Multiparameter assessment of hepatobiliary excretion dysfunction in cholestasis via dynamical photoacoustic and NIR-II fluorescence imaging

Cholestatic liver diseases (CLD) lead to bile accumulation, hepatobiliary dysfunction, and progressive liver damage. Early, accurate evaluation of cholestasis is essential for improving prognosis. In this study, we developed a cross-scale, noninvasive optical imaging platform designed to evaluate both microstructure and metabolic functions in cases of intrahepatic cholestasis, such as primary biliary cholangitis, as well as extrahepatic cholestasis resulting from bile duct ligation. We employed high-resolution photoacoustic microscopy to assess changes in bile duct permeability, hepatic lobular architecture, and blood oxygen saturation following varying degrees of bile duct injury. Meanwhile, we utilized near-infrared-II fluorescence imaging to track the transport of indocyanine green, thereby mapping the absorption and excretion dynamics throughout the liver. Liver function reserve was monitored in situ using contrast-enhanced photoacoustic computed tomography. The imaging manifestations of microstructural alterations and functional impairments associated with cholestasis were quantitatively characterized, demonstrating a correlation with disease progression and validation of our findings. This platform enables dynamic, high-resolution assessment of small bile duct injury and hepatobiliary dysfunction, offering a promising tool for early diagnosis, monitoring, and therapeutic evaluation of CLD.