Joint zonated quantification of multiple parameters in hepatic lobules

Abstract

Metabolic processes in the hepatic lobule are spatially organized. Consequently, many liver diseases have a distinct zonation pattern. Understanding the interplay between a zonated disease pattern and its impact on liver function requires the joint quantification of both phenomena. Our study presents an image analysis workflow for the joint zonated quantification of multiple parameters from whole-slide images of conventionally stained serial sections. Portal fields and central veins are annotated and transferred to adjacent slide images via image registration. This allows identifying the same lobules and zones in multiple slides, where zones are obtained by dividing the distance between portal fields and central veins in twelve intralobular zonal distributions of various parameter combinations quantified from multiple slides can then be plotted as scatter diagrams or visualized in the lobule/zone geometry. As a proof-of-concept, we quantify the distribution of periportal steatosis and pericentral cytochrome P-450 (CYP) expression using HE and immunohistochemically stained WSI. The data can be used to parameterize computational simulations of physiological processes in the lobules and zones more accurately.