Abstract
Non-alcoholic steatohepatitis (NASH) is a fatty liver disease characterized by accumulation of fat in hepatocytes with concurrent inflammation and is associated with morbidity, cirrhosis and liver failure. After extraction of a liver core biopsy, tissue sections are stained with hematoxylin and eosin (H&E) to grade NASH activity, and stained with trichrome to stage fibrosis. Methods to computationally transform one stain into another on digital whole slide images (WSI) can lessen the need for additional physical staining besides H&E, reducing personnel, equipment, and time costs. Generative adversarial networks (GAN) have shown promise for virtual staining of tissue. We conducted a large-scale validation study of the viability of GANs for H&E to trichrome conversion on WSI (n = 574). Pathologists were largely unable to distinguish real images from virtual/synthetic images given a set of twelve Turing Tests. We report high correlation between staging of real and virtual stains ({rho} = 0.86; 95% CI: 0.84–0.88). Stages assigned to both virtual and real stains correlated similarly with a number of clinical biomarkers and progression to End Stage Liver Disease (Hazard Ratio HR = 2.06, 95% CI: 1.36–3.12, p < 0.001 for real stains; HR = 2.02, 95% CI: 1.40–2.92, p < 0.001 for virtual stains). Our results demonstrate that virtual trichrome technologies may offer a software solution that can be employed in the clinical setting as a diagnostic decision aid.
Highlights
Non-alcoholic steatohepatitis (NASH), the most serious condition in the Non-alcoholic Fatty Liver Disease spectrum, is a liver disease characterized by serologic markers of Supplementary information The online version of this article contains supplementary material, which is available to authorized users.hepatocyte injury as well as distinct histological features [1]
We converted our entire set of 287 hematoxylin and eosin (H&E) stained whole slide images (WSI) into trichrome stained WSI; when processed in series, it took an average of 5 min to convert an entire H&E WSI into a virtual trichrome stained WSI
While other studies have chosen to assess the quality of the stain as the means of assessing the synthetic images, which is only tangentially related to the true utility of the virtual stain, we believe that the best way to assess the viability of the approach is whether pathologists can still assign the same fibrosis stage as if they were examining the true trichrome stain on an adjacent tissue section
Summary
Hepatocyte injury as well as distinct histological features [1]. Patients with NASH are at increased risk of progressive fibrosis with end-stage liver disease characterized by reduced hepatic synthetic function, portal hypertension, encephalopathy, and malignancy such as hepatocellular carcinoma. Portal hypertension can lead to variceal bleeding, splenomegaly, ascites, and renal injury [5]. Prevalence of NASH in the United States has been increasing in recent. It is predicted to become the leading cause of liver transplantation in the decade [7]
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