Mechanical analysis of arterial plaques in native geometry with OCT wall motion analysis

The mechanical behavior of an atherosclerotic plaque may encode information about the type, composition, and vulnerability to rupture. Human arterial segments with varying plaque burden were analyzed ex vivo with optical coherence tomography (OCT) to determine plaque type and to determine compliance during pulsatile inflation in their native geometry. Calcifications and lipid filled plaques showed markedly different compliance when analyzed with OCT wall motion analysis. There was also a trend towards increased circumferential variation in arterial compliance with increasing plaque burden.     

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.     

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.     

Intravascular ultrasound imaging of myocardial-infarction-related arteries after percutaneous transluminal coronary angioplasty reveals significant plaque burden and compensatory enlargement

We studied patients with acute myocardial infarction (MI) by intravascular ultrasound (IVUS) to elucidate the controversy as to the amount and severity of the atherosclerotic disease at the culprit lesion site in acute MI, as discrepancies exist between angiographic and pathological reports. Twenty-five consecutive patients (age 56 3 10.5 years), with acute MI, underwent IVUS study of the MI-related artery immediately following successful PTCA to the culprit lesion. The IVUS images were analyzed quantitatively and qualitatively and were compared with the angiography of the same arteries. At the PTCA site, 64% of the lesions had an area stenosis of 50-70% and the plaque cross-sectional area (CSA) averaged 0.5 3 0.18 of the arterial CSA. IVUS-defined atherosclerosis was found also in 72% of the segments proximal and distal to the culprit lesion with a plaque/artery CSA ratio of 0.25 3 0.2. The angiogram revealed only 30% of these segments to be abnormal (P 3 0.001). Sixty-nine per cent of all the plaques were defined as 'soft' (low echo-genecity) versus 31% 'hard' (high echo-genecity). The hard plaques were larger than the soft plaques (0.5 3 1.6 versus 0.37 3 0.19 CSA index, respectively, P 3 0.01). With the increase in plaque area there was a significant increase in arterial cross-sectional area. This was demonstrated for all the diseased segments with a correlation coefficient of 0.49 (P 3 0.0001) and for the diseased reference sites a similar correlation coefficient of 0.49 (P 3 0.003) was found. Contrary to coronary angiographic-based reports, this IVUS study revealed a significant atheromatous plaque burden at the culprit lesion of MI-related arteries as well as diffuse atherosclerosis in the reference segments proximal and distal to the lesion. The detection of compensatory enlargement may explain the discrepancies between the histopathological and the angiographic studies.     

Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques

The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress–strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation.     

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.     

糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测研究

摘要 目的：分析糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测价值。方法：选择自2020年1月至2022年6月我院经冠脉造影确诊的165例冠心病临界病变患者作为研究对象,分为不稳定型心绞痛组和稳定型心绞痛组。检测两组血清糖化清蛋白、高敏C反应蛋白表达水平,使用靶血管造影检测冠脉斑块形态学指标,Pearson相关性分析血清糖化清蛋白、高敏C反应蛋白与冠脉斑块形态学指标的关系,通过ROC曲线下面积（AUC）评价血清糖化清蛋白联合高敏C反应蛋白对功能性心肌缺血的预测价值。结果：不稳定型心绞痛组血清糖化清蛋白、高敏C反应蛋白表达水平均高于稳定型心绞痛组（P＜0.05）;不稳定型心绞痛组最小管腔直径、最小管腔面积均小于稳定型心绞痛组,直径狭窄率、管腔面积狭窄率、斑块面积均大于稳定型心绞痛组（P＜0.05）;在165例冠心病临界病变患者中,发生冠脉易损斑块53例;易损斑块组血清糖化清蛋白、高敏C反应蛋白表达水平均高于非易损斑块组（P＜0.05）;经Pearson相关性分析,冠心病临界病变患者血清糖化清蛋白、高敏C反应蛋白表达水平均与最小管腔直径、最小管腔面积呈负相关,与直径狭窄率、管腔面积狭窄率、斑块面积呈正相关（P＜0.05）;经ROC曲线分析,血清糖化清蛋白联合高敏C反应蛋白预测冠心病临界病变患者发生功能性心肌缺血的AUC为0.910。结论：糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征密切相关,有助于评估冠脉斑块易损性,联合预测功能性心肌缺血的效能较好,值得临床予以重视应用。     

Microstructural and mechanical insight into atherosclerotic plaques: an ex vivo DTI study to better assess plaque vulnerability

Non-invasive microstructural characterisation has the potential to determine the stability, or lack thereof, of atherosclerotic plaques and ultimately aid in better assessing plaques’ risk to rupture. If linked with mechanical characterisation using a clinically relevant imaging technique, mechanically sensitive rupture risk indicators could be possible. This study aims to provide this link–between a clinically relevant imaging technique and mechanical characterisation within human atherosclerotic plaques. Ex vivo diffusion tensor imaging, mechanical testing, and histological analysis were carried out on human carotid atherosclerotic plaques. DTI-derived tractography was found to yield significant mechanical insight into the mechanical properties of more stable and more vulnerable microstructures. Coupled with insights from digital image correlation and histology, specific failure characteristics of different microstructural arrangements furthered this finding. More circumferentially uniform microstructures failed at higher stresses and strains when compared to samples which had multiple microstructures, like those seen in a plaque cap. The novel findings in this study motivate diagnostic measures which use non-invasive characterisation of the underlying microstructure of plaques to determine their vulnerability to rupture.

Graphic abstract

     

Plaque Vulnerability as Assessed by Radiofrequency Intravascular Ultrasound in Patients with Valvular Calcification

BackgroundCardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.MethodsTransthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score–matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.ResultsPatients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.ConclusionsThere is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).     

Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities

Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques.     

Tensile and compressive properties of fresh human carotid atherosclerotic plaques

Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2 h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.     

Intravascular ultrasound observations of atherosclerotic lesion formation and restenosis in patients with diabetes mellitus

Coronary artery disease is more aggressive in diabetic patients than in nondiabetics; they have more diffuse disease, higher mortality rates and worse clinical outcomes after coronary interventions. Intravascular ultrasound (IVUS) produces transmural tomographic images of the coronary arteries in vivo. Recent IVUS studies have provided new insights into the mechanisms of stenosis formation and restenosis in both nondiabetic and diabetic patients. Arterial remodeling is defined as a change in arterial area. During atherogenesis, an increase in arterial area usually accompanies plaque accumulation to delay lumen compromise. Stenosis formation is related to: (a) the rate of plaque accumulation versus the rate of positive remodeling; and (b) the limits and ultimate failure of positive remodeling. However, there is a marked variability in remodeling. IVUS studies have suggested that remodeling may be impaired in some diabetic patients during atherogenesis. Following non-stent catheter-based interventions, serial (post-intervention and follow-up) IVUS studies have shown that the change in lumen area correlates better with the change in arterial area (remodeling) than with the change in plaque area (neointimal hyperplasia). In some patients, a positive remodeling response mitigates against the increase in plaque area to limit late lumen loss and restenosis. Neointimal hyperplasia is exaggerated in diabetic patients. Despite this, there is a reduced frequency of positive remodeling, potentially similar to the impaired positive remodeling in some diabetic patients during atherogenesis. Failed or inadequate arterial remodeling may contribute to the pathogenesis and natural history of atherosclerotic coronary artery disease in diabetic patients.     

Proteomic analysis of human vessels: application to atherosclerotic plaques

Atherosclerosis is a chronic disease that affects medium and large arteries. This process originates from the interaction between cells of the arterial wall, lipoproteins and inflammatory cells, leading to the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in acute clinical complications such as myocardial infarction and stroke. Owing to the heterogeneous cellular composition of the plaques, a proteomic analysis of the whole lesion is not appropriate. Therefore, we have studied the proteins secreted by human carotid atherosclerotic plaques, obtained by endarterectomy. Normal artery segments and different regions of the surgical pieces (noncomplicated plaque, complicated plaque with thrombus) were cultured in protein-free medium and the secreted proteins (supernatants) analyzed by two-dimensional gel electrophoresis. Normal artery segments secreted a moderate number of proteins (42 spots). However in the two-dimensional (2-D) gels (pH 3-10) of segments bearing a plaque, the number of spots increased markedly (154). The number of spots also increased (202) in the 2-D gels of artery segments with a ruptured plaque and thrombus. Thus, the more complicated the lesion, the higher the number of secreted proteins, suggesting the production of specific proteins relating to the complexity of the atherosclerotic lesion.     

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.     

Stress-Based Plaque Vulnerability Index and Assessment for Carotid Atherosclerotic Plaques Using Patient-Specific Vessel Material Properties

Cardiovascular diseases are closely linked to atherosclerotic plaque development and rupture. Assessment of plaque vulnerability is of fundamental significance to cardiovascular research and disease diagnosis, prevention, treatment and management. Magnetic resonance image (MRI) data of carotid atherosclerotic plaques from 8 patients (5 male, 3 female; age: 62-83, mean=71) were acquired at the University of Washington (UW), Seattle by the Vascular Imaging Laboratory (VIL) with written informed consent obtained. Patient-specific vessel material properties were quantified using Cine MRI data for modeling use. 3D thin-layer models were used to obtain plaque stress and strain for plaque assessment. A stress-based plaque vulnerability index (SPVI) was proposed to combine mechanical analysis, plaque morphology and composition for more complete carotid plaque vulnerability assessment. The five intervals (unit: kPa) [0, 46.8), [46.8, 80), [80, 92), [92, 103), and [103, +∞) from in vivo material models were used for SPVI values of 0, 1, 2, 3 and 4, respectively. The optimized agreement rate was 85.19%. The use of patient-specific material properties in plaque models could potentially improve the accuracy of model stress/strain calculations. SPVI has the potential to improve the current image-based screening and plaque vulnerability assessment schemes.     

Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF‐κB pathway

Unstable atherosclerotic plaques of the carotid arteries are at great risk for the development of ischemic cerebrovascular events. The degradation of the extracellular matrix by matrix metalloproteinases (MMPs) and nitric oxide induced apoptosis of vascular smooth muscle cells (VSMCs) contribute to the vulnerability of the atherosclerotic plaques. Basic fibroblast growth factor (bFGF) through its mitogenic and angiogenic properties has already been implicated in the pathogenesis of atherosclerosis. However, its role in plaque stability remains elusive. To address this issue, a panel of human carotid atherosclerotic plaques was analysed for bFGF, FGF‐receptors‐1 and ‐2 (FGFR‐1/‐2), inducible nitric oxide synthase (iNOS) and MMP‐9 expression. Our data revealed increased expression of bFGF and FGFR‐1 in VSMCs of unstable plaques, implying the existence of an autocrine loop, which significantly correlated with high iNOS and MMP‐9 levels. These results were recapitulated in vitro by treatment of VSMCs with bFGF. bFGF administration led to up‐regulation of both iNOS and MMP‐9 that was specifically mediated by nuclear factor‐κB (NF‐κB) activation. Collectively, our data demonstrate a novel NF‐κB‐mediated pathway linking bFGF with iNOS and MMP‐9 expression that is associated with carotid plaque vulnerability.     

Quantifying effects of plaque structure and material properties on stress distributions in human atherosclerotic plaques using 3D FSI models

BACKGROUND: Atherosclerotic plaques may rupture without warning and cause acute cardiovascular syndromes such as heart attack and stroke. Methods to assess plaque vulnerability noninvasively and predict possible plaque rupture are urgently needed. METHOD: MRI-based three-dimensional unsteady models for human atherosclerotic plaques with multi-component plaque structure and fluid-structure interactions are introduced to perform mechanical analysis for human atherosclerotic plaques. RESULTS: Stress variations on critical sites such as a thin cap in the plaque can be 300% higher than that at other normal sites. Large calcification block considerably changes stress/strain distributions. Stiffness variations of plaque components (50% reduction or 100% increase) may affect maximal stress values by 20-50%. Plaque cap erosion causes almost no change on maximal stress level at the cap, but leads to 50% increase in maximal strain value. CONCLUSIONS: Effects caused by atherosclerotic plaque structure, cap thickness and erosion, material properties, and pulsating pressure conditions on stress/strain distributions in the plaque are quantified by extensive computational case studies and parameter evaluations. Computational mechanical analysis has good potential to improve accuracy of plaque vulnerability assessment.     

糖尿病和非糖尿病动脉粥样硬化兔模型的建立

目的建立兔动脉粥样硬化和糖尿病动脉粥样硬化模型并比较其动脉粥样硬化病变的特点。方法四氧嘧啶静脉推注诱发糖尿病后,行腹主动脉球囊损伤术拉伤内皮并饲高脂饲料建立糖尿病动脉粥样硬化兔模型,非糖尿病动脉粥样硬化兔模型静脉推注生理盐水,余处理相同。喂养10周做腹主动脉造影和腹主动脉内超声后处死,取腹主动脉横切片做HE染色和免疫组化,比较两组兔主动脉内膜/中膜比值及巨噬细胞、平滑肌细胞含量,以评价动脉粥样硬化病变的程度和性质。结果所有兔胸主动脉粥样硬化病变明显轻于腹主动脉;糖尿病动脉粥样硬化兔腹主动脉壁特别是近血管腔处巨噬细胞浸润明显多于动脉粥样硬化兔,而平滑肌细胞含量显著减少。结论糖尿病动脉粥样硬化兔的腹主动脉粥样硬化病变内有更加活跃的炎症细胞浸润,提示病变性质更加不稳定。     

Macrophage autophagy regulates mitochondria‐mediated apoptosis and inhibits necrotic core formation in vulnerable plaques

The vulnerable plaque is a key distinguishing feature of atherosclerotic lesions that can cause acute atherothrombotic vascular disease. This study was designed to explore the effect of autophagy on mitochondria‐mediated macrophage apoptosis and vulnerable plaques. Here, we generated the mouse model of vulnerable carotid plaque in ApoE^?/? mice. Application of ApoE^?/? mice with rapamycin (an autophagy inducer) inhibited necrotic core formation in vulnerable plaques by decreasing macrophage apoptosis. However, 3‐methyladenine (an autophagy inhibitor) promoted plaque vulnerability through deteriorating these indexes. To further explore the mechanism of autophagy on macrophage apoptosis, we used macrophage apoptosis model in vitro and found that 7‐ketocholesterol (7‐KC, one of the primary oxysterols in oxLDL) caused macrophage apoptosis with concomitant impairment of mitochondria, characterized by the impairment of mitochondrial ultrastructure, cytochrome c release, mitochondrial potential dissipation, mitochondrial fragmentation, excessive ROS generation and both caspase‐9 and caspase‐3 activation. Interestingly, such mitochondrial apoptotic responses were ameliorated by autophagy activator, but exacerbated by autophagy inhibitor. Finally, we found that MAPK‐NF‐κB signalling pathway was involved in autophagy modulation of 7‐KC–induced macrophage apoptosis. So, we provide strong evidence for the potential therapeutic benefit of macrophage autophagy in regulating mitochondria‐mediated apoptosis and inhibiting necrotic core formation in vulnerable plaques.     

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.