Zhongzhao Teng

Sites of Rupture in Human Atherosclerotic Carotid Plaques Are Associated With High Structural Stresses An In Vivo MRI-Based 3D Fluid-Structure Interaction Study

Background and Purpose— 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. Methods— 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. Results— 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). Conclusion— 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.

An Experimental Study on the Ultimate Strength of the Adventitia and Media of Human Atherosclerotic Carotid Arteries in Circumferential and Axial Directions

Atherosclerotic plaque may rupture without warning causing heart attack or stroke. Knowledge of the ultimate strength of human atherosclerotic tissues is essential for understanding the rupture mechanism and predicting cardiovascular events. Despite its great importance, experimental data on ultimate strength of human atherosclerotic carotid artery remains very sparse. This study determined the uniaxial tensile strength of human carotid artery sections containing type II and III lesions (AHA classifications). Axial and circumferential oriented adventitia, media and intact specimens (total=73) were prepared from 6 arteries. The ultimate strength in uniaxial tension was taken as the peak stress recorded when the specimen showed the first evidence of failure and the extensibility was taken as the stretch ratio at failure. The mean adventitia strength values calculated using the first Piola-Kirchoff stress were 1996+/-867 and 1802+/-703 kPa in the axial and circumferential directions respectively, while the corresponding values for the media sections were 519+/-270 and 1230+/-533 kPa. The intact specimens showed ultimate strengths similar to media in circumferential direction but were twice as strong as the media in the axial direction. Results also indicated that adventitia, media and intact specimens exhibited similar extensibility at failure, in both the axial and circumferential directions (stretch ratio 1.50+/-0.22). These measurements of the material strength limits for human atherosclerotic carotid arteries could be useful in improving computational models that assess plaque vulnerability.

Association between Biomechanical Structural Stresses of Atherosclerotic Carotid Plaques and Subsequent Ischaemic Cerebrovascular Events – A Longitudinal in Vivo Magnetic Resonance Imaging-based Finite element Study

BACKGROUND High-resolution magnetic resonance (MR) imaging has been used for MR imaging-based structural stress analysis of atherosclerotic plaques. The biomechanical stress profile of stable plaques has been observed to differ from that of unstable plaques; however, the role that structural stresses play in determining plaque vulnerability remains speculative. METHODS A total of 61 patients with previous history of symptomatic carotid artery disease underwent carotid plaque MR imaging. Plaque components of the index artery such as fibrous tissue, lipid content and plaque haemorrhage (PH) were delineated and used for finite element analysis-based maximum structural stress (M-C Stress) quantification. These patients were followed up for 2 years. The clinical end point was occurrence of an ischaemic cerebrovascular event. The association of the time to the clinical end point with plaque morphology and M-C Stress was analysed. RESULTS During a median follow-up duration of 514 days, 20% of patients (n = 12) experienced an ischaemic event in the territory of the index carotid artery. Cox regression analysis indicated that M-C Stress (hazard ratio (HR): 12.98 (95% confidence interval (CI): 1.32-26.67, p = 0.02), fibrous cap (FC) disruption (HR: 7.39 (95% CI: 1.61-33.82), p = 0.009) and PH (HR: 5.85 (95% CI: 1.27-26.77), p = 0.02) are associated with the development of subsequent cerebrovascular events. Plaques associated with future events had higher M-C Stress than those which had remained asymptomatic (median (interquartile range, IQR): 330 kPa (229-494) vs. 254 kPa (166-290), p = 0.04). CONCLUSIONS High biomechanical structural stresses, in addition to FC rupture and PH, are associated with subsequent cerebrovascular events.

In Vivo IVUS-Based 3-D Fluid–Structure Interaction Models With Cyclic Bending and Anisotropic Vessel Properties for Human Atherosclerotic Coronary Plaque Mechanical Analysis

In this paper, a modeling approach combining in vivo intravascular ultrasound (IVUS) imaging, computational modeling, angiography, and mechanical testing is proposed to perform mechanical analysis for human coronary atherosclerotic plaques for potential more accurate plaque vulnerability assessment. A 44-slice in vivo IVUS dataset of a coronary plaque was acquired from one patient, and four 3-D models with fluid-structure interactions (FSIs) based on the data were constructed to quantify effects of anisotropic vessel properties and cyclic bending of the coronary plaque on flow and plaque stress/strain conditions. Compared to the isotropic model (model 1, no bending, no axial stretch), maximum stress-P1 (maximum principal stress) values on the cut surface with maximum bending (where applicable) from model 2 (anisotropic, no bending, no stretch), model 3 (anisotropic, with bending, no stretch), and model 4 (anisotropic with bending and stretch) were, respectively, 63%, 126%, and 345% higher than that from model 1. Effects of cyclic bending on flow behaviors were modest (5%-15%). Our preliminary results indicated that in vivo IVUS-based FSI models with cyclic bending and anisotropic material properties could improve the accuracies of plaque stress/strain predictions and plaque vulnerability assessment. Large-scale patient studies are needed to further validate our findings.

3D MRI-Based Anisotropic FSI Models With Cyclic Bending for Human Coronary Atherosclerotic Plaque Mechanical Analysis

Heart attack and stroke are often caused by atherosclerotic plaque rupture, which happens without warning most of the time. Magnetic resonance imaging (MRI)-based atherosclerotic plaque models with fluid-structure interactions (FSIs) have been introduced to perform flow and stress/strain analysis and identify possible mechanical and morphological indices for accurate plaque vulnerability assessment. For coronary arteries, cyclic bending associated with heart motion and anisotropy of the vessel walls may have significant influence on flow and stress/strain distributions in the plaque. FSI models with cyclic bending and anisotropic vessel properties for coronary plaques are lacking in the current literature. In this paper, cyclic bending and anisotropic vessel properties were added to 3D FSI coronary plaque models so that the models would be more realistic for more accurate computational flow and stress/strain predictions. Six computational models using one ex vivo MRI human coronary plaque specimen data were constructed to assess the effects of cyclic bending, anisotropic vessel properties, pulsating pressure, plaque structure, and axial stretch on plaque stress/strain distributions. Our results indicate that cyclic bending and anisotropic properties may cause 50-800% increase in maximum principal stress (Stress-P1) values at selected locations. The stress increase varies with location and is higher when bending is coupled with axial stretch, nonsmooth plaque structure, and resonant pressure conditions (zero phase angle shift). Effects of cyclic bending on flow behaviors are more modest (9.8% decrease in maximum velocity, 2.5% decrease in flow rate, 15% increase in maximum flow shear stress). Inclusion of cyclic bending, anisotropic vessel material properties, accurate plaque structure, and axial stretch in computational FSI models should lead to a considerable improvement of accuracy of computational stress/strain predictions for coronary plaque vulnerability assessment. Further studies incorporating additional mechanical property data and in vivo MRI data are needed to obtain more complete and accurate knowledge about flow and stress/strain behaviors in coronary plaques and to identify critical indicators for better plaque assessment and possible rupture predictions.

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.

Local critical stress correlates better than global maximum stress with plaque morphological features linked to atherosclerotic plaque vulnerability: an in vivo multi-patient study

BackgroundIt is believed that mechanical stresses play an important role in atherosclerotic plaque rupture process and may be used for better plaque vulnerability assessment and rupture risk predictions. Image-based plaque models have been introduced in recent years to perform mechanical stress analysis and identify critical stress indicators which may be linked to rupture risk. However, large-scale studies based on in vivo patient data combining mechanical stress analysis, plaque morphology and composition for carotid plaque vulnerability assessment are lacking in the current literature.Methods206 slices of in vivo magnetic resonance image (MRI) of carotid atherosclerotic plaques from 20 patients (age: 49–71, mean: 67.4; all male) were acquired for model construction. Modified Mooney-Rivlin models were used for vessel wall and all plaque components with parameter values chosen to match available data. A morphological plaque severity index (MPSI) was introduced based on in vivo plaque morphological characteristics known to correlate with plaque vulnerability. Critical stress, defined as the maximum of maximum- principal-stress (Stress-P1) values from all possible vulnerable sites, was determined for each slice for analysis. A computational plaque stress index (CPSI, with 5 grades 0–4, 4 being most vulnerable) was defined for each slice using its critical stress value and stress interval for each CPSI grade was optimized to reach best agreement with MPSI. Correlations between CPSI and MPSI, plaque cap thickness, and lipid core size were analyzed.ResultsCritical stress values correlated positively with lipid core size (r = 0.3879) and negatively with cap thickness (r = -0.3953). CPSI classifications had 71.4% agreement with MPSI classifications. The Pearson correlation coefficient between CPSI and MPSI was 0.849 (p < 0.0001). Using global maximum Stress-P1 value for each slice to define a global maximum stress-based CPSI (G-CPSI), the agreement rate with MPSI was only 34.0%. The Pearson correlation coefficient between G-CPSI and MPSI was 0.209.ConclusionResults from this in vivo study demonstrated that localized critical stress values had much better correlation with plaque morphological features known to be linked to plaque rupture risk, compared to global maximum stress conditions. Critical stress indicators have the potential to improve image-based screening and plaque vulnerability assessment schemes.

Coronary Plaque Structural Stress Is Associated With Plaque Composition and Subtype and Higher in Acute Coronary Syndrome The BEACON I (Biomechanical Evaluation of Atheromatous Coronary Arteries) Study

Background—Atherosclerotic plaques underlying most myocardial infarctions have thin fibrous caps and large necrotic cores; however, these features alone do not reliably identify plaques that rupture. Rupture occurs when plaque structural stress (PSS) exceeds mechanical strength. We examined whether PSS could be calculated in vivo based on virtual histology (VH) intravascular ultrasound and whether PSS varied according to plaque composition, subtype, or clinical presentation. Methods and Results—A total of 4429 VH intravascular ultrasound frames from 53 patients were analyzed, identifying 99 584 individual plaque components. PSS was calculated by finite element analysis in whole vessels, in individual plaques, and in higher-risk regions (plaque burden ≥70%, mean luminal area ⩽4 mm2, noncalcified VH-defined thin-cap fibroatheroma). Plaque components including total area/arc of calcification (R2=0.33; P<0.001 and R2=0.28; P<0.001) and necrotic core (R2=0.18; P<0.001 and R2=0.15; P<0.001) showed complex, nonlinear relationships with PSS. PSS was higher in noncalcified VH-defined thin-cap fibroatheroma compared with thick-cap fibroatheromas (median [Q1–Q3], 8.44 [6.97–10.64] versus 7.63 [6.37–9.68]; P=0.002). PSS was also higher in patients with an acute coronary syndrome, where mean luminal area ⩽4 mm2 (8.24 [7.06–9.93] versus 7.72 [6.33–9.34]; P=0.03), plaque burden ≥70% (9.18 [7.44–10.88] versus 7.93 [6.16–9.46]; P=0.02), and in noncalcified VH-defined thin-cap fibroatheroma (9.23 [7.33–11.44] versus 7.65 [6.45–8.62]; P=0.02). Finally, PSS increased the positive predictive value for VH intravascular ultrasound to identify clinical presentation. Conclusions—Finite element analysis modeling demonstrates that structural stress is highly variable within plaques, with increased PSS associated with plaque composition, subtype, and higher-risk regions in patients with acute coronary syndrome. PSS may represent a novel tool to analyze the dynamic behavior of coronary plaques with the potential to improve prediction of plaque rupture.

Role of biomechanical forces in the natural history of coronary atherosclerosis

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.

Ultrasmall Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Imaging of Abdominal Aortic Aneurysms–A Feasibility Study

OBJECTIVES Abdominal aortic aneurysms (AAAs), being predominantly atherosclerotic in nature, have underlying inflammatory activity. As it is well established that ultrasmall superparamagnetic iron oxide (USPIO) particles accumulate in the macrophages within atheromatous lesions, USPIO-enhanced magnetic resonance (MR) imaging can be potentially effective in the quantification of the associated inflammatory processes. METHODS A total of 14 patients underwent USPIO-enhanced MR imaging using a 1.5T-MR system. Quantitative T(2)* and T(2) relaxation time data were acquired before and 36 h after UPSIO infusion at identical AAA locations. The pre- and post-USPIO-infusion relaxation times (T(2)(∗) and T(2)) were quantified and the correlation between pre- and post-USPIO infusion T(2)* and T(2) values was investigated. RESULTS There was a significant difference between pre- and post-infusion T(2)* and T(2) values (both respective p-values = 0.005). A significant correlation between T(2)* and T(2) values post-USPIO infusion was observed (r = 0.90, p < 0.001), which indicates USPIO uptake by the aortic wall. CONCLUSIONS Aortic wall inflammation using USPIO-enhanced MR imaging is feasible. Use of quantitative T(2) and T(2)* pulse sequences provides a quantitative method for assessing USPIO uptake by the aortic wall.