用无透镜全息+深度学习实现低成本高通量自动测HER2,还带不确定性评估。
Automated HER2 scoring with uncertainty quantification using lensfree holography and deep learning
- 无透镜全息结合深度学习,从彩色激光成像中提取组织复杂场信息。
- 4分类准确率84.9%,二分类达94.8%,且30.4%预测可自动纠错。
- 适合资源匮乏地区,设备小、成本低、通量高,适合基层医疗部署。
准确评估表皮生长因子受体2(HER2)表达对乳腺癌诊断、预后和治疗选择至关重要;然而,现有数字HER2评分方法大多依赖大型昂贵的光学系统。本文提出一种紧凑且低成本的无透镜全息平台,结合深度学习,用于免疫组化染色乳腺组织切片的自动化HER2评分。该系统在RGB激光照射下捕获染色组织的无透镜衍射图样,在约1,250 mm²样本区域获取复场信息,有效通量达每分钟约84 mm²。为提升诊断可靠性,引入基于贝叶斯蒙特卡洛丢弃的不确定性量化策略,可自主生成每项预测的不确定性估计,支持可靠、鲁棒的HER2评分,整体校正率达30.4%。在412个独立组织样本的盲测集中,4类(0, 1+, 2+, 3+)分类测试准确率为84.9%,二分类(0/1+ vs. 2+/3+)准确率达94.8%。总体而言,该无透镜全息方法为便携、高通量、低成本的HER2评分提供了可行路径,尤其适用于传统数字病理基础设施缺失的资源有限地区。
原文摘要 · Abstract (English)
Accurate assessment of human epidermal growth factor receptor 2 (HER2) expression is critical for breast cancer diagnosis, prognosis, and therapy selection; yet, most existing digital HER2 scoring methods rely on bulky and expensive optical systems. Here, we present a compact and cost-effective lensfree holography platform integrated with deep learning for automated HER2 scoring of immunohistochemically stained breast tissue sections. The system captures lensfree diffraction patterns of stained HER2 tissue sections under RGB laser illumination and acquires complex field information over a sample area of ~1,250 mm^2 at an effective throughput of ~84 mm^2 per minute. To enhance diagnostic reliability, we incorporated an uncertainty quantification strategy based on Bayesian Monte Carlo dropout, which provides autonomous uncertainty estimates for each prediction and supports reliable, robust HER2 scoring, with an overall correction rate of 30.4%. Using a blinded test set of 412 unique tissue samples, our approach achieved a testing accuracy of 84.9% for 4-class (0, 1+, 2+, 3+) HER2 classification and 94.8% for binary (0/1+ vs. 2+/3+) HER2 scoring with uncertainty quantification. Overall, this lensfree holography approach provides a practical pathway toward portable, high-throughput, and cost-effective HER2 scoring, particularly suited for resource-limited settings, where traditional digital pathology infrastructure is unavailable.
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