Generation of a High-Precision Whole Liver Panorama and Cross-Scale 3D Pathological Analysis for Hepatic Fibrosis.

Abstract

The liver harbors complex cross-scale structures, and the fibrosis-related alterations to these structures have a severe impact on the diverse function of the liver. However, the hepatic anatomic structures and their pathological alterations in the whole-liver scale remain to be elucidated. Combining the micro-optical sectioning tomography (MOST) system and liver Nissl staining, a first high-precision whole mouse liver atlas is generated, enabling visualization and analysis of the entire mouse liver. Thus, a detailed 3D panorama of CCl4-induced liver fibrosis pathology is constructed, capturing the 3D details of the central veins, portal veins, arteries, bile ducts, hepatic sinusoids, and liver cells. Pathological changes, including damaged sinusoids, steatotic hepatocytes, and collagen deposition, are region-specific and concentrated in the pericentral areas. The quantitative analysis shows a significantly reduced diameter and increased length density of the central vein. Additionally, a deep learning tool is used to segment steatotic hepatocytes, finding that the volume proportion of steatotic regions is similar across liver lobes. Steatosis severity increases with proximity to the central vein, independent of central vein diameter. The approach allows the cross-scale visualization of multiple structural components in liver research and promotes pathological studies from a 2D to a 3D perspective.