Ali C. Akyildiz

Effects of intima stiffness and plaque morphology on peak cap stress

BackgroundRupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress.MethodsModels with idealized geometries based on histology images of human coronary arteries were generated by varying geometric plaque features. The constructed multi-layer models contained adventitia, media, intima, and necrotic core sections. For adventitia and media layers, anisotropic hyperelastic material models were used. For necrotic core and intima sections, isotropic hyperelastic material models were employed. Three different intima stiffness values were used to cover the wide range reported in literature. According to the intima stiffness, the models were classified as stiff, intermediate and soft intima models. Finite element method was used to compute peak cap stress.ResultsThe intima stiffness was an essential determinant of cap stresses. The computed peak cap stresses for the soft intima models were much lower than for stiff and intermediate intima models. Intima stiffness also affected the influence of morphological parameters on cap stresses. For the stiff and intermediate intima models, the cap thickness and necrotic core thickness were the most important determinants of cap stresses. The peak cap stress increased three-fold when the cap thickness was reduced from 0.25 mm to 0.05 mm for both stiff and intermediate intima models. Doubling the thickness of the necrotic core elevated the peak cap stress by 60% for the stiff intima models and by 90% for the intermediate intima models. Two-fold increase in the intima thickness behind the necrotic core reduced the peak cap stress by approximately 25% for both intima models. For the soft intima models, cap thickness was less critical and changed the peak cap stress by 55%. However, the necrotic core thickness was more influential and changed the peak cap stress by 100%. The necrotic core angle emerged as a critical determinant of cap stresses where a larger angle lowered the cap stresses. Contrary to the stiff and intermediate intima models, a thicker intima behind the necrotic core increased the peak cap stress by approximately 25% for the soft intima models. Adventitia thickness and local media regression had limited effects for all three intima models.ConclusionsFor the stiff and intermediate intima models, the cap thickness was the most important morphological risk factor. However for soft intima models, the necrotic core thickness and necrotic core angle had a bigger impact on the peak cap stress. We therefore need to enhance our knowledge of intima material properties if we want to derive critical morphological plaque features for risk evaluation.

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.

Local axial compressive mechanical properties of human carotid atherosclerotic plaques—characterisation by indentation test and inverse finite element analysis

The fibrous cap of an atherosclerotic plaque may be prone to rupture if the occurring stresses exceed the strength of the cap. Rupture can cause acute thrombosis and subsequent ischaemic stroke or myocardial infarction. A reliable prediction of the rupture probability is essential for the appropriate treatment of atherosclerosis. Biomechanical models, which compute stresses and strain, are promising to provide a more reliable rupture risk prediction. However, these models require knowledge of the local biomechanical properties of atherosclerotic plaque tissue. For this purpose, we examined human carotid plaques using indentation experiments. The test set-up was mounted on an inverted confocal microscope to visualise the collagen fibre structure during the tests. By using an inverse finite element (FE) approach, and assuming isotropic neo-Hookean behaviour, the corresponding Youngs moduli were found in the range from 6 to 891kPa (median 30kPa). The results correspond to the values obtained by other research groups who analysed the compressive Youngs modulus of atherosclerotic plaques. Collagen rich locations showed to be stiffer than collagen poor locations. No significant differences were found between the Youngs moduli of structured and unstructured collagen architectures as specified from confocal collagen data. Insignificant differences between the middle of the fibrous cap, the shoulder regions, and remaining plaque tissue locations indicate that axial, compressive mechanical properties of atherosclerotic plaques are independent of location within the plaque.

Mechanical properties of human atherosclerotic intima tissue

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification.

The influence of axial image resolution on atherosclerotic plaque stress computations

Biomechanical models are used extensively to study risk factors, such as peak stresses, for vulnerable atherosclerotic plaque rupture. Typically, 3D patient-specific arterial models are reconstructed by interpolating between cross sectional contour data which have a certain axial sampling, or image, resolution. The influence of the axial sampling resolution on computed stresses, as well as the comparison of 3D with 2D simulations, is quantified in this study. A set of histological data of four atherosclerotic human coronary arteries was used which were reconstructed in 3D with a high sampling (HS) and low sampling (LS) axial resolution, and 4 slices were treated separately for 2D simulations. Stresses were calculated using finite element analysis (FEA). High stresses were found in thin cap regions and regions of thin vessel walls, low stresses were found inside the necrotic cores and media and adventitia layers. Axial sampling resolution was found to have a minor effect on general stress distributions, peak plaque/cap stress locations and the relationship between peak cap stress and minimum cap thickness. Axial sampling resolution did have a profound influence on the error in computed magnitude of peak plaque/cap stresses (±15.5% for HS vs. LS geometries and ±24.0% for HS vs. 2D geometries for cap stresses). The findings of this study show that axial under sampling does not influence the qualitative stress distribution significantly but that high axially sampled 3D models are needed when accurate computation of peak stress magnitudes is required.

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.

Local anisotropic mechanical properties of human carotid atherosclerotic plaques:characterisation by micro-indentation and inverse finite element analysis

Biomechanical models have the potential to predict failure of atherosclerotic plaques and to improve the risk assessment of plaque rupture. The applicability of these models depends strongly on the used material models. Current biomechanical models employ isotropic material models, although it is generally accepted that plaque tissue behaves highly anisotropic. The aim of the present study is to determine the local anisotropic mechanical properties of human atherosclerotic plaque tissue by means of micro-indentation tests. The indentation was performed on top of an inverted confocal microscope allowing the visualisation and quantification of the collagen fibre deformations perpendicular to the indentation direction of the plaque. Based on this, the anisotropic properties of plaque tissue perpendicular to the indentation direction (middle of the fibrous cap, shoulder of the cap, remaining intima tissue) were derived. There were no significant differences between the different indentation locations for the fibre stiffness (total median 80.6kPa, 25th-75th percentile 17.7-157.0kPa), and fibre dispersion.

Intima heterogeneity in stress assessment of atherosclerotic plaques

Atherosclerotic plaque rupture is recognized as the primary cause of cardiac and cerebral ischaemic events. High structural plaque stresses have been shown to strongly correlate with plaque rupture. Plaque stresses can be computed with finite-element (FE) models. Current FE models employ homogeneous material properties for the heterogeneous atherosclerotic intima. This study aimed to evaluate the influence of intima heterogeneity on plaque stress computations. Two-dimensional FE models with homogeneous and heterogeneous intima were constructed from histological images of atherosclerotic human coronaries (n = 12). For homogeneous models, a single stiffness value was employed for the entire intima. For heterogeneous models, the intima was subdivided into four clusters based on the histological information and different stiffness values were assigned to the clusters. To cover the reported local intima stiffness range, 100 cluster stiffness combinations were simulated. Peak cap stresses (PCSs) from the homogeneous and heterogeneous models were analysed and compared. By using a global variance-based sensitivity analysis, the influence of the cluster stiffnesses on the PCS variation in the heterogeneous intima models was determined. Per plaque, the median PCS values of the heterogeneous models ranged from 27 to 160 kPa, and the PCS range varied between 43 and 218 kPa. On average, the homogeneous model PCS values differed from the median PCS values of heterogeneous models by 14%. A positive correlation (R2 = 0.72) was found between the homogeneous model PCS and the PCS range of the heterogeneous models. Sensitivity analysis showed that the highest main sensitivity index per plaque ranged from 0.26 to 0.83, and the average was 0.47. Intima heterogeneity resulted in substantial changes in PCS, warranting stress analyses with heterogeneous intima properties for plaque-specific, high accuracy stress assessment. Yet, computations with homogeneous intima assumption are still valuable to perform sensitivity analyses or parametric studies for testing the effect of plaque geometry on PCS. Moreover, homogeneous intima models can help identify low PCS, stable type plaques with thick caps. Yet, for thin cap plaques, accurate stiffness measurements of the clusters in the cap and stress analysis with heterogeneous cap properties are required to characterize the plaque stability.

3D fiber orientation in atherosclerotic carotid plaques

Atherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in atherosclerotic plaques for the first time. Seven carotid plaques were imaged ex-vivo with a state-of-the-art Diffusion Tensor Imaging (DTI) technique, using a high magnetic field (9.4Tesla) MRI scanner. A 3D spin-echo sequence with uni-polar diffusion sensitizing pulsed field gradients was utilized for DTI and fiber directions were assessed from diffusion tensor measurements. The distribution of the 3D fiber orientations in atherosclerotic plaques were quantified and the principal fiber orientations (circumferential, longitudinal or radial) were determined. Overall, 52% of the fiber orientations in the carotid plaque specimens were closest to the circumferential direction, 34% to the longitudinal direction, and 14% to the radial direction. Statistically no significant difference was measured in the amount of the fiber orientations between the concentric and eccentric plaque sites. However, concentric plaque sites showed a distinct structural organization, where the principally longitudinally oriented fibers were closer to the luminal side and the principally circumferentially oriented fibers were located more abluminally. The acquired unique information on 3D plaque fiber direction will help understanding pathobiological mechanisms of atherosclerotic plaque progression and pave the road to more realistic biomechanical plaque modeling for rupture assessment.

VESS09. Computed Tomography Angiography Structural Analysis of Carotid Plaque Burden, Juxtaluminal Dark Matter, and Calcification in Symptomatic and Contralateral Asymptomatic Stenosis (30%-70%): What Can Be Learned?

there was an overall increase in true lumen diameter and concomitant decrease in false lumen diameter in both acute and nonacute patients at the level of the largest diameter in both the thoracic and abdominal aorta. At 5 years, 66% of acute and 81% of nonacute patients exhibited either a stable or shrinking transaortic diameter in the thoracic aorta; 52% of acute and 24% of nonacute patients experienced growth in transaortic diameter in the abdominal aorta. Five-year freedom from secondary intervention was 66% 6 8% for acute and 71% 6 9% for nonacute patients (log-rank test, P 1⁄4 .71). Conclusions: Endovascular repair of complicated type B aortic dissection with a composite device design demonstrated low all-cause mortality at 30 days as well as low dissection-related mortality during follow-up. Overall, the acute and nonacute cohorts from the feasibility study appeared to respond similarly to treatment involving use of the stent graft and bare metal stent, demonstrating similar clinical outcomes and favorable aortic remodeling in the thoracic and abdominal aorta.