F.J.H. Gijsen

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.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

Temperature distribution in atherosclerotic coronary arteries: influence of plaque geometry and flow (a numerical study)

Intravascular coronary thermography is a method that may detect vulnerable, atherosclerotic plaques and is currently evaluated in a clinical setting. Active macrophages or enzymatic heat releasing processes in vulnerable plaques may act as heat sources. To better understand the parameters of influence on thermographic measurements, numerical simulations have been performed on a model of a coronary artery segment containing a heat source. Heat source parameters and flow were varied to study their influence on temperatures at the lumen wall. Maximal temperature differences at the lumen wall increased when the source volume increased and they differ with the source geometry. The simulations showed that blood flow acts as a coolant to the lumen wall. Blood flow decreased maximal temperatures depending on the source geometry, source volume and the maximal flow velocity. Influence of flow was highest for circumferentially extended sources, up to a factor 3.7, and lowest for longitudinally extended sources, down to a factor 1.9. When cap thickness increased, maximal temperatures decreased and the influence of flow increased. This study shows that correct interpretation of intravascular thermographic measurements requires data on the flow and on the morphologic characteristics of the atherosclerotic plaque.

High shear stress influences plaque vulnerability

Shear stress of the blood at the vessel wall plays an important role in many processes in the cardiovascular system primarily focused on the regulation of vessel lumen and wall dimensions. There is ample evidence that atherosclerotic plaques are generated at low shear stress regions in the cardiovascular system, while high shear stress regions are protected. In the course of plaque progression, advanced plaques start to encroach into the lumen, and thereby start to experience high shear stress at the endothelium. Until now the consequences of high shear stress working at the endothelium of an advanced plaque are unknown. As high shear stress influences tissue regression, we hypothesised that high shear stress can destabilise the plaque by cap weakening leading to ulceration. We investigated this hypothesis in a magnetic resonance imaging (MRI) dataset of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at ten-month follow-up. The lumen, plaque components (lipid/necrotic core, intraplaque haemorrhage) and ulcer were reconstructed three dimensionally and the geometry at baseline was used for shear stress calculation using computational fluid dynamics. Correlation of the change in plaque composition with the shear stress at baseline showed that the ulcer was generated exclusively at the high shear stress location. In this serial MRI study we found plaque ulceration at the high shear stress location of a protruding plaque in the carotid artery. Our data suggest that high shear stress influences plaque vulnerability and therefore may become a potential parameter for predicting future events. (Neth Heart J 2008;16:280-3.)

Computational fluid dynamics in Fontan patients to evaluate power loss during simulated exercise

Objective Exercise intolerance is common in total cavopulmonary connection (TCPC) patients. It has been suggested that power loss (Ploss) inside the TCPC plays a role in reduced exercise performance. Our objective is to establish the role of Ploss inside the TCPC during increased flow, simulating exercise in a patient-specific way. Methods Cardiac MRI (CMR) was used to obtain flow rates from the caval veins during rest and increased flow, simulating exercise with dobutamine. A 3D reconstruction of the TCPC was created using CMR data. Computational fluid dynamics (CFD) simulations were performed to calculate Ploss inside the TCPC structure for rest and stress conditions. To reflect the flow distribution during exercise, a condition where inferior caval vein (IVC) flow was increased twofold compared with rest was added. 29 TCPC patients (15 intra-atrial lateral tunnel (ILT) and 14 extracardiac conduit (ECC)) were included. Results Mean Ploss at rest was 1.36±0.94 (ILT) and 3.20±1.26 (ECC) mW/m2 (p<0.001), 2.84±1.95 (ILT) and 8.41±3.77 (ECC) mW/m2 (p<0.001) during dobutamine and 5.21±3.50 (ILT) and 15.28±8.30 (ECC) mW/m2 (p=0.001) with twofold IVC flow. The correlation between cardiac index and Ploss was exponential (ILT: R2=0.811, p<0.001; ECC: R2=0.690, p<0.001). Conclusions Ploss inside the TCPC structure is limited but increases with simulated exercise. This relates to the anatomy of TCPC and the surgical technique used. In all flow conditions, ILT patients have lower Ploss than ECC patients. We did not find a relationship between Ploss and exercise capacity.

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.

Animal models for plaque rupture: a biomechanical assessment

Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque rupture. Several animal models for the study of atherosclerosis are available. Plaque rupture in these models only occurs following severe surgical or pharmaceutical intervention. In the process of plaque rupture, composition, biology and mechanics each play a role, but the latter has been disregarded in many animal studies. The biomechanical environment for atherosclerotic plaques is comprised of two parts, the pressure-induced stress distribution, mainly - but not exclusively - influenced by plaque composition, and the strength distribution throughout the plaque, largely determined by the inflammatory state. This environment differs considerably between humans and most animals, resulting in suboptimal conditions for plaque rupture. In this review we describe the role of the biomechanical environment in plaque rupture and assess this environment in animal models that present with plaque rupture.

A CT-based medina classification in coronary bifurcations: Does the lumen assessment provide sufficient information?

To evaluate the distribution of atherosclerosis at bifurcations with computed tomography coronary angiography (CTCA) and propose a novel CT‐Medina classification for bifurcation lesions.

A numerical study on the influence of vulnerable plaque composition on intravascular thermography measurements

Intracoronary thermography is a technique that measures lumen wall temperatures for vulnerable plaque detection. In this paper the influence of vulnerable plaque composition on lumen wall temperatures was studied numerically. Concerning the vulnerable plaque heat generation, the location of the heat source and its heat production were varied. Concerning the heat transfer, the thermal properties of the lipid core and the location of the vasa vasorum were studied. The heat source location was the main determinant of the lumen wall temperature distribution. The strongest effect was noted when the heat producing macrophages were located in the shoulder region leading to focal spots of higher temperature. The maximal lumen wall temperature was mainly determined by the heat production of the macrophages and the cooling effect of blood. The insulating properties of the lipid core increased lumen wall temperatures when the heat source was located in the cap and the presence of vasa vasorum lowered the temperatures. These results show that the lumen wall temperature distribution is influenced by vulnerable plaque composition and that intracoronary thermography techniques require a high spatial resolution. To be able to couple temperature measurements to plaque vulnerability, intracoronary thermography needs to be combined with an imaging modality.