Dalin Tang

3D MRI-Based Multicomponent FSI Models for Atherosclerotic Plaques

A three-dimensional (3D) MRI-based computational model with multicomponent plaque structure and fluid–structure interactions (FSI) is introduced to perform mechanical analysis for human atherosclerotic plaques and identify critical flow and stress/strain conditions which may be related to plaque rupture. Three-dimensional geometry of a human carotid plaque was reconstructed from 3D MR images and computational mesh was generated using Visualization Toolkit. Both the artery wall and the plaque components were assumed to be hyperelastic, isotropic, incompressible, and homogeneous. The flow was assumed to be laminar, Newtonian, viscous, and incompressible. The fully coupled fluid and structure models were solved by ADINA, a well-tested finite element package. Results from two-dimensional (2D) and 3D models, based on ex vivo MRI and histological images (HI), with different component sizes and plaque cap thickness, under different pressure and axial stretch conditions, were obtained and compared. Our results indicate that large lipid pools and thin plaque caps are associated with both extreme maximum (stretch) and minimum (compression when negative) stress/strain levels. Large cyclic stress/strain variations in the plaque under pulsating pressure were observed which may lead to artery fatigue and possible plaque rupture. Large-scale patient studies are needed to validate the computational findings for possible plaque vulnerability assessment and rupture predictions.

Sites of Rupture in Human Atherosclerotic Carotid Plaques Are Associated With High Structural Stresses An In Vivo MRI-Based 3D Fluid-Structure Interaction Study

Background and Purpose— It has been hypothesized that high structural stress in atherosclerotic plaques at critical sites may contribute to plaque disruption. To test that hypothesis, 3D fluid-structure interaction models were constructed based on in vivo MRI data of human atherosclerotic carotid plaques to assess structural stress behaviors of plaques with and without rupture. Methods— In vivo MRI data of carotid plaques from 12 patients scheduled for endarterectomy were acquired for model reconstruction. Histology confirmed that 5 of the 12 plaques had rupture. Plaque wall stress (PWS) and flow maximum shear stress were extracted from all nodal points on the lumen surface of each plaque for analysis. A critical PWS (maximum of PWS values from all possible vulnerable sites) was determined for each plaque. Results— Mean PWS from all ulcer nodes in ruptured plaques was 86% higher than that from all nonulcer nodes (123.0 versus 66.3 kPa, P<0.0001). Mean flow maximum shear stress from all ulcer nodes in ruptured plaques was 170% higher than that from all nonulcer nodes (38.9 versus 14.4 dyn/cm2, P<0.0001). Mean critical PWS from the 5 ruptured plaques was 126% higher than that from the 7 nonruptured ones (247.3 versus 108 kPa, P=0.0016 using log transformation). Conclusion— The results of this study show that plaques with prior ruptures are associated with higher critical stress conditions, both at ulcer sites and when compared with nonruptured plaques. With further validations, plaque stress analysis may provide additional stress indicators helpful for image-based plaque vulnerability assessment.

Effect of a Lipid Pool on Stress/Strain Distributions in Stenotic Arteries: 3-D Fluid-Structure Interactions (FSI) Models

Nonlinear 3-D models with fluid-structure interactions (FSI) based on in vitro experiments are introduced and solved by ADINA to perform flow and stress/strain analysis for stenotic arteries with lipid cores. Navier-Stokes equations are used as the governing equations for the fluid. Hyperelastic Mooney-Rivlin models are used for both the arteries and lipid cores. Our results indicate that critical plaque stress/strain conditions are affected considerably by stenosis severity, eccentricity, lipid pool size, shape and position, plaque cap thickness, axial stretch, pressure, and fluid-structure interactions, and may be used for possible plaque rupture predictions.

A Negative Correlation between Human Carotid Atherosclerotic Plaque Progression and Plaque Wall Stress: In Vivo MRI-Based 2D/3D FSI Models

It is well accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses (FSS). However, this mechanism cannot explain why advanced plaques continue to grow under elevated FSS conditions. In vivo magnetic resonance imaging (MRI)-based 2D/3D multi-component models with fluid-structure interactions (FSI, 3D only) for human carotid atherosclerotic plaques were introduced to quantify correlations between plaque progression measured by wall thickness increase (WTI) and plaque wall (structure) stress (PWS) conditions. A histologically validated multi-contrast MRI protocol was used to acquire multi-year in vivo MRI images. Our results using 2D models (200-700 data points/patient) indicated that 18 out of 21 patients studied showed significant negative correlation between WTI and PWS at time 2 (T2). The 95% confidence interval for the Pearson correlation coefficient is (-0.443,-0.246), p<0.0001. Our 3D FSI model supported the 2D correlation results and further indicated that combining both plaque structure stress and flow shear stress gave better approximation results (PWS, T2: R(2)=0.279; FSS, T1: R(2)=0.276; combining both: R(2)=0.637). These pilot studies suggest that both lower PWS and lower FSS may contribute to continued plaque progression and should be taken into consideration in future investigations of diseases related to atherosclerosis.

Local Maximal Stress Hypothesis and Computational Plaque Vulnerability Index for Atherosclerotic Plaque Assessment

It is believed that atherosclerotic plaque rupture may be related to maximal stress conditions in the plaque. More careful examination of stress distributions in plaques reveals that it may be the local stress/strain behaviors at critical sites such as very thin plaque cap and locations with plaque cap weakness that are more closely related to plaque rupture risk. A “local maximal stress hypothesis” and a stress-based computational plaque vulnerability index (CPVI) are proposed to assess plaque vulnerability. A critical site selection (CSS) method is proposed to identify critical sites in the plaque and critical stress conditions which are be used to determine CPVI values. Our initial results based on 34 2D MRI slices from 14 human coronary plaque samples indicate that CPVI plaque assessment has an 85% agreement rate (91% if the square root of stress values is used) with assessment given by histopathological analysis. Large-scale and long-term patient studies are needed to further validate our findings for more accurate quantitative plaque vulnerability assessment.

Effect of Stenosis Asymmetry on Blood Flow and Artery Compression: A Three-Dimensional Fluid-Structure Interaction Model

AbstractA nonlinear three-dimensional thick-wall model with fluid-structure interactions is introduced to simulate blood flow in carotid arteries with an asymmetric stenosis to quantify the effects of stenosis severity, eccentricity, and pressure conditions on blood flow and artery compression (compressive stress in the wall). Mechanical properties of the tube wall are measured using a thick-wall stenosis model made of polyvinyl alcohal hydrogel whose mechanical properties are close to that of carotid arteries. A hyperelastic Mooney–Rivlin model is used to implement the experimentally measured nonlinear elastic properties of the tube wall. A 36.5% pre-axial stretch is applied to make the simulation physiological. The Navier–Stokes equations in curvilinear form are used for the fluid model. Our results indicate that severe stenosis causes critical flow conditions, high tensile stress, and considerable compressive stress in the stenosis plaque which may be related to artery compression and plaque cap rupture. Stenosis asymmetry leads to higher artery compression, higher shear stress and a larger flow separation region. Computational results are verified by available experimental data.

Quantifying Effects of Plaque Structure and Material Properties on Stress Distributions in Human Atherosclerotic Plaques Using 3D FSI Models

BACKGROUND Atherosclerotic plaques may rupture without warning and cause acute cardiovascular syndromes such as heart attack and stroke. Methods to assess plaque vulnerability noninvasively and predict possible plaque rupture are urgently needed. METHOD MRI-based three-dimensional unsteady models for human atherosclerotic plaques with multi-component plaque structure and fluid-structure interactions are introduced to perform mechanical analysis for human atherosclerotic plaques. RESULTS Stress variations on critical sites such as a thin cap in the plaque can be 300% higher than that at other normal sites. Large calcification block considerably changes stress/strain distributions. Stiffness variations of plaque components (50% reduction or 100% increase) may affect maximal stress values by 20-50%. Plaque cap erosion causes almost no change on maximal stress level at the cap, but leads to 50% increase in maximal strain value. CONCLUSIONS Effects caused by atherosclerotic plaque structure, cap thickness and erosion, material properties, and pulsating pressure conditions on stress/strain distributions in the plaque are quantified by extensive computational case studies and parameter evaluations. Computational mechanical analysis has good potential to improve accuracy of plaque vulnerability assessment.

Steady Flow and Wall Compression in Stenotic Arteries: A Three-Dimensional Thick-Wall Model With Fluid–Wall Interactions

Severe stenosis may cause critical flow and wall mechanical conditions related to artery fatigue, artery compression, and plaque rupture, which leads directly to heart attack and stroke. The exact mechanism involved is not well understood. In this paper a nonlinear three-dimensional thick-wall model with fluid-wall interactions is introduced to simulate blood flow in carotid arteries with stenosis and to quantify physiological conditions under which wall compression or even collapse may occur. The mechanical properties of the tube wall were selected to match a thick-wall stenosis model made of PVA hydrogel. The experimentally measured nonlinear stress-strain relationship is implemented in the computational model using an incremental linear elasticity approach. The Navier-Stokes equations are used for the fluid model. An incremental boundary iteration method is used to handle the fluid-wall interactions. Our results indicate that severe stenosis causes considerable compressive stress in the tube wall and critical flow conditions such as negative pressure, high shear stress, and flow separation which may be related to artery compression, plaque cap rupture, platelet activation, and thrombus formation. The stress distribution has a very localized pattern and both maximum tensile stress (five times higher than normal average stress) and maximum compressive stress occur inside the stenotic section. Wall deformation, flow rates, and true severities of the stenosis under different pressure conditions are calculated and compared with experimental measurements and reasonable agreement is found.

A 3-D thin-wall model with fluid–structure interactions for blood flow in carotid arteries with symmetric and asymmetric stenoses

Abstract Severe stenosis may lead to critical flow conditions related to artery collapse, plaque cap rupture which lead directly to stroke and heart attack. A three-dimensional (3-D) thin-wall model with flow-structure interactions was introduced and solved using ADINA to investigate the wall deformation and flow properties of blood flow in carotid arteries with symmetric and asymmetric stenoses. The Navier–Stokes equations were used as the governing equations for the fluid. The tube wall was assumed to be hyperelastic, homogeneous, isotropic and incompressible. The nonlinear large strain Ogden material model was used for the wall with the elastic properties determined experimentally for a silicone tube with a 78% stenosis by diameter. The results revealed that the behaviors of the 3-D flow pressure, velocity and shear stress fields are very different from those of 2-D models. Stenosis severity and asymmetry have considerable effects on those critical flow conditions such as negative pressure and high shear stress were found which may be related to artery collapse and plaque rupture.

An Experimental Study on the Ultimate Strength of the Adventitia and Media of Human Atherosclerotic Carotid Arteries in Circumferential and Axial Directions

Atherosclerotic plaque may rupture without warning causing heart attack or stroke. Knowledge of the ultimate strength of human atherosclerotic tissues is essential for understanding the rupture mechanism and predicting cardiovascular events. Despite its great importance, experimental data on ultimate strength of human atherosclerotic carotid artery remains very sparse. This study determined the uniaxial tensile strength of human carotid artery sections containing type II and III lesions (AHA classifications). Axial and circumferential oriented adventitia, media and intact specimens (total=73) were prepared from 6 arteries. The ultimate strength in uniaxial tension was taken as the peak stress recorded when the specimen showed the first evidence of failure and the extensibility was taken as the stretch ratio at failure. The mean adventitia strength values calculated using the first Piola-Kirchoff stress were 1996+/-867 and 1802+/-703 kPa in the axial and circumferential directions respectively, while the corresponding values for the media sections were 519+/-270 and 1230+/-533 kPa. The intact specimens showed ultimate strengths similar to media in circumferential direction but were twice as strong as the media in the axial direction. Results also indicated that adventitia, media and intact specimens exhibited similar extensibility at failure, in both the axial and circumferential directions (stretch ratio 1.50+/-0.22). These measurements of the material strength limits for human atherosclerotic carotid arteries could be useful in improving computational models that assess plaque vulnerability.