Noninvasive Evaluation of HepaRG Aggregates during Drug‐Induced Intrahepatic Cholestasis Using Optical Coherence Tomography

Abstract Intrahepatic cholestasis represents a typical manifestation of drug‐induced liver injury. Many researches have been made to understand the drug‐induced cholestasis using human cell based in vitro 3D model. Although noninvasive observation of 3D model will help unveil the hidden mechanism of this phenomenon, there have been few studies using the noninvasive methods. This study has attempted to evaluate the potential of noninvasive optical coherence tomography (OCT) combined with confocal laser scanning microscopy using the aggregates of a differentiated human hepatic cell line. From immunofluorescence staining images, the aggregates during drug‐induced cholestasis are divided into three groups: aggregates of mature phase (type I), immature phase (type II), and death phase (type III). OCT data reveal that different distributions of gray levels of OCT images are observed between heterogeneous (type I and II) and homogeneous cell populations (type III). A threshold based on gray levels of OCT data in each phenotype is determined, and the data can distinguish type III aggregates from the others. The results suggest that OCT data provide valuable information for noninvasively and quantitatively determining the transition of different types of cell population, i.e., from type I and II to type III, in drug‐induced intrahepatic cholestasis processes.