A U-Net based framework to quantify glomerulosclerosis in digitized PAS and H&E stained human tissues

Abstract

Reliable counting of glomeruli and evaluation of glomerulosclerosis in renal specimens are essential steps to assess morphological changes in kidney and identify individuals requiring treatment. Because microscopic identification of sclerosed glomeruli performed under the microscope is labor intensive, we developed a deep learning (DL) approach to identify and classify glomeruli as normal or sclerosed in digital whole slide images (WSIs). The segmentation and classification of glomeruli was performed by the U-Net model. Subsequently, glomerular classifications were refined based on glomerular histomorphometry. The U-Net model was trained using patches from Periodic Acid-Schiff (PAS) stained WSIs (n=31) from the AIDPATH - a multi-center dataset, and then tested on an independent set of WSIs (n=20) including PAS (n=6), and hematoxylin and eosin (H&E) stained WSIs (n=14) from four other institutions. The training and test WSIs were obtained from formalin fixed and paraffin embedded blocks with of human kidney specimens each presenting various proportions of normal and sclerosed glomeruli. In the PAS stained WSIs, normal and sclerosed glomeruli were respectively classified with the F1-score of 97.5% and 68.8%. In the H&E stained WSIs, the F1-scores of 90.8% and 78.1% were achieved. Regardless the tissue staining, the glomeruli in the test WSIs were classified with the F1-score of 94.5% (n=923, normal) and 76.8% for (n=261, sclerosed). These results demonstrate for the first time that a framework based on the U-Net model trained with glomerular patches from PAS stained WSIs can reliably segment and classify normal and sclerosed glomeruli in PAS and also H&E stained WSIs. Our approach yielded higher accuracy of glomerular classifications than some of the recently published methods. Additionally, our test set of images with ground truth is publicly available.