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  • 1. Auer, M.
    et al.
    Regitnig, P.
    Stollberger, R.
    Ebner, F.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A methodology to study the morphologic changes in lesions during in vitro angioplasty using MRI and image processing2008In: Medical Image Analysis, ISSN 1361-8415, E-ISSN 1361-8423, Vol. 12, no 2, p. 163-173Article in journal (Refereed)
    Abstract [en]

    The assessment of morphologic changes in atherosclerotic lesions during interventional procedures such as transluminal balloon angioplasty is an issue of highest clinical importance. We propose a methodology that allows realistic 3D morphomechanical modeling of the vessel, the plaque and the lumen at different stages of in vitro angioplasty. We elaborate on a novel device designed to guide angioplasty under controlled experimental conditions. The device allows to reproduce in vivo conditions as good as possible, i.e. axial in situ pre-stretch, 100 mmHg intraluminal pressure, 37 degrees C Tyrode solution, balloon inflation without external constraints using a high-pressure syringe and contrast medium. With a standard 1.5 T MR-system we accomplish multi-spectral images at different stages of the angioplasty experiment. After MR image acquisition the specimen is used for histopathological analysis and biomechanical tests. A segmentation process is used to generate NURBS-based 3D geometric models of the individual vessel and plaque components at different balloon pressures. Tissue components are segmented automatically using generalized gradient vector flow active contours. We investigated 10 human femoral arteries. The effects of balloon compression on the individual artery components is particularly described for two obstructed arteries with an intact collagenous cap, a pronounced lipid pool and with calcification. In both arteries we observe a significant increase in lumen area after angioplasty. Dissection between intima and media and reduction of the lipid pool are primary mechanisms of dilatation. This methodology provides a basis for studying plaque biomechanics under supra-physiological loading conditions. It has the potential to improve and validate finite element models of atherosclerotic plaques which may allow a better prediction of angioplasty procedures.

  • 2. Auer, M.
    et al.
    Stollberger, R.
    Regitnig, P.
    Ebner, F.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    3-D reconstruction of tissue components for atherosclerotic human arteries using ex vivo high-resolution MRI2006In: IEEE Transactions on Medical Imaging, ISSN 0278-0062, E-ISSN 1558-254X, Vol. 25, no 3, p. 345-357Article in journal (Refereed)
    Abstract [en]

    Automatic computer-based methods are well suited for the image analysis of the different components in atherosclerotic plaques. Although several groups work on such analysis some of the methods used are oversimplified and require improvements when used within a computational framework for predicting meaningful stress and strain distributions in the heterogeneous arterial wall under various loading conditions. Based on high-resolution magnetic resonance imaging of excised atherosclerotic human arteries and a series of two-dimensional (2-D) contours we present a segmentation tool that permits a three-dimensional (3-D) reconstruction of the most important tissue components of atherosclerotic arteries. The underlying principle of the proposed approach is a model-based snake algorithm for identifying 2-D contours, which uses information about the plaque composition and geometric data of the tissue layers. Validation of the computer-generated tissue boundaries is performed with 100 MR images, which are compared with the results of a manual segmentation performed by four experts. Based on the Hausdorff distance and the average distance for computer-to-expert differences and the interexpert differences for the outer boundary of the adventitia, the adventitia-media, media-intima, intima-lumen and calcification boundaries are less than 1 pixel (0.234 mm). The percentage statistic shows similar results to the modified Williams index in terms of accuracy. Except for the identification of lipid-rich regions the proposed algorithm is automatic. The nonuniform rational B-spline-based computer-generated 3-D models of the individual tissue components provide a basis for clinical and computational analysis.

  • 3. Auer, M.
    et al.
    Stollberger, R.
    Regitnig, P.
    Ebner, F.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    In Vitro Angioplasty of Atherosclerotic Human Femoral Arteries: Analysis of the Geometrical Changes in the Individual Tissues Using MRI and Image Processing2010In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, no 4, p. 1276-1287Article in journal (Refereed)
    Abstract [en]

    Existing atherosclerotic plaque imaging techniques such as intravascular ultrasound, multidetector computed tomography, optical coherence tomography, and high-resolution magnetic resonance imaging (hrMRI) require computerized methods to separate and analyze the plaque morphology. In this work, we perform in vitro balloon angioplasty experiments with 10 human femoral arteries using hrMRI and image processing. The vessel segments contain low-grade to high-grade lesions with very different plaque compositions. The experiments are designed to mimic the in vivo situation. We use a semi-automatic image processing tool to extract the three-dimensional (3D) geometries of the tissue components at four characteristic stages of the angioplasty procedure. The obtained geometries are then used to determine geometrical and mechanical indices in order to characterize, classify, and analyze the atherosclerotic plaques by their specific geometrical changes. During inflation, three vessels ruptured via helical crack propagation. The adventitia, media, and intima did not preserve their area/volume during inflation; the area changes of the lipid pool during inflation were significant. The characterization of changes in individual 3D tissue geometries, together with tissue-specific mechanical properties, may serve as a basis for refined finite element (FE) modeling, which is key to better understand stress evolution in various atherosclerotic plaque configurations.

  • 4.
    Auer, Martin
    et al.
    Develoment, Vascops GmbH, Graz, Austria.
    Gasser, Thomas Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Portugaller, R.
    Automatic Displacement and Strain measuring in the Aorta from dynamic electrocardiographically-gated Computed Tomographic Angiography2010Conference paper (Refereed)
    Abstract [en]

    Introduction

    Image modalities like Duplex Ultrasound, Transesophageal Echocardiography, Intravascular Ultrasound, Computed Tomography and Magnetic Resonance provide vascular interventionists and surgeons with useful diagnostic information for treatment planning. Recent developments in cross-sectional imaging, including multi-modality image fusion and new contrast agents have resulted in improved spatial resolution. Specifically, dynamic Electrocardiographically-Gated Computed Tomographic Angiography (ECG-gated CTA) provides valuable information regarding motion and deformation of the normal and diseased aorta during the cardiac cycle. Extracting and presenting (visualization) of accurate quantitative information from the recorded image data, however remains a challenging task of image post processing.

    Method

    The algorithm proposed within this paper processes ECG-gated CTA data (here goes the scanner model and manufacturer) in DICOM (digital imaging and communication in medicine) format, within which the user manually defines an Eulerian Region of Interest (ROI). 2D deformable (active) contour models are used to pre-segment the luminal surfaces of the selected vessels at an arbitrary time point during the cardiac cycle. A tessellation algorithm is used to define the initial configuration of a 3D deformable (active) contour model, which in turn is used for the final segmentation of the luminal surfaces continuously during the cardiac cycle. Specifically, Finite Element (FE) formulations [1] for frames and shells, as known from structural mechanics, are used to define the deformable contour modes. This allows a direct mechanical interpretation of the applied set of reconstruction parameters and leads to an efficient FE implementation of the models [2]; parallel processor architecture is used to solve the global set of non-linear FE equations. Finally displacement and strain measures are derived from the dynamic segmentations and color coded plots are used to visualize them.

    Results and Conclusions

    The clinical relevance of dynamic imaging has not been fully exploited and accurate and fast image processing tools are critical to extract valuable information from ECG-gated CTA data. Such information is not only of direct clinical relevance but also critical to process our current understanding regarding normal and pathological aortic motions and deformations. The image processing concept proposed in this paper leads to efficient and clinically applicable software that facilitates an analysis of the entire aorta on a standard Personal Computer within a few minutes. Deformable (active) contour models are known to be more accurate compared to threshold based segmentation concepts [3] and the accuracy of the present approach is in the range of the in-plane image resolution. Apart from direct diagnostic information the extracted geometrical data could also be used (once enriched by accurate pressure measurements) for none invasive (minimal invasive) estimation of biomechanical aortic tissue properties.

    References

    [1] O. C. Zienkiewicz and R. L. Taylor, vol.1,2, 5th ed. Oxford: Butterworth Heinemann, 2000.

    [2] M. Auer and T. C. Gasser,

    IEEE T. Med. Imaging, 2010 (in press).

    [3] M. Sonka and J. M. Fitzpatrick, editors.,

    Bellingham: Spie press, 2000

  • 5. Balzani, D.
    et al.
    Holzapfel, Gerhard
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics. Graz University of Technology, Institute of Biomechanics, Center of Biomedical Engineering.
    Brinkhues, S.
    Modeling of damage in soft biological tissues and application to arterial walls2011In: Computational Plasticity XI - Fundamentals and Applications, 2011, p. 764-775Conference paper (Refereed)
    Abstract [en]

    A new material model is proposed for the description of stress-softening observed in cyclic tension tests performed on soft biological tissues. The modeling framework is based on the concept of internal variables introducing a scalar-valued variable for the representation of fiber damage. Remanent strains in fiber direction can be represented as a result of microscopic damage of the fiber crosslinks. Particular internal variables are defined able to capture the nature of soft biological tissues that no damage occurs in the physiological loading domain. A specific model is adjusted to experimental data taking into account the supra-physiological loading regime. For the description of the physiological domain polyconvex functions are used which also take into account fiber dispersion in a phenomenological approach. The applicability of the model in numerical simulations is shown by a representative example where the damage distribution in an arterial cross-section is analyzed.

  • 6.
    Biasetti, Jacopo
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Physics of blood flow in arteries and its relation to intra-luminal thrombus and atherosclerosis2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Vascular pathologies such as Abdominal Aortic Aneurysm (AAA) and atherosclerosis are complex vascular diseases involving biological, mechanical, and fluid-dynamical factors. This thesis follows a multidisciplinary approach and presents an integrated fluid-chemical theory of ILT growth and analyzes the shear-induced migration of red blood cells (RBCs) in large arteries with respect to hypoxia and its possible role in atherosclerosis. The concept of Vortical Structures (VSs) is employed, with which a theory of uid-chemically-driven ILT growth is formulated. The theory proposes that VSs play an important role in convecting and activating platelets in the aneurysmatic bulge. In particular, platelets are convected toward the distal aneurysm region inside vortex cores and are activated via a combination of high residence times and relatively high shear stress at the vortex boundary. After vortex breakup, platelets are free to adhere to the thrombogenic wall surface. VSs also convect thrombin, a potent procoagulant enzyme, captured in their core, through the aneurysmatic lumen and force its accumulation in the distal portion of the AAA. This framework is in line with the clinical observation that the thickest ILT is usually seen in the distal AAA region. The investigation of the fluid-dynamics in arteries led to the study of the shear-induced migration of RBCs in large vessels such as the abdominal aorta and the carotid artery. Marked RBCs migration is observed in the region of the carotid sinus and in the iliac arteries, regions prone to atherogenesis. This leads to the hypothesis that oxyhemoglobin availability can decrease in the near-wall region thus contributing to wall hypoxia, a factor implicated in atherosclerosis. The thesis proposes a new potential mechanism of ILT growth, driven by fluid and chemical stimuli, which can be used to study ILT progression over physiologically relevant timeframes and be used as a framework to test new hypotheses; the thesis also provides new insights on the oxyhemoglobin availability in the near-wall region with direct inuence on atherosclerosis.

  • 7.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Auer, Martin
    VASCOPS GmbH, Graz, Austria.
    Hedin, Ulf
    Department of Molecular Medicine and Surgery, Karolinska Universty Hospital, Stockholm, Sweden.
    Labruto, Fausto
    Department of Radoilogy, Karolinska University Hospital, Stockholm, Sweden.
    Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism2010In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, no 2, p. 380-390Article in journal (Refereed)
    Abstract [en]

    Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau-Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.

  • 8.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Thomas Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A Blood Flow based model for Platelet Activation in Abdominal Aortic Aneurisms2010Conference paper (Refereed)
    Abstract [en]

    Introduction

    Thrombus formation is the physiological response to vascular injury, it prevents loss of blood and permits wound healing, however, it is also associated with pathological conditions like hypoxia, anoxia and infarction [1]. Consequently, thrombus development must be carefully modulated to avoid uncontrolled growth, which in turn could lead to organ malfunctions. Specifically, an Intra-Luminal Thrombus (ILT) is found in almost all larger (clinically relevant) Abdominal Aortic Aneurysms (AAAs) and multiple biochemical [2] and biomechanical [3] implications on the underlying wall tissue have been reported. Despite the dominant role played by the ILT in AAA disease little is known regarding its development, and hence, the present study investigates ILT formation with particular emphasis on platelet activation triggered by biomechanical and biochemical field variables.

    Method

    The proposed model assumes that platelet activation is defined by a single field variable

    representing the accumulation of mechanical [4] and chemical [5] factors as the platelet moves along its path line. Platelet activation is given as soon asovercomes a certain threshold thought to be a constitutive property of blood. Specifically, the rate of the activation variable is determined by the maximum shear stress and the local concentrations of agonists and antagonists. To implement the model the fluid mechanical problem was solved in (COMSOL, COMSOL AB) and a particle tracking analysis (MATLAB, The MathWorks) was applied as a post processing step. The flow in a circular tube and the Backward Facing Step (BFS) problem under varying initial conditions were used for a basic investigation of the model and to relate its predictions to available data in the literature. Finally, platelet activation in patient specific AAAs was predicted and related to ILT development, which was estimated from Computer Tomography-Angiography (CT-A) data recorded from patient follow-up studies.

    Results and Conclusions

    The platelet activation variable

     is complex distributed (highly heterogeneous) in the flow field, where, specifically, at the boundary of vortexes [6] and in the boundary layer of the non- endothelialized wall highest values were predicted. Continuous release of antagonists from the endothelialized wall lowers  in its vicinity, and hence, despite the high shear stress platelet activation

    is prevented. The proposed model links biomechanical and biochemical mechanisms of platelet activation and is able to predict the onset of thrombus formation of the BFS problem. The model is also able to predict some features of ILT development in the AAA, however, the change in luminal geometry is a cumulative effect of ILT growth, wall growth and their mechanical interactions, and hence, data recorded form patient follow-up studies needs to be analyzed carefully when validating the present model.

    References

    [1] J. D. Humphrey,

    Springer-Verlag, New York, 2002.

    [2] M. Kazi, et. al.

    J. Vasc. Surg., 38:1283-1292, 2003.

    [3] W. R. Mower et. al.,

    J. Vasc. Surg., 33:602-608, 1997.

    [4] J. D. Hellums,

    Ann. Biomed. Eng., 22: 445-455, 1994.

    [5] B. Alberts et. al.

    Molecular Biology of the cell, 2002.

    [6] J. Biasetti et. al.

    Ann. Biomed. Eng., 38: 380–390 2010.

  • 9.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Thomas Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A Fluid-chemical model of thrombus formation2011In: CMBE2011: 2nd International Conference on Mathematical and Computational Biomedical Engineering / [ed] P. Nithiarasu, R. Löhner, 2011Conference paper (Refereed)
    Abstract [en]

    Our understanding of the genesis and evolution of Abdominal Aortic Aneurysms (AAAs), withparticular emphasis on Intra-Luminal Thrombus’ evolution, may be improved by studying thecomplex interplay between fluid-dynamics and biochemistry. To investigate the evolution of prothromboticchemicals inside the blood flow, in particular thrombin (factor IIa), a fluido-chemicalmodel has been developed. To this end a series of convection-diffusion-reaction (CDR) equationsdescribing the tissue factor pathway to thrombin have been solved on top of the biofluiddynamics problem. The proposed model integrates biochemistry and fluids dynamics, and hence,supports a comprehensive understanding of how ILT in AAAs may develop.

  • 10.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Hussain, Fazle
    Department of Mechanical Engineering, University of Houston, Houstohn, TX, USA.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intraluminal thrombus formation2011In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 8, no 63, p. 1449-1461Article in journal (Refereed)
    Abstract [en]

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the lambda(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

  • 11.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Spazzini, Pier Giorgio
    Mechanics Division, National Institute of Metrological Research (INRiM), Turin, Italy.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Shear-induced migration of red blood cells in the abdominal aorta and thecarotid bifurcation: considerations on oxygen transport2013Report (Other academic)
    Abstract [en]

    Shear-induced migration of red blood cells (RBCs) is a well known phenomenon characterizing blood flow in the small vessels (micron to mm size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (mm to cm size), the extent of this migration has not been fully elucidated. RBCs migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface; this being of primary importance in, for example, intra-luminal thrombus (ILT) growth, atherosclerosis and intima hyperplasia. Phillips’ shear-induced particle migration model coupled to the Quemada viscosity model was employed to simulate the macroscopic behavior of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near wall region with a lowering of wall hematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and in the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, the inner curvature wall of the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall hematocrit are correlated with the near-wall shear layer and with the secondary flow induced by the vessel curvature. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus and, more in general, on the inner curvature wall. The lowering of wall hematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhemoglobin, hence contributing, with the lowered oxygen partial pressure, to local hypoxia.

  • 12.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Spazzini, Pier Giorgio
    Mechanics Division, National Institute of Metrological Research, Turin, Italy.
    Swedenborg, Jesper
    Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms2012In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 3, no 266Article in journal (Refereed)
    Abstract [en]

    Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

  • 13. Cacho, F.
    et al.
    Elbischger, P. J.
    Rodriguez, J. F.
    Doblare, M.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A constitutive model for fibrous tissues considering collagen fiber crimp2007In: International Journal of Non-Linear Mechanics, ISSN 0020-7462, E-ISSN 1878-5638, Vol. 42, no 2, p. 391-402Article in journal (Refereed)
    Abstract [en]

    A micromechanically based constitutive model for fibrous tissues is presented. The model considers the randomly crimped morphology of individual collagen fibers, a morphology typically seen in photomicrographs of tissue samples. It describes the relationship between the fiber endpoints and its arc-length in terms of a measurable quantity, which can be estimated from image data. The collective mechanical behavior of collagen fibers is presented in terms of an explicit expression for the strain-energy function, where a fiber-specific random variable is approximated by a Beta distribution. The model-related stress and elasticity tensors are provided. Two representative numerical examples are analyzed with the aim of demonstrating the peculiar mechanism of the constitutive model and quantifying the effect of parameter changes on the mechanical response. In particular, a fibrous tissue, assumed to be (nearly) incompressible, is subject to a uniaxial extension along the fiber direction, and, separately, to pure shear. It is shown that the fiber crimp model can reproduce several of the expected characteristics of fibrous tissues.

  • 14. Cacho, Fernando
    et al.
    Doblare, Manuel
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A procedure to simulate coronary artery bypass graft surgery2007In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 45, no 9, p. 819-827Article in journal (Refereed)
    Abstract [en]

    In coronary artery bypass graft (CABG) surgery the involved tissues are overstretched, which may lead to intimal hyperplasia and graft failure. We propose a computational methodology for the simulation of traditional CABG surgery, and analyze the effect of two clinically relevant parameters on the artery and graft responses, i.e., incision length and insertion angle for a given graft diameter. The computational structural analyses are based on actual three-dimensional vessel dimensions of a human coronary artery and a human saphenous vein. The analyses consider the structure of the end-to-side anastomosis, the residual stresses and the typical anisotropic and nonlinear vessel behaviors. The coronary artery is modeled as a three-layer thick-walled tube. The finite element method is employed to predict deformation and stress distribution at various stages of CABG surgery. Small variations of the arterial incision have relatively big effects on the size of the arterial opening, which depends solely on the residual stress state. The incision length has a critical influence on the graft shape and the stress in the graft wall. Stresses at the heel region are higher than those at the toe region. The changes in the mechanical environment are severe along all transitions between the venous tissue and the host artery. Particular stress concentrations occur at the incision ends. The proposed computational methodology may be useful in designing a coronary anastomotic device for reducing surgical trauma. It may improve the quantitative knowledge of vessel diseases and serve as a tool for virtual planning of vascular surgery.

  • 15.
    Forsell, Caroline
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Failure of vascular tissue with applications to the aneurysm wall, carotid plaque and myocardial tissue2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease is the leading cause of death in the modern world. Examples are thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA) and stroke due to plaque rupture. Failure in soft tissues caused by medical devices is also a medical challenge. In all these cardiovascular events a better prediction of failure of the tissue and a better understanding about the tissue properties will help in predicament and treatment. For example the diameter-based indication for surgical repair of AAA and TAAs is not sufficient and refined methods are needed. In this thesis failures of some soft vascular tissues, was studied. Experiments have been combined with numerical modeling to understand the elastic and failure properties of AAA, TAA and plaque tissue as well as the ventricular wall. Vascular tissue is anisotropic, time-dependent, nonlinear and shows large deformations. Among others this thesis showed the importance of viscoelasticity which motivates to develop a new continuum mechanical framework. In addition a large part of this thesis dealt with anisotropy of vascular tissue. For the first time the collagen orientation distribution in the AAA wall has been identified. Collagen and its distribution orientation is also an important feature of this tissue. There was a correlation between the strength and stiffness of the AAA samples with the decreasing wall thickness. Increased stiffness was found in the aortic wall of patients with chronic obstructive pulmonary disease (COPD) compared to patients that did not have COPD. As well as difference in stiffness of TAA tissue, in patients with non-pathologic and pathologic aortic valves. Some of the findings in this thesis could have a long-term consequence for management of risk of rupture in AAA, TAA and plaque.

  • 16.
    Forsell, Caroline
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Numerical simulation of failure response of vascular tissue due to deep penetration2011Licentiate thesis, comprehensive summary (Other academic)
  • 17.
    Forsell, Caroline
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Eriksson, Per
    France-Cereceda, Anders
    Gasser, Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Failure properties for the thoracic aneurysm wall: Differences between BicuspidAortic Valve (BAV) and Tricuspid Aortic Valve (TAV) patientsManuscript (preprint) (Other academic)
  • 18.
    Forsell, Caroline
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Numerical simulation of the failure of ventricular tissue due to deep penetration: The impact of constitutive properties2011In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 44, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Lead perforation is a rare but serious clinical complication of pacemaker implantation, and towards understanding this malfunction, the present study investigated myocardial failure due to deep penetration by an advancing rigid punch. To this end, a non-linear Finite Element model was developed that integrates constitutive data published in the literature with information from in vitro tensile testing in cross-fibre direction of porcine myocardial tissue. The Finite Element model considered non-linear, isotropic and visco-elastic properties of the myocardium, and tissue failure was phenomenologically described by a Traction Separation Law. In vitro penetration testing of porcine myocardium was used to validate the Finite Element model, and a particular objective of the study was to investigate the impact of different constitutive parameters on the simulated results. Specifically, results demonstrated that visco-elastic properties of the tissue strongly determine the failure process, whereas dissipative effects directly related to failure had a minor impact on the simulation results. In addition, non-linearity of the bulk material did not change the predicted peak penetration force and the simulations did not reveal elastic crack-tip blunting. The performed study provided novel insights into ventricular failure due to deep penetration, and provided useful information with which to develop numerical failure models.

  • 19.
    Forsell, Caroline
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Impact of material anisotropy on deformation of myocardial tissue due to pacemaker electrodes2011In: ASME 2011 Summer Bioengineering Conference, SBC 2011, 2011, no PARTS A AND B, p. 789-790Conference paper (Refereed)
    Abstract [en]

    A Pacemaker electrode can penetrate the heart wall, and to design a penetration-resistent lead tip sound knowledge regarding failure of ventricular tissue is required. Numerical simulations can be particular helpful in that respect, but depend on a reliable constitutive description for ventricular tissue. In this study an anisotropic hyperelastic model for the myocardium has been implemented and compared to predictions from an isotropic description. Specifically, the response due to pushing a rigid punch into the myocardium was studied. Results between anisotropic and isotropic descriptions of the myocardium differed significantly, which justified the implementation of an anisotropic model for the myocardium.

  • 20.
    Forsell, Caroline
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    The impact of constitutive properties on myocardial tissue perforation2010Conference paper (Refereed)
    Abstract [en]

    Introduction

    Acute or delayed lead perforation is a rare but serious complication of pacemaker implantation with numerous case reports and case series known [1]. A perforation-resistant lead tip design requires detailed knowledge regarding the mechanical failure of the ventricular wall. Like many other soft biological tissues, ventricular tissue exhibits complex mechanical properties like incompressibility, finite deformability, inhomogeneity, material non-linearity, anisotropy, strain rate-dependency, and a constitutive model should reflect that to the required degree of completeness. Within this work we investigate the failure mechanisms of myocardial penetration by advancing a rigid punch, conditions thought to be related to pacemaker lead perforation. Specifically, the impact of constitutive parameters related to the bulk material and the failure zone is analyzed.

    Method

    A single penetration site of our previous penetration experiment of biaxially-stretched myocardial tissue [2] was models by the non-linear Finite Element Method (ABAQUS,

    Dassault Systèmes). To this end a visco-elastic description was applied and a previously reported anisotropic constitutive model for myocardial tissue [3] was implemented using the user material model interface. All failure related inelastic deformations were lumped into a fracture process zone and captured by a triangular cohesive traction separation law. To this end the cohesive strength of ventricular tissue was experimentally determined by tensile testing in cross-fiber direction of porcine myocardial tissue. Simulated results with different visco-elastic and failure properties, i.e. by varying the associated sets of constitutive parameters of the myocardial tissue were investigated.

    Results and Conclusions

    Results demonstrated that visco-elastic properties of the myocardial tissue strongly determine the failure of myocardial tissue due to deep penetration. This finding is in line with failure of rubber-like materials, where visco-elastic energy dissipation in front of the crack tip was found to be an important factor of energy dissipation [4]. In contrast dissipative effects which are directly related to failure (i.e. captured by the cohesive zone model) had a minor impact on the simulated penetration force displacement characteristics. Likewise, non-linearity and anisotropy of the bulk material did not change the predicted peak penetration force and the simulations did not reveal elastic crack-tip blunting.

    The proposed numerical model integrates experimental data from different studies and allows a detailed investigation of failure related to pacemaker lead perforation. Results from the study provided novel insights into ventricular failure due to deep penetration, which might also be related to other soft biological tissues and helpful to design penetration resistant pacemaker leads.

    References

    [1] M.N. Khan, et. al.

    Pacing and Clinical Electrophysiology, 28, 251-253, 2005.

    [2] T.C. Gasser et. al.

    J. Biomech., 42, 626-633, 2009.

    [3] J. D. Humphrey et al.,

    J. Biomech. Engrg., 112, 340-346, 1990.

    [4] B.N.J. Persson,et. Al

    ., J.Phys. Condens. Matter., 17, R1071-R1142, 2005.

  • 21.
    Forsell, Caroline
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Swedenborg, Jesper
    Roy, Joy
    Gasser, Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    The Quasi-Static Failure Properties of the Abdominal Aortic Aneurysm Wall Estimated by a Mixed Experimental-Numerical Approach2012In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 41, no 7, p. 1554-1566Article in journal (Refereed)
    Abstract [en]

    Assessing the risk for abdominal aortic aneurysm (AAA) rupture is critical in the management of aneurysm patients and an individual assessment is possible with the biomechanical rupture risk assessment. Such an assessment could potentially be improved by a constitutive AAA wall model that accounts for irreversible damage-related deformations. Because of that the present study estimated the elastic and inelastic properties of the AAA wall through a mixed experimental-numerical approach. Specifically, finite element (FE) models of bone-shaped tensile specimens were used to merge data from failure testing of the AAA wall with their measured collagen orientation distribution. A histo-mechanical constitutive model for collagen fibers was employed, where plastic fibril sliding determined not only remaining deformations but also weakening of the fiber. The developed FE models were able to replicate the experimentally recorded load-displacement property of all 16 AAA wall specimens that were investigated in the study. Tensile testing in longitudinal direction of the AAA defined a Cauchy strength of 569(SD 411) kPa that was reached at a stretch of 1.436(SD 0.118). The stiffness and strength of specimens decreased with the wall thickness and were elevated (p = 0.018; p = 0.030) in patients with chronic obstructive pulmonary disease (COPD). Smoking affected the tissue parameters that were related to the irreversible deformation response, and no correlation with gender and age was found. The observed effects on the biomechanical properties of the AAA wall could have long-term consequences for the management of aneurysm patients, i.e., specifically they might influence future AAA rupture risk assessments. However, in order to design appropriate clinical validation studies our findings should firstly be verified in a larger patient cohort.

  • 22. Franceschini, G.
    et al.
    Bigoni, D.
    Regitnig, P.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Brain tissue deforms similarly to filled elastomers and follows consolidation theory2006In: Journal of the mechanics and physics of solids, ISSN 0022-5096, E-ISSN 1873-4782, Vol. 54, no 12, p. 2592-2620Article in journal (Refereed)
    Abstract [en]

    Slow, large deformations of human brain tissue-accompanying cranial vault deformation induced by positional plagiocephaly, occurring during hydrocephalus, and in the convolutional development-has surprisingly received scarce mechanical investigation. Since the effects of these deformations may be important, we performed a systematic series of in vitro experiments on human brain tissue, revealing the following features. (i) Under uniaxial (quasi-static), cyclic loading, brain tissue exhibits a peculiar nonlinear mechanical behaviour, exhibiting hysteresis, Mullins effect and residual strain, qualitatively similar to that observed in filled elastomers. As a consequence, the loading and unloading uniaxial curves have been found to follow the Ogden nonlinear elastic theory of rubber (and its variants to include Mullins effect and permanent strain). (ii) Loaded up to failure, the shape of the stress/strain curve qualitatively changes, evidencing softening related to local failure. (iii) Uniaxial (quasi-static) strain experiments under controlled drainage conditions provide the first direct evidence that the tissue obeys consolidation theory involving fluid migration, with properties similar to fine soils, but having much smaller volumetric compressibility. (iv) Our experimental findings also support the existence of a viscous component of the solid phase deformation. Brain tissue should, therefore, be modelled as a porous, fluid-saturated, nonlinear solid with very small volumetric (drained) compressibility.

  • 23.
    Gasser, Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Forsell, Caroline
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    The numerical implementation of invariant-based viscoelastic formulations at finite strains. An anisotropic model for the passive myocardium2011In: Computer Methods in Applied Mechanics and Engineering, ISSN 0045-7825, E-ISSN 1879-2138, Vol. 200, no 49-52, p. 3637-3645Article in journal (Refereed)
    Abstract [en]

    The present study developed a conceptual framework for finite strain viscoelasticity thought to be suitable to capture the salient features of a class of passive soft biological tissues like the myocardium. A superposition of a Maxwell Body and an Elastic Body defines the viscoelastic continuum, and its deformation is related to two independent reference configurations. The reference configuration of the Maxwell Body moves in space as it is described (apart from rigid body rotation) by a rate equation in strain space, and stores the history of the deformation. At thermodynamic equilibrium the reference configuration of the Maxwell Body coincides with the current configuration of the continuum. The Helmholtz free energy is expressed as a function of two independent strain variables and entirely renders the constitution of the viscoelastic body. Although this view is to some extent different from reported viscoelastic concepts for finite strains, its linearization around the thermodynamic equilibrium coincides with earlier suggested viscoelastic models. The linearized viscoelastic model has been implemented for a particular anisotropic constitutive model for the passive myocardium. Non-negative dissipation of the model is guaranteed. Material parameters were estimated from in vitro testing of porcine myocardium and the response due to pushing a rigid punch into the myocardium was studied. Results between anisotropic and isotropic descriptions of the myocardium differed significantly, which justified the implementation of an anisotropic model for the myocardium.

  • 24.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gallinetti, Sara
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Swedenborg, Jesper
    Roy, Joy
    Collagen fiber orientation in Abdominal Aortic Aneurysms wall2010Conference paper (Refereed)
    Abstract [en]

    Introduction

    Collagen is the most abundant protein in mammals and gives mechanical strength, stiffness and toughness to biological tissues like skin, tendon, bone, and vasculature [1]. Collagen fibrils of about 0.1 micrometers in diameters are the basic building blocks of fibrous collagenous tissues and their organization into suprafibrilar structures determines the tissue’s macroscopic mechanical properties. For example, detailed data regarding the organization of strong bundles of collagen might be critical to predict the onset of tissue failure, as it is clinically motivated by a rupture risk assessment of Abdominal Aortic Aneurysm (AAA). Previously proposed structural constitutive models for soft biological tissues [2, 3] integrated information regarding the collagen orientation, and regardless of their popularity, the requested microstructural information is not yet available in the open literature.

    Method and Materials

    The present study investigated the collagen formation in 12 AAA wall specimens stemming from 9 patients and harvested during elective aneurysm repair at Karolinska University Hospital, Stockholm, Sweden. Specimens of about 1.0 x 1.0 centimeter were squeezed between Plexiglas plates and fixated in formaldehyde for 24 hours. Fixated specimens were dehydrated and embedded in paraffin (Tissue Tek VIP 3000,

    Sakura)and sliced at a thickness of 7.0 micrometers (HM 360, Microm). To reinforce the birefringend properties of collagen the slices were stained with Picrus Sirius red before three-dimensional collagen fiber orientations were identified in a polarized light microscope (BX 50, Olympus) equipped with an Universal Rotary Stage (Zeiss). Specifically, the collagen orientations were measured at 36 points at each slice, where three slices across the thickness of the AAA wall were considered. The derived structural information was included in two different structural constitutive models and reported macroscopic mechanical data [4] was used to estimate mechanical parameters of the constitutive formulations.

    Results and Conclusions

    Collagen fiber orientation in the AAA wall is considerably spread out and no difference amongst medial and adventitial layers could be identified; a result in line with the layered structure of, e.g., cerebral aneurysms [5] but in clear contrast to the structural differences amongst the layers of normal arteries [6]. Collagen fibers in the AAA wall are predominantly aligned in circumferential direction, which might explain its higher stiffness along that direction [4]. Naturally, the complex collagen formation cannot be captured by a single (or two) families of collagen fibers and associated constitutive models are not applicable. Collagen turnover is thought to be mediated by the local stress or strain state [7] and the supra-physiological stresses in the AAA wall might cause the identified pathological collagen orientation.

    References

    [1] P. Fratzl, editor.

    Springer-Verlag, New York, 2008.

    [2] T. C. Gasser, et. al.

    J. R. Soc. Interface, 3:15–35, 2006.

    [3] S. Federico and T. C. Gasser.

    J. R.Soc. Interface, 2009.

    [4] J. P. Vande Geest et al..

    J Biomech. 39, 1324--1334, 2006.

    [5] P. B. Canham, et al..

    Neurological Res., 21, 618--626, 1999.

    [6] P. B. Canham, et al.

    Cardiovasc. Res. 23, 973-982, 1989.

    [7] J. D. Humphrey,

    Springer-Verlag, New York, 2002.

  • 25.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gallinetti, Sara
    Xing, Xiao
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Forsell, Caroline
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Swedenborg, Jesper
    Roy, Joy
    Spatial orientation of collagen fibers in the abdominal aortic aneurysm's wall and its relation to wall mechanics2012In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 8, no 8, p. 3091-3103Article in journal (Refereed)
    Abstract [en]

    Collagen is the most abundant protein in mammals and provides the abdominal aortic aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable microhistological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n = 24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated by polarized light microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AM wall was widely dispersed and could be captured by a Bingham distribution function (kappa(1) = 11.6, kappa(2) = 9.7). The dispersion was much larger in the tangential plane than in the cross-sectional plane, and no significant difference between the medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The collagen organization identified, combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers depend largely on their undulation, which is an important structural parameter that requires further experimental investigation.

  • 26.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    3D Crack propagation in unreinforced concrete. A two-step algorithm for tracking 3D crack paths2006In: Computer Methods in Applied Mechanics and Engineering, ISSN 0045-7825, E-ISSN 1879-2138, Vol. 195, no 37-40, p. 5198-5219Article in journal (Refereed)
    Abstract [en]

    Tensile failure of unreinforced concrete involves progressive micro-cracking, and the related strain-softening can coalesce into geometrical discontinuities, which separate the material. Advanced mechanical theories and numerical schemes are required to efficiently and adequately represent crack propagation in 3D. In this paper we use the concept of strong discontinuities to model concrete failure. We introduce a cohesive fracture process zone, which is characterized by a transversely isotropic traction-separation law. We combine the cohesive crack concept with the partition of unity finite element method, where the finite element space is enhanced by the Heaviside function. The concept is implemented for tetrahedral elements and the failure initialization is based on the simple (non-local) Rankine criterion. For each element we assume the embedded discontinuity to be flat in the reference configuration, which leads to a non-smooth crack surfaces approximation in 3D, in general; different concepts for tracking non-planar cracks in 3D are reviewed. In addition, we propose a two-step algorithm for tracking the crack path, where a predictor step defines discontinuities according to the (non-local) failure criterion and a corrector step draws in non-local information of the existing discontinuities in order to predict a 'closed' 3D crack surface; implementation details are provided. The proposed framework is used to analyze the predictability of concrete failure by two benchmark examples, i.e. the Nooru-Moharned test, and the Brokenshire test. We compare our numerical results, which are mesh independent, with experimental data and numerical results adopted from the literature.

  • 27.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Finite element modeling of balloon angioplasty by considering overstretch of remnant non-diseased tissues in lesions2007In: Computational Mechanics, ISSN 0178-7675, E-ISSN 1432-0924, Vol. 40, no 1, p. 47-60Article in journal (Refereed)
    Abstract [en]

    The paper deals with the modeling of balloon angioplasty by considering the balloon-induced overstretch of remnant non-diseased tissues in atherosclerotic arteries. A stenotic artery is modeled as a heterogenous structure composed of adventitia, media and a model plaque, and residual stresses are considered. The constitutive models are able to capture the anisotropic elastic tissue response in addition to the inelastic phenomena associated with tissue stretches beyond the physiological domain. The inelastic model describes the experimentally-observed changes of the wall during balloon inflation, i.e. non-recoverable deformation, and tissue weakening. The contact of the artery with a balloon catheter is simulated by a point-to-surface strategy. The states of deformations and stresses within the artery before, during and after balloon inflation are computed, compared and discussed. The 3D stress states at physiological loading conditions before and after balloon inflation differ significantly, and even compressive normal stresses may occur in the media after dilation.

  • 28. Gasser, T. Christian
    et al.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Modeling 3D crack propagation in unreinforced concrete using PUFEM2005In: Computer Methods in Applied Mechanics and Engineering, ISSN 0045-7825, E-ISSN 1879-2138, Vol. 194, no 25-26, p. 2859-2896Article in journal (Refereed)
    Abstract [en]

    Concrete is a quasi-brittle material, where tensile failure involves progressive micro-cracking, debounding and other complex irreversible processes of internal damage. Strain-softening is a dominate feature and advanced numerical schemes have to be applied in order to circumvent the ill-posdness of the Boundary-Value Problem to deal with. Throughout the paper we pursue the cohesive zone approach, where initialization and coalescence of micro-cracks is lumped into the cohesive fracture process zone in terms of accumulation of damage. We develop and employ a (discrete) constitutive description of the cohesive zone, which is based on a transversely isotropic traction separation law. The model reflects an exponential decreasing traction with respect to evolving opening displacement and is based on the theory of invariants. Non-negativeness of the damage dissipation is proven and the associated numerical embedded representation is based on the Partition of Unity Finite Element Method. A consistent linearization of the method is presented, where particular attention is paid to the (cohesive) traction terms. Based on the proposed concept three numerical examples are studied in detail, i.e. a double-notched specimen under tensile loading, a four point shear test and a pull-out test of unreinforced concrete. The computational results show mesh-independency and good correlation with experimental results. © 2004 Elsevier B.V. All rights reserved.

  • 29.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Modeling plaque fissuring and dissection during balloon angioplasty intervention2007In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 35, no 5, p. 711-723Article in journal (Refereed)
    Abstract [en]

    Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and/or dissection occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment site. We propose physical and finite element models, which are generally useable to trace fissuring and/or dissection in atherosclerotic plaques during balloon angioplasty interventions. The arterial wall is described as an anisotropic, heterogeneous, highly deformable, nearly incompressible body, whereas tissue failure is captured by a strong discontinuity kinematics and a novel cohesive zone model. The numerical implementation is based on the partition of unity finite element method and the interface element method. The later is used to link together meshes of the different tissue components. The balloon angioplasty-based failure mechanisms are numerically studied in 3D by means of an atherosclerotic-prone human external iliac artery, with a type V lesion. Image-based 3D geometry is generated and tissue-specific material properties are considered. Numerical results show that in a primary phase the plaque fissures at both shoulders of the fibrous cap and stops at the lamina elastica interna. In a secondary phase, local dissections between the intima and the media develop at the fibrous cap location with the smallest thickness. The predicted results indicate that plaque fissuring and dissection cause localized mechanical trauma, but prevent the main portion of the stenosis from high stress, and hence from continuous tissue damage.

  • 30.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Modeling the propagation of arterial dissection2006In: European journal of mechanics. A, Solids, ISSN 0997-7538, E-ISSN 1873-7285, Vol. 25, no 4, p. 617-633Article in journal (Refereed)
    Abstract [en]

    Arterial dissections are frequently observed in clinical practice and during road traffic accidents. In particular, the lamellarly arrangement of elastin, collagen, in addition to smooth muscle cells in the middle arterial layer, the media, favors dissection failure. Experimental studies and related biomechanical models are rare in the literature. Finite strain kinematics is employed, and the discontinuity in the displacement field accounts for tissue separation. Dissection is regarded as a gradual process in which separation between incipient material surfaces is resisted by cohesive traction. Two variational statements together with their consistent linearizations form the basis for a finite element implementation. We combine the cohesive crack concept with the partition of unity finite element method, where nodal degrees of freedom adjacent to the discontinuity are enhanced. The developed continuum mechanical and numerical frameworks allow the analysis of the propagation of dissections within general nonlinear boundary-value problems, where the constitutive description for the continuous and the cohesive material is considered independent from each other. The continuous material is modeled as a fiber-reinforced composite with the fibers corresponding to the collagenous component which are assumed to be embedded in a non-collagenous isotropic groundmatrix. Dispersion of the collagen fiber orientation is considered in a continuum sense by one structure parameter. A novel cohesive potential per unit undeformed area is used to derive a traction separation law appropriate for the description of the mechanical properties of medial dissection. The cohesive stiffness contribution to the element stiffness matrix is explicitly derived. In particular, the dissection propagation of a rectangular strip of a human aortic media is investigated. Cohesive material properties are quantified by comparing the experimentally measured load with the computed dissection load.

  • 31.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Martufi, Giampaolo
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Auer, M.
    Folkesson, M.
    Swedenborg, J.
    Micromechanical Characterization of Intra-luminal Thrombus Tissue from Abdominal Aortic Aneurysms2010In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, no 2, p. 371-379Article in journal (Refereed)
    Abstract [en]

    The reliable assessment of Abdominal Aortic Aneurysm rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. Intra-luminal thrombus (ILT) has multiple biomechanical and biochemical impacts on the underlying aneurysm wall and thrombus failure might be linked to aneurysm rupture. Histological slices from 7 ILTs were analyzed using a sequence of automatic image processing and feature analyzing steps. Derived microstructural data was used to define Representative Volume Elements (RVE), which in turn allowed the estimation of microscopic material properties using the non-linear Finite Element Method. ILT tissue exhibited complex microstructural arrangement with larger pores in the abluminal layer than in the luminal layer. The microstructure was isotropic in the abluminal layer, whereas pores started to orient along the circumferential direction towards the luminal site. ILT's macroscopic (reversible) deformability was supported by large pores in the microstructure and the inhomogeneous structure explains in part the radially changing macroscopic constitutive properties of ILT. Its microscopic properties decreased just slightly from the luminal to the abluminal layer. The present study provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture. Data provided in this study allow an integration of structural information from medical imaging for example, to estimate ILT's macroscopic mechanical properties.

  • 32.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Martufi, Giampaolo
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Auer, Martin
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    A constitutive model for vascular tissue that integrates fibril, fiber and continuum levels2011In: CMBE 2011: Proceedings of 2nd International Conference on Computational & Mathematical Biomedical Engineering, 2011Conference paper (Refereed)
  • 33.
    Gasser, Thomas Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Auer, M.
    Biasetti, Jacopo
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Structural and Hemodynamical analysis of Aortic Aneurysms from Computerized Tomography Angiography data2010In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, VOL 25, PT 4: IMAGE PROCESSING, BIOSIGNAL PROCESSING, MODELLING AND SIMULATION, BIOMECHANICS, 2010, p. 1584-1587Conference paper (Refereed)
    Abstract [en]

    Evaluating rupture risk of Abdominal Aortic Aneurysms is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. According to the current clinical practice aneurysm rupture risk is (mainly) estimated from its maximum diameter and/or expansion rate; an approach motivated from statistics but known to fail often in individuals. In particular, the role of the Intraluminal Thrombus is unclear and further research is required to investigate and understand its multiple impacts on aneurysm disease. Biomechanical simulations might be helpful to explore this question, however, model development is time consuming and operator-variability limits their reliability. In this study we propose an automatic procedure to develop hemodynamic and structural models of healthy and diseased abdominal aortas, where Deformable Models segment Computerized Tomography Angiography data. In total 29 numerical models of the health and diseased abdominal aorta have been developed to investigate aneurysm's rupture risk and hemodynamic consequences of aneurismal dilations. The derived results underline the suitability of biomechanical simulations to enrich diagnostic information and to uncover mechanisms of aneurysm pathology.

  • 34. Georgakarakos, Efstratios
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Xenos, Michalis
    Kontopodis, Nikolaos
    Georgiadis, George S.
    Ioannou, Chris V.
    Applying Findings of Computational Studies in Vascular Clinical Practice: Fact, Fiction, or Misunderstanding?2014In: Journal of Endovascular Therapy, ISSN 1526-6028, E-ISSN 1545-1550, Vol. 21, no 3, p. 434-438Article in journal (Other academic)
  • 35.
    Giampaolo, Martufi
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Thomas Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Auer, Martin
    Labruto, Fausto
    Swedenborg, Jesper
    Abdominal Aortic Aneurysm development over time: Experimental evidence and constitutive modeling2010In: Proceedings of the 6th World Congress of Biomechanics, Springer, 2010Conference paper (Refereed)
    Abstract [en]

    Abdominal Aortic Aneurysms (AAAs) are defined as a localized permanent dilatation of the infrarenal aorta at least 50 % of its normal diameter. AAAs are frequently diagnosed in the elderly male population and evaluating rupture risk is critically important as aneurysm rupture carries high mortality rates. Growth predictors might be helpful to assess AAA rupture risk and could therefore give a better graded indication for elective repair in order to reduce related mortality without unnecessarily increasing the rate of interventions. Factors associated with AAA growth are still limited but there are some evidence that higher initial AAA diameter is related to faster AAA expansion [1]. The initial dilatation is dependent on elastin degradation, but strength of the AAA is maintained by increased production of collagen. It has been suggested that rupture occurs when collagen production is insufficient to counteract load-bearing at high pressure [2].

    AAA growth quantification

    30 patients with infrarenal AAAs were included in this study. Criteria for inclusion were 1-year follow-up and availability of at least two high-resolution Computer Tomography-Angiography (CTA) scans. Consequently, 60 CT-A scans were systematically segmented, reconstructed and analyzed (A4research, VASCOPS GmbH), in order to investigate geometrical and mechanical factors likely to be correlated with AAA growth. Derived results were analyzed with an especially developed (automatic) analyzing schema (MatLab, The MathWorks), and the derived information aims at guiding the development of an analytical growth model for AAAs.

    Constitutive Modeling

    Collagen is a structural protein responsible for the mechanical strength, stiffness and toughness of biological tissues like skin, tendon, bone, cornea, lung and vasculature. In the present study we considered the enlargement of the aneurysm as a consequence of a pathological degradation and synthesis of collagen, i.e. malfunction of collagen turn-over. Consequently, the vascular wall is modeled by an (inert) matrix material representing the elastin, which is reinforced by a dynamic structure of bundles of collagen. Specifically, collagen is formed by a continuous stress-mediated process and deposited in the current configuration [3] and removed by a constant degradation rate. Finally the micro-plane concept [4] is used for the Finite Element implementation [5] of the constitutive model.

    Results and conclusions

    The quantitative description of AAA growth by examining patient follow-up data revealed novel insights into the natural history of this disease. Most interestingly not all portions of the AAA seem to enlarge, some might be stable or even shrink over time; a feature that has not yet been considered by models reported in the literature. The model proposed within this study has a

    strong biological motivation and captures saline feature of AAA growth. Besides that, the micro-plane approach allows a straight forward FE implementation and preliminary results indicate its numerical robustness.

    References

    [1]

    F.J.V. Schlösser, et al., J Vasc Surg, 47:1127–1133 2008.

    [2]

    E. Choke, et al., Eur.j.Vasc.endovasc.surg, 30(3):227-44 2005.

    [3]

    J.D.Humphrey, J Biomech Eng, 121:591–597 1999.

    [4]

    Z.P. Bazant and P.C. Prat, J Eng Mech, 113(7) 1050-1064 1987.

    [5]

    S. Federico and T.C Gasser, J R Soc Interface (in press)

  • 36.
    Grytsan, Andrii
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Abdominal aortic aneurysm inception and evolution - A computational model2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Abdominal aortic aneurysm (AAA) is characterized by a bulge in the abdominal aorta. AAA development is mostly asymptomatic, but such a bulge may suddenly rupture, which is associated with a high mortality rate. Unfortunately, there is no medication that can prevent AAA from expanding or rupturing. Therefore, patients with detected AAA are monitored until treatment indication, such as maximum AAA diameter of 55 mm or expansion rate of 1 cm/year. Models of AAA development may help to understand the disease progression and to inform decision-making on a patient-specific basis. AAA growth and remodeling (G&R) models are rather complex, and before the challenge is undertaken, sound clinical validation is required.

    In Paper A, an existing thick-walled model of growth and remodeling of one layer of an AAA slice has been extended to a two-layered model, which better reflects the layered structure of the vessel wall. A parameter study was performed to investigate the influence of mechanical properties and G&R parameters of such a model on the aneurysm growth.

    In Paper B, the model from Paper A was extended to an organ level model of AAA growth. Furthermore, the model was incorporated into a Fluid-Solid-Growth (FSG) framework. A patient-specific geometry of the abdominal aorta is used to illustrate the model capabilities.

    In Paper C, the evolution of the patient-specific biomechanical characteristics of the AAA was investigated. Four patients with five to eight Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. Several non-trivial statistical correlations were found between the analyzed parameters.

    In Paper D, the effect of different growth kinematics on AAA growth was investigated. The transverse isotropic in-thickness growth was the most suitable AAA growth assumption, while fully isotropic growth and transverse isotropic in-plane growth produced unrealistic results. In addition, modeling of the tissue volume change improved the wall thickness prediction, but still overestimated thinning of the wall during aneurysm expansion.

  • 37.
    Grytsan, Andrii
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Computational model of abdominal aortic aneurysm inception and evolution2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Incidence of abdominal aortic aneurysm (AAA) is increasing in the aging society of the western world. Development of AAA is mostly asymptomatic and is characterized by a bulge in the abdominal aorta. However, AAA may suddenly rupture, which results in an internal bleeding associated with a high mortality rate. Patients with AAA undergo regular screening until treatment indication. To date, statistical criteria are used to decide whether the risk of rupture exceeds the risk of intervention. Models of AAA development help to understand the disease progression and to yield patient-specific criterion for AAA rupture.

    Up to date, sophisticated models of AAA development exist. These models assume the abdominal aorta as a thin-walled structure, which saves the computational effort. This thesis aims at investigating the importance of employing a thick-walled model of the aorta. The effects on AAA development that cannot be captured with a thin-walled model are of interest. In Paper A, the thick-walled model of growth and remodeling of one layer of a AAA slice has been extended to a two-layered model. The parameter study has been performed to investigate the influence of mechanical properties and growth and remodeling (G&R) parameters of two individual layers on the gross mechanical response and G&R of the artery. It was concluded that the adventitia acts to protect the arterial wall against rupture even in pathological state.

    In Paper B, the model was extended to an organ level model of AAA development. Furthermore, the model was incorporated into a so-called Fluid-Solid-Growth (FSG) framework, where the AAA development is loosely coupled to the blood flow conditions such as wall shear stress. One patient-specific geometry of the abdominal aorta is used to illustrate the model capabilities. A transmurally non-uniform distribution of the strains of individual arterial constituents was observed. In addition, an increased aneurysm tortuosity was observed in comparison to a thin-walled approach. These findings signify the importance of a thick-walled approach to model the aneurysm development. Finally, the proposed methodology provides a realistic basis to further explore the growth and remodeling of AAA on a patient-specific basis.

  • 38.
    Grytsan, Andrii
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Eriksson, Thomas S.E.
    Swedish Defence Research Agency.
    Watton, Paul N.
    Department of Computer Science, University of Sheffield, Sheffield, UK.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Growth description for vessel wall adaptation: a thick-walled mixture model of abdominal aortic aneurysm evolution2016Report (Other academic)
    Abstract [en]

    Modeling the soft tissue volumetric growth has received considerable attention in the literature.However, due to the lack of experimental observations, the growth kinematics, that are reported in the literature, are based on a number of assumptions.The present study tested the plausibility of different growth descriptions when applied to the abdominal aortic aneurysm (AAA) evolution.

    A structurally motivated material model and the multi-constituent tissue growth descriptions were utilized. The mass increment of the individual constituents preserved either the density or the volume.Four different growth descriptions were tested, namely isotropic (IVG), in-plane (PVG), in-thickness (TVG) growth and no volume growth (NVG) models.

    Based on the model sensitivity to the increased collagen deposition, TVG and NVG models were found to be plausible scenarios, while IVG and PVG were found to be implausible. In addition, TVG and NVG models were less sensitive to the initial constituent volume fractions, than IVG and PVG models.In conclusion, the choice of the growth kinematics is of crucial importance when modeling the AAA growth and remodeling, and,probably, also for other soft biological tissues.

  • 39.
    Grytsan, Andrii
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Watton, Paul N.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A thick-walled fluid–solid–growth model of abdominal aortic aneurysm evolution: Application to a patient-specific geometry2014Report (Other academic)
    Abstract [en]

    We propose a model for abdominal aortic aneurysms that considers the wall (solid), the blood (fluid) and the wall growth within a three-dimensional finite element framework. The arterial wall is considered as a thick-walled nonlinearly elastic circular cylindrical tube consisting of two layers corresponding to the media-intima and adventitia, where each layer is treated as a fiber-reinforced material with the fibers corresponding to the collagenous component. The blood is modeled as a Newtonian fluid with constant density and viscosity; no slip and no-flux conditions are applied at the arterial wall. The metabolic activity in the arterial wall is reflected by elastin degradation which is coupled with the level of wall shear stress, while the collagen fiber network is continuously remodeled in the artery such that the collagen fiber strain tends towards a homeostatic strain. The computational framework consists of a structural FE-solver (CMISS), a fluid solver using a finite volume formulation and additional routines which pass the aneurysm geometry to the fluid solver and feeds CMISS with the information on the blood flow conditions. One illustrative patient-specific geometry of an abdominal aortic wall is discretized with hexahedral finite elements and the fluid domain is generated by an unstructured tetrahedral mesh with prism layers lining the boundary. The evolution of wall shear stress and elastin degradation is investigated over a time period of 10 years; the influence of transmurally non-uniform elastin degradation is analyzed. The results show that both the elastin and the collagen strains can become transmurally non-uniform during the aneurysm development. This effect cannot be captured by membrane formulations. The proposed methodology provides a realistic basis to further explore the development of patient-specific aneurysmal disease.

  • 40. Hariton, I.
    et al.
    deBotton, G.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Stress-driven collagen fiber remodeling in arterial walls2007In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 6, no 3, p. 163-175Article in journal (Refereed)
    Abstract [en]

    A stress-driven model for the relation between the collagen morphology and the loading conditions in arterial walls is proposed. We assume that the two families of collagen fibers in arterial walls are aligned along preferred directions, located between the directions of the two maximal principal stresses. For the determination of these directions an iterative finite element based procedure is developed. As an example the remodeling of a section of a human common carotid artery is simulated. We find that the predicted fiber morphology correlates well with experimental observations. Interesting outcomes of the model including local shear minimization and the possibility of axial compressions due to high blood pressure are revealed and discussed.

  • 41.
    Heiland, Vincent M.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Forsell, Caroline
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Roy, Joy
    Hedin, Ulf
    Gasser, Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Identification of carotid plaque tissue properties using an experimental-numerical approach2013In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 27, p. 226-238Article in journal (Refereed)
    Abstract [en]

    A biomechanical stress analysis could help to identify carotid plaques that are vulnerable to rupture, and hence reduce the risk of thrombotic strokes. Mechanical stress predictions critically depend on the plaque's constitutive properties, and the present study introduces a concept to derive viscoelastic parameters through an experimental-numerical approach. Carotid plaques were harvested from two patients during carotid endarterectomy (CEA), and, in total, nine test specimens were investigated. A novel in-vitro mechanical testing protocol, which allows for dynamic testing, keeping the carotid plaque components together, was introduced. Macroscopic pictures overlaid by histological stains allowed for the segmentation of plaque tissues, in order to develop high-fidelity and low-fidelity Finite Element Method (FEM) models of the test specimens. The FEM models together with load-displacement data from the mechanical testing were used to extract constitutive parameters through inverse parameter estimation. The applied inverse parameter estimation runs in stages, first addressing the hyperelastic parameters then the viscoelastic ones. Load-displacement curves from the mechanical testing showed strain stiffening and viscoelasticity, as is expected for both normal and diseased carotid tissue. The estimated constitutive properties of plaque tissue were comparable to previously reported studies, Due to the highly non-linear elasticity of vascular tissue, the applied parameter estimation approach is, as with many similar approaches, sensitive to the initial guess of the parameters.

  • 42.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Ogden, R. W.
    Constitutive modelling of passive myocardium: a structurally based framework for material characterization2009In: Philosophical Transactions. Series A: Mathematical, physical, and engineering science, ISSN 1364-503X, E-ISSN 1471-2962, Vol. 367, no 1902, p. 3445-3475Article in journal (Refereed)
    Abstract [en]

    In this paper, we first of all review the morphology and structure of the myocardium and discuss the main features of the mechanical response of passive myocardium tissue, which is an orthotropic material. Locally within the architecture of the myocardium three mutually orthogonal directions can be identified, forming planes with distinct material responses. We treat the left ventricular myocardium as a non-homogeneous, thick-walled, nonlinearly elastic and incompressible material and develop a general theoretical framework based on invariants associated with the three directions. Within this framework we review existing constitutive models and then develop a structurally based model that accounts for the muscle fibre direction and the myocyte sheet structure. The model is applied to simple shear and biaxial deformations and a specific form fitted to the existing (and somewhat limited) experimental data, emphasizing the orthotropy and the limitations of biaxial tests. The need for additional data is highlighted. A brief discussion of issues of convexity of the model and related matters concludes the paper.

  • 43.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Ogden, R. W.
    On planar biaxial tests for anisotropic nonlinearly elastic solids. A continuum mechanical framework2009In: Mathematics and mechanics of solids, ISSN 1081-2865, E-ISSN 1741-3028, Vol. 14, no 5, p. 474-489Article in journal (Refereed)
    Abstract [en]

    The mechanical testing of anisotropic nonlinearly elastic solids is a topic of considerable and increasing interest. The results of such testing are important, in particular, for the characterization of the material properties and the development of constitutive laws that can be used for predictive purposes. However, the literature on this topic in the context of soft tissue biomechanics, in particular, includes some papers that are misleading since they contain errors and false statements. Claims that planar biaxial testing can fully characterize the three-dimensional anisotropic elastic properties of soft tissues are incorrect. There is therefore a need to clarify the extent to which biaxial testing can be used for determining the elastic properties of these materials. In this paper this is explained on the basis of the equations of finite deformation transversely isotropic elasticity, and general planar anisotropic elasticity. It is shown that it is theoretically impossible to fully characterize the properties of anisotropic elastic materials using such tests unless some assumption is made that enables a suitable subclass of models to be preselected. Moreover, it is shown that certain assumptions underlying the analysis of planar biaxial tests are inconsistent with the classical linear theory of orthotropic elasticity. Possible sets of independent tests required for full material characterization are then enumerated.

  • 44.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Ogden, Ray W.
    Constitutive modelling of arteries2010In: Proceedings of the Royal Society. Mathematical, Physical and Engineering Sciences, ISSN 1364-5021, E-ISSN 1471-2946, Vol. 466, no 2118, p. 1551-1596Article, review/survey (Refereed)
    Abstract [en]

    This review article is concerned with the mathematical modelling of the mechanical properties of the soft biological tissues that constitute the walls of arteries. Many important aspects of the mechanical behaviour of arterial tissue can be treated on the basis of elasticity theory, and the focus of the article is therefore on the constitutive modelling of the anisotropic and highly nonlinear elastic properties of the artery wall. The discussion focuses primarily on developments over the last decade based on the theory of deformation invariants, in particular invariants that in part capture structural aspects of the tissue, specifically the orientation of collagen fibres, the dispersion in the orientation, and the associated anisotropy of the material properties. The main features of the relevant theory are summarized briefly and particular forms of the elastic strain-energy function are discussed and then applied to an artery considered as a thickwalled circular cylindrical tube in order to illustrate its extension-inflation behaviour. The wide range of applications of the constitutive modelling framework to artery walls in both health and disease and to the other fibrous soft tissues is discussed in detail. Since the main modelling effort in the literature has been on the passive response of arteries, this is also the concern of the major part of this article. A section is nevertheless devoted to reviewing the limited literature within the continuum mechanics framework on the active response of artery walls, i.e. the mechanical behaviour associated with the activation of smooth muscle, a very important but also very challenging topic that requires substantial further development. A final section provides a brief summary of the current state of arterial wall mechanical modelling and points to key areas that need further modelling effort in order to improve understanding of the biomechanics and mechanobiology of arteries and other soft tissues, from the molecular, to the cellular, tissue and organ levels.

  • 45.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Sommer, Gerhard
    Auer, Martin
    Regitnig, Peter
    Ogden, Ray W.
    Layer-specific 3D residual deformations of human aortas with non-atherosclerotic intimal thickening2007In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 35, no 4, p. 530-545Article in journal (Refereed)
    Abstract [en]

    Data relating to residual deformations in human arteries are scarce. In this paper we investigate three-dimensional residual deformations for intact strips and for their separate layers from human aortas in their passive state. From 11 abdominal aortas with identified anamnesis, 16 pairs of rings and axial strips were harvested, and the rings cut open. After 16 h images of the resulting geometries were recorded, and the strips were separated into their three layers; after another 6 h images were again recorded. Image processing and analysis was then used to quantify residual stretches and curvatures. For each specimen histological analysis established that the intima, media and adventitia were clearly separated, and the separation was atraumatic. Axial in situ stretches were determined to be 1.196 +/- 0.084. On separation, the strips from the adventitia and media shortened (between 4.03 and 8.76% on average), while the intimal strips elongated on average by 3.84% (circumferential) and 4.28% (axial) relative to the associated intact strips. After separation, the adventitia from the ring sprang open by about 180 degrees on average, becoming flat, the intima opened only slightly, but the media sprang open by more than 180 degrees (as did the intact strip). The adventitia and intima from the axial strips remained flat, while the media (and the intact strip) bent away from the vessel axis. This study has shown that residual deformations are three dimensional and cannot be described by a single parameter such as 'the' opening angle. Their quantification and modeling therefore require consideration of both stretching and bending, which are highly layer-specific and axially dependent.

  • 46.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Sommer, Gerhard
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Christian T.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Regitnig, P
    Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling2005In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 289, no 5, p. H2048-H2058Article in journal (Refereed)
    Abstract [en]

    At autopsy, 13 nonstenotic human left anterior descending coronary arteries [71.5 +/- 7.3 ( mean +/- SD) yr old] were harvested, and related anamnesis was documented. Preconditioned prepared strips (n = 78) of segments from the midregion of the left anterior descending coronary artery from the individual layers in axial and circumferential directions were subjected to cyclic quasi-static uniaxial tension tests, and ultimate tensile stresses and stretches were documented. The ratio of outer diameter to total wall thickness was 0.189 +/- 0.014; ratios of adventitia, media, and intima thickness to total wall thickness were 0.4 +/- 0.03, 0.36 +/- 0.03, and 0.27 +/- 0.02, respectively; axial in situ stretch of 1.044 +/- 0.06 decreased with age. Stress-stretch responses for the individual tissues showed pronounced mechanical heterogeneity. The intima is the stiffest layer over the whole deformation domain, whereas the media in the longitudinal direction is the softest. All specimens exhibited small hysteresis and anisotropic and strong nonlinear behavior in both loading directions. The media and intima showed similar ultimate tensile stresses, which are on average three times smaller than ultimate tensile stresses in the adventitia (1,430 +/- 604 kPa circumferential and 1,300 +/- 692 kPa longitudinal). The ultimate tensile stretches are similar for all tissue layers. A recently proposed constitutive model was extended and used to represent the deformation behavior for each tissue type over the entire loading range. The study showed the need to model nonstenotic human coronary arteries with nonatherosclerotic intimal thickening as a composite structure composed of three solid mechanically relevant layers with different mechanical properties. The intima showed significant thickness, load-bearing capacity, and mechanical strength compared with the media and adventitia.

  • 47.
    Holzapfel, Gerhard. A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Stadler, M.
    Gasser, Th. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Towards a computational methodology for optimizing angioplasty treatments with stenting2006In: Mechanics of Biological TIssue / [ed] Holzapfel, GA; Ogden, RW, 2006, p. 225-240Conference paper (Refereed)
    Abstract [en]

    We propose a computational methodology that allows a set of stent parameters to he varied, with the aim of evaluating the difference in the mechanical environment within the wall before and after angioplasty with stenting. Proposed scalar quantities attempt to characterize the wall changes in the form of the contact pressure caused by the stent struts and the stresses within the individual components of the wall caused by the stent. These quantities are derived numerically and serve as indicators. which allow the determination of the correct size and type of the stent for each individual stenosis. In addition, the luminal change due to angioplasty may be computed as well. The methodology is demonstrated by using an image-based three-dimensional geometrical model of a postmortem specimen of a human iliac artery with a stenosis. To describe the material behavior of the artery, we considered mechanical data, of eight different vascular tissues, which formed the stenosis. The constitutive models for the tissue components capture the typical mechanical characteristics under supra-physiological loading conditions. Three-dimensional stent models were parameterized in such a way as to enable new designs to he generated simply with regard to variations in their geometric structure.

  • 48. Hyhlik-Dürr, A.
    et al.
    Kriegerl, T.
    Geisbuesch, P.
    Able, T.
    Gasser, Thomas Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Boeckler, D.
    Finite-Elemente-Analyse abdomineller Aortenaneurysmen: Erste Ergebnisse der Intra- und Interobserver Validierung2010Conference paper (Refereed)
    Abstract [de]

    Hintergrund:

    Die Therapie des abdominellen Aortenaneurysmas (AAA) ist indiziert, wenn das Rupturrisiko das Risiko der elektiven Operation übersteigt. Die Abschätzung des individuellen Rupturrisikos gilt als Basis der Indikationsstellung zur offenen oder endovaskulären Chirurgie. Bisher wird der Durchmesser des AAA als maßgeblicher Risikofaktor für die Ruptur herangezogen. Für eine sensitivere Indikationsstellung sollten jedoch andere morphologische oder biomechanische Faktoren wie die Volumenveränderung im Verlauf und/oder die Wandspannung im Aneurysma untersucht werden.

    Ziel dieser Studie ist die Analyse der Reproduzierbarkeit der Durchmesserbestimmung sowie der Volumen- und Wandspannungsberechnung anhand eines geometrischen Modells, basierend auf der Finite Elemente Methode.

    Methode:

    Computertomographische Daten von vier gesunden und zehn Patienten mit infrarenalen abdominellen Aneurysmen werden von drei unabhängigen Untersuchern analysiert. Die abdominelle Aorta wird semiautomatisch von Computertomographie-Angiographie (CTA) Bilddaten segmentiert, wobei zwei und drei-dimensionale aktive Konturmodelle, wie sie aus der Bildverarbeitung bekannt sind, zum Einsatz kommen. Der maximale Durchmesser (cernterline-basiert) sowie das aortale Volumen werden aus den rekonstruierten dreidimensionalen Modellen berechnet. Zusätzlich werden nicht-lineare Finite Elemente Modelle verwendet, um die mechanische Spannung in der Aortenwand zwischen der Aortenbifurkation und den Nierenarterien zu bestimmen. Zu diesen Zweck wird der mittlere arterielle Druck als Belastung

    angenommen und nicht-lineare isotrope Materialmodelle erfassen die mechanischen Eigenschaften der Aortenwand und des Thrombusgewebes.

    Die Intra- und Interobserver Variabilität der fünf Messungen des maximalen Durchmessers, des Volumens und der maximalen Wandspannung wurden durch die Berechnung des Variationskoeffizienten (CV=SD*100/Arithmethisches Mittel in %) ausgedrückt. Die methodische Variation berechnet sich aus der Abweichung des Duchmessers (mm), des Volumens (ml) und der maximalen Wandspannung (kPA) zwischen den drei Untersuchern.

    Ergebnisse:

    Die Reproduzierbarkeit gesunder Gefäßen lag bei einem Durchmesser zwischen 16.1mm und 16.6mm zwischen CV=2,5% und CV=4,9%. Das aortale Volumen lag zwischen 14ml und 15ml, die Reproduzierbarkeit bei den gesunden Gefäßen streute zwischen CV=5.8% und CV=11.5%. Die maximale Wandspannung variierte zwischen 53 kPA and 55 kPa, der CV% lag hierbei zwischen 3 und 13. Die Interobserver Variabilität lag < 10% für den Durchmesser, die Volumenbestimmung und die Bestimmung der maximale Wandspannung.

    Der maximale Durchmesser der Aorta bei 3 Patienten mit infrarenalem Aneurysma wurde mit durchschnittlich 58.9mm, 54.6mm und 71.2mm berechnet (Stand bei Abstracteinreichung). Der Variationskoeffizient zeigte dabei eine hohe Übereinstimmung mit Werten unter 5%. Das Volumen der Aneurysmen schwankte zwischen 130 ml und 300 ml (CV<10%), die berechnete Wandspannung lag zwischen 172 kPA und 296 kPA (CV<10%). Die Variabilität zwischen den drei Untersuchern betrug 0,7-6,0 mm für den Durchmesser, 11-28 ml für das Volumen und 4-27 kPA für die maximale Wandspannung.

    Zusammenfassung:

    Sowohl an gesunden als auch an degenerativ veränderten Gefäßen ergibt die Reproduzierbarkeit des Aortendurchmessers und des aortalen Volumens basierend auf dem dreidimensionalen rekonstruierten Modellen eine hohe Übereinstimmung. Die berechnete Wandspannung basierend auf den Finiten Elemente Modellen zeigt einen geringen Grad an Variabilität sowohl zwischen verschiedenen Untersuchern als auch bei wiederholter Messung. Daher könnten die Volumenbestimmung und die Analyse der Wandspannung zusätzliche Größen bei der Bestimmung des individuellen Rupturrisikos bei Patienten mit Aortenaneurysmen darstellen, um eine präzisere Indikationsstellung zu ermöglichen.

  • 49. Kiousis, D. E.
    et al.
    Rubinigg, S. F.
    Auer, M.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    A Methodology to Analyze Changes in Lipid Core and Calcification Onto Fibrous Cap Vulnerability: The Human Atherosclerotic Carotid Bifurcation as an Illustratory Example2009In: Journal of Biomechanical Engineering, ISSN 0148-0731, E-ISSN 1528-8951, Vol. 131, no 12Article in journal (Refereed)
    Abstract [en]

    A lipid core that occupies a high proportion of the plaque volume in addition to a thin fibrous cap is a predominant indicator of plaque vulnerability. Nowadays, noninvasive. imaging modalities can identify such structural components, however morphological criteria alone cannot reliably identify high-risk plaques. Information, such as stresses in the lesions components, seems to be essential. This work presents a methodology able to analyze the effect of changes in the lipid core and calcification on the wall stresses, in particular on the fibrous cap vulnerability. Using high-resolution magnetic resonance imaging and histology of an ex vivo human atherosclerotic carotid bifurcation, a patient is gen-specific three-dimensional geometric model, consisting of four tissue components, erated. The adopted constitutive model accounts for the nonlinear and anisotropic tissue behavior incorporating the collagen fiber orientation by means of a novel and robust algorithm. The material parameters are identified from experimental data. A novel stress-based computational cap vulnerability index is proposed to assess quantitatively the rupture-risk of fibrous caps. Nonlinear finite element analyses identify that the highest stress regions are located at the vicinity of the shoulders of the fibrous cap and in the stiff calcified tissue. A parametric analysis reveals a positive correlation between the increase in lipid core portion and the mechanical stress in the fibrous cap and, hence, the risk for cap rupture. The highest values of the vulnerability index, which cot-relate to more vulnerable caps, are obtained for morphologies for which the lipid cores were severe; heavily loaded fibrous caps were thus detected. The proposed multidisciplinary methodology is able to investigate quantitatively the mechanical behavior of atherosclerotic plaques in patient-specific stenoses. The introduced vulnerability index may serve as a more quantitative tool for diagnosis, treatment and prevention. [DOI: 10.1115/1.4000078]

  • 50. Kiousis, D.
    et al.
    Wulff, Alexander
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Experimental Studies and Numerical Analysis of the Inflation and Interaction of Vascular Balloon Catheter-Stent Systems2009In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 37, no 2, p. 315-330Article in journal (Refereed)
    Abstract [en]

    Balloon angioplasty with stenting is a well-established interventional procedure to treat stenotic arteries. Despite recent advances such as drug eluting stents, clinical studies suggest that stent design is linked to vascular injury. Additionally, dilation of the medical devices may trigger pathological responses such as growth and migration of vascular smooth cells, and may be a potent stimulus for neointimal hyperplasia. The purpose of this study is to experimentally investigate the mechanical characteristics of the transient expansion of six commercially available balloon-expandable stent systems, and to develop a robust finite element model based on the obtained experimental results. To reproduce the inflation of stent systems as in clinical practice, a pneumatic-hydraulic experimental setup is built, able to record loads and deformations. Characteristic pressure-diameter diagrams for the balloon-expandable stents and the detached balloons are experimentally obtained. Additionally, typical measures such as the burst opening pressure, the maximum dog-boning and foreshortening, and the elastic recoil are determined. The adopted constitutive models account for elastoplastic deformation of the stent, and for the nonlinear and anisotropic behavior of the balloon. The employed contact algorithm, based on a C (2)-continuous surface parametrization, efficiently simulates the interaction of the balloon and stent. The computational model is able to successfully capture the experimentally observed deformation mechanisms. Overall, the numerical results are in satisfactory agreement with experimental data.

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