Stress analysis of carotid plaque rupture based on in vivo high resolution MRI

Atheromatous carotid plaque rupture is responsible for the majority of ischaemic strokes in the developed world. Plaque rupture has been associated with plaque morphology, plaque components' properties, inflammation and local stress concentration. High resolution multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in vivo. This study combined the recent advances in finite element analysis (FEA) and MRI, and performed stress analysis of five vulnerable carotid plaques based on the geometry derived from in vivo MRI. Image segmentation was based on multi-spectral MRI and co-registered with histology for plaque characterization. Plaque fibrous cap, lipid pool and vessel wall were modelled as isotropic, incompressible hyperelastic materials undergoing large deformation under pulse pressure loading. High stress concentrations were predicted at the shoulders and the thinnest fibrous cap regions of the plaque, and the mean maximal stresses were found to be higher in the ruptured plaques (683.3 kPa) than those in the unruptured plaques (226.9 kPa). The effect of the relative stiffness of fibrous cap to lipid pool on the stress within the cap itself was studied. It was shown that larger relative stiffness of fibrous cap to lipid pool resulted in higher stress within the cap. Thus, it is likely that high stress concentrations in vulnerable plaque may cause plaque rupture and lead to acute ischaemic sequelae. A combination of in vivo high resolution MRI and FEA could potentially act as a useful tool to assess plaque vulnerability and risk stratify patients with carotid atheroma.     

3D computational parametric analysis of eccentric atheroma plaque: influence of axial and circumferential residual stresses

Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has usually been associated with stress concentrations, which are mainly affected by the plaque geometry and the tissue properties. The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including the main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model. The geometrical parameters used to define and design the idealized coronary plaque anatomy were the lipid core length, the stenosis ratio, the fibrous cap thickness, and the lipid core ratio. Finally, residual stresses in longitudinal and circumferential directions were incorporated into the model to analyse the influence of the important mechanical factors in the vulnerability of the plaque. Viewing the results, we conclude that residual stresses should be considered in the modelling of this kind of problems since they cause a significant alteration of the vulnerable plaque region limits. The obtained results show that the fibrous cap thickness and the lipid core length, in combination with the lipid core width, appear to be the key morphological parameters that play a determinant role in the maximal principal stress (MPS). However, the stenosis ratio is found to not play a significant role in vulnerability related to the MPS. Plaque rupture should therefore be observed as a consequence, not only of the cap thickness, but as a combination of the stenosis ratio, the fibrous cap thickness and the lipid core dimensions.     

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.     

Effects of intima stiffness and plaque morphology on peak cap stress

Background  

Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress.     

Study of carotid arterial plaque stress for symptomatic and asymptomatic patients

Stroke is one of the leading causes of death in the world, resulting mostly from the sudden ruptures of atherosclerosis carotid plaques. Until now, the exact plaque rupture mechanism has not been fully understood, and also the plaque rupture risk stratification. The advanced multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in-vivo and reconstructed by computational modeling. In the study, plaque stress analysis using fully coupled fluid structure interaction was applied to 20 patients (12 symptomatic and 8 asymptomatic) reconstructed from in-vivo MRI, followed by a detailed biomechanics analysis, and morphological feature study. The locally extreme stress conditions can be found in the fibrous cap region, 85% at the plaque shoulder based on the present study cases. Local maximum stress values predicted in the plaque region were found to be significantly higher in symptomatic patients than that in asymptomatic patients (200 ± 43 kPa vs. 127 ± 37 kPa, p=0.001). Plaque stress level, defined by excluding 5% highest stress nodes in the fibrous cap region based on the accumulative histogram of stress experienced on the computational nodes in the fibrous cap, was also significantly higher in symptomatic patients than that in asymptomatic patients (154 ± 32 kPa vs. 111 ± 23 kPa, p<0.05). Although there was no significant difference in lipid core size between the two patient groups, symptomatic group normally had a larger lipid core and a significantly thinner fibrous cap based on the reconstructed plaques using 3D interpolation from stacks of 2D contours. Plaques with a higher stenosis were more likely to have extreme stress conditions upstream of plaque throat. The combined analyses of plaque MR image and plaque stress will advance our understanding of plaque rupture, and provide a useful tool on assessing plaque rupture risk.     

Initial stress in biomechanical models of atherosclerotic plaques

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.     

Genes potentially involved in plaque rupture

PURPOSE OF REVIEW: Rupture of an atherosclerotic plaque is the predominant underlying event in the pathogenesis of acute coronary syndromes and stroke. While ruptured plaques are morphologically well described, the precise molecular mechanisms involved in plaque rupture are still incompletely understood. Over the last few years, techniques like microarray, suppression subtractive hybridization and differential display enabled us to study complex gene expression profiles that occur during the process of atherogenesis. In this review we focus on recent large-scale gene expression profiles performed on whole mount vascular specimens. RECENT FINDINGS: The gene expression profiles on whole mount vascular tissue confirmed that at least three mechanisms are involved in plaque rupture: (1) a disturbed balance in extracellular matrix turnover, (2) disturbed regulation of cell turnover and (3) processes involved in lipid metabolism. Animal models exhibiting features of plaque rupture reflect the involvement of these three mechanisms. The most dramatic mouse phenotypes were observed after interventions in at least two of these mechanisms. SUMMARY: The observation of plaque rupture in recent mice models is indicative of the multifactorial process of plaque rupture. This multifactorial character of plaque rupture suggests that interventions may be most effective when they influence more than one mechanisms at a time.     

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.     

小型猪动脉粥样硬化斑块稳定性模型研究

目前已有的动物模型在研究动脉粥样硬化斑块破裂、破裂的可控性及量化研究方面均不能满足研究的需要.为了建立类似于人类动脉粥样硬化病变的斑块模型,体外研究斑块稳定性,应用传统的高脂高胆固醇膳食诱导建立了小型猪动脉粥样硬化模型,并从血脂水平和斑块病理形态学特征方面加以了证实.该模型中斑块与人类成熟斑块的高度相似性使其成为研究斑块稳定性和斑块破裂的较好模型.从量化比较这一出发点着手,建立了一个体外可控可量化诱导斑块破裂模型,方法简单易行,是一个较好的量化研究斑块破裂和破裂相关因素间关系的实验模型.     

Relationship among coronary plaque compliance, coronary risk factors and tissue characteristics evaluated by integrated backscatter intravascular ultrasound

ABSTRACT: BACKGROUND: The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification [less than or equal to]10) in 36 patients and 22 plaques (moderately calcified group: 10< an arc of calcification [less than or equal to]60) in 22 patients were evaluated. External elastic membrane volume (EEMV) compliance, lumen volume (LV) compliance, plaque volume (PV) response (difference between PV in systole and diastole), EEM area stiffness index were measured at the minimal lumen site. Relative lipid volume (lipid volume/internal elastic membrane volume) was calculated by IB-IVUS. Results: In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r=0.456, p=0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p=0.032, r =-0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 +/- 1.49 vs. 2.47 +/- 1.79 %/10 mmHg, p =0.014 and 28.3 +/- 26.0 vs. 15.7 +/- 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 +/- 0.68 vs. 1.57 +/- 0.95 %/10 mmHg, p =0.012 and 26.5 +/- 24.3 vs. 13.0 +/- 16.7, p =0.020). These relationships were not seen in the moderately calcified group. Conclusion: The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.     

The effects of plaque morphology and material properties on peak cap stress in human coronary arteries

Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries.     

Carotid arterial plaque stress analysis using fluid–structure interactive simulation based on in-vivo magnetic resonance images of four patients

The rupture of atherosclerotic plaques is known to be associated with the stresses that act on or within the arterial wall. The extreme wall tensile stress (WTS) is usually recognized as a primary trigger for the rupture of vulnerable plaque. The present study used the in-vivo high-resolution multi-spectral magnetic resonance imaging (MRI) for carotid arterial plaque morphology reconstruction. Image segmentation of different plaque components was based on the multi-spectral MRI and co-registered with different sequences for the patient. Stress analysis was performed on totally four subjects with different plaque burden by fluid–structure interaction (FSI) simulations. Wall shear stress distributions are highly related to the degree of stenosis, while the level of its magnitude is much lower than the WTS in the fibrous cap. WTS is higher in the luminal wall and lower at the outer wall, with the lowest stress at the lipid region. Local stress concentrations are well confined in the thinner fibrous cap region, and usually locating in the plaque shoulder; the introduction of relative stress variation during a cycle in the fibrous cap can be a potential indicator for plaque fatigue process in the thin fibrous cap. According to stress analysis of the four subjects, a risk assessment in terms of mechanical factors could be made, which may be helpful in clinical practice. However, more subjects with patient specific analysis are desirable for plaque-stability study.     

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

BackgroundRupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).MethodsAtherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.ResultsDMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05).ConclusionAfter successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.     

Effects of varied lipid core volume and fibrous cap thickness on stress distribution in carotid arterial plaques

The rupture of atherosclerotic plaques is known to be associated with the stresses that act on or within the arterial wall. The extreme wall tensile stress is usually recognized as a primary trigger for the rupture of the plaque. The present study used one-way fluid-structure interaction simulation to investigate the impacts of fibrous cap thickness and lipid core volume to the wall tensile stress value and distributions on the fibrous cap. Von Mises stress was employed to represent the wall tensile stress (VWTS). A total of 13 carotid bifurcation cases were manipulated based on a base geometry in the study with varied combinations of fibrous cap thickness and lipid core volume in the plaque. Values of maximum VWTS and a stress value of VWTS_90, which represents the cut-off VWTS value of 90% in cumulative histogram of VWTS possessed at the computational nodes on the luminal surface of fibrous cap, were used to assess the risk of plaque rupture for each case. Both parameters are capable of separating the simulation cases into vulnerable and more stable plaque groups, while VWTS_90 is more robust for plaque rupture risk assessment. The results show that the stress level on the fibrous cap is much more sensitive to the changes in the fibrous cap thickness than the lipid core volume. A slight decrease of cap thickness can cause a significant increase of stress. For all simulation cases, high VWTS appears at the fibrous cap near the lipid core (plaque shoulder) regions.     

Finite element analysis of mechanics of neovessels with intraplaque hemorrhage in carotid atherosclerosis

Background

Intraplaque hemorrhage is a widely known factor facilitating plaque instability. Neovascularization of plaque can be regarded as a compensatory response to the blood supply in the deep intimal and medial areas of the artery. Due to the physiological function, the deformation of carotid atherosclerotic plaque would happen under the action of blood pressure and blood flow. Neovessels are subject to mechanical loading and likely undergo deformation. The rupture of neovessels may deteriorate the instability of plaque. This study focuses on the local mechanical environments around neovessels and investigates the relationship between the biomechanics and the morphological specificity of neovessels.

Methods

Stress and stretch were used to evaluate the rupture risk of the neovessels in plaque. Computational structural analysis was performed based on two human carotid plaque slice samples. Two-dimensional models containing neovessels and other components were built according to the plaque slice samples. Each component was assumed to be non-linear isotropic, piecewise homogeneous and incompressible. Different mechanical boundary conditions, i.e. static pressures, were imposed in the carotid lumen and neovessels lumen respectively. Finite element method was used to simulate the mechanical conditions in the atherosclerotic plaque.

Results

Those neovessels closer to the carotid lumen undergo larger stress and stretch. With the same distance to the carotid lumen, the longer the perimeter of neovessels is, the larger stress and the deformation of the neovessels will be. Under the same conditions, the neovessels with larger curvature suffer greater stress and stretch. Neovessels surrounded by red blood cells undergo a much larger stretch.

Conclusions

Local mechanical conditions may result in the hemorrhage of neovessels and accelerate the rupture of plaque. The mechanical environments of the neovessel are related to its shape, curvature, distance to the carotid lumen and the material properties of plaque.

     

Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy

Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE(-/-)) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz's contact mechanics were used to determine elasticity (Young's) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4±5.7kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4±47.4kPa, locally rising up to ～250kPa. Lipid rich areas exhibit a rather large range of Young's moduli, with average value of 5.5±3.5kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.     

Cap inflammation leads to higher plaque cap strain and lower cap stress: An MRI-PET/CT-based FSI modeling approach

Plaque rupture may be triggered by extreme stress/strain conditions. Inflammation is also implicated and can be imaged using novel imaging techniques. The impact of cap inflammation on plaque stress/strain and flow shear stress were investigated. A patient-specific MRI-PET/CT-based modeling approach was used to develop 3D fluid-structure interaction models and investigate the impact of inflammation on plaque stress/strain conditions for better plaque assessment. 18FDG-PET/CT and MRI data were acquired from 4 male patients (average age: 66) to assess plaque characteristics and inflammation. Material stiffness for the fibrous cap was adjusted lower to reflect cap weakening causing by inflammation. Setting stiffness ratio (SR) to be 1.0 (fibrous tissue) for baseline, results for SR=0.5, 0.25, and 0.1 were obtained. Thin cap and hypertension were also considered. Combining results from the 4 patients, mean cap stress from 729 cap nodes was lowered by 25.2% as SR went from 1.0 to 0.1. Mean cap strain value for SR=0.1 was 0.313, 114% higher than that from SR=1.0 model. The thin cap SR=0.1 model had 40% mean cap stress decrease and 81% cap strain increase compared with SR=1.0 model. The hypertension SR=0.1 model had 19.5% cap stress decrease and 98.6% cap strain increase compared with SR=1.0 model. Differences of flow shear stress with 4 different SR values were limited (<10%). Cap inflammation may lead to large cap strain conditions when combined with thin cap and hypertension. Inflammation also led to lower cap stress. This shows the influence of inflammation on stress/strain calculations which are closely related to plaque assessment.     

Lumen irregularity dominates the relationship between mechanical stress condition, fibrous-cap thickness, and lumen curvature in carotid atherosclerotic plaque

High mechanical stress condition over the fibrous cap (FC) has been widely accepted as a contributor to plaque rupture. The relationships between the stress, lumen curvature, and FC thickness have not been explored in detail. In this study, we investigate lumen irregularity-dependent relationships between mechanical stress conditions, local FC thickness (LT(FC)), and lumen curvature (LC(lumen)). Magnetic resonance imaging slices of carotid plaque from 100 patients with delineated atherosclerotic components were used. Two-dimensional structure-only finite element simulations were performed for the mechanical analysis, and maximum principal stress (stress-P?) at all integral nodes along the lumen was obtained. LT(FC) and LC(lumen) were computed using the segmented contour. The lumen irregularity (L-δir) was defined as the difference between the largest and the smallest lumen curvature. The results indicated that the relationship between stress-P?, LT(FC), and LC(lumen) is largely dependent on L-δir. When L-δir ≥ .31 (irregular lumen), stress-P? strongly correlated with lumen curvature and had a weak/no correlation with local FC thickness, and in 73.4% of magnetic resonance (MR) slices, the critical stress (maximum of stress-P? over the diseased region) was found at the site where the lumen curvature was large. When L-δir ≤ 0.28 (relatively round lumen), stress-P? showed a strong correlation with local FC thickness but weak/no correlation with lumen curvature, and in 71.7% of MR slices, the critical stress was located at the site of minimum FC thickness. Using lumen irregularity as a method of identifying vulnerable plaque sites by referring to the lumen shape is a novel and simple method, which can be used for mechanics-based plaque vulnerability assessment.     

IL-7R blockade reduces post-myocardial infarction-induced atherosclerotic plaque inflammation in ApoE−/- mice

Modulating inflammation by targeting IL-1β reduces recurrent athero-thrombotic cardiovascular events without lipid lowering. This presents an opportunity to explore other pathways associated with the IL-1β signaling cascade to modulate the inflammatory response post-myocardial infarction (MI). IL-7 is a mediator of the inflammatory pathway involved in monocyte trafficking into atherosclerotic plaques and levels of IL-7 have been shown to be elevated in patients with acute MI. Recurrent athero-thrombotic events are believed to be mediated in part by index MI-induced exacerbation of inflammation in atherosclerotic plaques. The objective of the study was to assess the feasibility of IL-7R blockade to modulate atherosclerotic plaque inflammation following acute MI in ApoE^?/- mice. Mice were fed Western diet for 12 weeks and then subjected to coronary occlusion to induce an acute MI. IL-7 expression was determined using qRT-PCR and immuno-staining, and IL-7R was assessed using flow cytometry. Plaque inflammation was evaluated using immunohistochemistry. IL-7R blockade was accomplished with monoclonal antibody to IL-7R. IL-7 mRNA expression was significantly increased in the cardiac tissue of mice subjected to MI but not in controls. IL-7 staining was observed in the coronary artery. Plaque macrophage and lipid content were significantly increased after MI. IL-7R antibody treatment but not control IgG significantly reduced macrophage and lipid content in atherosclerotic plaques. The results show that IL-7R antibody treatment reduces monocyte/macrophage and lipid content in the atherosclerotic plaque following MI suggesting a potential new target to mitigate increased plaque inflammation post-MI.     

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.