Deep Neural Network Based Histological Scoring of Lung Fibrosis and Inflammation in the Mouse Model System

Preclinical studies of novel compounds rely on quantitative readouts from animal models. Frequently employed readouts from histopathological tissue scoring are time consuming, require highly specialized staff and are subject to inherent variability. Recent advances in deep convolutional neural networks (CNN) now allow automating such scoring tasks. Here, we demonstrate this for the case of the Ashcroft fibrosis score and a newly developed inflammation score to characterize fibrotic and inflammatory lung diseases. Sections of lung tissue from mice exhibiting a wide range of fibrotic and inflammatory states were stained with Masson trichrome. Whole slide scans using a 20x objective were acquired and cut into smaller tiles of 512x512 pixels. The tiles were subsequently classified by specialized CNNs, either an "Ashcroft fibrosis CNN" or an "inflammation CNN". For the Ashcroft fibrosis score the CNN was fine-tuned by using 14000 labelled tiles. For the inflammation score the CNN was trained with 3500 labelled tiles. After training, the Ashcroft fibrosis CNN achieved an accuracy of 79.5% and the inflammation CNN an accuracy of 80.0%. An error analysis revealed that misclassifications are almost exclusively with neighboring scores, which reflects the inherent ambiguity of parts of the data. The variability between two experts was found to be larger than the variability between the CNN classifications and the ground truth. The CNN generated Ashcroft score was in very good agreement with the score of a pathologist (r2 = 0.92). Our results demonstrate that costly and time consuming scoring tasks can be automated and standardized with deep learning. New scores such as the inflammation score can be easily developed with the approach presented here.