通过扰动保真度提升肺腺癌亚型分类的边界鲁棒性。
Margin-Consistent Deep Subtyping of Invasive Lung Adenocarcinoma via Perturbation Fidelity in Whole-Slide Image Analysis
- 设计扰动保真度机制,增强模型在图像扰动下的稳定性。
- 在五种亚型上实现超99%的AUC,ResNet101误差降低50%。
- 适用于临床病理诊断,尤其适合跨机构数据迁移场景。
侵袭性肺腺癌全切片图像分型仍易受真实世界成像扰动影响,导致决策边界可靠性下降。本研究在包含143张全切片图像、203,226个图像块的BMIRDS-LUAD数据集上,提出一种边缘一致性框架。结合注意力加权块聚合与边缘感知训练,使特征-逻辑空间对齐的肯德尔相关系数在训练阶段达0.88,验证阶段为0.64。对比正则化虽能增强类别分离,但易过度聚类并抑制细微形态变化;为此引入基于贝叶斯优化参数的结构化扰动机制——扰动保真度(PF)评分。Vision Transformer-Large达到95.20 ± 4.65%准确率,较基线92.00 ± 5.36%减少40%误差;带注意力机制的ResNet101达95.89 ± 5.37%,相较91.73 ± 9.23%降低50%误差。所有五种亚型均超过0.99的AUC。在外部基准WSSS4LUAD上,带注意力机制的ResNet50取得80.1%准确率,尽管存在约15%-20%领域偏移导致的性能下降,仍展现出跨机构泛化能力,揭示未来适应性研究的潜力。
原文摘要 · Abstract (English)
Whole-slide image classification for invasive lung adenocarcinoma subtyping remains vulnerable to real-world imaging perturbations that undermine model reliability at the decision boundary. We propose a margin consistency framework evaluated on 203,226 patches from 143 whole-slide images spanning five adenocarcinoma subtypes in the BMIRDS-LUAD dataset. By combining attention-weighted patch aggregation with margin-aware training, our approach achieves robust feature-logit space alignment measured by Kendall correlations of 0.88 during training and 0.64 during validation. Contrastive regularization, while effective at improving class separation, tends to over-cluster features and suppress fine-grained morphological variation; to counteract this, we introduce Perturbation Fidelity (PF) scoring, which imposes structured perturbations through Bayesian-optimized parameters. Vision Transformer-Large achieves 95.20 +/- 4.65% accuracy, representing a 40% error reduction from the 92.00 +/- 5.36% baseline, while ResNet101 with an attention mechanism reaches 95.89 +/- 5.37% from 91.73 +/- 9.23%, a 50% error reduction. All five subtypes exceed an area under the receiver operating characteristic curve (AUC) of 0.99. On the WSSS4LUAD external benchmark, ResNet50 with an attention mechanism attains 80.1% accuracy, demonstrating cross-institutional generalizability despite approximately 15-20% domain-shift-related degradation and identifying opportunities for future adaptation research.
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