Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

肝纤维化是细胞外基质蛋白（如胶原蛋白）的过度积聚，这可能导致肝硬化、肝衰竭和门静脉高压。在这项研究中，我们应用一个开发的多模态非线性光学显微镜平台，对通过胆管结扎（BDL）手术建立的大鼠模型中的肝纤维化疾病进行研究。三种非线性显微镜成像模式依次在患病模型的相同切片组织上实施：即二次谐波产生（SHG）成像量化胶原蛋白的含量，双光子激发荧光（TPEF）成像揭示肝细胞的形态，而相干反斯托克斯拉曼散射（CARS）成像定量绘制脂肪或脂质在组织中的分布。我们的成像结果表明，在BDL模型中肝纤维化（胶原蛋白）发展过程中，脂肪肝疾病也会发生。肝纤维化模型中胶原蛋白和脂肪成分的聚集浓度彼此之间呈现出一定的相关性。