High-Resolution Quantitative Reconstruction of Microvascular Architectures in Mouse Hepatocellular Carcinoma Models

<b>Background/Objectives</b>: Alterations in liver vascularization play a remarkable role in liver disease development, including hepatocellular carcinoma (HCC), but remain understudied. This study evaluated the hepatic microvascular imaging method and provided high-resolution quantitative anatomical data on the characteristics and architecture of liver vasculature in wild-type (WT) mice and HCC mouse models. <b>Methods</b>: C57BL/6 mice were injected with Akt/Ras or Sleeping Beauty transposon to induce HCC. Liver tissues from normal and Akt/Ras mice underwent hematoxylin and eosin, Masson's trichrome, Ki67, and lymphatic endothelial receptor-1 staining. Using cutting-edge high-definition fluorescence micro-optical sectioning tomography, high-precision microvascular visualization of the liver was performed in WT and Akt/Ras HCC mice. <b>Results</b>: The sectioned volumes of normal and HCC liver tissues were 204.8 mm³ and 212.8 mm³, respectively. The microvascular systems associated with the tissues of the Akt/Ras HCC mouse were twisted, disordered, and compressed by tumor nodules. In the four tumor nodules, the path of the hepatic artery was more around the tumor edge, whereas the portal vein occupied the central position and constituted the main blood vessel entering the tumors. The porosity of HCC and paracancerous cirrhotic tissues was significantly less than that of normal tissues. The radii of the central vessels in the hepatic sinusoid of paratumoral cirrhotic tissues were significantly higher than those of normal tissues; however, the hepatic sinusoid density of paratumoral cirrhotic tissues was lower. <b>Conclusions</b>: This research provides a deeper understanding of the normal liver microvasculature and alterations in cases of cirrhosis and HCC, which complements scientific insights into liver morphology and physiology. This straightforward research approach involving the novel 3D liver microvasculature can be used in multiscale physiological and pathophysiological studies regarding liver diseases.