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Stroke remains the most prevalent disabling illness today, with internal carotid artery luminal stenosis due to atheroma formation responsible for the majority of ischemic cerebrovascular events. Severity of luminal stenosis continues to dictate both patient risk stratification and the likelihood of surgical intervention. But there is growing evidence to suggest that plaque morphology may help improve pre-existing risk stratification criteria. Plaque components such a fibrous tissue, lipid rich necrotic core and calcium have been well investigated but plaque hemorrhage (PH) has been somewhat overlooked. In this review we discuss the pathogenesis of PH, its role in dictating plaque vulnerability, PH imaging techniques, marterial properties of atherosclerotic tissues, in particular, those obtained based on in vivo measurements and effect of PH in modulating local biomechanics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Intracranial atherosclerotic disease is increasingly recognized as a major stroke subtype worldwide. Current diagnostic evaluation of atherosclerotic disease of the middle cerebral artery (MCA) relies on detection of stenoses with luminographic imaging studies that do not directly visualize plaque unlike high-resolution MRI. This retrospective study seeks to evaluate the accuracy of high-resolution MRI vessel wall imaging, computed tomographic angiography (CTA) and digital subtraction angiography (DSA) in measuring the degree of stenosis within the MCA. 28 recently symptomatic patients with MCA territory symptoms underwent preliminary imaging with CTA followed by high-resolution MRI at 3-Tesla and definitive imaging with DSA for detection of M1 territory steno-occlusive lesions. Measurements of MCA segments on MRI and CTA were compared with reference to DSA values. Sensitivity and specificity of high-resolution MRI vessel wall imaging, CTA using maximum intensity projection (MIP) and CTA using volume rendering (VR) for the detection of stenosis > 50 % and occlusion were 80.0 and 53.6 %, 72.2 and 72.7 %, and 77.8 and 18.2 %, respectively. MRI-derived values correlated better with DSA (Spearman R = 0.68, p < 0.01) than CTA MIP and VR (Spearman R = 0.45, 0.22; p = 0.02, 0.24, respectively). High-resolution MRI of the MCA is capable of accurately measuring the degree of stenosis and is more sensitive than CTA in a sample of high-risk, symptomatic patients. This study, combined with previous reports, supports the potential of morphological MRI to measure intracranial atherosclerotic plaque non-invasively.

Atherosclerosis is becoming the number one cause of death worldwide. In this study, three-dimensional computer model of plaque formation and development for human carotid artery is developed. The three-dimensional blood flow is described by the Navier-Stokes equation, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modeled by a convection-diffusion equation. The low-density lipoproteins transports in lumen of the vessel and through the vessel tissue are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. Fluid-structure interaction is used to estimate effective wall stress analysis. Plaque growth functions for volume progression are correlated with shear stress and effective wall stress distribution. We choose two specific patients from MRI study with significant plaque progression. Plaque volume progression using three time points for baseline, 3- and 12-month follow up is fitted. Our results for plaque localization correspond to low shear stress zone and we fitted parameters from our model using nonlinear least-square method. Determination of plaque location and composition, and computer simulation of progression in time for a specific patient shows a potential benefit for the prediction of disease progression. The proof of validity of three-dimensional computer modeling in the evaluation of atherosclerotic plaque burden may shift the clinical information of MRI from morphological assessment toward a functional tool. Understanding and prediction of the evolution of atherosclerotic plaques either into vulnerable or stable plaques are major tasks for the medical community.

Objective: Intraplaque hemorrhage is an increasingly recognized contributor to plaque instability. Neovascularization of plaque is believed to facilitate the entry of inflammatory and red blood cells (RBC). Under physiological conditions, neovessels are subject to mechanical loading from the deformation of atherosclerotic plaque by blood pressure and flow. Local mechanical environments around neovessels and their relevant pathophysiologic significance have not yet been examined., Methods and Results: Four carotid plaque samples removed at endarcterectomy were collected for histopathological examination. Neovessels and other components were manually segmented to build numerical models for mechanical analysis. Each component was assumed to be non-linear isotropic, piecewise homogeneous and incompressible. The results indicated that local maximum principal stress and stretch and their variations during one cardiac cycle were greatest around neovessels. Neovessels surrounded by RBC underwent a much larger stretch during systole than those without RBCs present nearby (median [inter quartile range]; 1.089 [1.056, 1.131] vs. 1.034 [1.020, 1.067]; p<0.0001) and much larger stress (5.3kPa [3.4, 8.3] vs. 3.1kPa [1.6, 5.5]; p<0.0001) and stretch (0.0282 [0.0190, 0.0427] vs. 0.0087 [0.0045, 0.0185]; p<0.0001) variations during the cardiac cycle., Conclusions: Local critical mechanical conditions may lead to the rupture of neovessels resulting in the formation and expansion of intraplaque hemorrhage., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Plaque haemorrhage (PH) in atherosclerotic plaques is associated with recurrent thromboembolic ischaemic events. The healing process predominantly involves the repair of the plaque rupture site and the replacement of fresh PH with chronic PH, which is either reabsorbed or replaced by fibrous tissue. The extent to which the presence of PH, and its type i.e. fresh or chronic, affects plaque stability remains unexplored. Finite element analysis (FEA)-based biomechanical stress simulations can provide quantification of the percentage contribution of PH and its types to the biomechanical stresses of plaques, thereby providing information about its role in plaque stability. Fifty-two patients with atherosclerotic carotid disease underwent high resolution magnetic resonance (MR) imaging of their carotid arteries in a 1.5 Tesla MR system. Twenty-three patients had MR-identifiable PH and were selected. Only those images of these patients were used for simulations, which had evidence of PH. Manual segmentation of plaque components, such as lipid pool, fibrous tissue, calcium and PH, was done using carotid MR images. Plaque components and vessel wall were modelled as isotropic, incompressible hyperelastic materials with non-linear properties undergoing deformation under patient-specific blood pressure loading. Two dimensional structure-only FEA was used for quantification of maximum critical stress (M-CStress) of plaques. The median M-CStress of symptomatic patients with fresh PH was 159 kPa (IQR: 114-253). Because PH usually occurs within the lipid pool, when the simulation was repeated with lipid pool replacing fresh PH to simulate the pre-rupture plaque state, M-CStress was reduced by 26% [118 kPa (IQR: 79-189) (P=0.001)]. When fresh PH was replaced with chronic PH it resulted in a 30% reduction in the M-CStress [118 kP (IQR: 79-189), (P=0.001)]. PH affects stresses within atheroma to various degrees depending on its type, thereby influencing plaque stability to a different extent, with fresh PH significantly increasing the biomechanical stresses. Plaque component-dependent stress analysis has the potential of identifying the critical nature of various plaque components., (© Springer Science+Business Media, B.V. 2010)

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.

The shape of tracheal cartilage has been widely treated as symmetric in analytical and numerical models. However, according to both histological images and in vivo medical image, tracheal cartilage is of highly asymmetric shape. Taking the cartilage as symmetric structure will induce bias in calculation of the collapse behavior, as well as compliance and muscular stress. However, this has been rarely discussed. In this paper, tracheal collapse is represented by considering its asymmetric shape. For comparison, the symmetric shape, which is reconstructed by half of the cartilage, is also presented. A comparison of cross-sectional area, compliance of airway and stress in the muscular membrane, determined by asymmetric shape and symmetric shape is made. The result indicates that the symmetric assumption brings a small error, around 5% in predicting the cross-sectional area under loading conditions. The relative error of compliance is more than 10%. Particularly when the pressure is close to zero, the error could be more than 50%. The model considering the symmetric shape results in a significant difference in predicting stress in muscular membrane by either under- or over-estimating it. In conclusion, tracheal cartilage should not be treated as a symmetric structure. The results obtained in this study are helpful in evaluating the error induced by the assumption in geometry.

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.

The mechanical property of the trachea affects the flow in the airway and may contribute to the biological function of the lung. Like many other biological tissues, the tracheal cartilage is likely to be a nonlinear material. To investigate the nonlinearity of tracheal cartilage, Fung-type strain energy density function was used. A mathematical model for analyzing the deformation of tracheal cartilage was developed and a bending test on pig trachea was performed. By fitting the experimental data, the constants included in the strain energy density function were therefore determined. The experimental data shows that tracheal cartilage displays higher strength in compression than in extension. Fung-type strain energy density function can capture this nonlinear behavior very well, whilst the linear stress-strain relation cannot. This study contributes to a better understanding of the material of tracheal cartilage and further benefits to its mechanical behavior under physiological and pathological conditions.