SimLivA II – SIMulation supported LIVer Assessment for donor organs II - Continuum-biomechanical modeling for staging of ischemia-reperfusion injury during liver transplantation and machine perfusion

• Applicants: Professorin Dr. Uta Dahmen; Dr. Matthias König; Professor Dr.-Ing. Tim Ricken; Privatdozent Dr. Hans-Michael Tautenhahn
• Subject Area: Applied Mechanics, Statics and Dynamics ; General and Visceral Surgery ; Bioinformatics and Theoretical Biology ; Mechanics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465194077

Background: Liver transplantation (LTx) is the only curative treatment option for acute and chronic end-stage liver disease. Demographic change and western lifestyle result in an increasing rate of elderly multi-morbid potential recipients and donors. Liver grafts from such donors, so-called marginal liver grafts, are often affected by hepatic steatosis compromising the quality of the donor organ substantially. One reason is the alteration of the tissue structure, resulting in an impaired perfusion, which in turn affects hepatic metabolism and organ function. In case of a marginal graft, the surgeon is faced with the clinical decision to either accept or reject the organ, significantly increasing the postoperative risk for the recipient or increasing the risk of death on the waiting list, respectively. Two major challenges for marginal grafts are the storage between procurement of the organ and transplantation (cold ischemia time) and damage after reperfusion (ischemia-reperfusion injury or IRI). Machine perfusion is currently the most promising strategy for prolonging the viability of organs from marginal donors. Goal: Our co-designed interdisciplinary project “SIMulation supported LIVer Assessment for donor organs (SimLivA 2)” aims to mathematically model the effects of different machine perfusion strategies on organ vitality. We address the following research questions: (i) How can we include temperature as a material property into the existing models? (ii) How can we extend the existing model to include the bile phase with a two-way pathway? (iii) How can the models be verified as well as parameterized and validated with experimental and clinical data? (iv) How can we translate the model predictions into a clinically applicable simulation-supported scoring system for decision support? Methods: To achieve these goals, we will extend and adapt our coupled continuum-biomechanical multiphase and multi-scale PDE-ODE model of the liver lobule to numerically simulate machine perfusion strategies. Experimental and clinical data acquisition for model parameterization and validation is designed in close collaboration with modeling. Our model couples structure, perfusion and function of the liver via the interplay between mechanical properties of the graft, hepatic sinusoidal perfusion and the affected molecular pathways, which might facilitate these decision processes and is urgently needed. We want to simulate processes during machine perfusion numerically and transfer the results into a simulation-supported scoring system. This will be the first step towards an in-silico clinical decision support tool to reach a better decision pro or contra the transplantation of a marginal organ and the use of machine perfusion by in-silico predicting hepatic damage and early graft function.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2311: Robust coupling of continuum-biomechanical in silico models to establish active biological system models for later use in clinical applications - Co-design of modeling, numerics and usability