Plaque Longitudinal Heterogeneity in Morphology, Property, and Mechanobiology.

BACKGROUND AND PURPOSE: The hemodynamic environment of an atherosclerotic plaque varies along the longitudinal direction. Investigating the changes in plaque morphology and its biomechanical environment along the longitudinal direction and their correlations will enhance our understanding of plaque progression and arterial remodeling. METHODS: Six male patients with carotid stenosis >70% were recruited. Multisequence high-resolution MRI was performed at the carotid bifurcation. Carotid endarterectomy was performed following MRI, and the plaque tissue was collected for histological and mechanical testing. Patient-specific biomechanical modeling and simulations were conducted to calculate the mechanical stresses (wall shear stress [WSS] and von Mises stress [VMS]). Changes in plaque cross-sectional morphology, WSS, and VMS as well as their correlations were evaluated. RESULTS: Positive correlations were found between % stenosis and % inflammation (MA) (p = 0.019), % lipid area and % MA (p = 0.026), and % calcification area and VMS (p = 0.007). Negative correlations were found between VMS and % stenosis (p = 0.028) and VMS and average WSS (p = 0.034). Moreover, the peak stresses and neovessels were found to be in the shoulder regions. High-stress concentrations were found in the interface regions of the calcification and surrounding tissue, thereby increasing plaque vulnerability. CONCLUSIONS: Correlations between the morphology and stresses suggest that arterial remodeling is a dynamic interaction between mechanical environment and plaque progression resulting in plaque heterogeneity. Our finding indicates that plaque heterogeneity is associated with plaque progression and can be combined with mechanical stresses for identifying high-risk plaques.

Case Report: Evaluating Biomechanical Risk Factors in Carotid Stenosis by Patient-Specific Fluid-Structural Interaction Biomechanical Analysis.

BACKGROUND: Carotid atherosclerosis is one of the main underlying inducements of stroke, which is a leading cause of disability. The morphological feature and biomechanical environment have been found to play important roles in atherosclerotic plaque progression. However, the biomechanics in each patient's blood vessel is complicated and unique. METHOD: To analyse the biomechanical risk of the patient-specific carotid stenosis, this study used the fluid-structure interaction (FSI) computational biomechanical model. This model coupled both structural and hemodynamic analysis. Two patients with carotid stenosis planned for carotid endarterectomy were included in this study. The 3D models of carotid bifurcation were reconstructed using our in-house-developed protocol based on multisequence magnetic resonance imaging (MRI) data. Patient-specific flow and pressure waveforms were used in the computational analysis. Multiple biomechanical risk factors including structural and hemodynamic stresses were employed in post-processing to assess the plaque vulnerability. RESULTS: Significant difference in morphological and biomechanical conditions between 2 patients was observed. Patient I had a large lipid core and serve stenosis at carotid bulb. The stenosis changed the cross-sectional shape of the lumen. The blood flow pattern changed consequently and led to a complex biomechanical environment. The FSI results suggested a potential plaque progression may lead to a high-risk plaque, if no proper treatment was performed. The patient II had significant tandem stenosis at both common and internal carotid artery (CCA and ICA). From the results of biomechanical factors, both stenoses had a high potential of plaque progression. Especially for the plaque at ICA branch, the current 2 small plaques might further enlarge and merge as a large vulnerable plaque. The risk of plaque rupture would also increase. CONCLUSIONS: Computational biomechanical analysis is a useful tool to provide the biomechanical risk factors to help clinicians assess and predict the patient-specific plaque vulnerability. The FSI computational model coupling the structural and hemodynamic computational analysis, better replicates the in vivo biomechanical condition, which can provide multiple structural and flow-based risk factors to assess plaque vulnerability.

MRI-based mechanical analysis of carotid atherosclerotic plaque using a material-property-mapping approach: A material-property-mapping method for plaque stress analysis.

BACKGROUND AND OBJECTIVE: Atherosclerosis is a major underlying cause of cardiovascular conditions. In order to understand the biomechanics involved in the generation and rupture of atherosclerotic plaques, numerical analysis methods have been widely used. However, several factors limit the practical use of this information in a clinical setting. One of the key challenges in finite element analysis (FEA) is the reconstruction of the structure and the generation of a mesh. The complexity of the shapes associated with carotid plaques, including multiple components, makes the generation of meshes for biomechanical computation a difficult and in some cases, an impossible task. To address these challenges, in this study, we propose a novel material-property-mapping method for carotid atherosclerotic plaque stress analysis that aims to simplify the process. METHODS: The different carotid plaque components were identified and segmented using magnetic resonance imaging (MRI). For the mapping method, this information was used in conjunction with an in-house code, which provided the coordinates for each pixel/voxel and tissue type within a predetermined region of interest. These coordinates were utilized to assign specific material properties to each element in the volume mesh which provides a region of transition. The proposed method was subsequently compared to the traditional method, which involves creating a composed mesh for the arterial wall and plaque components, based on its location and size. RESULTS: The comparison between the proposed material-property-mapping method and the traditional method was performed in 2D, 3D structural-only, and fluid-structure interaction (FSI) simulations in terms of stress, wall shear stress (WSS), time-averaged WSS (TAWSS), and oscillatory shear index (OSI). The stress contours from both methods were found to be similar, although the proposed method tended to produce lower local maximum stress values. The WSS contours were also in agreement between the two methods. The velocity contours generated by the proposed method were verified against phase-contrast magnetic resonance imaging (MRI) measurements, for a higher level of confidence. CONCLUSION: This study shows that a material-property-mapping method can effectively be used for analyzing the biomechanics of carotid plaques in a patient-specific manner. This approach has the potential to streamline the process of creating volume meshes for complex biological structures, such as carotid plaques, and to provide a more efficient and less labor-intensive method.

Differences in Carotid Artery Geometry and Flow Caused by Body Postural Changes and Physical Exercise.

Different body postures and physical exercises may lead to changes in arterial geometry and hemodynamics, which may be associated with the distribution of atherosclerosis lesions. This study was aimed at investigating potential geometric and hemodynamic changes of the carotid bifurcation in different body postures and after high-intensity interval training (HIIT) workouts. Three-dimensional vascular ultrasound (3DVUS) and Doppler ultrasound images were acquired for 21 healthy participants (aged 29 ± 6 y, 14 men and 7 women) in different body postures (sitting and three sleeping postures [supine, left lateral and right lateral]) and after physical exercises. The common carotid artery (CCA) and internal carotid artery (ICA) diameters of the left carotid artery were found to increase significantly from supine to left lateral (both p <0.05). CCA diameters (p < 0.05) and ICA/CCA diameter ratio (p < 0.01) of the left carotid artery changed significantly from supine to sitting. Significant differences in CCA peak systolic velocity (CCA PSV, p < 0.001), CCA end-diastolic velocity (CCA EDV, p < 0.001), CCA pulsatility index (CCA PI, p < 0.001) and maximum velocity-based wall shear stress at the CCA (WSS(max) at the CCA, p < 0.001) were identified in different postures. After physical exercises, significant increases were observed in the CCA diameter (p < 0.001), CCA PSV (p < 0.001), ICA PSV (p < 0.05), WSS(max) at the CCA (p < 0.001) and WSS(max) at the ICA (p < 0.05), as were significantly lower values of the CCA EDV (p < 0.01) and ICA/CCA PSV ratio (p < 0.05). Side-to-side differences were also detected in different postural change scenarios and after physical exercise; more significant differences were found to occur only in the left-sided carotid artery. Significant differences were identified under postural change and after physical exercise among healthy adults, suggesting that daily activity has an effect on the carotid bifurcation. These changes may be associated with formation and development of carotid atherosclerosis. Moreover, these side differences might be severe for patients and worth further attention in clinical practice.

Reproducibility of the computational fluid dynamic analysis of a cerebral aneurysm monitored over a decade.

Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress divergence (WSSD) contributed to the growth of a daughter sac.

Impact of cyclic bending on coronary hemodynamics.

It remains unknown that the degree of bias in computational fluid dynamics results without considering coronary cyclic bending. This study aims to investigate the influence of different rates of coronary cyclic bending on coronary hemodynamics. To model coronary bending, a multi-ring-controlled fluid-structural interaction model was designed. A coronary artery was simulated with various cyclic bending rates (0.5, 0.75 and 1 s, corresponding to heart rates of 120, 80 and 60 bpm) and compared against a stable model. The simulated results show that the hemodynamic parameters of vortex Q-criterion, temporal wall shear stress (WSS), time-averaged WSS (TaWSS) and oscillatory shear index (OSI) were sensitive to the changes in cyclic rate. A higher heart rate resulted in higher magnitude and larger variance in the hemodynamic parameters. Whereas, the values and distributions of flow velocity and relative residence time (RRT) did not show significant differences between different bending periods. This study suggests that a stable coronary model is not sufficient to represent the hemodynamics in a bending coronary artery. Different heart rate conditions were found to have significant impact on the hemodynamic parameters. Thus, cyclic bending should be considered to mimic the realistic hemodynamics in future patient-specific coronary hemodynamics studies.

The Need to Shift from Morphological to Structural Assessment for Carotid Plaque Vulnerability.

Degree of luminal stenosis is generally considered to be an important indicator for judging the risk of atherosclerosis burden. However, patients with the same or similar degree of stenosis may have significant differences in plaque morphology and biomechanical factors. This study investigated three patients with carotid atherosclerosis within a similar range of stenosis. Using our developed fluid-structure interaction (FSI) modelling method, this study analyzed and compared the morphological and biomechanical parameters of the three patients. Although their degrees of carotid stenosis were similar, the plaque components showed a significant difference. The distribution range of time-averaged wall shear stress (TAWSS) of patient 2 was wider than that of patient 1 and patient 3. Patient 2 also had a much smaller plaque stress compared to the other two patients. There were significant differences in TAWSS and plaque stresses among three patients. This study suggests that plaque vulnerability is not determined by a single morphological factor, but rather by the combined structure. It is necessary to transform the morphological assessment into a structural assessment of the risk of plaque rupture.

Evaluating the Impact of Calcification on Plaque Vulnerability from the Aspect of Mechanical Interaction Between Blood Flow and Artery Based on MRI.

Acute cerebral ischemic events and thrombosis are associated with the rupture/erosion of carotid atherosclerotic plaques. The aim of the present study was to determine the impact of calcification deposition on the wall shear stress (WSS) and stresses within the plaques using 3D fluid-structure interaction (FSI) models. Six patients with calcified carotid atherosclerosis underwent multisequence magnetic resonance imaging (MRI) and were divided into three groups according to the calcification volume. To evaluate the role of the calcification deposition on the stresses, the calcification content was replaced by lipids and arterial tissue, respectively. By comparing the results from the simulation with calcification, and when changing it to lipids there was a significant increment in the stresses at the fibrous cap (p = 0.004). Instead, by changing it to arterial tissue, there was no significant difference (p = 0.07). The calcification shapes that presented the highest stresses were thin concave arc-shaped (AS1) and thin convex arc-shaped (AS3), with mean stress values of 107 ± 54.2 and 99.6 ± 23.4 kPa, respectively. It was also observed that, the calcification shape has more influence on the level of stress than its distance to the lumen. Higher WSS values were associated with the presence of calcification. Calcification shape plays an important role in producing high stresses in the plaque. This work further clarifies the impact of calcification on plaque vulnerability.

The importance of blood rheology in patient-specific computational fluid dynamics simulation of stenotic carotid arteries.

The initiation and progression of atherosclerosis, which is the main cause of cardiovascular diseases, correlate with local haemodynamic factors such as wall shear stress (WSS). Numerical simulations such as computational fluid dynamics (CFD) based on medical imaging have been employed to analyse blood flow in different arteries with and without luminal stenosis. Patient-specific CFD models, however, have assumptions on blood rheology. The differences in the calculated haemodynamic factors between different rheological models have not been fully evaluated. In this study, carotid magnetic resonance imaging (MRI) was performed on six patients with different degrees of carotid stenosis and two healthy volunteers. Using the 3D reconstructed carotid geometries and the patient-specific boundary conditions, CFD simulations were performed by applying a Newtonian and four non-Newtonian models (Carreau, Cross, Quemada and Power-law). WSS descriptors and pressure gradient were analysed and compared between the models. The differences in the maximum and the average oscillatory shear index between the Newtonian and the non-Newtonian models were lower than 12.7% and 12%, respectively. The differences in pressure gradient were also within 15%. The differences in the mean time-averaged WSS (TAWSS) between the Newtonian and Cross, Carreau and Power-law models were lower than 6%. In contrast, a higher difference (26%) was found in Quemada. For the low TAWSS, the differences from the Newtonian to the non-Newtonian models were much larger, in the range of 0.4-31% for Carreau, 3-22% for Cross, 5-51% for Quemada and 10-41% for Power-law. The study suggests that the assumption of a Newtonian model is reasonable when the overall flow pattern or the mean values of the WSS descriptors are investigated. However, the non-Newtonian model is necessary when the low TAWSS region is the focus, especially for arteries with severe stenosis.

Optical coherence tomography-based patient-specific coronary artery reconstruction and fluid-structure interaction simulation.

Plaque rupture is related to the mechanical stress it suffered. The value and distribution of the mechanical stress in plaque could help on assessing plaque vulnerability. To look into the stress conditions in the coronary artery, a patient-specific coronary model was created by using optical coherence tomography (OCT) and angiography imaging data. The reconstructed coronary model consisted of the structure of the lumen, the arterial wall and plaque components. Benefited by the high resolution of OCT, detailed structures such as the thin fibrous cap could be observed and built into the geometry. On this reconstructed coronary model, a fully coupled fluid-structure interaction (FSI) simulation was performed. The principle stress in coronary plaque and the wall shear stress (WSS) were analyzed. The FSI simulation results show that the cap thickness had a significant effect on the stress, and the principle stress at the thin cap area was more than double of those at the locations with a larger thickness. WSS is thought as an important parameter to assess the potentially dangerous areas of the atherosclerosis-prone (caused by low WSS) and the plaque rupture (high WSS). From the WSS plots of our FSI model, the area with abnormal WSS value was detected around the position where a lipid core existed. The FSI simulation results were compared with the results from the conventional structure-only and the computational fluid dynamics (CFD)-only computational models to quantify the difference between the three models. We found little difference in the principle stress results between the FSI and the structure-only model, but a significant difference between the FSI and the CFD-only model when looking into the WSS. The WSS values at the two observation spots from the CFD-only model were higher than the values from the FSI model by 17.95% and 22.66% in average, respectively. Furthermore, the FSI model detected more areas of low WSS, because the fluid domain could expand circumferentially when pressure loaded on the flexible arterial. This study suggests that OCT-based FSI model may be useful for plaque vulnerability assessment and it may be critical to perform the FSI simulation if an accurate WSS value is required.

Stress-Relaxation and Cyclic Behavior of Human Carotid Plaque Tissue.

Atherosclerotic plaque rupture is a catastrophic event that contributes to mortality and long-term disability. A better understanding of the plaque mechanical behavior is essential for the identification of vulnerable plaques pre-rupture. Plaque is subjected to a natural dynamic mechanical environment under hemodynamic loading. Therefore, it is important to understand the mechanical response of plaque tissue under cyclic loading conditions. Moreover, experimental data of such mechanical properties are fundamental for more clinically relevant biomechanical modeling and numerical simulations for risk stratification. This study aims to experimentally and numerically characterize the stress-relaxation and cyclic mechanical behavior of carotid plaque tissue. Instron microtester equipped with a custom-developed setup was used for the experiments. Carotid plaque samples excised at endarterectomy were subjected to uniaxial tensile, stress-relaxation, and cyclic loading protocols. Thirty percent of the underlying load level obtained from the uniaxial tensile test results was used to determine the change in mechanical properties of the tissue over time under a controlled testing environment (Control tests). The stress-relaxation test data was used to calibrate the hyperelastic (neo-Hookean, Ogden, Yeoh) and linear viscoelastic (Prony series) material parameters. The normalized relaxation force increased initially and slowly stabilized toward the end of relaxation phase, highlighting the viscoelastic behavior. During the cyclic tests, there was a decrease in the peak force as a function of the cycle number indicating mechanical distension due to repeated loading that varied with different frequencies. The material also accumulated residual deformation, which increased with the cycle number. This trend showed softening behavior of the samples. The results of this preliminary study provide an enhanced understanding of in vivo stress-relaxation and cyclic behavior of the human atherosclerotic plaque tissue.

Carotid Bifurcation With Tandem Stenosis-A Patient-Specific Case Study Combined in vivo Imaging, in vitro Histology and in silico Simulation.

A patient-specific carotid bifurcation with tandem stenosis found at both internal carotid artery (ICA) and common carotid artery (CCA) was studied. The in vivo pre-carotid endarterectomy (pre-CEA) multi-spectral magnetic resonance imaging (MRI) were performed and in vitro post-CEA carotid plaque tissue sample was collected. MR imaging data and tissue sample staining histology were used to recognize the plaque components. Further, the computational fluid dynamics (CFD) were performed on four MR-based reconstructed 3D carotid bifurcation models (the patient-specific geometry with tandem stenosis and three presumptive geometries by removing the stenosis part). The flow and shear stress behavior affected by the tandem stenosis was analyzed. From the results of MR segmentation and histology analysis, plaque lipid pool and calcification were found at both ICA and CCA. From the result of CFD simulation, the flow shear stress behavior suggested the tandem stenosis as a more "dangerous" situation than a single-stenosis artery. Besides, the CFD results deduced that the stenosis at the CCA location formed initially and led to the subsequent formation of stenosis at ICA. This study suggests that when planning CEA, CFD simulation on the presumptive models could help clinicians to estimate the blood flow behavior after surgery. Particular attention should be paid to the case of tandem stenosis, as the local hemodynamic environment is more complex and treatment of one stenosis may lead to a variation in the hemodynamic loading on the second plaque, which may result in either a higher risk of plaque rupture or restenosis.