Removing Batch Effects From Histopathological Images for Enhanced Cancer Diagnosis

Researchers have developed computer-aided decision support systems for translational medicine that aim to objectively and efficiently diagnose cancer using histopathological images. However, the performance of such systems is confounded by nonbiological experimental variations or batch effects that can commonly occur in histopathological data, especially when images are acquired using different imaging devices and patient samples. This is even more problematic in large-scale studies in which cross-laboratory sharing of large volumes of data is necessary. Batch effects can change quantitative morphological image features and decrease the prediction performance. Using four batches of renal tumor images, we compare one image-level and five feature-level batch effect removal methods. Principal component variation analysis shows that batch is a large source of variance in image features. Results show that feature-level normalization methods reduce batch-contributed variance to almost zero. Moreover, feature-level normalization, especially ComBatN, improves crossbatch and combined-batch prediction performance. Compared to no normalization, ComBatN improves performance in 83% and 90% of cross-batch and combined-batch prediction models, respectively.