Multiscale X-ray phase-contrast CT uncovers adaptive changes and compensatory mechanisms of circulatory pathways during acute liver injury

Intrahepatic circulation is essential for the repair of acute liver injury (ALI); however, very limited information is available concerning changes in the circulatory pathways during ALI. Therefore, multi-scale X-ray phase-contrast CT combined with three-dimensional (3D) visualization is used to quantitatively analyze the intrahepatic circulation pathway (including the hepatic vein, portal vein and hepatic sinusoid) in the mouse model via the intraperitoneal injection of carbon tetrachloride (CCl 4 ) from acute injury to recovery. The results demonstrate that the liver still preserves some vessel-like channels accessed to the central vein when the injury causes the severe collapse of the hepatic sinusoids that cannot be observed in two-dimensional pathologic slices. Moreover, angiogenesis is observed in the terminal branches of the hepatic vein and portal vein. Additionally, we extend the two-dimensional primary lobule to a 3D model and find that the sinusoids in zone III have the most severe injury. The sinusoids in different zones also show changes in parameters such as density and mean diameter during the ALI. In conclusion, phase-contrast CT can reveal the intact vascular system within the liver lobes, thus providing critical information for studying the mechanisms involved in the evolution of circulatory structures from damage to repair. Multiscale phase-contrast CT combined with 3D visualization provides insights into the morphological mechanisms of damage, compensation and repair of blood circulation pathways within the intact liver lobe during acute liver injury in mice.