Virtual multi-staining in a single-section view for renal pathology using generative adversarial networks

Abstract

Sections stained in periodic acid-Schiff (PAS), periodic acid-methenamine silver (PAM), hematoxylin and eosin (H&E), and Masson's trichrome (MT) stain with minimal morphological discordance are helpful for pathological diagnosis in renal biopsy. Here, we propose an artificial intelligence-based re-stainer called PPHM-GAN (PAS, PAM, H&E, and MT-generative adversarial networks) with multi-stain to multi-stain transformation capability. We trained three GAN models on 512 × 512-pixel patches from 26 training cases. The model with the best transformation quality was selected for each pair of stain transformations by human evaluation. Frechet inception distances, peak signal-to-noise ratio, structural similarity index measure, contrast structural similarity, and newly introduced domain shift inception score were calculated as auxiliary quality metrics. We validated the diagnostic utility using 5120 × 5120 patches of ten validation cases for major glomerular and interstitial abnormalities. Transformed stains were sometimes superior to original stains for the recognition of crescent formation, mesangial hypercellularity, glomerular sclerosis, interstitial lesions, or arteriosclerosis. 23 of 24 glomeruli (95.83 %) from 9 additional validation cases transformed to PAM, PAS, or MT facilitated recognition of crescent formation. Stain transformations to PAM (p = 4.0E-11) and transformations from H&E (p = 4.8E-9) most improved crescent formation recognition. PPHM-GAN maximizes information from a given section by providing several stains in a virtual single-section view, and may change the staining and diagnostic strategy.