Deep Learning in Toxicologic Pathology: A New Approach to Evaluate Rodent Retinal Atrophy

Abstract

Quantification of retinal atrophy, caused by therapeutics and/or light, by manual measurement of retinal layers is labor intensive and time-consuming. In this study, we explored the role of deep learning (DL) in automating the assessment of retinal atrophy, particularly of the outer and inner nuclear layers, in rats. Herein, we report our experience creating and employing a hybrid approach, which combines conventional image processing and DL to quantify rodent retinal atrophy. Utilizing a DL approach based upon the VGG16 model architecture, models were trained, tested, and validated using 10,746 image patches scanned from whole slide images (WSIs) of hematoxylin-eosin stained rodent retina. The accuracy of this computational method was validated using pathologist annotated WSIs throughout and used to separately quantify the thickness of the outer and inner nuclear layers of the retina. Our results show that DL can facilitate the evaluation of therapeutic and/or light-induced atrophy, particularly of the outer retina, efficiently in rodents. In addition, this study provides a template which can be used to train, validate, and analyze the results of toxicologic pathology DL models across different animal species used in preclinical efficacy and safety studies.