Peak Cap Stress Research Articles

Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis.

Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 ± 67 vs. 52 ± 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 ± 233 vs. 90 ± 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 ± 30.3° for PCS vs. 20.7 ± 23.7° for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress.

Moderate thickness of lipid core in shoulder region of atherosclerotic plaque determines vulnerable plaque [sbnd] A parametric study

Peak stress in the fibrous cap of atherosclerotic plaque is largely determined by the cap thickness which cannot be accurately estimated in vivo. This parametric study investigates idealized atherosclerotic plaque geometries. Finite element modeling is applied to search for larger morphological features associated with high cap stresses. By varying seven geometrical and two loading parameters, 100 3D model geometries of atherosclerotic plaques in common iliac artery were generated. In each model peak cap stress was calculated, and statistical comparison of the geometries generating the highest and lowest peak cap stresses was performed. The analysis showed that, compared to geometries generating the lowest stresses, those with high peak cap stress had a significantly lower cap thickness, higher stenosis ratio, lower relative lipid core volume, and cap shoulder radius larger than lipid core radius. High cap stress was observed for cap thicknesses up to 0.13 mm. It can be concluded that vulnerable plaques contain thin fibrous cap, large stenosis ratio and only moderate small-radius lipid core which reaches the shoulder region of the fibrous cap.

Effect of distal thickening and stiffening of plaque cap on arterial wall mechanics.

To investigate the effect of longitudinal variations of cap thickness and tissue properties on wall stresses and strains along the atherosclerotic stenosis, stenotic plaque models (uniformly thick, distally thickened, homogenous, and distally stiffened) were constructed and subjected to computational stress analyses with due consideration of fluid-structure interactions (FSI). The analysis considered three different cap thicknesses-45, 65, and 200μm-and tissue properties-soft, fibrous, and hard. The maximum peak cap stress (PCS) and strain were observed in the upstream throat section and demonstrated increases of the order of 345 and 190%, respectively, as the cap thickness was reduced from 200 to 45μm in uniformly thick models. Distal stiffening increased PCS in the downstream region; however, the overall effect of this increase was rather small. Distal thickening did not affect maximum PCS and strain values for cap thicknesses exceeding 65μm; however, a noticeable increase in maximum PCS and corresponding longitudinal variation (or spatial gradient) in stress was observed in the very thin (45-μm-thick) cap. It was, therefore, inferred that existence of a rather thin upstream cap demonstrating distal cap thickening indicates an increased risk of plaque progression and rupture. Graphical Abstract ᅟ.

Model-based cap thickness and peak cap stress prediction for carotid MRI

A rupture-prone carotid plaque can potentially be identified by calculating the peak cap stress (PCS). For these calculations, plaque geometry from MRI is often used. Unfortunately, MRI is hampered by a low resolution, leading to an overestimation of cap thickness and an underestimation of PCS. We developed a model to reconstruct the cap based on plaque geometry to better predict cap thickness and PCS.We used histological stained plaques from 34 patients. These plaques were segmented and served as the ground truth. Sections of these plaques contained 93 necrotic cores with a cap thickness <0.62mm which were used to generate a geometry-based model. The histological data was used to simulate in vivo MRI images, which were manually delineated by three experienced MRI readers. Caps below the MRI resolution (n=31) were (digitally removed and) reconstructed according to the geometry-based model. Cap thickness and PCS were determined for the ground truth, readers, and reconstructed geometries.Cap thickness was 0.07mm for the ground truth, 0.23mm for the readers, and 0.12mm for the reconstructed geometries. The model predicts cap thickness significantly better than the readers. PCS was 464kPa for the ground truth, 262kPa for the readers and 384kPa for the reconstructed geometries. The model did not predict the PCS significantly better than the readers.The geometry-based model provided a significant improvement for cap thickness estimation and can potentially help in rupture-risk prediction, solely based on cap thickness. Estimation of PCS estimation did not improve, probably due to the complex shape of the plaques.

Peak cap stress calculations in coronary atherosclerotic plaques with an incomplete necrotic core geometry.

BackgroundStress calculations in atherosclerotic coronary vulnerable plaques can aid in predicting coronary cap rupture. In vivo plaque geometry and composition of coronary arteries can merely be obtained via intravascular imaging. Only optical driven imaging techniques have sufficient resolution to visualize the fibrous cap, but due to limited penetration depth deeper components such as the backside of the necrotic core (NC) are generally not visible. The goal of this study was to investigate whether peak cap stresses can be approximated by reconstructing the backside of the NC.MethodsManual segmentations of coronary histological cross-sections served as a geometrical ground truth and were obtained from seven patients resulting in 73 NCs. Next, the backside was removed and reconstructed according to an estimation of the relative necrotic core thickness (rNCt). The rNCt was estimated at three locations along the NC angle and based on either group averaged parameters or plaque specific parameters. Stress calculations were performed in both the ground truth geometry and the reconstructed geometries and compared.ResultsGood geometrical agreement was found between the ground truth NC and the reconstructed NCs, based on group averaged rNCt estimation and plaque specific rNCt estimation, measuring the NC area difference (25.1 % IQR 14.0–41.3 % and 17.9 % IQR 9.81–32.7 %) and similarity index (0.85 IQR 0.77–0.90 and 0.88 IQR 0.79–0.91). The peak cap stresses obtained with both reconstruction methods showed a high correlation with respect to the ground truth, r2 = 0.91 and r2 = 0.95, respectively. For high stress plaques, the peak cap stress difference with respect to the ground truth significantly improved for the NC reconstruction based plaque specific features (6 %) compared to the reconstruction group averaged based (16 %).ConclusionsIn conclusion, good geometry and stress agreement was observed between the ground truth NC geometry and the reconstructed geometries. Although group averaged rNCt estimation seemed to be sufficient for the NC reconstruction and stress calculations, including plaque specific data further improved stress predictions, especially for higher stresses.

An intravascular coronary plaque elasticity reconstruction method using limited depth penetration ultrasound signals

Vulnerable atherosclerotic plaque (VP) rupture is the leading cause of acute coronary syndrome, myocardial infarction and stroke in the Western world (Go et al. 2013). Although past studies have identified fibrous cap thickness (Capthick) as the primary predictor of coronary plaque rupture (Virmani et al. 2006), biomechanical studies have recognized peak cap stress (PCS) as an additional key predictor of plaque disruption (Ohayon et al. 2008). Quantification of PCS amplitude requires not only an accurate description of plaque morphology but also a precise knowledge of the mechanical properties of plaque components. An early and accurate determination of these properties remains an essential step to implement preventive therapeutic strategies. A previous approach (named iMOD for imaging modulography) has been conducted by our group to reconstruct the Young’s modulus map (i.e. modulogram) from intravascular ultrasound (IVUS) strain-elastogram (Le Floc’h et al. 2009). However, one major limitation of such a method is the need to accurately estimate the strain field in the entire lesion, which may be often difficult when using HD-IVUS techniques with limited depth penetration signals (Kobayashi et al. 2014). Therefore, an extended iMOD approach (E-iMOD), based on the continuum mechanics theory prescribing the strain field in the limited atherosclerotic endoluminal region, was designed and successfully applied to coronary lesions of patients imaged in vivo with IVUS.

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.

A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling.

BackgroundThe benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations.MethodsIn order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models.ResultsA decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2–3 fold reduction in measurement error) and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress.ConclusionsThis study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging), but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.

The Influence of Inaccuracies in Carotid MRI Segmentation on Atherosclerotic Plaque Stress Computations

Biomechanical finite element analysis (FEA) based on in vivo carotid magnetic resonance imaging (MRI) can be used to assess carotid plaque vulnerability noninvasively by computing peak cap stress. However, the accuracy of MRI plaque segmentation and the influence this has on FEA has remained unreported due to the lack of a reliable submillimeter ground truth. In this study, we quantify this influence using novel numerical simulations of carotid MRI. Histological sections from carotid plaques from 12 patients were used to create 33 ground truth plaque models. These models were subjected to numerical computer simulations of a currently used clinically applied 3.0 T T1-weighted black-blood carotid MRI protocol (in-plane acquisition voxel size of 0.62 × 0.62 mm2) to generate simulated in vivo MR images from a known underlying ground truth. The simulated images were manually segmented by three MRI readers. FEA models based on the MRI segmentations were compared with the FEA models based on the ground truth. MRI-based FEA model peak cap stress was consistently underestimated, but still correlated (R) moderately with the ground truth stress: R = 0.71, R = 0.47, and R = 0.76 for the three MRI readers respectively (p &lt; 0.01). Peak plaque stretch was underestimated as well. The peak cap stress in thick-cap, low stress plaques was substantially more accurately and precisely predicted (error of -12 ± 44 kPa) than the peak cap stress in plaques with caps thinner than the acquisition voxel size (error of -177 ± 168 kPa). For reliable MRI-based FEA to compute the peak cap stress of carotid plaques with thin caps, the current clinically used in-plane acquisition voxel size (∼0.6 mm) is inadequate. FEA plaque stress computations would be considerably more reliable if they would be used to identify thick-cap carotid plaques with low stresses instead.

Effects of mechanical properties and atherosclerotic artery size on biomechanical plaque disruption – Mouse vs. human

Mouse models of atherosclerosis are extensively being used to study the mechanisms of atherosclerotic plaque development and the results are frequently extrapolated to humans. However, major differences have been described between murine and human atherosclerotic lesions and the determination of similarities and differences between these species has been largely addressed recently. This study takes over and extends previous studies performed by our group and related to the biomechanical characterization of both mouse and human atherosclerotic lesions. Its main objective was to determine the distribution and amplitude of mechanical stresses including peak cap stress (PCS) in aortic vessels from atherosclerotic apoE-/- mice, in order to evaluate whether such biomechanical data would be in accordance with the previously suggested lack of plaque rupture in this model. Successful finite element analysis was performed from the zero-stress configuration of aortic arch sections and mainly indicated (1) the modest role of atherosclerotic lesions in the observed increase in residual parietal stresses in apoE-/- mouse vessels and (2) the low amplitude of murine PCS as compared to humans. Overall, the results from the present study support the hypothesis that murine biomechanical properties and artery size confer less propensity to rupture for mouse lesions in comparison with those of humans.

Effect of residual stress on peak cap stress in arteries.

Vulnerable plaques are a subset of atherosclerotic plaques that are prone to rupture when high stresses occur in the cap. The roles of residual stress, plaque morphology, and cap stiffness on the cap stress are not completely understood. Here, arteries are modeled within the framework of nonlinear elasticity as incompressible cylindrical structures that are residually stressed through differential growth. These structures are assumed to have a nonlinear, anisotropic, hyperelastic response to stresses in the media and adventitia layers and an isotropic response in the intima and necrotic layers. The effect of differential growth on the peak stress is explored in a simple, concentric geometry and it is shown that axial differential growth decreases the peak stress in the inner layer. Furthermore, morphological risk factors are explored. The peak stress in residually stressed cylinders is not greatly affected by changing the thickness of the intima. The thickness of the necrotic layer is shown to be the most important morphological feature that affects the peak stress in a residually stressed vessel.

A direct vulnerable atherosclerotic plaque elasticity reconstruction method based on an original material-finite element formulation: theoretical framework

The peak cap stress (PCS) amplitude is recognized as a biomechanical predictor of vulnerable plaque (VP) rupture. However, quantifying PCS in vivo remains a challenge since the stress depends on the plaque mechanical properties. In response, an iterative material finite element (FE) elasticity reconstruction method using strain measurements has been implemented for the solution of these inverse problems. Although this approach could resolve the mechanical characterization of VPs, it suffers from major limitations since (i) it is not adapted to characterize VPs exhibiting high material discontinuities between inclusions, and (ii) does not permit real time elasticity reconstruction for clinical use. The present theoretical study was therefore designed to develop a direct material-FE algorithm for elasticity reconstruction problems which accounts for material heterogeneities. We originally modified and adapted the extended FE method (Xfem), used mainly in crack analysis, to model material heterogeneities. This new algorithm was successfully applied to six coronary lesions of patients imaged in vivo with intravascular ultrasound. The results demonstrated that the mean relative absolute errors of the reconstructed Young's moduli obtained for the arterial wall, fibrosis, necrotic core, and calcified regions of the VPs decreased from 95.3±15.56%, 98.85±72.42%, 103.29±111.86% and 95.3±10.49%, respectively, to values smaller than 2.6 × 10−8±5.7 × 10−8% (i.e. close to the exact solutions) when including modified-Xfem method into our direct elasticity reconstruction method.

The influence of axial image resolution on atherosclerotic plaque stress computations

Biomechanical models are used extensively to study risk factors, such as peak stresses, for vulnerable atherosclerotic plaque rupture. Typically, 3D patient-specific arterial models are reconstructed by interpolating between cross sectional contour data which have a certain axial sampling, or image, resolution. The influence of the axial sampling resolution on computed stresses, as well as the comparison of 3D with 2D simulations, is quantified in this study. A set of histological data of four atherosclerotic human coronary arteries was used which were reconstructed in 3D with a high sampling (HS) and low sampling (LS) axial resolution, and 4 slices were treated separately for 2D simulations. Stresses were calculated using finite element analysis (FEA). High stresses were found in thin cap regions and regions of thin vessel walls, low stresses were found inside the necrotic cores and media and adventitia layers. Axial sampling resolution was found to have a minor effect on general stress distributions, peak plaque/cap stress locations and the relationship between peak cap stress and minimum cap thickness. Axial sampling resolution did have a profound influence on the error in computed magnitude of peak plaque/cap stresses (±15.5% for HS vs. LS geometries and ±24.0% for HS vs. 2D geometries for cap stresses). The findings of this study show that axial under sampling does not influence the qualitative stress distribution significantly but that high axially sampled 3D models are needed when accurate computation of peak stress magnitudes is required.

Influence of plaque geometry on peak cap stress

Influence of plaque geometry on peak cap stress

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 100mmHg, 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.

Effects of intima stiffness and plaque morphology on peak cap stress

BackgroundRupture 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.MethodsModels with idealized geometries based on histology images of human coronary arteries were generated by varying geometric plaque features. The constructed multi-layer models contained adventitia, media, intima, and necrotic core sections. For adventitia and media layers, anisotropic hyperelastic material models were used. For necrotic core and intima sections, isotropic hyperelastic material models were employed. Three different intima stiffness values were used to cover the wide range reported in literature. According to the intima stiffness, the models were classified as stiff, intermediate and soft intima models. Finite element method was used to compute peak cap stress.ResultsThe intima stiffness was an essential determinant of cap stresses. The computed peak cap stresses for the soft intima models were much lower than for stiff and intermediate intima models. Intima stiffness also affected the influence of morphological parameters on cap stresses. For the stiff and intermediate intima models, the cap thickness and necrotic core thickness were the most important determinants of cap stresses. The peak cap stress increased three-fold when the cap thickness was reduced from 0.25 mm to 0.05 mm for both stiff and intermediate intima models. Doubling the thickness of the necrotic core elevated the peak cap stress by 60% for the stiff intima models and by 90% for the intermediate intima models. Two-fold increase in the intima thickness behind the necrotic core reduced the peak cap stress by approximately 25% for both intima models. For the soft intima models, cap thickness was less critical and changed the peak cap stress by 55%. However, the necrotic core thickness was more influential and changed the peak cap stress by 100%. The necrotic core angle emerged as a critical determinant of cap stresses where a larger angle lowered the cap stresses. Contrary to the stiff and intermediate intima models, a thicker intima behind the necrotic core increased the peak cap stress by approximately 25% for the soft intima models. Adventitia thickness and local media regression had limited effects for all three intima models.ConclusionsFor the stiff and intermediate intima models, the cap thickness was the most important morphological risk factor. However for soft intima models, the necrotic core thickness and necrotic core angle had a bigger impact on the peak cap stress. We therefore need to enhance our knowledge of intima material properties if we want to derive critical morphological plaque features for risk evaluation.

On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study

Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 µm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young`s moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

Combined imaging, computational and histological analysis of a ruptured carotid plaque: A patient-specific analysis

Background Rupture of carotid plaques is an important cause of cerebrovascular events. Several factors, including wall shear stress (WSS), plaque morphology and peak cap stress, have been associated with plaque vulnerability. The aim of this study was to investigate the relationship between these factors in an in vivo human ruptured carotid plaque. Methods A 74-year-old male presenting with a transient ischemic attack underwent carotid magnetic resonance imaging (MRI), which indicated a ruptured plaque, followed by carotid endarterectomy, from which plaque histology was assessed. The carotid bifurcation was reconstructed from the MRI data, and three-dimensional flow simulations were performed using computational fluid dynamics to determine WSS and related parameters. Plaque vulnerability was assessed using a biomechanical method based on modified Glagov criteria. Results The plaque rupture was just distal to the site of maximum stenosis in a region of low WSS, where MRI and histology both demonstrated fibrous cap thinning, a large lipid pool and calcification in the shoulder region. Plaque vulnerability analysis indicated critically vulnerable plaque at the rupture site by a wide margin. Conclusions Both low and high WSS have been associated with plaque vulnerability, and high mechanical stress in the cap has been linked to plaque rupture, but these parameters are not routinely assessed clinically. This study demonstrates a complete analysis by combining imaging, histology and bio-fluid and biomechanical modelling.

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.