Modeling of Intraluminal Thrombus Formation

ILT Cross-section of an intraluminal thrombus with its three individual layers: luminal (L), medial (M), abluminal (A).

ILT Configurations are important in arterial growth and remodeling (G&R): the current (in vivo) mixture configurations track both deformations and G&R of the vessel. The (individual) natural configurations of the constituents are stress free and separated for each constituent. Deformations and G&R are best considered at the generic time.

Effective biomechanical modeling of the development of an intraluminal thrombus (ILT) has the potential to help us answer the question "Why do certain abdominal aortic aneurysms (AAAs) grow and eventually rupture?"

The goal of this project, therefore, is to quantify the development of ILT from the initial blood clot to a mature formation, with special attention to axial changes in the clot structure. Our hypothesis is that AAA growth is a direct consequence of ILT development. We combine and exploit three recent advances: development of a general theoretical framework for ILT growth and remodeling, FE simulations capable of addressing mass changes, and a well-equipped laboratory with precisely defined experimental procedures for ILT specimens. Thus, the aims for this project are:

  1. To develop a mathematical theory of growth and remodeling of ILT considering its three main layers. To employ a rule-of-mixtures relation for the stress response and a full mixture theory for the turnover of constituents in a stressed configuration on axially symmetric geometry (axial and radial changes are addressed).

  2. To perform a set of experiments with samples harvested from open surgical aneurysm repair. To use specimens for mechanical tests and histological analyses (radial and axial changes of biomolecules, including proteases). To use the results to tune unknown parameters in the numerical model with mechanical and histological data. This leads to more accurate ILT models capable of predicting the layered thrombus structure, concentrations of elastases and collagenases, and eventually the rate of AAA enlargement.

  3. To implement the developed model in a FE code capable of simulating evolving changes in AAA structures and properties. To verify the results with available experimental data.

Successful realization advances the field of vascular mechanics by allowing, for the first time, quantification of the kinetics of an ILT within AAAs, and factors that influence aneurysmal growth and rupture risk.

Funding: Austrian Science Fund (FWF) – Lise-Meitner-Program and Medical University of Graz – Clinical Department of Vascular Surgery