risk stratification in carotid atheroma: which is more important for patient selection, luminaal...

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$640 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) and stress in the ECM during cyst formation. Results from a case study showed detailed information regarding the mechanical interactions between cells and ECM. Information such as the magnitudes and directions of stresses and displacements at any point in the ECM, as well as the forces acting on the surface of a cell or cell aggregate was obtained at the cellular level through the entire course of cyst formation and with high time resolution during lumen formation, Forces exerted on a force-sensor array were measured and compared against computational results to validate our numerical model. The forces we detected during cystogenesis are in the nano Newton (nN) range and represent the first validated forces in the 3D space. 7524 We-Th, no. 3 (P67) Geometric changes in heart valve interstitial cell nuclei with transvalvular pressure H.-'~S. Huang, M.S. Sacks. Department of Bioengineering, University of Pittsburgh, USA Valvular tissue fiber architecture is related to mechanical loading of the tissue, however how the cells respond to the surrounded fiber network re-orientation are still unclear. The deformation of aortic valve interstitial cells (AVIC) under various physiological relevant transvalvular pressures were investigated in this study. Aspect ratios of AVIC within different layers of the tissue were quantified and ANOVA F-distribution statistical analyses were performed due to our special nested specimen database. Finite element method was utilized to further study the interaction of cell and tissue; the model was created containing only one AVIC nucleus embedded in the surrounding extracellular matrix (ECM). The increasing aspect ratio of cellular nucleus within the increas- ing transvalvular pressure was observed and quantitative layer specific AVIC nuclei aspect ratio was found. Furthermore, a coupling exit between the AVIC nuclei and fiber network response to the transvalvular pressure were related to the previous experimental findings. While fiber straightening and un-crimping effects were well-studied between 0 and 4 mmHg in our laboratory, additional fiber micromechanical events and fiber-compaction under higher pressure levels might induce AVIC nuclei deformation. This information forms the basis of an interaction of AVIC nuclei and ECM and leads to an understanding of AVIC nucleus capable of responding to mechanical stimulation. 4179 We-Th, no. 4 (P67) Matrix remodeling is essential for chondrocyte hypertrophy R.C.C. van Donkelaar, W. Wilson. Dept Biomedical Engineering, Eindhoven University of Technology, Netherlands Introduction: The ultimate size of hypertrophic growth-plate chondrocytes is decisive for the rate of longitudinal bone growth [1]. Since hypertrophy is constrained by straining of extracellular collagen, we hypothesize that collagen remodeling is required for chondrocytes to reach their ultimate size. In vivo, the presence of MMP's in the hypertrophic zone indicates active collagen degradation, and ongoing synthesis is apparent from the increase of extra- cellular matrix volume and collagen fraction in the hypertrophic zone [1,2]. We aim to assess the importance of matrix remodeling for the ultimate size of hypertrophic chondrocytes. Method: For this study we adopted a finite-element model for cartilage, which contains descriptions of swelling and collagen-reinforcement [3]. Matrix remodeling is incorporated by incrementally updating the original lengths of collagen fibers at varying locations. Additionally, collagen and proteoglycan volumes are gradually changed in time to represent changes in total content. Hypertrophy is induced by gradually changing intracellular fixed charges. Hypertrophy of a single chondrocyte with its associated pericellular and in- terterritorial matrices is simulated. Initial volumes and collagen fractions of the chondrocyte and the matrices, as well as changes in collagen and proteoglycan contents during hypertrophy, are obtained from the literature [2]. Simulations differ with regard to the rate of collagen remodeling. Results: In all simulations the chondrocytes change from disc-like to the characteristic cubic shape. Without collagen remodeling the cell increases volume on the expense of pericellular and interterritorial matrix volumes. The cell hardly increases in height. Total tissue height increases 8%. At optimized collagen remodeling rates, volumes and dimensions of cell and matrix compartments as well as collagen fractions, are in agreement with the literature [2]. Conclusion: A new remodeling algorithm was applied to the matrix around hypertrophying chondrocytes. It was concluded that collagen remodeling is essential for physiological longitudinal bone growth. References [1] Wilsman. JOR 1996; 14: 927-936. [2] Noonan. JOR 1998; 16: 500-508. [3] Wilson. J Biomech 2005; 38: 1195-1204. Poster Presentations 4302 We-Th, no. 5 (P67) Numerical analysis of thrombolytic characteristics of the arterial and venous thrombus for different injection methods K. Rhee 1, W.W. Jeong 1, G. Khang 2. 1Department of Mechanical Engineering, Myongji University, Yongin, Korea, 2Department of Biomedical Engineering, Kyunghee University, Yongin, Korea In order to dissolve a blood clot and restore the patency of a blood vessel, various treatments have been used. Direct or intravenous injection of throm- bolytic agents, such as tissue plasminogen activator (tPA), urokinase(uPA), streptokinase (SK), has been used for the treatment of thrombosis. Direct injection of thrombolytic agents to the clot with high speed may increase the effectiveness of thrombolysis by enhancing the permeation of a thrombolytic agent into the blood clot. Injection velocity and methodology, such as con- tinuous infuson and pulsed injection, would affect the thrombolytic efficiecy. In order to explore the effectivenesss of injection methods, we modelled thrombolysis numerically. Species transport equation was solved along with the three dimensional momentum equations. The blood clot was modelled as a prorous media. Pressure, velocity and species concentration fields were calcualted by computational fluid mechanics methods. Two different thrombus models - arterial and venous thrombus - were simulated. The results showed that thrombolytic speed increased as the injection velocity increased, and inter- mittent injection was more efficient in dissolving clots comparing to comtinuous perfusion. 4635 We-Th, no. 6 (P68) Risk stratification in carotid atheroma: which is more important for patient selection, luminal stenosis or plaque morphology? Z.-'~ Li 1,2, J.H. Gillard 1. Departments of 1Radiology and 2Engineering, University of Cambridge, UK Background: Approximately 60% of strokes are caused by rupture of carotid plaques. Such strokes are potentially preventable by carotid interventions such as carotid endarterectomy, angioplasty or stenting. Selection of patients for intervention is currently based on the severity of carotid luminal stenosis. It has been, however, widely accepted that luminal stenosis alone may not be an adequate predictor of risk. Factors such as fibrous cap thickness and biomechanical stress are increasingly thought to be other important risk factors for plaque rupture. To evaluate the effects of degree of luminal stenosis and fibrous cap thickness on plaque stability, we used a flow-structure interaction model and simulated the interaction between blood flow and atheromatous plaque in the modelled carotid artery. Methods: A nonlinear time-dependent fluid-structure interaction model was used to perform flow and stress/strain analysis in modelled stenotic arteries. The Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian (ALE) for- mulation were used as the governing equations for the fluid. Large deformation transient analysis was used for the simulation of the interaction between fibrous cap and lipid pool. The plaque Principal stresses and flow conditions were calculated for every case when varying the fibrous cap thickness from 0.15 mm to 3 mm and the degree of luminal stenosis from 10% to 90%. Principal stress within the fibrous cap was taken to indicate plaque vulnerability. Results: Severe stenosis led to high flow velocities and high shear stresses, but a low or even negative pressure at the throat of the stenosis. Higher degree of stenosis and thinner fibrous cap led to larger plaque stresses. A 50% decrease of fibrous cap thickness resulted in a 40% increase of maximal stress. Conclusions: This model suggests that fibrous cap thickness is critically related to plaque vulnerability and that, even within presence of moderate stenosis, may play an important role in the future risk stratification of those patients when identified in vivo using high resolution MR imaging. 6026 We-Th, no. 7 (P68) Computational analysis of drug-eluting stents, from deployment to drug delivery D. Berry 1, V. Dhurva 2, M. Horner 3, R. Kroeger 4, S. Sett 1, S. Stewart 5. 1Abaqus Inc., Providence, RI, USA, 2Abaqus Central, West Lafayette, IN, USA, 3Fluent Inc., Evanston, IL, USA, 4Fluent Deutschland, Darmstadt, Germany, 5USFDA Center for Devices and Radiologic Health, Gaithersburg, MD, USA A computational analysis of the deployment and drug delivery from a proto- typical cardiovascular stent is analyzed. The simulation begins with the unde- ployed stent present in a section of cylindrical artery. ABAQUS v. 6.5 (Abaqus Inc., Providence, RI) is used to deploy the stent to the vessel wall. Full contact is permitted in the simulation, therefore the stresses predicted by this model may be considered a realistic representation of those present at the end of an actual deployment. The drug elution process is modeled with FLUENT v. 6.3 (Fluent Inc., Lebanon, NH). A two-species model is used to capture the partitioning of the hydrophobic

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Page 1: Risk stratification in carotid atheroma: which is more important for patient selection, luminaal stenosis or plaque morphology?

$640 Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)

and stress in the ECM during cyst formation. Results from a case study showed detailed information regarding the mechanical interactions between cells and ECM. Information such as the magnitudes and directions of stresses and displacements at any point in the ECM, as well as the forces acting on the surface of a cell or cell aggregate was obtained at the cellular level through the entire course of cyst formation and with high time resolution during lumen formation, Forces exerted on a force-sensor array were measured and compared against computational results to validate our numerical model. The forces we detected during cystogenesis are in the nano Newton (nN) range and represent the first validated forces in the 3D space.

7524 We-Th, no. 3 (P67) Geometric changes in heart valve interstitial cell nuclei with transvalvular pressure H.-'~S. Huang, M.S. Sacks. Department of Bioengineering, University of Pittsburgh, USA

Valvular tissue fiber architecture is related to mechanical loading of the tissue, however how the cells respond to the surrounded fiber network re-orientation are still unclear. The deformation of aortic valve interstitial cells (AVIC) under various physiological relevant transvalvular pressures were investigated in this study. Aspect ratios of AVIC within different layers of the tissue were quantified and ANOVA F-distribution statistical analyses were performed due to our special nested specimen database. Finite element method was utilized to further study the interaction of cell and tissue; the model was created containing only one AVIC nucleus embedded in the surrounding extracellular matrix (ECM). The increasing aspect ratio of cellular nucleus within the increas- ing transvalvular pressure was observed and quantitative layer specific AVIC nuclei aspect ratio was found. Furthermore, a coupling exit between the AVIC nuclei and fiber network response to the transvalvular pressure were related to the previous experimental findings. While fiber straightening and un-crimping effects were well-studied between 0 and 4 mmHg in our laboratory, additional fiber micromechanical events and fiber-compaction under higher pressure levels might induce AVIC nuclei deformation. This information forms the basis of an interaction of AVIC nuclei and ECM and leads to an understanding of AVIC nucleus capable of responding to mechanical stimulation.

4179 We-Th, no. 4 (P67) Matrix remodeling is essential for chondrocyte hypertrophy R.C.C. van Donkelaar, W. Wilson. Dept Biomedical Engineering, Eindhoven University of Technology, Netherlands

Introduction: The ultimate size of hypertrophic growth-plate chondrocytes is decisive for the rate of longitudinal bone growth [1]. Since hypertrophy is constrained by straining of extracellular collagen, we hypothesize that collagen remodeling is required for chondrocytes to reach their ultimate size. In vivo, the presence of MMP's in the hypertrophic zone indicates active collagen degradation, and ongoing synthesis is apparent from the increase of extra- cellular matrix volume and collagen fraction in the hypertrophic zone [1,2]. We aim to assess the importance of matrix remodeling for the ultimate size of hypertrophic chondrocytes. Method: For this study we adopted a finite-element model for cartilage, which contains descriptions of swelling and collagen-reinforcement [3]. Matrix remodeling is incorporated by incrementally updating the original lengths of collagen fibers at varying locations. Additionally, collagen and proteoglycan volumes are gradually changed in time to represent changes in total content. Hypertrophy is induced by gradually changing intracellular fixed charges. Hypertrophy of a single chondrocyte with its associated pericellular and in- terterritorial matrices is simulated. Initial volumes and collagen fractions of the chondrocyte and the matrices, as well as changes in collagen and proteoglycan contents during hypertrophy, are obtained from the literature [2]. Simulations differ with regard to the rate of collagen remodeling. Results: In all simulations the chondrocytes change from disc-like to the characteristic cubic shape. Without collagen remodeling the cell increases volume on the expense of pericellular and interterritorial matrix volumes. The cell hardly increases in height. Total tissue height increases 8%. At optimized collagen remodeling rates, volumes and dimensions of cell and matrix compartments as well as collagen fractions, are in agreement with the literature [2]. Conclusion: A new remodeling algorithm was applied to the matrix around hypertrophying chondrocytes. It was concluded that collagen remodeling is essential for physiological longitudinal bone growth.

References [1] Wilsman. JOR 1996; 14: 927-936. [2] Noonan. JOR 1998; 16: 500-508. [3] Wilson. J Biomech 2005; 38: 1195-1204.

Poster Presentations

4302 We-Th, no. 5 (P67) Numerical analysis of thrombolytic characteristics of the arterial and venous thrombus for different injection methods K. Rhee 1 , W.W. Jeong 1 , G. Khang 2. 1Department of Mechanical Engineering, Myongji University, Yongin, Korea, 2Department of Biomedical Engineering, Kyunghee University, Yongin, Korea

In order to dissolve a blood clot and restore the patency of a blood vessel, various treatments have been used. Direct or intravenous injection of throm- bolytic agents, such as tissue plasminogen activator (tPA), urokinase(uPA), streptokinase (SK), has been used for the treatment of thrombosis. Direct injection of thrombolytic agents to the clot with high speed may increase the effectiveness of thrombolysis by enhancing the permeation of a thrombolytic agent into the blood clot. Injection velocity and methodology, such as con- tinuous infuson and pulsed injection, would affect the thrombolytic efficiecy. In order to explore the effectivenesss of injection methods, we modelled thrombolysis numerically. Species transport equation was solved along with the three dimensional momentum equations. The blood clot was modelled as a prorous media. Pressure, velocity and species concentration fields were calcualted by computational fluid mechanics methods. Two different thrombus models - arterial and venous thrombus - were simulated. The results showed that thrombolytic speed increased as the injection velocity increased, and inter- mittent injection was more efficient in dissolving clots comparing to comtinuous perfusion.

4635 We-Th, no. 6 (P68) Risk strat i f icat ion in carotid atheroma: which is more important for patient selection, luminal stenosis or plaque morphology? Z.-'~ Li 1,2, J.H. Gillard 1 . Departments of 1Radiology and 2Engineering, University of Cambridge, UK

Background: Approximately 60% of strokes are caused by rupture of carotid plaques. Such strokes are potentially preventable by carotid interventions such as carotid endarterectomy, angioplasty or stenting. Selection of patients for intervention is currently based on the severity of carotid luminal stenosis. It has been, however, widely accepted that luminal stenosis alone may not be an adequate predictor of risk. Factors such as fibrous cap thickness and biomechanical stress are increasingly thought to be other important risk factors for plaque rupture. To evaluate the effects of degree of luminal stenosis and fibrous cap thickness on plaque stability, we used a flow-structure interaction model and simulated the interaction between blood flow and atheromatous plaque in the modelled carotid artery. Methods: A nonlinear time-dependent fluid-structure interaction model was used to perform flow and stress/strain analysis in modelled stenotic arteries. The Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian (ALE) for- mulation were used as the governing equations for the fluid. Large deformation transient analysis was used for the simulation of the interaction between fibrous cap and lipid pool. The plaque Principal stresses and flow conditions were calculated for every case when varying the fibrous cap thickness from 0.15 mm to 3 mm and the degree of luminal stenosis from 10% to 90%. Principal stress within the fibrous cap was taken to indicate plaque vulnerability. Results: Severe stenosis led to high flow velocities and high shear stresses, but a low or even negative pressure at the throat of the stenosis. Higher degree of stenosis and thinner fibrous cap led to larger plaque stresses. A 50% decrease of fibrous cap thickness resulted in a 40% increase of maximal stress. Conclusions: This model suggests that fibrous cap thickness is critically related to plaque vulnerability and that, even within presence of moderate stenosis, may play an important role in the future risk stratification of those patients when identified in vivo using high resolution MR imaging.

6026 We-Th, no. 7 (P68) Computational analysis of drug-elut ing stents, from deployment to drug delivery D. Berry 1 , V. Dhurva 2, M. Horner 3, R. Kroeger 4, S. Sett 1 , S. Stewart 5. 1Abaqus Inc., Providence, RI, USA, 2Abaqus Central, West Lafayette, IN, USA, 3Fluent Inc., Evanston, IL, USA, 4Fluent Deutschland, Darmstadt, Germany, 5 USFDA Center for Devices and Radiologic Health, Gaithersburg, MD, USA

A computational analysis of the deployment and drug delivery from a proto- typical cardiovascular stent is analyzed. The simulation begins with the unde- ployed stent present in a section of cylindrical artery. ABAQUS v. 6.5 (Abaqus Inc., Providence, RI) is used to deploy the stent to the vessel wall. Full contact is permitted in the simulation, therefore the stresses predicted by this model may be considered a realistic representation of those present at the end of an actual deployment. The drug elution process is modeled with FLUENT v. 6.3 (Fluent Inc., Lebanon, NH). A two-species model is used to capture the partitioning of the hydrophobic