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.

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.

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.

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.

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.

Staged management of a primary aortobronchial fistula: a novel approach using a trapezius flap repair.

There have been few reported cases of management of an aortobronchial fistula. We describe the case of a 68 year-old male with a very high operative risk who had a successful staged management of a primary aortobronchial fistula. An endovascular stent was placed initially, however due to recurrence of the fistula a second stent was deployed within the first one some three months after. Fifteen months later he represented with massive haemoptysis, severe cachexia and at this stage the best course of surgical management was thought to be lobectomy via thoracotomy followed by trapezius flap overlay covering the exposed stent and separating it from the remaining lung.