Actin Network
Continuum Mechanical Modeling of Actin Networks
The cytoskeleton is the main promoter of cell stiffness and plays a crucial role in maintaining the cell shape. It is involved in cell migration, cell division and active contraction. Interactions are ... [read more]
Collagen Fiber Morphology
Quantification of Collagen Fiber Morphologies utilizing Multiphoton Microscopy
The mechanical behavior of an arterial wall is mainly governed by the organization and composition of the three major microstructural components: collagen, elastin, smooth muscle cells. Their influence ... [read more]
Aortic Dissection
Mathematical Modeling and Computer Simulation of Aortic Dissection
During aortic dissection an intimal tear in the aortic wall propagates into the media to form a false lumen within the vessel wall, which can quickly lead to death. Surgical treatment for aortic dissection ... [read more]
lead1
Mechanics, Modeling and Simulation of Aortic Dissection
In the Lead project a consortium of scientists from biomechanical-, civil-, electrical-, and mechanical engineering, computer science, mathematics, and physics from TU Graz has set itself the goal ... [read more]
Supraphysiological loading conditions
Biomechanics of Arterial Walls under Supra-Physiological Loading Conditions
This DACH project deals with the analysis and modeling of traumatic degenerations of overstretched arterial walls that occur in therapeutical interventions ... [read more]
AAA
Biomechanical Characterization of Abdominal Aortic Aneurysms
An abdominal aortic aneurysm (AAA) is a vascular pathology associated with permanent and localized dilatation (ballooning) of the abdominal aorta. The continuous growth ... [read more]
MSA
Multiscale Biomechanical Investigation of Human Aortas
Arteries have a remarkable ability to adapt in response to altered hemodynamics, disease progression, and injury. Altered arterial tissue properties in diseased conditions such as atherosclerosis arise from ... [read more]
figure1
Computational Modeling of Vesicle-Mediated Cell Transport
One important characteristics of eukaryotic cells are the enormous complexity of their membrane anatomy and the high level of organization of the transport processes. The surprisingly precise manner of ... [read more]
ILT
Modeling of Intraluminal Thrombus Formation
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 ... [read more]
Aortic Aneurysms
Biomechanical Simulation of Evolving Aortic Aneurysms for Designing Intervention
Abdominal aortic aneurysms (AAAs) are most common in men aged 65 and older, and the incidence of this disease is therefore on the rise in our aging population. It is universally agreed that ... [read more]
Human Myocardium
Biaxial Tensile and Triaxial Shear Measurements of the Human Myocardium, and Related Continuum Modeling
In the research area of cardiac mechanics and electrophysiology it is of utmost importance ... [read more]
Articular Cartilage
Characterization and Computational Modeling of Articular Cartilage
Cartilage tissue is a multi-phase material composed of fluid, electrolytes, chondrocytes, collagen fibers, proteoglycans and other glycoproteins, and it contains a fiber network of ... [read more]
SCATh - Smart Catheterization
Modern medicine is irreversibly shifting towards less invasive surgical procedures. Conventional open surgery approaches are systematically being replaced by interventions that reduce access ... [read more]

Continuum Mechanical Modeling of Actin Networks

Actin Network

Sketch of a typical cell with mechanically important components.

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Finite element analysis of the aspiration of a droplet consisting of actin network enveloping a very soft core.

The cytoskeleton is the main promoter of cell stiffness and plays a crucial role in maintaining cell shape. It is involved in cell migration, cell division and active contraction. Interactions are not limited to mechanical transmission of forces but also biochemical processes are triggered. Such interactions may be summarized with the term mechanotransduction, which includes cell force transmission from the extracellular matrix to the cytoskeleton. Experiments show that the orientation of the cytoskeleton is a function of the interplay between biochemical activity and the magnitude of stretching. Cell mechanics and thus the mechanics of the cytoskeleton are also important in a great number of diseases, e.g., malaria, asthma, arthritis, atherosclerosis, glaucoma and cancer, where the considered cells show different stiffness compared to their healthy counterparts. Knowledge of the mechanics may help to understand and improve diagnosis.

Actin is one of the key constituents of the cytoskeleton and has been the subject of extensive research over the last two decades. It is a globular protein that assembles into filaments. These filaments are linked together by actin binding proteins to form bundles and networks. The hierarchy implied by these assemblies leads to efforts to find mechanical material models for actin networks that describe their properties on more than one scale.

Our research focusses on continuum mechanical models that derive the constitutive equation based on the properties of the filaments and the microstructure. We strive to capture important biophysical features, e.g., viscoelasticity or the normal stress behavior under shear, which is remarkably different from that of ‘soft’ engineering materials such as rubber. Actin networks with relatively low network density are known to involve non-affine deformations and the actin binding proteins exhibit finite stiffness. Both phenomena are subject to our investigations.

Funding: Graz University of Technology

Quantification of Collagen Fiber Morphologies utilizing Multiphoton Microscopy

Morphology 1

Segment of a human abdominal aorta after optical clearing. The translucent appearance allows for an increased penetration depth during multiphoton microscopy.

Morphology 2

Collagen fiber bundles in the adventitia of a human abdominal aorta. Image taken by detecting the second-harmonic generation signal of collagen using a multiphoton microscope.

The mechanical behavior of an arterial wall is mainly governed by the organization and composition of the three major microstructural components: collagen, elastin, smooth muscle cells. Their influence on the cardiovascular function in health and disease has been the subject of extensive research. Among these components, it is collagen that endows the arterial wall with strength and load resistance, thus making it the most relevant mechanical tissue constituent.

Research indicates that changes in the mechanical properties of healthy arterial walls play a role in arterial disease and degeneration (e.g., increased stiffening of vessel walls with age, atherosclerosis, etc.). Meaningful quantifications of morphological collagen data in human arteries, therefore, are fundamental to a better understanding of the underlying mechanical principles governing the biomechanical response of vessel walls.

Collagen can be visualized by utilizing either stained histological sections or different microscopy techniques, e.g., polarized microscopy, electron microscopy, fluorescence microscopy and multiphoton microscopy (MPM), featuring enhanced penetration depth in soft biological tissues, good optical sectioning and resolution. Both, fluorescence microscopy and MPM use collagen as a source of second-harmonic generation and autofluorescence, enabling direct observation without staining.

We developed a unique method for the extraction and quantification of collagen fiber distributions from 2D images, and for a statistical analysis among varying length-scales. In aiming to move beyond a 2D quantification, a novel approach followed ultimately, which combines a new sample preparation technique for intact arterial segments with optical tissue clearing and subsequent imaging using second-harmonic generation microscopy. This approach yields 3D image stacks throughout the thickness of the arterial wall (up to 1.5 mm). The collagen structures are extracted and quantified, resulting in a representative 3D distribution of collagen fiber orientations from which structural parameters are determined in order to be utilized directly in numerical codes using fiber-reinforced material laws.

Funding: DACH Project support by Austrian Science Fund (FWF) and German Research Foundation (DFG); Graz University of Technology

Mathematical Modeling and Computer Simulation of Aortic Dissection

Aortic Dissection

Two-dimensional (plane strain) dynamic immersed boundary FSI simulation of aortic dissection induced by fluid loading using a layer-specific, fiber-reinforced hyperelastic model of the human thoracic aorta with residual stresses: (a) initial configuration; (b) aortic dissection induced by supra-physiological pressure load (~750 mmHg).

During aortic dissection an intimal tear in the aortic wall propagates into the media to form a false lumen within the vessel wall, which can quickly lead to death. Surgical treatment for aortic dissection consists of either replacement of a portion of the aorta or endovascular stent implantation to cover the affected segment. Both approaches carry significant risks, and determining the optimal choice and timing of an intervention is challenging.

While aortic dissections can be induced in animal models such models do not replicate the clinical pathology. Consequently, modeling studies of aortic dissection must use physical and/or computational models. Existing computational models of aortic dissection use conventional CFD approaches (vessel wall and flap are treated as rigid). Although CFD models are able to predict wall shear stress distributions, they are unable to account for the interactions between the blood and the vascular tissues or for the effects of such interactions on the dynamics of the dissected aorta.

This NIH project is in cooperation with the School of Medicine at New York University, USA. It develops fluid-structure interaction models of both the dissected and dissecting aorta that overcome the limitations of CFD models. Realistic patient anatomical geometries are derived from computed tomography and/or magnetic resonance imaging studies. To characterize the mechanical response and the damage and failure characteristics of human aortic tissues, experimental tests are performed using tissue samples collected from both normal and diseased human aortas. Experimental data are then used to develop healthy and disease-specific constitutive models that include innovative models of tissue damage and failure. The impact of these characterizations is not limited to aortic dissection; this work has potential applications to a range of arterial pathologies, including aneurysmal rupture.

These predictive models are used to perform patient-specific simulations that ultimately aid the clinical decision making. Finally, these models are used to study the surgical and medical management of patients who require or who have undergone partial repair of a Stanford Type A dissection.

Funding: National Institutes of Health (NIH)

Mechanics, Modeling and Simulation of Aortic Dissection

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Cauchy shear stress vs amount of shear curves for dissected human thoracic aortas under "in-plane" shear.


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Schematic overview of the eXtended Finite Element Method: Crack is within elements and considered by enrichment functions at selected nodes.

In the Lead project a consortium of scientists from biomechanical-, civil-, electrical-, and mechanical engineering, computer science, mathematics, and physics from TU Graz has set itself the goal of unraveling the cause and the formation of the various stages of an aortic dissection (AD). Advanced computational tools and algorithms will be developed to assist clinicians with the diagnosis, treatment, and management of AD patients. In addition, related topics such as the optimization of implants, the better design for tissue engineering and of coatings and stent platforms for drug delivery will be investigated.

In particular, new multiscale constitutive models that include innovative parameters and failure criteria will be developed, which will allow the simulation of the rupture of aortic tissue and propagation of the false lumen. The development of thrombus in the false lumen will be modeled by using the theory of porous media, while the blood will be modeled as a non-Newtonian fluid. The 3D geometry of patient-specific morphologies will be reconstructed from medical images of carefully selected AD patients. Finally, computational fluid-structure interaction simulations will be performed in order to investigate the wall stresses, the hemodynamics, the false lumen propagation, and the thrombus formation and growth, etc. In addition, the 3D computational simulation results will be visualized by virtual reality techniques. We expect that this project will improve awareness of this life-threatening disease, and lead to its more effective treatment and control within the general public of Austria and beyond.

The Lead project will be carried out in the frame of the Graz Center of Computational Engineering (GCCE), which has been founded in 2016 as an interdisciplinary cooperation platform for basic research in the realm of computational science and engineering. The mission of GCCE is to improve computational techniques and its applicability by bringing together the expertise of leading scientists form different areas.

Funding: Graz University of Technology

Biomechanics of Arterial Walls under Supra-Physiological Loading Conditions

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TEM images: (a) various tissue components including collagen fibrils coming in and out of the imaging plane at various angles; (b) subdomain of (a) highlighting cross-sectioned collagen fibrils (green circles) and their nearest neighbors (white lines) that were automatically identified by a custom made ImageJ plugin. Scale bars: (a) 500 nm; (b) 200 nm.

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3D reconstruction of the arterial microstructure of a human media through electron tomography. The orange strings indicate the orientations of collagen fibrils, while the green structures correspond to proteoglycans (PGs). Such 3D images are used to extract and quantify angular distributions between collagen and PGs, and to investigate their potential changes as a function of supra-physiological loading conditions.

This DACH project deals with the analysis and modeling of traumatic degenerations of overstretched arterial walls that occur in therapeutical interventions ("DACH" stands for Germany, D; Austria, A; and Switzerland, CH). For example, clinical interventions for treating atherosclerotic degeneration resulting in luminal narrowing often include balloon angioplasty. This invasive procedure involves the inflation of a catheter with the aim of increasing the lumen dimensions by pushing the obstructing plaque into the vessel wall. Naturally, for this procedure a much higher pressure than the physiological blood pressure is required, and this causes microscopic-level tissue damage and results in stress-softening of the collagenous tissue.

A database for the qualitative and quantitative description of arterial tissues will be obtained from uniaxial and biaxial extension tests performed on the tissue components of individual arterial layers loaded far beyond the physiological domain. Towards this end cyclic tension-tests will be carried out on healthy as well as on collagenase and elastase treated arterial tissues to investigate component-specific stress softening behavior. Such tests enable the analysis of the macroscopic mechanical tissue response. In addition, structural analysis techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy and nano-tomography will be used to study damage at the microscopic length scale, with a special focus on damage induced changes in the interfibrillar collagen distances and angular proteoglycan distributions.

The macroscopic response of the fiber-reinforced tissues will be described by a formulation based on micro-mechanical models characterizing the individual tissue components. These models take into account alterations of stochastic distributions of fiber properties as a consequence of the tissue overstretch. In order to obtain a quantitative prediction of the material response, the model parameters will be adjusted to so as to fit data from the performed experiments based on least-squares minimization.

Finally, the models will be validated by comparing finite element calculations with experiments performed on whole arterial wall segments.

Funding: DACH Project support by Austrian Science Fund (FWF) and German Research Foundation (DFG)

Biomechanical Characterization of Abdominal Aortic Aneurysms

ILT

Histological image characterizing the morphology of the thrombus-covered arterial wall.

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Mounted patch of a carotid artery (a) before the peeling test, shown from the side, and (b) during the testing procedure, shown from the top.

An abdominal aortic aneurysm (AAA) is a vascular pathology associated with permanent and localized dilatation (ballooning) of the abdominal aorta. Continuous growth of AAAs may lead to wall rupture, which is a catastrophic event frequently associated with high mortality and serious life-threatening morbidity if not addressed. AAA development is multifactorial and is primarily related to elastolysis. From a pathohistological point of view, aneurysmal degeneration is mainly attributed to loss of elastin and turnover of collagen within the aortic wall. Such structural alterations and excessive aged collagen deposition result in significant changes in the tissue’s mechanical properties. Therefore, investigation of the biomechanical properties of AAA tissues provides an essential insight into growth and remodeling, and advances our understanding of disease progression and intrinsic rupture mechanism.

In our lab we focus on a few fields in AAA research:

  1. mechanical testing of aneurysmal tissues harvested from open surgical repair

  2. microstructural characterization by histology and multiphoton microscopy

  3. biochemical quantification of mass fractions of the main protein components within the tissues

  4. histomechanical characterization of the intraluminal thrombus.

By performing biaxial extension and peeling tests of the intraluminal thrombus (ILT) and the thrombus-covered wall (see figure), the mechanical responses are systematically explored and more appropriate 3D material models developed. The microstructural characterization of ILT samples serves as the basis for the determination of relative thrombus ages. We propose the four age phases: very fresh, young, intermediate and old. Mass fraction analyses determine dry weight percentages of elastin and collagen within the layer-specific aneurysmal aortic structure, which, in turn, affect the mechanical properties at the tissue level. In addition, our effort is also aimed at a refined understanding of the effect of ILT age on AAA wall mechanics and gender differences.

Funding: Graz University of Technology and Medical University of Graz – Clinical Department of Vascular Surgery

Multiscale biomechanical investigation of human aortas

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Multiscale assessment of human aortic tissues: biaxial extension testing simultaneously applied to two-photon fluorescence microscopy and second harmonic generation imaging to obtain material properties of collagen, elastin and SMC at the micro and macroscales.

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Microstructural changes of collagen, elastin and SMCs as a function of macroscopic deformation and stress/loading.

Arteries have a remarkable ability to adapt in response to altered hemodynamics, disease progression, and injury. Altered arterial tissue properties in diseased conditions such as atherosclerosis arise from tissue remodeling which is associated with changes in wall constituents at different length scales.

This project is based on the fact that multiscale biomechanical analyses of healthy and diseased arteries and its modeling can be used to better understand several pathophysiological processes at different length scales. This also allows the identification of relationships between structural alterations and diseases. In this study aortic tissue imaging and mechanical characterization techniques will be combined at the macro-, micro- and nanoscale to develop and validate next generation multiscale constitutive models. Biaxial extension testing and second-harmonic generation/two-photon excited fluorescence imaging will be simultaneously used to obtain properties at the micro- and macroscale of healthy and atherosclerotic human aortas. Moreover, load-dependent ultrastructural characteristics of interfibrillar proteoglycans, and of constituents of collagen (e.g., tropocollagen, fibrils), elastin (e.g., tropoelastin, fibrillin), and smooth muscle cells (e.g., myosin, actin) will be determined by three-dimensional transmission electron microscopy (3D-TEM) which is also known as electron tomography.

The combination of the obtained data is used for the development of novel constitutive models based on multiscale homogenization techniques that explicitly incorporate nanoscale, microscale and macroscale mechanisms as well as their coupling effects. The novelties of this project are the application and development of experimental methods on different hierarchical scales, and the intelligent combination, integration and validation of experimental techniques to give an explanation for the role of important constituents in arterial mechanics, physiology, and pathology.

The pursued approach is a step forward to investigate and understand the development, growth and remodeling principles of biological tissues and their response to pathological conditions. This project approaches well-defined clinical problems from engineering and biological perspectives.

Funding: Austrian Science Fund (FWF)

Computational Modeling of Vesicle-Mediated Cell Transport

figure1

Three (main) stages of the intracellular vesicle transport; graphics adapted from Olkkonen and Ikonen (2000).


figure2

Within the multiscale FEM the simulation of a material with a heterogeneous microstructure is split into two boundary-value problems.

One important characteristics of eukaryotic cells are the enormous complexity of their membrane anatomy and the high level of organization of the transport processes. The surprisingly precise manner of the routing of vesicles to various intracellular and extracellular destinations can be illustrated by numerous examples such as the release of neurotransmitters into the presynaptic region of a nerve cell and the export of insulin to the cell surface.

The key idea of this particular project is to couple results of biomedical investigations and mechano-mathematical models with the highly efficient engineering software packages in order to simulate this type of processes, in particular the vesicle transport. The results bridge the theoretical investigations and medical practice and shift the paradigm in understanding and remedying different diseases, which certainly is the primary and long-term goal of the project. The project objectives coincide with the modeling of single aspects of the vesicle transport, namely with the simulation of mechanisms by which the vesicles form, find their correct destination, fuse with organelles and deliver their cargo. The application of several different approaches is envisaged for this purpose, but three main strategies build the underlying skeleton: the theory of lipid bilayer membranes, the homogenization method and the diffusion theory. The mentioned approaches will furthermore be combined with the modern numerical techniques such as the finite element method and the multiscale finite element method.

In the final stage, the realization of single objectives will allow the simulation of vesicle transport as a continuous process and the study of the impact of various factors on the whole process. In this way, the project will yield a significant shift from "static" bio-computations related to the single cell compartments and substeps of its activities, to the "dynamic" simulation of the real living processes.

Funding: Austrian Science Fund (FWF)

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

Biomechanical Simulation of Evolving Aortic Aneurysms for Designing Intervention

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Finite elment analysis of two different geometrical AAA models. Maximum principal stress fields in an asymmetric (a) and a symmetric (b) aneurysm.

Abdominal aortic aneurysms (AAAs) are most common in men aged 65 and older, and the incidence of this disease is therefore on the rise in our aging population. It is universally agreed that mechanical factors play key roles in the natural history of AAAs and their response to treatment, yet there is no widely accepted tool for quantifying or predict the mechanobiology and biomechanics of AAAs.

Our overall goal is to support and extend the Cardio- vascular Fluid Dynamics Project at the Symbios National Center for Biomedical Computing at Stanford University by

  1. developing novel constitutive relations that describe complex chemo-mechanical changes experienced by the abdominal aorta during the progression of aneurysmal disease

  2. implementing these relations in a custom nonlinear FE code

  3. interfacing this arterial mechanics code with the Stanford biofluid mechanics code to enable us to quantify, for the first time, the fluid-solid-growth mechanics of a growing AAA

  4. using parametric studies and data to refine and verify the predictive capability of this computational tool.

We bring together expertise from different institutions: JD Humphrey (Yale University) has expertise in developing complex constitutive theories for soft tissues, D Vorp (University of Pittsburgh) has expertise in quantifying biomechanical properties of abdominal aortic aneurysms and associated intraluminal thrombi, GA Holzapfel (TU Graz) has expertise in computational biosolid mechanics, C Taylor (Stanford University) with expertise in computational biofluid mechanics, and C Zarins (Stanford University) with expertise in vascular surgery and animal models of disease progression. Together, we will develop the first computational tool to better understand the natural history of aneurysms and responses to intervention of AAA. The tool extends the cardiovascular research capabilities at the Stanford University National Center for Biomedical Computing.

Funding: National Institutes of Health (NIH)

 

Biaxial Tensile and Triaxial Shear Measurements of the Human Myocardium, and Related Continuum Modeling

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Prepared myocardial specimen, clamped into a biaxial testing device.

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(a) Ellipsoidal geometrical model representing the left ventricle of the heart. The orientation of the fiber directions are in red; (b) contour plots of the fiber stress component of the strain-energy function for 116mmHg.

In the research area of cardiac mechanics and electrophysiology it is of utmost importance to identify accurate material properties of the myocardium. This is important for the description of various phenomena such as mechanoelectric feedback or heart wall thickening. To better understand the highly nonlinear mechanics of complex structures such as the passive myocardium under different loading conditions, a rationally-based material model is required. Unfortunately, there are insufficient experimental data of the human myocardium available for material parameter estimation and for the development of adequate material models.

This project aims at determining the biaxial tensile and triaxial shear properties of the passive human myocardium. Moreover, the underlying microstructure of tissues will be determined, and structurally-based material models will be fitted to experimental data. Using new state-of-the-art equipment, planar biaxial extension tests will be performed to determine the biaxial tensile properties of the human myocardium. Shear properties will be examined using triaxial shear tests on cubic specimens excised from an adjacent region of the biaxial tensile specimens. Multiphoton microscopy will be used to study the 3D microstructure of the tissue to emphasize the 3D orientation and dispersion of the muscle fibers and the adjacent collagen fabrics.

The novel combination of biaxial tensile test data with different loading protocols and shear test data at different specimen orientations will facilitate capture of the direction-dependent material response. With these mechanical data sets, combined with structural data, a better material model can be constructed. Such a model will then be used in numerical simulations to better understand ventricular mechanics, a step that is needed for the improvement of the medical treatment of heart diseases. An improved mechanical characterization may also lead to a better understanding of the mechanical deformation of the heart during the cardiac cycle, and, in particular, of how diseased/ischemic regions can impair pumping ability.

Funding: Austrian Science Fund (FWF)

Biomechanical and Histo-Structural Investigations of Human Abdominal Adipose Tissues: a Basis for Preoperative Simulations

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Photograph of a prepared adipose tissue specimen inserted in a biaxial tensile device ready for biaxial tensile tests.

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Photograph of a cube-shaped adipose tissue specimen inserted in a triaxial testing device and subjected to simple shear loading.

A considerable number of plastic surgery procedures relate to reconstructive surgery associated with complex soft tissue contour defects, mainly subcutaneous adipose tissue, in different anatomical regions arising from trauma, burn injuries, cancer resections or congenital deformities. The most appropriate surgical intervention necessary for reconstructing the contour defect is by use of equivalent soft tissues, resulting in optimal restoration of form and function. It includes autologous soft tissue transfer from the patient’s own healthy body regions to the affected anatomical area.

A preoperative simulation of the resulting soft tissue deformation is desirable to support the surgeon’s preoperative planning, and to potentially improve surgical outcomes. Promising results in the field of plastic and reconstructive surgery are apparent in breast and facial soft tissue simulation using the finite element method. Currently, the development of a constitutive model for adipose tissues, which could be implemented in multilayer numerical models for human soft tissue deformation simulation, is difficult because knowledge of the mechanical parameters of fat tissue is limited.

Therefore, this study aims to determine the multiaxial mechanical properties and the underlying microstructure of human abdominal adipose tissues. Human abdominal adipose tissue samples remaining from breast reconstruction surgeries or from abdominal plastic surgeries are mechanically investigated. Two types of mechanical tests are conducted: biaxial tensile and triaxial shear tests. Moreover, dynamic biaxial tensile and shear tests are performed in order to account for the viscous features of the adipose tissue. Additionally, the microstructure of the specimens is examined by histology.

Funding: http://www.cadfem.at

Characterization and Computational Modeling of Articular Cartilage

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Second-harmonic generation image showing collagen fibers in a transversal section of the cartilage with calculated local 3D fiber directions projected onto the image (red lines).

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Indentation experiment with an impermeable, plane-ended cylinder of diameter 1mm compressing a cartilage sample to 1% global strain in 150s. Top: stress distribution based on a model with patient-specific collagen fibers and inhomogeneous material properties; Bottom: stress distribution based on a model without collagen fibers and homogeneous material properties.

Cartilage tissue is a multi-phase material composed of fluid, electrolytes, chondrocytes, collagen fibers, proteoglycans and other glycoproteins, and it contains a fiber network of predominantly Type II collagen which provides tensile strength and stiffness to the solid phase, a proteoglycan gel.

Working with international collaborators, we proposed several 3D, large deformation constitutive models for articular cartilage to facilitate finite element (FE) simulation of cartilage morphology and material response. An initial phenomenological and patient-specific simulation approach focuses on incorporating the collagen fiber fabric in a 3D viscoelastic fiber-reinforced finite-strain setting, where each material parameter has a clear physical interpretation. A novel feature of the proposed method is 3D sample-specific numerical tracking of the fiber fabric deformation under general loading.

Next, we proposed an extended constitutive model for human articular cartilage that considers fiber dispersion, and demonstrated a numerical approach for incorporating DT-MRI (17.6 T) data by predicting collagen fiber fabric deformation for an indentation experiment. We developed a FE approach to determine the geometry, the meshing, and the fiber structural input (estimated principal fiber direction and dispersion). This approach allows the generation of fiber stretch plots and fiber tension/compression plots, providing new insight to fiber fabric deformation.

To further improve FE modeling fidelity, we quantified the 3D morphology of articular cartilage using second-harmonic imaging microscopy, and connected the imaging data to specific parameters of a new 3D large-strain constitutive model. Using representative numerical examples on the mechanical response of cartilage, we reproduced several features which have been demonstrated experimentally in the cartilage mechanics literature, e.g., solid and fluid anisotropy, tension-compression nonlinearity, creep displacement with significant fluid pressure load support, variable instantaneous and equilibrium Poisson's ratios, as well as inhomogeneous, depth-dependent strain.

Funding: Austrian Science Fund, Graz University of Technology

SCATh - Smart Catheterization

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(a) Schematic diagram of intended stent-graft for treatment of an abdominal aortic aneurysm; (b) surgeons test a new visualization tool for catheter guidance.

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Surface mesh of an abdominal aortic aneurysm extruded radially to determine the arterial wall layers.

Modern medicine is irreversibly shifting towards less invasive surgical procedures. Conventional open surgery approaches are systematically being replaced by interventions that reduce access trauma and thereby minimize pain and hospitalization periods for patients. The downside of this approach is that it is highly demanding for the interventionalist, entailing unacceptable risks for the patient. In the perspective of patient safety, the project SCATh, i.e. a STREP project funded within the 7th Framework Program of the European Commission, aims at minimizing these drawbacks specifically for a series of new and promising catheterization procedures. These procedures have the common denominator of dealing with cardiovascular disease, the main cause of death in the EU.

SCATh provides the interventionalist with visual and haptic tools for robust and accurate catheter guidance, which is developed through novel approaches, by fusing preoperative patient-specific anatomical and mechanical models and intra-operative data streams from in situ sensors. By complementing and augmenting the skills of the interventionalist, patient safety drastically increases and at the same time, potentially life-threatening complications, which result from poor or damaging (X-ray, use of contrast agents) visualization or poor surgical technique, can be avoided. The new concept for tracking, sensing, modeling and manipulation of the surgical environment is integrated with existing technological state-of-the-art in close cooperation with clinical experts and industrial partners, both in the design and in the evaluation phases.

The common efforts delivered during this project result in a demonstrator applied to a carefully selected set of catheter procedures. Moreover, many of the technological advances created during SCATh touch upon minimally invasive surgical procedures in general.

Website: http://www.scath.net

Funding: European Union