Automatic Detection of Granuloma Necrosis in Pulmonary Tuberculosis Using a Two-Phase Algorithm: 2D-TB

Granuloma necrosis occurs in hosts susceptible to pathogenic mycobacteria and is a diagnostic visual feature of pulmonary tuberculosis (TB) in humans and in super-susceptible Diversity Outbred (DO) mice infected with Mycobacterium tuberculosis. Currently, no published automated algorithms can detect granuloma necrosis in pulmonary TB. However, such a method could reduce variability, and transform visual patterns into quantitative data for statistical and machine learning analyses. Here, we used histopathological images from super-susceptible DO mice to train, validate, and performance test an algorithm to detect regions of cell-poor necrosis. The algorithm, named 2D-TB, works on 2-dimensional histopathological images in 2 phases. In phase 1, granulomas are detected following background elimination. In phase 2, 2D-TB searches within granulomas for regions of cell-poor necrosis. We used 8 lung sections from 8 different super-susceptible DO mice for training and 10-fold cross validation. We used 13 new lung sections from 10 different super-susceptible DO mice for performance testing. 2D-TB reached 100.0% sensitivity and 91.8% positive prediction value. Compared to an expert pathologist, agreement was 95.5% and there was a statistically significant positive correlation for area detected by 2D-TB and the pathologist. These results show the development, validation, and accurate performance of 2D-TB to detect granuloma necrosis.