Plaque Wall Stress Research Articles

Abstract 9424: Coronary Artery Disease-Related Death May Be Associated With Higher Critical Plaque Wall Stress: A Multi-Patient 3D Fluid-Structure Interaction Study Comparing Plaque Wall Stress, Flow Shear Stress, and Plaque Burden as Risk Indicators

Introduction: Plaque burden has been used to predict cardiovascular events. However, many patients without flow-limiting atherosclerosis and without prior symptomatology develop catastrophic syndromes including stroke, or sudden cardiac death. We hypothesized that plaque wall stresses play an important role in vulnerable plaque rupture and may serve as a risk factor for cardiovascular event. The objective of this study was to compare plaque wall stress, flow shear stress, and plaque burden and identify their possible association with coronary artery disease (CAD)-related death. Methods: Ex vivo MRI data of coronary plaques from 12 patients (6 died from CAD cause and 6 died from non-CAD cause, based on autopsy reports) were used to construct 3D fluid-structure interaction models. Plaque wall stress and flow shear stress were extracted from all nodal points on the lumen surface of each 3D plaque model for analysis. The maxima of plaque wall stress and flow shear stress from all local maxima (excluding those on healthy sites) of each plaque were defined as the 3D critical plaque wall stress (CPWS) and 3D critical flow shear stress (CFSS), respectively. Plaque burden was calculated as plaque+media area/total vessel area bounded by the out-boundary. Two-sided Student t-test was used to compare the difference of CPWS, CFSS and plaque burden between the CAD and non-CAD groups. Results: Table 1 shows that mean 3D CPWS from CAD Group was 94.3% higher than that from non-CAD Group (265.6 vs. 136.7 kPa, P=0.0029). No difference was found for 3D CFSS values (p=0.851) and plaque burden (p=0.552) between the two groups. Conclusion: The results showed that plaques from the CAD group were associated with higher critical plaque wall stresses compared with plaques from the non-CAD group, suggesting that CPWS may serve to predict event risk, and may provide more accurate plaque vulnerability assessment. Prospective and large-scale studies are needed to further validate our findings.

Correlations between carotid plaque progression and mechanical stresses change sign over time: a patient follow up study using MRI and 3D FSI models

BackgroundIncreasing evidence suggests that mechanisms governing advanced plaque progression may be different from those for early progression and require further investigation. Serial MRI data and 3D fluid–structure interaction (FSI) models were employed to identify possible correlations between mechanical stresses and advanced plaque progression measured by vessel wall thickness increase (WTI). Long-term patient follow up was used to gather data and investigate if the correlations identified above were reproducible.MethodsIn vivo MRI data were acquired from 16 patients in a follow-up study with 2 to 4 scans for each patient (scan interval: average 18 months and standard deviation 6.8 months). A total of 38 scan pairs (baseline and follow-up) were formed for analysis using the carotid bifurcation as the registration point. 3D FSI models were constructed to obtain plaque wall stress (PWS) and flow shear stress (FSS) to quantify their correlations with plaque progression. The Linear Mixed-Effects models were used to study possible correlations between WTI and baseline PWS and FSS with nodal dependence taken into consideration.ResultsOf the 38 scan pairs, 22 pairs showed positive correlation between baseline PWS and WTI, 1 pair showed negative correlation, and 15 pairs showed no correlation. Thirteen patients changed their correlation sign (81.25%). Between baseline FSS and WTI, 16 pairs showed negative correlation, 1 pair showed positive correlation. Twelve patients changed correlation sign (75%).ConclusionOur results showed that advanced plaque progression had an overall positive correlation with plaque wall stress and a negative correlation with flow shear stress at baseline. However, long-term follow up showed that correlations between plaque progress and mechanical stresses (FSS and PWS) identified for one time period were not re-producible for most cases (>80%). Further investigations are needed to identify the reasons causing the correlation sign changes.

Quantifying Effect of Intraplaque Hemorrhage on Critical Plaque Wall Stress in Human Atherosclerotic Plaques Using Three-Dimensional Fluid-Structure Interaction Models

Recent magnetic resonance studies have indicated that intraplaque hemorrhage (IPH) may accelerate plaque progression and play an important role in plaque destabilization. However, the impact of hemorrhage on critical plaque wall stress (CPWS) and strain (CPWSn) has yet to be determined. The objective of this study was to assess the effect of the presence and size of IPH on wall mechanics. The magnetic resonance image (MRI) of one patient with histology-confirmed IPH was used to build eight 3D fluid-structure interaction (FSI) models by altering the dimensions of the existing IPH. As a secondary end point, the combined effect of IPH and fibrous cap thickness (FCT) was assessed. A volume curve fitting method (VCFM) was applied to generate a mesh that would guarantee numerical convergence. Plaque wall stress (PWS), strain (PWSn), and flow shear stress (FSS) were extracted from all nodal points on the lumen surface for analysis. Keeping other conditions unchanged, the presence of intraplaque hemorrhage caused a significant increase (27.5%) in CPWS; reduced FCT caused an increase of 22.6% of CPWS. Similar results were found for CPWSn. Furthermore, combination of IPH presence, reduced FCT, and increased IPH volume caused an 85% and 75% increase in CPWS and CPWSn, respectively. These results show that intraplaque hemorrhage has considerable impact on plaque stress and strain conditions and accurate quantification of IPH could lead to more accurate assessment of plaque vulnerability. Large-scale studies are needed to further validate our findings.

In Vivo Serial MRI-Based Models and Statistical Methods to Quantify Sensitivity and Specificity of Mechanical Predictors for Carotid Plaque Rupture: Location and Beyond

It has been hypothesized that mechanical risk factors may be used to predict future atherosclerotic plaque rupture. Truly predictive methods for plaque rupture and methods to identify the best predictor(s) from all the candidates are lacking in the literature. A novel combination of computational and statistical models based on serial magnetic resonance imaging (MRI) was introduced to quantify sensitivity and specificity of mechanical predictors to identify the best candidate for plaque rupture site prediction. Serial in vivo MRI data of carotid plaque from one patient was acquired with follow-up scan showing ulceration. 3D computational fluid-structure interaction (FSI) models using both baseline and follow-up data were constructed and plaque wall stress (PWS) and strain (PWSn) and flow maximum shear stress (FSS) were extracted from all 600 matched nodal points (100 points per matched slice, baseline matching follow-up) on the lumen surface for analysis. Each of the 600 points was marked "ulcer" or "nonulcer" using follow-up scan. Predictive statistical models for each of the seven combinations of PWS, PWSn, and FSS were trained using the follow-up data and applied to the baseline data to assess their sensitivity and specificity using the 600 data points for ulcer predictions. Sensitivity of prediction is defined as the proportion of the true positive outcomes that are predicted to be positive. Specificity of prediction is defined as the proportion of the true negative outcomes that are correctly predicted to be negative. Using probability 0.3 as a threshold to infer ulcer occurrence at the prediction stage, the combination of PWS and PWSn provided the best predictive accuracy with (sensitivity, specificity) = (0.97, 0.958). Sensitivity and specificity given by PWS, PWSn, and FSS individually were (0.788, 0.968), (0.515, 0.968), and (0.758, 0.928), respectively. The proposed computational-statistical process provides a novel method and a framework to assess the sensitivity and specificity of various risk indicators and offers the potential to identify the optimized predictor for plaque rupture using serial MRI with follow-up scan showing ulceration as the gold standard for method validation. While serial MRI data with actual rupture are hard to acquire, this single-case study suggests that combination of multiple predictors may provide potential improvement to existing plaque assessment schemes. With large-scale patient studies, this predictive modeling process may provide more solid ground for rupture predictor selection strategies and methods for image-based plaque vulnerability assessment.

Stress Analysis of Carotid Atheroma in Transient Ischemic Attack Patients: Evidence for Extreme Stress-Induced Plaque Rupture

Plaque rupture has been considered to be the result of its structural failure. The aim of this study is to suggest a possible link between higher stresses and rupture sites observed from in vivo magnetic resonance imaging (MRI) of transient ischemic attack (TIA) patients, by using stress analysis methods. Three patients, who had recently suffered a TIA, underwent in vivo multi-spectral MR imaging. Based on plaque geometries reconstructed from the post-rupture status, six pre-rupture plaque models were generated for each patient dataset with different reconstructions of rupture sites to bridge the gap of fibrous cap from original MRI images. Stress analysis by fluid structure interaction simulation was performed on the models, followed by analysis of local stress concentration distribution and plaque rupture sites. Furthermore, the sensitivity of stress analysis to the pre-rupture plaque geometry reconstruction was examined. Local stress concentrations were found to be located at the plaque rupture sites for the three subjects studied. In the total of 18 models created, the locations of the stress concentration regions were similar in 17 models in which rupture sites were always associated with high stresses. The local stress concentration region moved from circumferential center to the shoulder region (slightly away from the rupture site) for a case with a thick fibrous cap. Plaque wall stress level in the rupture locations was found to be much higher than the value in non-rupture locations. The good correlation between local stress concentrations and plaque rupture sites, and generally higher plaque wall stress level in rupture locations in the subjects studied could provide indirect evidence for the extreme stress-induced plaque rupture hypothesis. Local stress concentration in the plaque region could be one of the factors contributing to plaque rupture.

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

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

Patient-Specific Carotid Plaque Progression Simulation Using 3D Meshless Generalized Finite Difference Models with Fluid-Structure Interactions Based on Serial In Vivo MRI Data.

Previously, we introduced a computational procedure based on three-dimensional meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data to quantify patient-specific carotid atherosclerotic plaque growth functions and simulate plaque progression. Structure-only models were used in our previous report. In this paper, fluid-stricture interaction (FSI) was added to improve on prediction accuracy. One participating patient was scanned three times (T1, T2, and T3, at intervals of about 18 months) to obtain plaque progression data. Blood flow was assumed to laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations. Plaque material was assumed to be uniform, homogeneous, isotropic, linear, and nearly incompressible. The linear elastic model was used. The 3D FSI plaque model was discretized and solved using a meshless generalized finite difference (GFD) method. Growth functions with a) morphology alone; b) morphology and plaque wall stress (PWS); morphology and flow shear stress (FSS), and d) morphology, PWS and FSS were introduced to predict future plaque growth based on previous time point data. Starting from the T2 plaque geometry, plaque progression was simulated by solving the FSI model and adjusting plaque geometry using plaque growth functions iteratively until T3 is reached. Numerically simulated plaque progression agreed very well with the target T3 plaque geometry with errors ranging from 8.62%, 7.22%, 5.77% and 4.39%, with the growth function including morphology, plaque wall stress and flow shear stress terms giving the best predictions. Adding flow shear stress term to the growth function improved the prediction error from 7.22% to 4.39%, a 40% improvement. We believe this is the first time 3D plaque progression FSI simulation based on multi-year patient-tracking data was reported. Serial MRI-based progression simulation adds time dimension to plaque vulnerability assessment and will improve prediction accuracy for potential plaque rupture risk.

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

BackgroundStudies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and flow shear stress (FSS).MethodsIn vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear Stress (FSS) were extracted from all nodal points on the lumen surface of each plaque for analysis.ResultsThe mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5) than those from non-hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the 5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0 versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance.ConclusionThe results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage) linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide additional stress indicators for image-based vulnerability assessment.

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/cm 2, 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.

3D Critical Plaque Wall Stress Is a Better Predictor of Carotid Plaque Rupture Sites Than Flow Shear Stress: An In Vivo MRI-Based 3D FSI Study

Atherosclerotic plaque rupture leading to stroke is the major cause of long-term disability as well as the third most common cause of mortality. Image-based computational models have been introduced seeking critical mechanical indicators, which may be used for plaque vulnerability assessment. This study extends the previous 2D critical stress concept to 3D by using in vivo magnetic resonance image (MRI) data of human atherosclerotic carotid plaques and 3D fluid-structure interaction (FSI) models to: identify 3D critical plaque wall stress (CPWS) and critical flow shear stress (CFSS) and to investigate their associations with plaque rupture. In vivo MRI data of carotid plaques from 18 patients scheduled for endarterectomy were acquired using histologically validated multicontrast protocols. Of the 18 plaques, histology-confirmed that six had prior rupture (group 1) as evidenced by presence of ulceration. The remaining 12 plaques (group 2) contained no rupture. The 3D multicomponent FSI models were constructed for each plaque to obtain 3D plaque wall stress (PWS) and flow shear stress (FSS) distributions. Three-dimensional CPWS and CFSS, defined as maxima of PWS and FSS from all vulnerable sites, were determined for each plaque to investigate their association with plaque rupture. Slice-based critical PWS and FSS were also calculated for all slices for more detailed analysis and comparison. The mean 3D CPWS of group 1 was 263.44 kPa, which was 100% higher than that from group 2 (132.77, p=0.03984). Five of the six ruptured plaques had 3D CPWS sites, matching the histology-confirmed rupture sites with an 83% agreement. Although the mean 3D CFSS (92.94 dyn/cm(2)) for group 1 was 76% higher than that for group 2 (52.70 dyn/cm(2)), slice-based CFSS showed no significant difference between the two groups. Only two of the six ruptured plaques had 3D CFSS sites matching the histology-confirmed rupture sites with a 33% agreement. CFSS had a good correlation with plaque stenosis severity (R(2)=0.40 with an exponential function fitting 3D CFSS data). This in vivo MRI pilot study using plaques with and without rupture demonstrates that 3D critical plaque wall stress values are more closely associated with atherosclerotic plaque rupture then critical flow shear stresses. Critical wall stress values may become indicators of high risk sites of rupture. Future work with a larger population will establish a possible CPWS-based plaque vulnerability classification.

Sites of Rupture in Human Atherosclerotic Carotid Plaques Are Associated With High Structural Stresses

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

A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: In vivo MRI-based 2D/3D FSI models

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