A Weakly Supervised Deep Learning Framework for Whole Slide Classification to Facilitate Digital Pathology in Animal Study
Abstract
The pathology of animal studies is crucial for toxicity evaluations and regulatory assessments, but the manual examination of slides by pathologists remains time-consuming and requires extensive training. One inherent challenge in this process is the interobserver variability, which can compromise the consistency and accuracy of a study. Artificial intelligence (AI) has demonstrated its ability to automate similar examinations in clinical applications with enhanced efficiency, consistency, and accuracy. However, training AI models typically relies on costly pixel-level annotation of injured regions and is often not available for animal pathology. To address this, we developed the PathologAI system, a “weakly” supervised approach for WSI classification in rat images without explicit lesion annotation at the pixel level. Using rat liver imaging data from the Open TG-GATEs system, PathologAI was applied to predict necrosis of n = 816 WSIs (377 controls). TG-GATEs studied 170 compounds at three dose levels (low, middle, and high) for four time points (3, 7, 14, and 28 days). PathologAI first preprocessed WSIs at the tile level to generate a high-level representation with a Generative Adversarial Network architecture. The prediction of liver necrosis relied on an ensemble model of 5 CNN classifiers trained on 335 WSIs. The ensemble model achieved notable classification accuracy on the holdout test set: 87% among 87 control slides free of findings, 83% among 120 controls with…
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