Image Monitoring of the Impaired Phagocytic Activity of Kupffer Cells and Liver Oxygen Saturation in a Mouse Cholangitis Model Using Contrast-Enhanced Ultrasound Imaging and Photoacoustic Imaging

Bile duct ligation (BDL) can cause cholangitis, which is known to induce impaired Kupffer cell (KC) function and increased oxygen consumption in a mouse model. It is important to monitor changes in KC function and tissue oxygen saturation, both of which are critical factors in the progression of cholangitis. The purpose of this study is to investigate the impaired phagocytic activity of KC and liver oxygen saturation (sO2) in a mouse cholangitis model using contrast-enhanced ultrasound imaging (CEUS) and photoacoustic imaging (PAI). A mouse cholangitis model was created by ligation of the common bile duct (CBDL, n = 20), and the left intrahepatic bile duct (BDL-L, n = 19), both of which were compared with the non-ligation groups—right lobe measurement group after left intrahepatic bile duct ligation (BDL-R, n = 19) and the control group (n = 14). The echogenicity and sO2were measured by CEUS and PAI and the KC fraction was assessed at 1, 2 and 4 wk after ligation. We found a significantly lower echogenicity of the Kupffer phase in the CBDL and BDL-L groups compared with that in the control and BDL-R groups at 2 wk (p <.01). The CBDL and BDL-L groups showed a lower echogenicity than that of the BDL-R group at 4 wk (p <.01). We found a significantly lower sO2of the CBDL and BDL-L groups compared with that of the control and BDL-R groups at 4 wk (p <.01). The CBDL and BDL-L groups showed a higher KC fraction than that of the BDL-R and control groups at each time point (p <.01). In conclusion, our study suggests that the Sonazoid CEUS and PAI could be a useful tool for monitoring impaired KC phagocytic activity and the liver hypoxic state.