SPP2311

logo_spp
logo_spp

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

PIs: Uta Dahmen, Matthias König, Tim Ricken, Hans-Michael Tautenhahn

Circulatory systems in the liver. The liver is perfused by oxygenated blood from the hepatic artery and by nutrient-rich blood from the
portal vein. In the liver lobules, blood flows from the terminal branches of these vessels to the central vein, which is located in the center of
the hexagonal structure. Bile is produced in the liver and drained from the liver in a separate biliary system. Drainage occurs in the opposite
direction to blood flow and is driven by diffusion due to concentration differences. Image created with BioRender.com.

Aim:

SimLivA aims to model the impact of mechanical alterations due to steatosis and ischemia on early ischemia reperfusion injury during liver transplantation and machine perfusion. Experimental and clinical data is used to validate the multiphase and multiscale PDE-ODE model of the liver lobule.

Flow chart of key steps of liver transplantation i) Organ procurement. Donor condition (e.g. obesity) affects graft quality (e.g. hepatic steatosis). ii)
Organ transport. Graft is stored in a cold preservation solution for the transport (cold ischemia time), leading to energy depletion and ischemic
damage of unknown severity. iii) Organ transplantation. Reconnecting graft and recipient blood vessels initiates reperfusion and reoxygenation
of the transplanted graft, resulting in ischemia reperfusion injury (IRI). iv) Outcome. Within 48h after transplantation, severity of IRI (damage and function
of the graft) can be assessed (delayed graft function/primary non-function), indicative of graft and patient survival. The three time-critical
decision points to accept or reject a liver graft are (1) before procurement; (2) after procurement and (3) immediately before transplantation.

Description:

Background and Motivation:
Liver transplantation (LTx) is a life-saving treatment for end-stage liver disease, but a critical shortage of donor organs remains a persistent challenge. The growing number of marginal donors—often older, multimorbid individuals—and the simultaneous increase in multimorbid recipients complicate clinical decision-making. Marginal liver grafts, typically affected by hepatic steatosis, exhibit impaired perfusion, metabolism, and function, increasing the risk of post-transplant complications.
Ischemia-reperfusion injury (IRI) during transplantation significantly impacts graft and patient outcomes. Machine perfusion has emerged as a promising strategy to mitigate these effects, extending preservation times and enabling ex vivo repair. However, there remains considerable uncertainty about the optimal perfusion method—normothermic or hypothermic oxygenated perfusion – and how to tailor these approaches to specific clinical scenarios.

Objective:
Building on the success of SimLivA I, which developed a coupled continuum-biomechanical model for IRI on liver lobule and cell scale, SimLivA II aims to refine this model to better predict IRI and support decision-making in LTx. Specifically, the project will extend the existing model to simulate different machine perfusion strategies and incorporate bile production as an indicator of liver function. SimLivA II seeks to develop a robust simulation-supported scoring system for organ allocation, enabling clinicians to optimize outcomes for marginal grafts.

Methods:
The project employs an iterative co-design approach to integrate modeling, experimental, and clinical perspectives. The project begins by developing finite element meshes based on experimental and clinical samples, enabling detailed simulations of liver tissue. Lobular geometries will be extracted, and zonated quantifications of proteins, damage, and steatosis will be incorporated to create simulation-ready geometries.
To capture the complexity of liver graft perfusion, the existing model will be extended to couple ordinary and partial differential equations across organ, lobule, and cellular scales. Temperature-dependent tissue properties, including deformation, permeability, and solute diffusivity, will also be incorporated to refine the simulation’s realism under varying machine perfusion conditions. A key extension involves adding bile transport and metabolism as a second diffusive pathway, complementing the blood transport mechanism and providing a more comprehensive representation of liver function under stress.
To support clinical decision-making, a surrogate modeling framework will be developed, leveraging a physics-informed, data-driven operator learning approach. This framework will enable near real-time predictions based on the complex multi-scale model. Experimental and clinical validation will be conducted using ex vivo liver perfusion and archived clinical samples, ensuring the model’s accuracy and applicability. The experimental findings will also guide parameterization, focusing on the effects of donor pathology, cold storage, and machine perfusion conditions.
The project culminates in the development of a simulation-supported scoring system that translates model outputs into actionable clinical insights. This scoring system will synthesize existing scoring methodologies with new data derived from the model, enhancing decision-making for marginal liver graft allocation and optimizing patient outcomes.

Impact:
SimLivA II will advance predictive modeling for LTx by mapping machine perfusion strategies into a multi-scale, continuum-biomechanical simulation framework. The project aims to provide clinicians with a robust decision-support tool to optimize the use of marginal grafts, ultimately improving patient outcomes and addressing the organ shortage crisis.

Involved Institutions:

Experimental Transplantation Surgery, Department of General, Vascular and Visceral Surgery, Jena University Hospital;
Institute of Structural Mechanics and Dynamics in Aerospace Engineering (ISD), University of Stuttgart;
Institute for Theoretical Biology, Humboldt University Berlin;
Experimental Hepatobiliary Surgery, Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig Medical Center

Applicants:

Prof. Dr. med. Uta Dahmen

Prof. Dr. med. Uta Dahmen

Experimental Transplantation Surgery, Department of General, Vascular and Visceral Surgery, Jena University Hospital
Dr. rer. nat. Matthias König

Dr. rer. nat. Matthias König

Institute for Biology, Institute for Theoretical Biology, Humboldt University Berlin
Prof. Dr.-Ing. Tim Ricken

Prof. Dr.-Ing. Tim Ricken

Institute of Structural Mechanics and Dynamics in Aerospace Engineering, University of Stuttgart
PD Dr. med. Hans-Michael Tautenhahn

PD Dr. med. Hans-Michael Tautenhahn

Experimental Hepatobiliary Surgery, Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig Medical Center
Luis Mandl

Luis Mandl

Institute of Structural Mechanics and Dynamics in Aerospace Engineering, University of Stuttgart & Experimental Hepatobiliary Surgery, Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig Medical Center

Publications

94 Einträge « 1 von 2 »

2024

Spitz, Iam Lena; Korte, Jana; Gaidzik, Franziska; Larsen, Naomi; Preim, Bernhard; Saalfeld, Sylvia

Assessment of intracranial aneurysm neck deformation after contour deployment Artikel

In: International Journal of Computer Assisted Radiology and Surgery, Bd. 1, S. 1:8, 2024.

Links | BibTeX

Manjunatha, K.; Ranno, A.; Shi, J.; Schaaps, N.; Florescu, R.; Nilcham, P.; Cornelissen, A.; Behr, M.; Reese, S.

In Silico Reproduction of the Pathophysiology of In-Stent Restenosis Unveröffentlicht

2024.

Abstract | Links | BibTeX

Manjunatha, K.; Ranno, A.; Shi, J.; Schaaps, N.; Florescu, R.; Nilcham, P.; Cornelissen, A.; Behr, M.; Reese, S.

In Silico Reproduction of the Pathophysiology of In-Stent Restenosis Unveröffentlicht

2024.

Abstract | Links | BibTeX

Danesini, Paolo Carlo; Heim, Maximilian; Tomalka, André; Siebert, Tobias; Ates, Filiz

Endomysium determines active and passive force production in muscle fibers Artikel

In: Journal of Biomechanics, Bd. Volume 168, Ausg. May 2024, 2024.

Abstract | Links | BibTeX

Maier, Benjamin; Göddeke, Dominik; Huber, Felix; Klotz, Thomas; Röhrle, Oliver; Schulte, Miriam

OpenDiHu: An efficient and scalable framework for biophysical simulations of the neuromuscular system Artikel

In: Journal of Computational Science, Ausg. 79, S. 102291, 2024, ISBN: 1877-7503.

Abstract | Links | BibTeX

Gaidzik, Franziska; Korte, Jana; Saalfeld, Sylvia; Janiga, Gabor; Berg, Philipp

Image-based Hemodynamic Simulations for Intracranial Aneurysms – The Impact of Complex Vasculatures Artikel

In: International Journal of Computer Assisted Radiology and Surgery, Bd. 19, Ausg. 4, S. 687-697, 2024.

Links | BibTeX

Homs-Pons, Carme; Lautenschlager, Robin; Schmid, Laura; Ernst, Jennifer; Göddeke, Dominik; Röhrle, Oliver; Schulte, Miriam

Coupled simulations and parameter inversion for neural system and electrophysiological muscle models Artikel

In: GAMM-Mitteilungen, 2024.

Abstract | Links | BibTeX

Gerhäusser, Steffen; Lambers, Lena; Mandl, Luis; Franquinet, Julian; Ricken, Tim; König, Matthias

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

In: [PrePrint], bioRxiv, 2024.

Abstract | Links | BibTeX

Stahl, Janneck; McGuire, Laura Stone; Rizko, Mark; Saalfeld, Sylvia; Berg, Philipp; Alaraj, Ali

Are hemodynamics responsible for inflammatory changes in venous vessel walls? A quantitative study of wall-enhancing intracranial arteriovenous malformation draining veins Artikel

In: Journal of Neurosurgery, 2024.

Links | BibTeX

Obermeier, Lukas; Wiegand, M.; Hellmeier, F.; Manini, C.; Kuehne, Titus; Goubergrits, Leonid

Verification Study of In Silico Computed Intracardiac Blood Flow With 4D Flow MRI Artikel

In: IEEE Transactions on Biomedical Engineering, Bd. 71, Ausg. 9, S. 2568 - 2579, 2024.

Abstract | Links | BibTeX

Ates, Filiz; Roehrle, Oliver

Experiments meet simulations: Understanding skeletal muscle mechanics to address clinical problems Artikel

In: GAMM Mitteilungen, Bd. 2024, 2024.

Abstract | Links | BibTeX

Schwarting, Julian; Holzberger, Fabian; Muhr, Markus; Renz, Martin; Boeckh-Behrens, Tobias; Wohlmuth, Barbara; Kirschke, Jan

Numerical simulation of individual coil placement – A proof-of-concept study for the prediction of recurrence after aneurysm coiling Artikel

In: [PrePrint], arXiv, 2024.

Abstract | Links | BibTeX

Duswald, Tobias; Keith, Brendan; Lazarov, Boyan; Petrides, Socratis; Wohlmuth, Barbara

Finite elements for Matérn-type random fields: Uncertainty in computational mechanics and design optimization Artikel

In: [PrePrint], arXiv, 2024.

Abstract | Links | BibTeX

Han, Mertcan; Yildiz, Erdost; Bozuyuk, Ugur; Aydin, Asli; Yu, Yan; Bhargava, Aarushi; Karaz, Selcan; Sitti, Metin

Janus microparticles-based targeted and spatially-controlled piezoelectric neural stimulation via low-intensity focused ultrasound Artikel

In: Nature Communications, Bd. 15, Ausg. 1, S. 2013, 2024.

Abstract | Links | BibTeX

Lambers, Lena; Waschinsky, Navina; Schleicher, Jana; König, Matthias; Tautenhahn, Hans-Michael; Albadry, Mohamed; Dahmen, Uta; Ricken, Tim

Quantifying Fat Zonation in Liver Lobules: An Integrated Multiscale In-silico Model Combining Disturbed Microperfusion and Fat Metabolism via a Continuum-Biomechanical Bi-scale, Tri-phasic Approach Artikel

In: Biomechanics and Modeling in Mechanobiology, 2024.

Abstract | Links | BibTeX

Thormann, Maximilian; Stahl, Janneck; Marsh, Laurel; Saalfeld, Sylvia; Sillis, Nele; Ding, Andreas; Mpotsaris, Anastasios; Berg, Philipp; Behme, Daniel

Computational Flow Diverter Implantation—A Comparative Study on Pre-Interventional Simulation and Post-Interventional Device Positioning for a Novel Blood Flow Modulator Artikel

In: Fluids, Bd. 9, Ausg. 3, Nr. 55, 2024.

Links | BibTeX

Villota-Narvaez, Yesid; Bleiler, Christian; Roehrle, Oliver

Data sharing in modeling and simulation of biomechanical systems in interdisciplinary environments Artikel

In: GAMM Mitteilungen, Bd. 47, Ausg. 2, 2024.

Abstract | Links | BibTeX

Horvat, Medeea; Lunowa, Stephan B.; Sytnyk, Dmytro; Wohlmuth, Barbara

A lattice Boltzmann method for non-Newtonian blood flow in coiled intracranial aneurysms Artikel

In: [PrePrint], arXiv, 2024.

Abstract | Links | BibTeX

Swiatek, Vanessa M; Amini, Amir; Ortuño, Celina E Sandalcioglu; Spitz, Lena; Hartmann, Karl; Rashidi, Ali; Stein, Klaus-Peter; Saalfeld, Sylvia; Sandalcioglu, I Erol; Neyazi, Belal

Unveiling rupture risk and clinical outcomes in midline aneurysms: A matched cohort analysis investigating the impact of localization within the anterior or posterior circulation Artikel

In: Neurosurgical Review, Bd. 47, Ausg. 76, 2024.

Links | BibTeX

Holzberger, Fabian; Muhr, Markus; Wohlmuth, Barbara

A Comprehensive Numerical Approach to Coil Placement in Cerebral Aneurysms: Mathematical Modeling and In Silico Occlusion Classification Artikel

In: [PrePrint], arXiv, 2024.

Abstract | Links | BibTeX

Frank, Martin; Holzberger, Fabian; Horvat, Medeea; Kirschke, Jan; Mayr, Matthias; Muhr, Markus; Nebulishvili, Natalia; Popp, Alexander; Schwarting, Julian; Wohlmuth, Barbara

Numerical simulation of endovascular treatment options for cerebral aneurysms Artikel

In: [PrePrint], arXiv, 2024.

Abstract | Links | BibTeX

König, Matthias

Python utilities for porous media analysis and visualization Online

Zenodo, (Hrsg.): 2024.

Abstract | Links | BibTeX

Tautenhahn, Hans-Michael; Ricken, Tim; Dahmen, Uta; Mandl, Luis; Bütow, Laura; Gerhäusser, Steffen; Lambers, Lena; Chen, Xinpei; Lehmann, Elina; Dirsch, Olaf; König, Matthias

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

In: GAMM-Mitteilungen e202370003, 2024.

Abstract | Links | BibTeX

Obermeier, Lukas; Korte, Jana; Vellguth, Katharina; Barbieri, Fabian; Hellmeier, Florian; Berg, Philipp; Goubergrits, Leonid

Inter-model and inter-modality analysis of left ventricular hemodynamics: comparative study of two CFD approaches based on TTE and MRI Artikel

In: GAMM-Mitteilungen, 2024.

Links | BibTeX

Schmid, Laura; Klotz, Thomas; Röhrle, Oliver; Powers, Randall K.; Negro, Francesco; Yavuz, Utku Ş.

Postinhibitory excitation in motoneurons Artikel

In: PLOS Computational Biology, Bd. 20, Ausg. 1, 2024.

Abstract | Links | BibTeX

Korte, Jana; Marsh, Laurel M. M.; Saalfeld, Sylvia; Behme, Daniel; Aliseda, Alberto; Berg, Philipp

Fusiform versus Saccular Intracranial Aneurysms—Hemodynamic Evaluation of the Pre-Aneurysmal, Pathological, and Post-Interventional State Artikel

In: Journal of Clinical Medicine, Bd. 13, Ausg. 2, Nr. 551, S. 1-14, 2024.

Links | BibTeX

Ranno, A.; Manjunatha, K.; Glitz, A.; Schaaps, N.; Reese, S.; Vogt, F.; Behr, M.

In-silico Analysis of Hemodynamic Indicators in Idealized Stented Coronary Arteries for Varying Stent Indentation Unveröffentlicht

2024.

Abstract | Links | BibTeX

Gerach, Tobias; Loewe, Axel

Differential effects of mechano-electric feedback mechanisms on whole-heart activation, repolarization, and tension Artikel

In: The Journal of Physiology, 2024.

Abstract | Links | BibTeX

Korte, Jana; Klopp, Ehlar Sophie; Berg, Philipp

Multi-Dimensional Modeling of Cerebral Hemodynamics: A Systematic Review Artikel

In: Bioengineering, Bd. 11, Ausg. 1, S. 1-24, 2024.

Links | BibTeX

Fröhlich, Jonathan; Gerach, Tobias; Krauß, Jonathan; Loewe, Axel; Stengel, Laura; Wieners, Christian

Numerical evaluation of elasto-mechanical and visco-elastic electro-mechanical models of the human heart Artikel

In: GAMM Mitteilungen, Bd. 46, Ausg. 2, 2024, ISSN: 1522-2608.

Abstract | Links | BibTeX

Yildiz, Erdost; Han, Mertcan; Werneck, Linda; Keip, Marc-Andre; Sitti, Metin; Ortiz, Michael

Experimental model for strain-induced mechanical neurostimulation on human progenitor neurons Artikel

In: Science Communications World Wide, 2024.

Abstract | Links | BibTeX

2023

Gjerde, Ingeborg G.; Kuchta, Miroslav; Rognes, Marie E.; Wohlmuth, Barbara

Directional flow in perivascular networks: Mixed finite elements for reduced-dimensional models on graphs Artikel

In: [PrePrint], arXiv, 2023.

Abstract | Links | BibTeX

Albadry, Mohamed; Kuettner, Jonas; Grzegorzewski, Jan; Dirsch, Olaf; Kindler, Eva; Klopfleisch, Robert; Liska, Vaclav; Moulisova, Vladimira; Nickel, Sandra; Palek, Richard; Rosendorf, Jachym; Saalfeld, Sylvia; Settmacher, Utz; Tautenhahn, Hans-Michael; König, Matthias; Dahmen, Uta

Cross-Species Variability in Lobular Geometry and Cytochrome P450 Hepatic Zonation: Insights into CYP1A2, CYP2E1, CYP2D6 and CYP3A4 Artikel

In: [PrePrint], bioRxiv, 2023.

Abstract | Links | BibTeX

Holzberger, Fabian; Kirschke, Jan; Muhr, Markus; Nebulishvili, Natalia; Schwarting, Julian; Wohlmuth, Barbara

Breaking Blood Flow with Wires in Aneurysm Coiling Treatment Simulations Online

SIAM, News (Hrsg.): 2023, besucht am: 19.12.2023.

Links | BibTeX

Manjunatha, K.; Schaaps, N.; Behr, M.; Vogt, F.; Reese, S.

Computational Modeling of In-Stent Restenosis: Pharmacokinetic and Pharmacodynamic Evaluation Artikel

In: Computers in Biology and Medicine, Ausg. 167, 2023.

Abstract | Links | BibTeX

Azhdari, Mohammad; Seyedpour, Seyed Morteza; Lambers, Lena; Tautenhahn, Hans-Michael; Tautenhahn, Franziska; Ricken, Tim; Rezazadeh, Ghader

Non-local three phase lag bio thermal modeling of skin tissue and experimental evaluation Artikel

In: Heat and Mass Transfer (149), 2023.

Abstract | Links | BibTeX

Korte, Jana; Gaidzik, Franziska; Larsen, Naomi; Schütz, Erik; Damm, Timo; Wodarg, Fritz; Hövener, Jan-Bernd; Jansen, Olav; Janiga, Gábor; Berg, Philipp; Pravdivtseva, Mariya S

In vitro and in silico assessment of flow modulation after deploying the Contour Neurovascular System in intracranial aneurysm models Artikel

In: Journal of NeuroInterventional Surgery, 2023.

Links | BibTeX

Mandl, Luis; Mielke, André; Seyedpour, Seyed Morteza; Ricken, Tim

Affine transformations accelerate the training of physics-informed neural networks of a one-dimensional consolidation problem Artikel

In: Nature Scientific Reports, 2023.

Abstract | Links | BibTeX

Stahl, Janneck; Kassem, Leheng; Behme, Daniel; Klebingat, Stefan; Saalfeld, Sylvia; Berg, Philipp

Fabrication of flexible intracranial aneurysm models using stereolithography 3D printing Artikel

In: Current Directions in Biomedical Engineering, Bd. 9, Ausg. 1, S. 395-389, 2023.

Links | BibTeX

Korte, Jana; Groschopp, Paula; Berg, Philipp

Resolution-based comparative analysis of 4D-phase-contrast magnetic resonance images and hemodynamic simulations of the aortic arch Artikel

In: Current Directions in Biomedical Engineering, Bd. 9, Ausg. 1, S. 650-653, 2023.

Links | BibTeX

Werneck, Linda; Han, Mertcan; Yildiz, Erdost; Keip, Marc-André; Sitti, Metin; Ortiz, Michael

A Simple Quantitative Model of Neuromodulation. Part I: Ion Flow Through Neural Ion Channels Artikel

In: Biological Physics, 2023.

Abstract | Links | BibTeX

Sveric, Krunoslav Michael; Cansız, Barış; Winkler, Anna; Ulbrich, Stefan; Ende, Georg; Heidrich, Felix; Kaliske, Michael; Linke, Axel; Jellinghaus, Stefanie

Accuracy of Devereaux and Teichholz formulas for left ventricular mass calculation in different geometric patterns: comparison with cardiac magnetic resonance imaging Artikel

In: Scientific reports, Bd. 13, 2023.

Abstract | Links | BibTeX

Korte, Jana; Voß, Samuel; Janiga, Gábor; Beuing, Oliver; Behme, Daniel; Saalfeld, Sylvia; Berg, Philipp

Is accurate lumen segmentation more important than outlet boundary condition in image-based blood flow simulations for intracranial aneurysms? Artikel

In: Cardiovascular Engineering and Technology, Bd. 14, Ausg. 5, S. 617–630, 2023.

Links | BibTeX

Maheshvare, M. Deepa; Raha, Soumyendu; König, Matthias; Pal, Debnath

A pathway model of glucose-stimulated insulin secretion in the pancreatic β-cell Artikel

In: Frontiers in Endocrinology, 2023.

Abstract | Links | BibTeX

Cornelissen, A.; Florescu, R. A.; Reese, S.; Behr, M.; Ranno, A.; Manjunatha, K.; Schaaps, N.; Böhm, C.; Liehn, E. A.; Zhao, L.; Nilcham, P.; Milzi, A.; Schröder, J.; Vogt, F. J.

In-Vivo Assessment of Vascular Injury for the Prediction of In-Stent Restenosis Artikel

In: International Journal of Cardiology, Ausg. 388, 2023.

Abstract | Links | BibTeX

König, Matthias

Hepatocyte model of ischemia reperfusion injury (IRI) Online

Zenodo, (Hrsg.): 2023, besucht am: 30.06.2023.

Abstract | Links | BibTeX

Lee, Yongjae; Cansız, Barış; Kaliske, Michael

A multiphysical computational model of myocardial growth adopted to human pathological ventricular remodelling Artikel

In: 2023.

Links | BibTeX

Haggie, Lysea; Schmid, Laura; Röhrle, Oliver; Besier, Thor; McMorland, Angus; Saini, Harnoor

Linking cortex and contraction—Integrating models along the corticomuscular pathway Artikel

In: Frontiers in Physiology, Sec. Computational Physiology and Medicine, Ausg. Vol 14-2023, 2023.

Abstract | Links | BibTeX

Simeon, Bernd

Die Macht der Computermodelle. Quellen der Erkenntnis oder digitale Orakel? Buch

1, Springer Berlin, Heidelberg, 2023, ISBN: 978-3-662-66298-4.

Abstract | Links | BibTeX

Stahl, Janneck; Marsh, Laurel Morgan Miller; Thormann, Maximilian; Ding, Andreas; Saalfeld, Sylvia; Behme, Daniel; Berg, Philipp

Assessment of the Flow-Diverter Efficacy for Intracranial Aneurysm Treatment Considering Pre- and Post-Interventional Hemodynamics Artikel

In: Computers in Biology and Medicine, Bd. 156, Ausg. 106720, 2023.

Links | BibTeX

94 Einträge « 1 von 2 »