arXiv:2505.10294cs.CVq-bio.TO2025-05中稿 · manuscript, 24 pag…被引 2

用H&E图像预测多路免疫荧光标记,助力癌症病理分析

MIPHEI-ViT: Multiplex Immunofluorescence Prediction from H&E Images using ViT Foundation Models

  • 基于ViT基础模型的U-Net架构,从H&E图像推断mIF信号
  • 在5个独立数据集上验证,对多种细胞类型标记预测准确率超基准
  • 适合需要低成本细胞类型分析的病理研究者使用

组织病理学分析是癌症诊断的核心,常规采用苏木精-伊红(H&E)染色观察细胞形态与组织结构。而多路免疫荧光(mIF)可通过蛋白标志物实现更精准的细胞类型识别,但受限于成本与操作复杂性,尚未广泛临床应用。为此,我们提出MIPHEI(基于H&E图像预测多路免疫荧光),采用受U-Net启发的架构,以ViT病理基础模型作为编码器,利用丰富的预训练表征从H&E图像中预测mIF信号。该模型覆盖核成分、免疫谱系(T细胞、B细胞、髓系)、上皮、间质、血管及增殖等多类标志物。模型在公开的OrionCRC数据集(含结直肠癌组织重染H&E与mIF图像)上训练,并在五个独立数据集(HEMIT、PathoCell、IMMUcan、Lizard、PanNuke)上验证。在OrionCRC测试集上,仅凭H&E图像即实现高精度细胞类型分类,各项指标为:Pan-CK F1=0.93,alpha-SMA F1=0.83,CD3e F1=0.68,CD20 F1=0.36,CD68 F1=0.28,显著优于当前最优基线和随机分类器。结果表明,对于部分分子标志物,模型成功捕捉了组织背景下核形态与特定细胞类型之间的复杂关联。MIPHEI为大规模H&E数据集的细胞类型感知分析提供了可能,有助于揭示空间细胞组织与患者预后的关系。

原文摘要 · Abstract (English)

Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E Images), a U-Net-inspired architecture that leverages a ViT pathology foundation model as encoder to predict mIF signals from H&E images using rich pretrained representations. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available OrionCRC dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on five independent datasets: HEMIT, PathoCell, IMMUcan, Lizard and PanNuke. On OrionCRC test set, MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.93 for Pan-CK, 0.83 for alpha-SMA, 0.68 for CD3e, 0.36 for CD20, and 0.28 for CD68, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that, for some molecular markers, our model captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.

病理图像ViT模型多路免疫荧光细胞类型识别

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