The Digital Liver Lab (DiLiLab) of the Institute of Structural Mechanics and Dynamics in Aerospace Engineering deals with the multiscale and multiphase description of the liver based on the Theory of Porous Media (TPM). The key aspect of knowledge-driven modeling is the continuum-biomechanical description of the lobular level coupled with a systems biology approach at the cellular level while taking into account the blood pressure at the organ level. In addition, data-driven surrogate modeling applications are investigated.
The liver is the central metabolic organ in the human body. The main tasks of the liver are metabolic homeostasis, e.g., lipid and carbohydrate metabolism, detoxification of drugs and toxins and storage as well as depletion of high-emergy substances. The functionality of the liver is mainly influenced by the perfusion of the smallest repetitive sub-elements, the so-called lobules. A dysfunctional perfusion is mainly caused by diseases of the liver, such as steatosis, cirrhosis or tumor growth as well as surgical interventions like (extended) liver resection or liver transplantation.
To simulate the processes in the liver, we use a multicomponent, poro-elastic, multiphasic and multiscale function-perfusion approach. On the organ scale, the total perfusion as well as the blood pressure is calculated. This affects the blood perfusion through the liver lobules on the lobule scale, where we have an anisotropic blood flow along the sinusoid, the liver cells. On the lobule scale, the complex biological structure of the liver lobules is described by the Theory of Porous Media. The metabolism processes take place on the cell scale, where we use ordinary differential equations to describe the extensive procedures.
Simulation of outflow obstruction
Anatomical details in different scales of the liver model
Fat distribution in liver lobule
Using this multiphasic, continuum-mechanical formulation of the liver, taking the macro scale (organ level), meso scale (liver lobule) and micro scale (metabolism in the hepatocytes) into account, various disorders and therapeutic procedures in addition to the general function can be described. This numerical model allows a non-invasive, patient-specific analysis of the liver and can help to improve therapy as well as actual surgical procedures.
All completed and ongoing projects are listed below.
Ongoing Projects
This project is part of the Project Network 2: In Silico Models of Coupled Biological Systems of the Cluster of Excellence "Data-Integrated Simulation Science (SimTech)" and thus funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2075 – 390740016.
The project aims at a better understanding of the development of tumors in the liver, which is necessary to predict the process of cancer growth and retardation in the liver. The scope is as follows:
- Develop a deterministic multiscale model for tumor growth and metastases,
- improve the efficiency in the numerical calculation,
- integrate data obtained experimentally and in silico, and
- develop and apply polymorphic uncertainty quantification (UQ) procedures.
Further information: https://www.simtech.uni-stuttgart.de/exc/research/pn/pn2/pn2-2a/
Contact:
Lena Lambers, Tim Ricken
This project is funded through German Research Foundation (DFG) within the Research Unit Programme FOR 5151 "QuaLiPerF (Quantifying Liver Perfusion–Function Relationship in Complex Resection––A Systems Medicine Approach)" by grant number 436883643. Within this research unit, this project aims to numerically simulate the mechanically and biologically coupled perfusion-function processes on the lobular level. The model will provide information on perfusion changes induced by fat accumulation via portal vein ligation and liver resection. The following issues are addressed:
- Development and verification of function-perfusion biscale model on liver lobule level including metabolism and heterogeneities of the normal and steatotic liver.
- Validation of the model on the basis of animal model data and clinical data provided by the partners in the FOR 5151.
- Transfer and application of the model to investigate the influence of liver perfusion disturbance and resection on the distribution of hepatic functions as well as on the recovery of liver function and perfusion during regeneration.
- Development of a workflow for the semi-automated preparation of relevant patient data, numerical calculation and delivery of the results to the clinic as a basis for a clinically applicable planning tool.
Further information: https://qualiperf.de/projects/P7
Contact: Steffen Gerhäusser, Tim Ricken
As part of the Priority Programme 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, SimLivA (Grant number 465194077) aims to mathematically model the impact of mechanical alterations due to steatosis and cold ischemia on early ischemia reperfusion injury in liver transplantation. Experimental and clinical data will be used to validate the coupled multiphase and multiscale PDE-ODE model of the liver lobule.
The project addresses the following research questions:
- How to co-design computational methods, experimental studies, clinical processes, and technical workflows?
- How to improve the multiscale continuum-biomechanical model for prediction of IRI?
- How to obtain experimental and clinical data that are essential to quantify the relationship between steatosis, ischemia and reperfusion injury?
- How to evaluate the clinical usability of the model?
For further information, click here.
Contact: Luis Mandl, Tim Ricken
Completed Projects
The foundation for the establishment of the Digital Liver Lab was laid by studies on the introduction of glucose metabolism at the cellular level and on growth effects in the human liver. The former dealt with the integration of an ODE model of metabolism to the storage and depletion of glycogen in the mechanical model of the liver lobule, while the latter dealt with the biomechanical modeling of mass transfer in tissues of the liver.
Cooperation Partners
- Matthias König, Humboldt Universität Berlin
- Uta Dahmen, Uniklinikum Jena
- Hans-Michael Tautenhahn, Uniklinikum Jena
- Nicole Radde, Universität Stuttgart
- Lars Ole Schwen, MEVIS Bremen
- Bruno Christ, Uniklinikum Leipzig
- Jürgen Reichenbach, Uniklinikum Jena
- Karl-Heinz Herrmann, Uniklinikum Jena
Publications
Tim Ricken, Jörg Schröder, Joachim Bluhm, Florian Bartel
Theoretical formulation and computational aspects of a two-scale homogenization scheme combining the TPM and FE 2 method for poro-elastic fluid-saturated porous media, International Journal of Solids and Structures, 2022, 10.1016/j.ijsolstr.2021.111412
Bruno Christ, Maximilian Collatz, Uta Dahmen, Karl-Heinz Herrmann, Sebastian Höpfl, Matthias König, Lena Lambers, Manja Marz, Daria Meyer, Nicole Radde, Jürgen R. Reichenbach, Tim Ricken, Hans-Michael Tautenhahn
Hepatectomy-induced alterations in hepatic perfusion and function - toward multi-scale computational modeling for a better prediction of post-hepatectomy liver function. Frontiers in Physiology, 12, November 2021, 10.3389/fphys.2021.733868
Seyed M. Seyedpour, Mehdi Nabati, Lena Lambers, Sara Nafisi, Hans-Michael Tautenhahn, Ingolf Sack, Jürgen R. Reichenbach, Tim Ricken
Application of magnetic resonance imagingin liver biomechanics: A systematic review. Frontiers in Physiology, 12, September 2021, 10.3389/fphys.2021.733393
Lena Lambers, André Mielke, Tim Ricken.
Semi-automated Data-driven FE Mesh Generation and Inverse Parameter Identification for a Multiscale and Multiphase Model of Function-Perfusion Processes in the Liver. PAMM, 21(1), Article 1, 20221, https://doi.org/10.1002/pamm.202100190
Lena Lambers, Marlon Suditsch, Arndt Wagner, Tim Ricken
A Multiscale and Multiphase Model of Function‐Perfusion Growth Processes in the Human Liver
PAMM 20(1), 2021
Fleurianne Bertrand, Lena Lambers, Tim Ricken
Least Squares Finite Element Method for Hepatic Sinusoidal Blood Flow. PAMM, 20(1), Article 1, 2020, https://doi.org/10.1002/pamm.202000306
Marlon Suditsch, Patrick Schröder, Lena Lambers, Tim Ricken, Wolfgang Ehlers, Arndt Wagner
Modelling basal‐cell carcinoma behaviour in avascular skin, PAMM, 20(1), 2021
Tim Ricken, Lena Lambers
On computational approaches of liver lobule function and perfusion simulation
GAMM-Mitteilungen 42 (4), 2019
Lena Lambers, Tim Ricken, Matthias König
Model Order Reduction (MOR) of Function‐Perfusion‐Growth Simulation in the Human Fatty Liver via Artificial Neural Network (ANN)
PAMM 19, 2019
Daniel Werner, Tim Ricken, Hermann-Georg Holzhütter, Matthias König, Uta Dahmen, Olaf Dirsch
On growth effects in the human liver
PAMM, Volume 14, Issue 1, pages 105–106, December 2014 [DOI: 10.1002/pamm.201410040]
Tim Ricken, Daniel Werner, Hermann-Georg Holzhütter, Matthias König, Uta Dahmen, Olaf Dirsch
Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach.
Biomechanics and Modeling in Mechanobiology, 09/2014;
DOI: 10.1007/s10237-014-0619-z
Tim Ricken, Uta Dahmen, Olaf Dirsch, Daniel Werner
A Biphasic 3D-FEM Model for the Remodeling of Microcirculation in Liver Lobes.
Computer Models in Biomechanics, 2013, pp 277-292
ISBN: 978-94-007-5463-8 (Print) 978-94-007-5464-5 (Online)
Daniel Werner, Tim Ricken, Anne Ferreira Pfeiffer
On a FEM model for isotropic and transversely isotropic growth in biphasic materials.
PAMM 12/2013; 13(1). [DOI:10.1002/pamm.201310027]
Thomas Schmidt, Daniel Balzani, Tim Ricken, Daniel Werner
A Biphasic Approach for the Simulation of Growth Processes in Soft Biological Tissues Incorporating Damage-Induced Stress Softening.
PAMM 12/2012; [DOI:10.1002/pamm.201210037]
Contact
Tim Ricken
Univ.-Prof. Dr.-Ing.Head of Department