types and subtypes in routine histopathology is fundamental for understanding disease. Existing tile-based models capture nuclear detail but miss the broader tissue context that influences cell identity. Current human annotations are coarse-grained and uneven across studies, making fine-grained, subtype-level classification difficult. In this study, we build a marker-guided dataset from Xenium spatial transcriptomics with single-cell resolution labels for more than two million cells across eight organs and 16 classes to address the lack of high-quality annotations. Leveraging this data resource, we introduce NuClass, a pathologist workflow inspired framework for cell-wise multi-scale integration of nuclear morphology and microenvironmental context. It combines Path local, which focuses on nuclear morphology from 224x224 pixel crops, and Path global, which models the surrounding 1024x1024 pixel neighborhood, through a learnable gating module that balances local and global information. An uncertainty-guided objective directs the global path to prioritize regions where the local path is uncertain, and we provide calibrated confidence estimates and Grad-CAM maps for interpretability. Evaluated on three fully held-out cohorts, NuClass achieves up to 96 percent F1 for its best-performing class, outperforming strong baselines. Our results demonstrate that multi-scale, uncertainty-aware fusion can bridge the gap between slide-level pathological foundation models and reliable, cell-level phenotype prediction.
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