3D reconstruction of human liver tissue at cellular resolution

Area of Science:

• Hepatology
• Pathology
• Medical Imaging

Background:

• Liver microstructure is crucial for function; architectural disruption is pathologic.
• Two-dimensional (2D) histopathology has limitations in capturing complex 3D liver structures.
• Understanding 3D liver architecture is vital for diagnosing and treating liver diseases.

Purpose of the Study:

• To create detailed 3D reconstructions of nonfibrotic and cirrhotic human liver tissue.
• To analyze architectural changes in cirrhotic livers using advanced imaging techniques.
• To identify specific structural alterations associated with liver cirrhosis.

Main Methods:

• Immunostaining and tissue clearing techniques were employed.
• Advanced microscopy and computational software were used for 3D reconstruction.
• Multilobular reconstructions of human liver tissue (nonfibrotic and cirrhotic) were generated.

Main Results:

• Cirrhotic livers showed sinusoid zonal dysregulation.
• A reduction in glutamine synthetase-expressing pericentral hepatocytes was observed.
• Regression of central vein and hepatic arterial networks, along with biliary network fragmentation, was identified, suggesting a pro-portalization phenotype.

Conclusions:

• Three-dimensional (3D) pathological analysis reveals significant architectural disruption in cirrhotic human livers.
• The observed changes indicate a pro-portalization/decentralization phenotype in cirrhotic tissue.
• Further implementation of 3D pathological analyses can deepen the understanding of cirrhotic pathobiology and guide novel therapeutic strategies.