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.     

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.     

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.

     

Using 2D In Vivo IVUS-Based Models for Human Coronary Plaque Progression Analysis and Comparison with 3D Fluid-Structure Interaction Models: A Multi-Patient Study

Computational modeling has been used extensively in cardiovascular and biological research, providing valuable information. However, 3D vulnerable plaque model construction with complex geometrical features and multicomponents is often very time consuming and not practical for clinical implementation. This paper investigated if 2D atherosclerotic plaque models could be used to replace 3D models to perform correlation analysis and achieve similar results. In vivo intravascular ultrasound (IVUS) coronary plaque data were acquired from a patient follow-up study to construct 2D structure-only and 3D FSI models to obtain plaque wall stress (PWS) and strain (PWSn) data. One hundred and twenty-seven (127) matched IVUS slices at baseline and follow up were obtained from 3 patients. Our results showed that 2D models overestimated stress and strain by 30% and 33%, respectively, compared to results from 3D FSI models. 2D/3D correlation comparison indicated that 116 out of 127 slices had a consistent correlation between plaque progression (WTI) and wall thickness; 103 out of 127 slices had a consistent correlation between WTI and PWS; and 99 out of 127 slices had a consistent correlation between WTI and PWSn. This leads to the potential that 2D models could be used in actual clinical implementation where quick analysis delivery time is essential.     

Non-uniform shrinkage for obtaining computational start shape for in-vivo MRI-based plaque vulnerability assessment

BackgroundCritical mechanical conditions, such as stress within the structure and shear stress due to blood flow, predicted from in-vivo magnetic resonance image (MRI)-based computational simulations have shown to be potential in assessing carotid plaque vulnerability. Plaque contours obtained from in-vivo MRI are a result of a pressurized configuration due to physiological loading. However, in order to make accurate predictions, the computational model must be based on the loading-free geometry. A shrinkage procedure can be used to obtain the computational start shape.MethodIn this study, electrocardiograph (ECG)-gated MR-images of carotid plaques were obtained from 28 patients. The contours of each plaque were segmented manually. Additional to a uniform shrinkage procedure, a non-uniform shrinkage refinement procedure was used. This procedure was repeated until the pressurized lumen contour and fibrous cap thickness had the best match with the in-vivo image.ResultsCompared to the uniform shrinkage procedure, the non-uniform shrinkage significantly reduced the difference in lumen shape and in cap thickness at the thinnest site. Results indicate that uniform shrinkage would underestimate the critical stress in the structure by 20.5±10.7%.ConclusionFor slices with an irregular lumen shape (the ratio of the maximum width to the minimum width is more than 1.05), the non-uniform shrinkage procedure is needed to get an accurate stress profile for mechanics and MRI-based carotid plaque vulnerability assessment.     

Advanced human carotid plaque progression correlates positively with flow shear stress using follow-up scan data: An in vivo MRI multi-patient 3D FSI study

Although it has been well-accepted that atherosclerosis initiation and early progression correlate negatively with flow wall shear stresses (FSS), increasing evidence suggests mechanisms governing advanced plaque progression are not well understood. Fourteen patients were scanned 2–4 times at 18 month intervals using a histologically validated multi-contrast magnetic resonance imaging (MRI) protocol to acquire carotid plaque progression data. Thirty-two scan pairs (baseline and follow-up scans) were formed with slices matched for model construction and analysis. 3D fluid–structure interaction (FSI) models were constructed and plaque wall stress (PWS) and flow shear stress (FSS) were obtained from all matching lumen data points (400–1000 per plaque; 100 points per matched slice) to quantify correlations with plaque progression measured by vessel wall thickness increase (WTI). Using FSS and PWS data from follow-up scan, 21 out of 32 scan pairs showed a significant positive correlation between WTI and FSS (positive/negative/no significance ratio=21/8/3), and 26 out of 32 scan pairs showed a significant negative correlation between WTI and PWS (positive/negative/no significance ratio=2/26/4). The mean FSS value of lipid core nodes (n=5294) from all 47 plaque models was 63.5 dyn/cm², which was 45% higher than that from all normal vessel nodes (n=27553, p<0.00001). The results from this intensive FSI study indicate that flow shear stress from follow-up scan correlates positively with advanced plaque progression which is different from what has been observed in plaque initiation and early-stage progression. It should be noted that the correlation results do not automatically lead to any causality conclusions.     

A pragmatic approach to understand peripheral artery lumen surface stiffness due to plaque heterogeneity

The goal of this study was to develop a pragmatic approach to build patient-specific models of the peripheral artery that are aware of plaque inhomogeneity. Patient-specific models using element-specific material definition (to understand the role of plaque composition) and homogeneous material definition (to understand the role of artery diameter and thickness) were automatically built from intravascular ultrasound images of three artery segments classified with low, average, and high calcification. The element-specific material models had average surface stiffness values of 0.0735, 0.0826, and 0.0973?MPa/mm, whereas the homogeneous material models had average surface stiffness values of 0.1392, 0.1276, and 0.1922?MPa/mm for low, average, and high calcification, respectively. Localization of peak lumen stiffness and differences in patient-specific average surface stiffness for homogeneous and element-specific models suggest the role of plaque composition on surface stiffness in addition to local arterial diameter and thickness.     

Fluid flow and plaque formation in an aortic bifurcation

Considering steady laminar flow in a two-dimensional symmetric branching channel with local occlusions, a finite element model has been developed to study velocity fields including reverse flow regions, pressure profiles and wall shear stress distributions for different Reynolds numbers, bifurcation angles and lumen reductions. The flow analysis has been extended to include a new submodel for the pseudo-transient formation of plaque at sites and deposition rates defined by the physical characteristics of the flow. Specifically, simulating the onset of atherosclerotic lesions, sinusoidal plaque layers have been placed in areas of critically low wall shear stresses, and simulating the growth of particle depositions, plaque layers have been added in a stepwise fashion in regions of critically high and low shear. Thus two somewhat conflicting hypothetical correlations between critical wall shear stress levels and atheroma have been tested and a solution has been postulated. The validated computer simulation model is a predictive tool for analyzing the effects of local changes in wall curvature due to surgical reconstruction and/or atherosclerotic lesions, and for investigating the design of aortic bifurcations which mitigate plaque formation.     

Quantification of liver fat in mice: comparing dual-echo Dixon imaging, chemical shift imaging, and 1H-MR spectroscopy

We evaluated dual-echo Dixon in-phase and out-of-phase (IP-OP), chemical shift imaging (CSI), and (1)H MRS (hydrogen MR spectroscopy) in estimating fat content (FC) in phantoms and in livers of mice. Phantoms were made according to the volume percentage of fat ranging from 0% to 100%. The three MR methods were performed to measure FC in phantoms and in livers of obese leptin-deficient (ob/ob), human BSCL2/seipin gene knockout (SKO), and wild-type (WT) mice. The results were compared with known FC in phantoms and to a reference standard from mice by histological semiautomatic vacuole segmentation (HIS-S) procedure and liver lipid (LL) chemical analysis. In phantoms, CSI underestimated FC from 50% to 100%, to a lesser extent than IP-OP. In vivo, liver FC in ob/ob and SKO mice measured by the three MR methods were all significantly higher than that in WT mice. Liver FC measured by IP-OP were significantly lower than that measured by CSI and MRS, with no significant difference between CSI and MRS. CSI and MRS showed a linear correlation with LL analysis and with each other. IP-OP underestimated FC, whereas CSI and MRS were more accurate for quantifying FC in both phantoms and liver. CSI and MRS have the potential to replace HIS-S and LL analysis in longitudinal studies.     

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.     

IVUS-based computational modeling and planar biaxial artery material properties for human coronary plaque vulnerability assessment

Image-based computational modeling has been introduced for vulnerable atherosclerotic plaques to identify critical mechanical conditions which may be used for better plaque assessment and rupture predictions. In vivo patient-specific coronary plaque models are lagging due to limitations on non-invasive image resolution, flow data, and vessel material properties. A framework is proposed to combine intravascular ultrasound (IVUS) imaging, biaxial mechanical testing and computational modeling with fluid-structure interactions and anisotropic material properties to acquire better and more complete plaque data and make more accurate plaque vulnerability assessment and predictions. Impact of pre-shrink-stretch process, vessel curvature and high blood pressure on stress, strain, flow velocity and flow maximum principal shear stress was investigated.     

Longitudinal MRI study on the natural history of carotid artery plaques in symptomatic patients

Purpose

To investigate the natural history of carotid atherosclerosis in patients who experienced a TIA or ischemic stroke.

Patients and Methods

Ninety-two TIA/stroke patients (57 men, mean age 67.7±9.8 years) with ipsilateral <70% carotid stenosis underwent multisequence MRI of the plaque ipsilateral to the symptomatic side at baseline and after one year. For each plaque, several parameters were assessed at both time points.

Results

Carotid lumen, wall and total vessel ( = carotid lumen and wall) volume did not significantly change. Forty-four patients had a plaque with a lipid-rich necrotic core (LRNC) at baseline, of which 34 also had a LRNC after one year. In three patients a LRNC appeared after one year. Thirty patients had a plaque with a thin and/or ruptured fibrous cap (FC) at both time points. In seven patients, FC status changed from thin and/or ruptured into thick and intact. In three patients, FC status changed from thick and intact into thin and/or ruptured. Twenty patients had intraplaque hemorrhage (IPH) at both time points. In four patients, IPH disappeared, whereas in three patients, new IPH appeared at follow-up.

Conclusion

In TIA/stroke patients, carotid plaque morphology does not significantly change over a one-year period. IPH and FC status change in a minority of patients.     

A new imaging technique to study 3-D plaque and shear stress distribution in human coronary artery bifurcations in vivo

OBJECTIVE: Bifurcations of coronary arteries are predilection sites for atherosclerosis and expansive remodeling, the latter being associated with plaque vulnerability. Both are related to blood flow-induced shear stress (SS). We present a new approach to generate 3-D reconstructions of coronary artery bifurcations in vivo and investigate the relationship between SS, wall thickness (WT) and remodeling. METHODS: The patient specific 3-D reconstruction of the main branch of the bifurcation was obtained by combining intravascular ultrasound and biplane angiography, and the 3-D lumen of the side branch was based on biplane angiography only. The two data sets were fused and computational methods were applied to determine the SS distribution, using patient derived flow and viscosity data. The intravascular ultrasound data allowed us to measure local WT and remodeling in the main branch. RESULTS: The lumen reconstruction procedure was successful and it was shown that the impact of the side branch on SS distribution in the main branch diminished within 3mm. Distal to the bifurcation, two continuous regions in the main branch were identified. In the proximal region, we observed lumen preservation, and expansive remodeling. Although a plaque was observed in the low SS region at the non-divider wall, no relationship between SS and WT was found. In the distal region, we observed lumen narrowing and a significant positive relationship between SS and WT. CONCLUSIONS: A new imaging technique was applied to generate a 3-D reconstruction of a human coronary artery bifurcation in vivo. The observed relationship between SS, WT and remodeling in this specific patient illustrates the spatial heterogeneity of the atherosclerosis in the vicinity of arterial bifurcations.     

Fluid-structure interaction models based on patient-specific IVUS at baseline and follow-up for prediction of coronary plaque progression by morphological and biomechanical factors: A preliminary study

Plaque morphology and biomechanics are believed to be closely associated with plaque progression. In this paper, we test the hypothesis that integrating morphological and biomechanical risk factors would result in better predictive power for plaque progression prediction. A sample size of 374 intravascular ultrasound (IVUS) slices was obtained from 9 patients with IVUS follow-up data. 3D fluid-structure interaction models were constructed to obtain both structural stress/strain and fluid biomechanical conditions. Data for eight morphological and biomechanical risk factors were extracted for each slice. Plaque area increase (PAI) and wall thickness increase (WTI) were chosen as two measures for plaque progression. Progression measure and risk factors were fed to generalized linear mixed models and linear mixed-effect models to perform prediction and correlation analysis, respectively. All combinations of eight risk factors were exhausted to identify the optimal predictor(s) with highest prediction accuracy defined as sum of sensitivity and specificity. When using a single risk factor, plaque wall stress (PWS) at baseline was the best predictor for plaque progression (PAI and WTI). The optimal predictor among all possible combinations for PAI was PWS + PWSn + Lipid percent + Min cap thickness + Plaque Area (PA) + Plaque Burden (PB) (prediction accuracy = 1.5928) while Wall Thickness (WT) + Plaque Wall Strain (PWSn) + Plaque Area (PA) was the best for WTI (1.2589). This indicated that PAI was a more predictable measure than WTI. The combination including both morphological and biomechanical parameters had improved prediction accuracy, compared to predictions using only morphological features.     

湖南栎类天然次生林幼树更新特征及影响因子

以湖南典型栎类天然次生林为研究对象,基于51块样地的调查数据,采用k-means聚类分析划分林分类型,研究湖南不同栎类天然次生林幼树更新特征,分析了湖南不同栎类天然次生林幼树更新指标(幼树密度、幼树平均地径、平均高以及平均冠幅)与环境因子、林分因子的相关性,旨在阐明环境因子、林分因子对幼树更新的影响,以期为湖南不同栎类天然次生林的恢复与经营管理提供理论依据。结果表明:(1)利用聚类分析可将研究区内栎类天然次生林划分为5个类型,包括甜槠锥栗混交林(CC)、亮叶水青冈多脉青冈混交林(FC)、石栎樟树混交林(LC)、枹栎甜槠混交林(QC)、青冈栎混交林(CG)。(2)不同类型栎类天然次生林更新幼树优势种分化明显,物种丰富度差异显著(P0.05)。5种不同栎类次生林幼树密度均未超过500株/hm~2,更新情况较差;幼树数量差异显著(P0.05),为亮叶水青冈多脉青冈混交林石栎樟树混交林青冈栎混交林枹栎甜槠混交林甜槠锥栗混交林;生长情况差异显著(P0.05),为青冈栎混交林亮叶水青冈多脉青冈混交林枹栎甜槠混交林甜槠锥栗混交林石栎樟树混交林。(3)相关分析结果显示,不同类型次生林幼树更新的主要影响因子存在差异。甜槠锥栗混交林中幼树密度与腐殖质厚度呈显著负相关(P0.05);幼树平均高与灌木盖度呈显著正相关(P0.05);幼树平均地径与草本盖度、灌木盖度呈显著正相关(P0.05)。亮叶水青冈多脉青冈混交林中幼树密度与海拔、腐殖质厚度、枯落物厚度呈显著正相关(P0.05),与草本盖度呈极显著正相关(P0.01);幼树平均地径与郁闭度呈显著负相关(P0.05);幼树平均高、幼树平均冠幅与坡位呈显著正相关(P0.05)。石栎樟树混交林中幼树密度与坡向、土壤厚度呈显著正相关(P0.05),其余因子对幼树生长无显著影响。枹栎甜槠混交林中幼树密度与郁闭度、乔木密度呈极显著正相关(P0.01),与坡位呈显著负相关(P0.05);幼树平均冠幅与坡度呈显著负相关(P0.05)。青冈栎混交林中幼树平均地径与土壤厚度呈显著正相关(P0.05),与乔木密度呈极显著正相关(P0.01);幼树平均冠幅与灌木盖度呈显著正相关(P0.05)。     

Influence of plant-growth-promoting bacteria on germination,growth and nutrients’ uptake of Onobrychis sativa L. under drought stress

The study was conducted to investigate the effect of growth-promoting bacteria (Azotobacter vinelandii?=?A, Pantoea agglomerans?+?P. putida?=?P, combined A?+?P, control) on the germination, growth and nutrient uptake of Onobrychis sativa L. under drought stress (field capacity (FC), 0.7?FC, 0.4?FC). The results showed that the highest and lowest germination rate (GR) was related to the P and control treatments in FC level, respectively. The maximum root and shoot length at the FC level was related to the treatment A. In the A?+?P treatment, the maximum shoot dry weight was measured in 0.7?FC level. The lowest root dry weight was also related to the A?+?P treatment in the FC level. Bio-fertilizers had the maximum impact in increasing the nutrients uptake in 0.7?FC and FC levels. The fertilizers in 0.7?FC and FC levels increased the plant traits and played no significant role in mitigating the effects of drought stress.     

Multi-patient study for coronary vulnerable plaque model comparisons: 2D/3D and fluid–structure interaction simulations

Several image-based computational models have been used to perform mechanical analysis for atherosclerotic plaque progression and vulnerability investigations. However, differences of computational predictions from those models have not been quantified at multi-patient level. In vivo intravascular ultrasound (IVUS) coronary plaque data were acquired from seven patients. Seven 2D/3D models with/without circumferential shrink, cyclic bending and fluid–structure interactions (FSI) were constructed for the seven patients to perform model comparisons and quantify impact of 2D simplification, circumferential shrink, FSI and cyclic bending plaque wall stress/strain (PWS/PWSn) and flow shear stress (FSS) calculations. PWS/PWSn and FSS averages from seven patients (388 slices for 2D and 3D thin-layer models) were used for comparison. Compared to 2D models with shrink process, 2D models without shrink process overestimated PWS by 17.26%. PWS change at location with greatest curvature change from 3D FSI models with/without cyclic bending varied from 15.07% to 49.52% for the seven patients (average = 30.13%). Mean Max-FSS, Min-FSS and Ave-FSS from the flow-only models under maximum pressure condition were 4.02%, 11.29% and 5.45% higher than those from full FSI models with cycle bending, respectively. Mean PWS and PWSn differences between FSI and structure-only models were only 4.38% and 1.78%. Model differences had noticeable patient variations. FSI and flow-only model differences were greater for minimum FSS predictions, notable since low FSS is known to be related to plaque progression. Structure-only models could provide PWS/PWSn calculations as good approximations to FSI models for simplicity and time savings in calculation.

     

Necrotic core thickness and positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture

Fibrous cap thickness is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Core(area)) and the arterial remodeling index (Remod(index)), on the other hand, are difficult to use as clinical morphological indexes: literature data show a wide dispersion of Core(area) thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Core(area) and Remod(index), it remains unclear how these interact and affect peak cap stress (Cap(stress)), a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Cap(stress) value was calculated on 5,500 idealized atherosclerotic vessel models that had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty-four nonruptured plaques acquired by intravascular ultrasound on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Cap(stress). It was found that: 1) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques and 2) in addition to cap thickness, necrotic core thickness, rather than area, was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone but rather as a combination of cap thickness, necrotic core thickness, and the arterial remodeling index.     

Cyclic Bending Contributes to High Stress in a Human Coronary Atherosclerotic Plaque and Rupture Risk: In Vitro Experimental Modeling and Ex Vivo MRI-Based Computational Modeling Approach

Many acute cardiovascular syndromes such as heart attack and stroke are caused by atherosclerotic plaque ruptures which often happen without warning. MRI-based models with fluid-structure interactions (FSI) have been introduced to perform flow and stress/strain analysis for atherosclerotic plaques and identify possible mechanical and morphological indices for accurate plaque vulnerability assessment. In this paper, cyclic bending was added to 3D FSI coronary plaque models for more accurate mechanical predictions. Curvature variation was prescribed using the data of a human left anterior descending (LAD) coronary artery. Five computational models were constructed based on ex vivo MRI human coronary plaque data to assess the effects of cyclic bending, pulsating pressure, plaque structure, and axial stretch on plaque stress/strain distributions. In vitro experiments using a hydrogel stenosis model with cyclical bending were performed to observe effect of cyclical bending on flow conditions. Our results indicate that cyclical bending may cause more than 100% or even up to more than 1000% increase in maximum principal stress values at locations where the plaque is bent most. Stress increase is higher when bending is coupled with axial stretch, non-smooth plaque structure, or resonant pressure conditions (zero phase angle shift). Effects of cyclic bending on flow behaviors are more modest (21.6% decrease in maximum velocity, 10.8% decrease in flow rate, maximum flow shear stress changes were < 5%). Computational FSI models including cyclic bending, plaque components and structure, axial stretch, accurate in vivo measurements of pressure, curvature, and material properties should lead to significant improvement on stress-based plaque mechanical analysis and more accurate coronary plaque vulnerability assessment.     

A Feasibility Study of an Intravascular Imaging Antenna to Image Atherosclerotic Plaques in Swine Using 3.0 T MRI

Purpose

To investigate the feasibility of an intravascular imaging antenna to image abdominal aorta atherosclerotic plaque in swine using 3.0T magnetic resonance imaging (MRI).

Methods

Atherosclerotic model was established in 6 swine. After 8 months, swine underwent an MR examination, which was performed using an intravascular imaging guide-wire, and images of the common iliac artery and the abdominal aorta were acquired. Intravascular ultrasound (IVUS) was performed in the right femoral artery; images at the same position as for the MR examination were obtained. The luminal border and external elastic membrane of the targeted arteries were individually drawn in the MR and IVUS images. After co-registering these images, the vessel, lumen, and vessel wall areas and the plaque burden in the same lesions imaged using different modalities were calculated and compared. The diagnostic accuracy of intravascular MR examination in delineating the vessel wall and detecting plaques were analyzed and compared using IVUS.

Results

Compared with IVUS, good agreement was found between MRI and IVUS for delineating vessel, lumen, and vessel wall areas and plaque burden (r value: 0.98, 0.95, 0.96 and 0.91, respectively; P<0.001).

Conclusion

Compared with IVUS, using an intravascular imaging guide-wire to image deep seated arteries allowed determination of the vessel, lumen and vessel wall areas and plaque size and burden. This may provide an alternative method for detecting atherosclerotic plaques in the future.