Zonated Quantification of Steatosis for Pharmacokinetics Simulations

Lars Ole Schwen (Fraunhofer MEVIS)

Hepatic physiological processes and pathological conditions are typically heterogeneous in space, both varying across the entire organ and forming patterns at the lobular scale. Additional heterogeneity is introduced by surgical interventions. To accurately simulate and predict effects of drugs, the heterogeneity of the pathology needs to be quantified in sufficient detail and pharmacokinetics (PK) simulations need to take into account the pathology.

In a previous study [1], we considered steatosis in mice. We developed a method to automatically quantify the amount of macrovesicular steatosis from histological serial sections, including zonation and organ-scale heterogeneity, in an entire mouse liver.

The quantified steatosis patterns were predominantly periportal, with a substantial variation across the organ. An example PK simulation illustrated the impact of different steatosis zonation patterns on the local hepatic drug uptake.

The analysis provides a quantitative, zonated description of steatosis in unprecedented detail. It can be extended to other liver diseases that can be assessed by histological images, providing diagnosis support. Perspectively, the combination with PK simulations can provide therapy support via dosage optimization.

[1] Schwen, Homeyer, Schwier, Dahmen, Dirsch, Schenk, Kuepfer, Preusser, Schenk: Zonated Quantification of Steatosis in an Entire Mouse Liver, Comput. Biol. Med. 73, 108–118, 2016, DOI 10.1016/j.compbiomed.2016.04.004.