Case Study: Intra-Patient Heterogeneity of Aneurysmal Tissue Properties

Introduction: Current recommendations for surgical treatment of abdominal aortic aneurysms (AAAs) rely on the assessment of aortic diameter as a marker for risk of rupture. The use of aortic size alone may overlook the role that vessel heterogeneity plays in aneurysmal progression and rupture risk. The aim of the current study was to investigate intra-patient heterogeneity of mechanical and fluid mechanical stresses on the aortic wall and wall tissue histopathology from tissue collected at the time of surgical repair.Methods: Finite element analysis (FEA) and computational fluid dynamics (CFD) simulations were used to predict the mechanical wall stress and the wall shear stress fields for a non-ruptured aneurysm 2 weeks prior to scheduled surgery. During open repair surgery one specimen partitioned into different regions was collected from the patient's diseased aorta according to a pre-operative map. Histological analysis and mechanical testing were performed on the aortic samples and the results were compared with the predicted stresses.Results: The preoperative simulations highlighted the presence of altered local hemodynamics particularly at the proximal segment of the left anterior area of the aneurysm. Results from the post-operative assessment on the surgical samples revealed a considerable heterogeneity throughout the aortic wall. There was a positive correlation between elastin fragmentation and collagen content in the media. The tensile tests demonstrated a good prediction of the locally varying constitutive model properties predicted using geometrical variables, i.e., wall thickness and thrombus thickness.Conclusions: The observed large regional differences highlight the local response of the tissue to both mechanical and biological factors. Aortic size alone appears to be insufficient to characterize the large degree of heterogeneity in the aneurysmal wall. Local assessment of wall vulnerability may provide better risk of rupture predictions

Biomechanics of abdominal aortic aneurysm:Experimental evidence and multiscale constitutive modeling

The reliable assessment of Abdominal Aortic Aneurysm (AAA) rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. A multi-disciplinary approach including vascular biomechanics and constitutive modeling is needed to better understand and more effectively treat these diseases. AAAs are formed through irreversible pathological remodeling of the vascular wall and integrating this biological process in the constitutive description could improve the current understanding of this disease as well as the predictability of biomechanical simulations. First in this thesis, multiple centerline-based diameter measurements between renal arteries and aortic bifurcation have been used to monitor aneurysm growth of in total 51 patients from Computer Tomography-Angiography (CT-A) data. Secondly, the thesis proposes a novel multi-scale constitutive model for the vascular wall, where collagen fibers are assembled by proteoglycan cross-linked collagen fibrils and reinforce an otherwise isotropic matrix (elastin). Collagen fibrils are dynamically formed by a continuous stretch-mediated process, deposited in the current configuration and removed by a constant degradation rate. The micro-plane concept is then used for the Finite Element (FE) implementation of the constitutive model. Finally, histological slices from intra-luminal thrombus (ILT) tissue were analyzed using a sequence of automatic image processing steps. Derived microstructural data were used to define Representative Volume Elements (RVEs), which in turn allowed the estimation of microscopic material properties using the non-linear FE. The thesis showed that localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements all over the AAA sac. Consequently, this information might further reinforce the quality of aneurysm surveillance programs. The novel constitutive model proposed in the thesis has a strong biological motivation and provides an interface with biochemistry. Apart from modeling the tissue’s passive response, the presented model is helpful to predict saline feature of aneurysm growth and remodeling. Finally, the thesis provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture.QC 20120907</p

Multiscale Modeling of the Normal and Aneurysmatic Abdominal Aorta

QC 20110127</p

A constitutive model for vascular tissue that integrates fibril, fiber andcontinuum levels

A fundamental understanding of the mechanical properties of the extracellular matrix (ECM) is critically important to quantify the amount of macroscopic stress and/or strain transmitted to the cellular level of vascular tissue. Structural constitutive models integrate histological and mechanical information, and hence, allocate stress and strain to the different micro-structural components of the vascular wall. The present work proposes a novel multi-scale structural constitutive model for passive vascular tissue, where collagen fibers are assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an otherwise isotropic matrix material. Multiplicative kinematics account for straightening and stretching of collagen fibrils and an orientation density function captures the spatial organization of collagen fibers in the tissue. Mechanical and structural assumptions at the collagen fibril level define a piece-wise analytical stress-stretch response of collagen fibers, which in turn is integrated over the unit sphere to constitute the tissue’s macroscopic mechanical properties. The proposed model displays salient macroscopic feature of vascular tissue, and employs material and structural parameters of clear physical meaning. Model parameters were estimated from meanpopulation data of the normal and aneurysmatic aortic wall and used to predict in-vivo stress states of patient-specific vascular geometries, thought to demonstrate the robustness of the particular Finite Element (FE) implementation. The collagen fibril level of the multi-scale constitutive formulation provides an interface to integrate vascular wall biology and to account for collagen turn-over for example.QC 20110

A constitutive model for vascular tissue that integrates fibril, fiber andcontinuum levels

A fundamental understanding of the mechanical properties of the extracellular matrix (ECM) is critically important to quantify the amount of macroscopic stress and/or strain transmitted to the cellular level of vascular tissue. Structural constitutive models integrate histological and mechanical information, and hence, allocate stress and strain to the different micro-structural components of the vascular wall. The present work proposes a novel multi-scale structural constitutive model for passive vascular tissue, where collagen fibers are assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an otherwise isotropic matrix material. Multiplicative kinematics account for straightening and stretching of collagen fibrils and an orientation density function captures the spatial organization of collagen fibers in the tissue. Mechanical and structural assumptions at the collagen fibril level define a piece-wise analytical stress-stretch response of collagen fibers, which in turn is integrated over the unit sphere to constitute the tissue’s macroscopic mechanical properties. The proposed model displays salient macroscopic feature of vascular tissue, and employs material and structural parameters of clear physical meaning. Model parameters were estimated from meanpopulation data of the normal and aneurysmatic aortic wall and used to predict in-vivo stress states of patient-specific vascular geometries, thought to demonstrate the robustness of the particular Finite Element (FE) implementation. The collagen fibril level of the multi-scale constitutive formulation provides an interface to integrate vascular wall biology and to account for collagen turn-over for example.QC 20110