SimLivA–Modeling ischemia‐reperfusion injury in the liver: A first step towards a clinical decision support tool

Abstract

SummaryThe SIMulation supported LIVer Assessment for donor organs (SimLivA) project aims to develop a mathematical model to accurately simulate the influence of mechanical alterations in marginal liver grafts (specifically steatotic ones) and cold ischemia on early ischemia‐reperfusion injury (IRI) during liver transplantation. Our project tackles significant research challenges, including the co‐development of computational methodologies, experimental studies, clinical processes, and technical workflows. We aim to refine a continuum‐biomechanical model for enhanced IRI prediction, collect pivotal experimental and clinical data, and assess the clinical applicability of our model. Our efforts involve augmenting and tailoring a coupled continuum‐biomechanical, multiphase, and multi‐scale partial differential equation‐ordinary differential equation (PDE‐ODE) model of the liver lobule, allowing us to numerically simulate IRI depending on the degree of steatosis and the duration of ischemia. The envisaged model will intertwine the structure, perfusion, and function of the liver, serving as a crucial aid in clinical decision‐making processes. We view this as the initial step towards an in‐silico clinical decision support tool aimed at enhancing the outcomes of liver transplantation. In this paper, we provide an overview of the SimLivA project and our preliminary findings, which include: a cellular model that delineates critical processes in the context of IRI during transplantation; and the integration of this model into a multi‐scale PDE‐ODE model using a homogenized, multi‐scale, multi‐component approach within the Theory of Porous Media (TPM) framework. The model has successfully simulated the interconnected relationship between structure, perfusion, and function—all of which are integral to IRI. Initial results show simulations at the cellular scale that describe critical processes related to IRI during transplantation. After integrating this model into a multiscale PDE‐ODE model, first simulations were performed on the spatial distribution of key functions during warm and cold ischaemia. In addition, we were able to study the effect of tissue perfusion and temperature, two critical parameters in the context of liver transplantation and IRI.

Simulation of zonation-function relationships in the liver using coupled multiscale models: Application to drug-induced liver injury

“…This was achieved by encoding them in SBML [44] and leveraging existing high-performance simulators designed for SBML [48, 49]. Such a methodology not only facilitated the adaptation of our developed model to diverse research inquiries, such as ischemia-reperfusion injury [78], but also provided a streamlined process for updating the cellular models simply by modifying the SBML files. This approach enabled domain experts in tissue-based TPM and cellular ODE models to concentrate effectively on their respective areas of model development.…”