A Multiscale and Multiphase Digital Twin of Function-Perfusion Processes in the Human Liver

  • Ricken, Tim (University of Stuttgart)
  • Mandl, Luis (University of Stuttgart)
  • Gerhäusser, Steffen (University of Stuttgart)
  • Lambers, Lena (University of Stuttgart)
  • Mielke, Andre (University of Stuttgart)

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As the key organ for metabolic processes in the human body, the liver is responsible for essential processes like fat storage or detoxification. Liver diseases can trigger growth processes in the liver, disrupting important hepatic function-perfusion processes. To better understand the interplay between hepatic perfusion, metabolism and tissue in the hierarchically organized liver structure, we developed a multicomponent, poro-elastic multiphasic and multiscale function-perfusion model, using a multicomponent mixture theory based on the Theory of Porous Media (TPM). The multiscale approach considers the different functional units of the liver, so-called liver lobules, with an anisotropic blood flow via the sinusoids (slender capillaries between periportal field and central vein), and the hepatocytes, where the biochemical metabolic reactions take place. On the lobular scale, we consider a tetra-phasic body, composed of a porous solid structure representing healthy tissue, a liquid phase describing the blood, and two solid phases with the ability of growth and depletion representing the fat tissue and the tumor tissue. The hases consist of a carrier phase, called solvent, and solutes, representing microscopic components, e.g. nutrients, dissolved in the solvent. To describe the influences of the resulting tissue growth, the model is enhanced by a kinematic growth approach using a multiplicative split of the deformation gradient into an elastic and a growth part, dependent on the fat accumulation and tumor development. To describe the metabolic processes as well as the production, utilization and storage of the metabolites on the cellular scale, a bi-scale PDE-ODE approach with embedded coupled ordinary differential equations is used. In order to represent realistic conditions of the liver, experimentally or clinically obtained data such as changes in perfusion, material parameters or tissue morphology and geometry are integrated as initial boundary conditions or used for parametrization and validation. Data integration approaches like machine learning are developed for the identification, processing and integration of data. A workflow is designed that directly prepares the model for clinical application by (semi-)automatically processing the data, considering uncertainties, and reducing computation time.