arXiv:2602.02124cs.CVcs.AI2026-02

用新方法检测老鼠肝组织切片中的已知和未知异常,提升药物毒性筛查效率。

Toxicity Assessment in Preclinical Histopathology via Class-Aware Mahalanobis Distance for Known and Novel Anomalies

  • 基于类感知马氏距离与微调ViT模型,实现像素级异常检测
  • 健康组织误判率仅0.16%,正常组织误判为病灶率0.35%
  • 适合药企和病理实验室用于早期毒性筛查

药物诱导毒性是临床前及早期临床试验失败的主要原因,早期发现至关重要。组织病理学是毒性评估的金标准,但依赖专家病理医生,限制了大规模筛查。本文提出一种基于AI的全切片图像(WSI)异常检测框架,针对小鼠肝脏组织,识别健康组织与已知病灶,并将无训练数据的样本标记为分布外(OOD)。在两个独立类别上评估:凋亡(单细胞,近OOD)和染色/制片伪影(异质性,远OOD)。构建首个像素级标注数据集,通过低秩适应(LoRA)微调预训练视觉变换器(DINOv2)进行分割,再使用马氏距离结合类特定阈值进行OOD检测。在控制假阴性率前提下优化假阳性率,仅0.16%的病灶被误判为健康,0.35%的健康组织被误判为病灶。该方法不惩罚跨类型错误,符合安全优先原则;在更严格的正确类别标准下,93.93%的已知异常和89.38%的分布外异常被正确分类。结果验证了小鼠肝组织像素级异常检测的技术可行性,有望提升临床前流程与药物研发效率。

原文摘要 · Abstract (English)

Drug-induced toxicity is a leading cause of preclinical and early-clinical failure, making early detection critical. Histopathology is the gold standard for toxicity assessment but relies on expert pathologists, creating a bottleneck for large-scale screening. We introduce an AI-based anomaly detection framework for whole-slide images (WSIs) of rodent liver that identifies healthy tissue and known pathologies (anomalies) and flags samples without training data as out-of-distribution (OOD). We evaluate OOD detection on two held-out categories: apoptosis (single-cell, near-OOD) and staining/processing artifacts (heterogeneous, far-OOD). We build a novel pixelwise-annotated dataset and fine-tune a pre-trained Vision Transformer (DINOv2) via Low-Rank Adaptation (LoRA) for segmentation, then use the Mahalanobis distance for OOD detection with class-specific thresholds. Optimizing the false positive rate subject to a predefined constraint on the false negative rate yields only 0.16% of pathological tissue classified as healthy and 0.35% of healthy tissue classified as pathological. Our false negative rate does not penalise cross-type errors, reflecting the safety-first objective of never overlooking a lesion; under the stricter correct-class criterion our method assigns 93.93% of ID and 89.38% of OOD findings to their own class. The study demonstrates technical feasibility of pixel-level anomaly detection for mouse liver histopathology, indicating possible applications in improving preclinical workflows and drug development efficiency.

病理分析异常检测AI医疗

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