In Vivo MRI-Based Three-Dimensional Fluid-Structure Interaction Models and Mechanical Image Analysis for Human Carotid Atherosclerotic Plaques

Introduction. Atherosclerotic plaque rupture may occur without warning leading to severe clinical events such as heart attack and stroke. The mechanisms causing plaque rupture are not well understood. It is hypothesized that mechanical forces may play an important role in the plaque rupture process and that image-based computational mechanical analysis may provide useful information for more accurate plaque vulnerability assessment. The objectives of this dissertation are: a) develop in vivo magnetic resonance imaging (MRI)-based 3D computational models with fluid-structure Interactions (FSI) for human atherosclerotic carotid plaques; b) perform mechanical analysis using 3D FSI models to identify critical stress/strain conditions which may be used for possible plaque rupture predictions. Data, Model, and Methods. Histological, ex vivo/ in vivo MRI data of human carotid plaques were provided by the University of Washington Medical School and Washington University Medical School. Blood flow was assumed to be laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations for the flow model. The vessel and plaque components were assumed to be hyperelastic, isotropic, nearly-incompressible and homogeneous. The nonlinear Mooney-Rivlin model was used to describe the nonlinear properties of the materials with parameter values chosen to match available experimental data. The fully-coupled FSI models were solved by a commercial finite element software ADINA to obtain full 3D flow and stress/strain distributions for analysis. Validation of the computational models and Adina software were provided by comparing computational solutions with analytic solutions and experimental data. Several novel methods were introduced to address some fundamental issues for construction of in vivo MRI-based 3D FSI models: a) an automated MRI segmentation technique using a Bayes theorem with normal probability distribution was implemented to obtain plaque geometry with enclosed components; b) a pre-shrink process was introduced to shrink the in vivo MRI geometry to obtain the no-load shape of the plaque; c) a Volume Component-Fitting Method was introduced to generate a 3D computational mesh for the plaque model with deformable complex geometry, FSI and inclusions; d) a method using MRI data obtained under in vitro pressurized conditions was introduced to determine vessel material properties. Results. The effects of material properties on flow and wall stress/strain behaviors were evaluated. The results indicate that a 100% stiffness increase may decrease maximal values of maximum principal stress (Stress-P1) and maximum principal strain (Strain-P1) by about 20% and 40%, respectively; flow Maximum-Shear-Stress (FMSS) and flow velocity did not show noticeable changes. By comparing ex vivo and in vivo data of 10 plaque samples, the average axial (25%) and inner circumferential (7.9%) shrinkages of the plaques between loaded and unloaded state were obtained. Effects of the shrink-stretch process on plaque stress/strain distributions were demonstrated based on six adjusted 3D FSI models with different shrinkages. Stress-P1 and Strain-P1 increased 349.8% and 249% respectively with 33% axial stretch. The effects of a lipid-rich necrotic core and fibrous cap thickness on structure/flow behaviors were investigated. The mean values of wall Stress-P1 and Strain-P1 from lipid nodes from a ruptured plaque were significantly higher than those from a non-ruptured plaque (112.3 kPa, 0.235 & 80.1 kPa, 0.185), which was 40.2% and 26.8% higher, respectively (p\u3c0.001). High stress/strain concentrations were found at the thin fibrous cap regions. These results indicate that high stress concentrations and thin fibrous cap thickness might be critical indicators for plaque vulnerability. Conclusion. In vivo image-based 3D FSI models and mechanical image analysis may have the potential to provide quantitative risk indicators for plaque vulnerability assessment

Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3D fluid-structure interaction study.

BACKGROUND: Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and flow shear stress (FSS). METHODS: In vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear Stress (FSS) were extracted from all nodal points on the lumen surface of each plaque for analysis. RESULTS: The mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5) than those from non-hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the 5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0 versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance. CONCLUSION: The results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage) linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide additional stress indicators for image-based vulnerability assessment.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Carotid plaque stress analysis by fluid structure interaction based on in-vivo MRI: Implications to plaque vulnerability assessment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University, 2010.Stroke is one of the leading causes of death in the world, resulting mostly from the sudden rupture of atherosclerotic plaques. From a biomechanical view, plaque rupture can be considered as a mechanical failure caused by extremely high plaque stress. In this PhD project, we are aiming to predict 3D plaque stress based on in-vivo MRI by using fluid structure interaction (FSI) method, and provide information for plaque rupture risk assessment. Fluid structure interaction was implemented with ANSYS 11.0, followed by a parameter study on fibrous cap thickness and lipid core size with realistic carotid plaque geometry. Twenty patients with carotid plaques imaged by in-vivo MRI were provided in the project. A framework of reconstructing 3D plaque geometry from in-vivo multispectral MRI was designed. The followed reproducibility study on plaque geometry reconstruction procedure and its effect on plaque stress analysis filled the gap in the literature on imaging based plaque stress modeling. The results demonstrated that current MRI technology can provide sufficient information for plaque structure characterization; however stress analysis result is highly affected by MRI resolution and quality. The application of FSI stress analysis to 4 patients with different plaque burdens has showed that the whole procedure from plaque geometry reconstruction to FSI stress analysis was applicable. In the study, plaque geometries from three patients with recent transient ischemic attack were reconstructed by repairing ruptured fibrous cap. The well correlated relationship between local stress concentrations and plaque rupture sites indicated that extremely high plaque stress could be a factor responsible for plaque rupture. Based on the 20 reconstructed carotid plaques from two groups (symptomatic and asymptomatic), fully coupled fluid structure interaction was performed. It was found that there is a significant difference between symptomatic and asymptomatic patients in plaque stress levels, indicating plaque stress could be used as one of the factors for plaque vulnerability assessment. A corresponding plaque morphological feature study showed that plaque stress is significantly affected by fibrous cap thickness, lipid core size and fibrous cap surface irregularities (curvedness). A procedure was proposed for predicting plaque stress by using fibrous cap thickness and curvedness, which requires much less computational time, and has the potential for clinical routine application. The effects of residual stress on plaque stress analysis and arterial wall material property characterization by using in-vivo MRI data were also discussed for patient specific modeling. As the further development, histological study of plaque sample has been combined with conventional plaque stress analysis by assigning material properties to each computational element, based on the data from histological analysis. This method could bridge the gap between biochemistry and biomechanical study of atherosclerosis plaques. In conclusion, extreme stress distributions in the plaque region can be predicted by modern numerical methods, and used for plaque rupture risk assessment, which will be helpful in clinical practice. The combination of plaque MR imaging analysis, computational modelling, and clinical study/ validation would advance our understandings of plaque rupture, prediction of future rupture, and establish new procedures for patient diagnose, management, and treatment.Financial Support was obtained from British Heart Foundation, Brunel Institute for Bioengineering and Brunel Graduate School

A numerical parametric study of the mechanical action of pulsatile blood flow onto axisymmetric stenosed arteries

International audienceIn the present paper, a fluid-structure interaction model is developed, questioning how the mechanical action of the blood onto an atheromatous plaque is affected by the length and the severity of the stenosis. An axisymmetric model is considered. The fluid is assumed Newtonian. The plaque is modelled as a heterogeneous hyperelastic anisotropic solid composed of the arterial wall, the lipid core and the fibrous cap. Transient velocity and pressure conditions of actual pulsatile blood flow are prescribed. The simulation is achieved using the Arbitrary Lagrangian Eulerian scheme in the COMSOL commercial Finite Element package. The results reveal different types of behavior in function of the length (denoted L) and severity (denoted S) of the stenosis. Whereas large plaques (L > 10 mm) are mostly deformed under the action of the blood pressure, it appears that shorter plaques (L < 10 mm) are significantly affected by the shear stresses. The shear stresses tend to deform the plaque by pinching it. This effect is called: "the pinching effect". It has an essential influence on the mechanical response of the plaque. For two plaques having the same radius severity S = 45%, the maximum stress in the fibrous cap is 50% larger for the short plaque (L = 5 mm) than for a larger plaque (L = 10 mm), and the maximum wall shear stress is increased by 100%. Provided that they are confirmed by experimental investigations, these results may offer some new perspectives for understanding the vulnerability of short plaques

Evolution and rupture of vulnerable plaques: a review of mechanical effects

Atherosclerosis occurs as a result of the buildup and infiltration of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is of critical importance, since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those that rupture (vulnerable) and those that are less likely to rupture (stable). In the last few decades, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces, and structural stress) on the plaque formation and rupture processes. In the literature, physiological experimental studies are limited by the complexity of in vivo experiments to study such effects, whereas the numerical approach often uses simplified models compared with realistic conditions, so that no general agreement of the mechanisms responsible for plaque formation has yet been reached. In addition, in a large number of cases, the presence of plaques in arteries is asymptomatic. The prediction of plaque rupture remains a complex question to elucidate, not only because of the interaction of numerous phenomena involved in this process (biological, chemical, and mechanical) but also because of the large time scale on which plaques develop. The purpose of the present article is to review the current mechanical models used to describe the blood flow in arteries in the presence of plaques, as well as reviewing the literature treating the influence of mechanical effects on plaque formation, development, and rupture. Finally, some directions of research, including those being undertaken by the authors, are described

Morphological and stress vulnerability indices for human coronary plaques and their correlations with cap thickness and lipid percent: An IVUS-based fluid-structure interaction multi-patient study

Plaque vulnerability, defined as the likelihood that a plaque would rupture, is difficult to quantify due to lack of in vivo plaque rupture data. Morphological and stress-based plaque vulnerability indices were introduced as alternatives to obtain quantitative vulnerability assessment. Correlations between these indices and key plaque features were investigated. In vivo intravascular ultrasound (IVUS) data were acquired from 14 patients and IVUS-based 3D fluid-structure interaction (FSI) coronary plaque models with cyclic bending were constructed to obtain plaque wall stress/strain and flow shear stress for analysis. For the 617 slices from the 14 patients, lipid percentage, min cap thickness, critical plaque wall stress (CPWS), strain (CPWSn) and flow shear stress (CFSS) were recorded, and cap index, lipid index and morphological index were assigned to each slice using methods consistent with American Heart Association (AHA) plaque classification schemes. A stress index was introduced based on CPWS. Linear Mixed-Effects (LME) models were used to analyze the correlations between the mechanical and morphological indices and key morphological factors associated with plaque rupture. Our results indicated that for all 617 slices, CPWS correlated with min cap thickness, cap index, morphological index with r = -0.6414, 0.7852, and 0.7411 respectively (p<0.0001). The correlation between CPWS and lipid percentage, lipid index were weaker (r = 0.2445, r = 0.2338, p<0.0001). Stress index correlated with cap index, lipid index, morphological index positively with r = 0.8185, 0.3067, and 0.7715, respectively, all with p<0.0001. For all 617 slices, the stress index has 66.77% agreement with morphological index. Morphological and stress indices may serve as quantitative plaque vulnerability assessment supported by their strong correlations with morphological features associated with plaque rupture. Differences between the two indices may lead to better plaque assessment schemes when both indices were jointly used with further validations from clinical studies

Role of biomechanical forces in the natural history of coronary atherosclerosis.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203

Impact of flow rates in a cardiac cycle on correlations between advanced human carotid plaque progression and mechanical flow shear stress and plaque wall stress

<p>Abstract</p> <p>Background</p> <p>Mechanical stresses are known to play important roles in atherosclerotic plaque initiation, progression and rupture. It has been well-accepted that atherosclerosis initiation and early progression correlate negatively with flow wall shear stresses (FSS). However, mechanisms governing <it>advanced </it>plaque progression are not well understood.</p> <p>Method</p> <p>In vivo serial MRI data (patient follow-up) were acquired from 14 patients after informed consent. Each patient had 2-4 scans (scan interval: 18 months). Thirty-two scan pairs (baseline and follow-up scans) were formed with slices matched for model construction and analysis. Each scan pair had 4-10 matched slices which gave 400-1000 data points for analysis (100 points per slice on lumen). Point-wise plaque progression was defined as the wall thickness increase (WTI) at each data point. 3D computational models with fluid-structure interactions were constructed based on in vivo serial MRI data to extract flow shear stress and plaque wall stress (PWS) on all data points to quantify correlations between plaque progression and mechanical stresses (FSS and PWS). FSS and PWS data corresponding to both maximum and minimum flow rates in a cardiac cycle were used to investigate the impact of flow rates on those correlations.</p> <p>Results</p> <p>Using follow-up scans and maximum flow rates, 19 out of 32 scan pairs showed a significant <it>positive </it>correlation between WTI and FSS (positive/negative/no significance correlation ratio = 19/9/4), and 26 out of 32 scan pairs showed a significant <it>negative </it>correlation between WTI and PWS (correlation ratio = 2/26/4). Corresponding to minimum flow rates, the correlation ratio for WTI vs. FSS and WTI vs. PWS were (20/7/5) and (2/26/4), respectively. Using baseline scans, the correlation ratios for WTI vs. FSS were (10/12/10) and (9/13/10) for maximum and minimum flow rates, respectively. The correlation ratios for WTI vs. PWS were the same (18/5/9), corresponding to maximum and minimum flow rates.</p> <p>Conclusion</p> <p>Flow shear stress corresponding to the minimum flow rates in a cardiac cycle had slightly better correlation with WTI, compared to FSS corresponding to maximum flow rates. Choice of maximum or minimum flow rates had no impact on PWS correlations. Advanced plaque progression correlated positively with flow shear stress and negatively with plaque wall stress using follow-up scans. Correlation results using FSS at the baseline scan were inconclusive.</p

Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: An IVUS-based fluid-structure interaction multi-patient study

BACKGROUND: Atherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions. METHODS: IVUS data were acquired from 10 patients after voluntary informed consent. The X-ray angiogram was obtained prior to the pullback of the IVUS catheter to determine the location of the coronary artery stenosis, vessel curvature and cardiac motion. Cyclic bending was specified in the model representing the effect by heart contraction. 3D anisotropic FSI models were constructed and solved to obtain flow shear stress (FSS) and plaque wall stress (PWS) values. FSS and PWS values were obtained for statistical analysis. Correlations with p < 0.05 were deemed significant. RESULTS: Nine out of the 10 patients showed positive correlation between wall thickness and flow shear stress. The mean Pearson correlation r-value was 0.278 ± 0.181. Similarly, 9 out of the 10 patients showed negative correlation between wall thickness and plaque wall stress. The mean Pearson correlation r-value was -0.530 ± 0.210. CONCLUSION: Our results showed that plaque vessel wall thickness correlated positively with FSS and negatively with PWS. The patient-specific IVUS-based modeling approach has the potential to be used to investigate and identify possible mechanisms governing plaque progression and rupture and assist in diagnosis and intervention procedures. This represents a new direction of research. Further investigations using more patient follow-up data are warranted