Building a 3D Virtual Liver: Methods for Simulating Blood Flow and Hepatic Clearance on 3D Structures

Area of Science:

• Computational modeling
• Liver physiology
• Pharmacokinetics

Background:

• Accurate simulation of liver processes is crucial for drug development.
• Existing models often lack integration of vasculature and tissue dynamics.
• A unified approach is needed for simulating blood flow and drug metabolism.

Purpose of the Study:

• To develop a spatio-temporal modeling approach for liver blood and drug flow.
• To simulate drug uptake and elimination within a 3D liver approximation.
• To integrate fluid dynamics and hepatic clearance into a single computational framework.

Main Methods:

• Generated a 3D liver approximation with portal and hepatic vasculature using constrained constructive optimization.
• Converted vasculature to a spatial grid and assigned upscaled lobule tissue properties.
• Simulated fluid flow and drug metabolism using discretized convective-diffusive-reactive partial differential equations.

Main Results:

• Developed a consistent method for simulating blood and drug flow on a representative 3D liver structure.
• Enabled simulation of drug metabolism (hepatic clearance) within the integrated model.
• Provided a unified computational approach for studying liver drug dynamics.

Conclusions:

• The developed spatio-temporal model offers a robust platform for in silico liver drug studies.
• This approach enhances understanding of drug distribution and metabolism in the liver.
• The method facilitates more accurate predictions of drug efficacy and toxicity.