Arthur Creane

Tensile and compressive properties of fresh human carotid atherosclerotic plaques

Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

An anisotropic inelastic constitutive model to describe stress softening and permanent deformation in arterial tissue.

Inelastic phenomena such as softening and unrecoverable inelastic strains induced by loading have been observed experimentally in soft tissues such as arteries. These phenomena need to be accounted for in constitutive models of arterial tissue so that computational models can accurately predict the outcomes of interventional procedures such as balloon angioplasty and stenting that involve non-physiological loading of the tissue. In this study, a novel constitutive model is described that accounts for inelastic effects such as Mullins-type softening and permanent set in a fibre reinforced tissue. The evolution of inelasticity is governed by a set of internal variables. Softening is introduced through a typical continuum damage mechanics approach, while the inelastic residual strains are introduced through an additive split in the stress tensor. Numerical simulations of aorta and carotid arterial tissue subjected to uniaxial testing in the longitudinal, circumferential and axial directions are used to demonstrate the models ability to reproduce the anisotropic inelastic behaviour of the tissue. Material parameters derived from best-fits to experimental data are provided to describe these inelastic effects for both aortic and carotid tissue.

Finite element modelling of diseased carotid bifurcations generated from in vivo computerised tomographic angiography

It has been hypothesised that the stress distribution within the arterial wall may provide an indicator of atherosclerotic plaque rupture. This study presents an automated method for the generation of finite element models of the carotid bifurcation from in vivo computerised tomographic angiography. Models generated using this method have been used to investigate plaque vulnerability, assessing the influence of geometric factors and the stress distribution within the wall. Structured hexahedral meshes of the carotid bifurcation were created using a custom built automated system. Systolic pressure and appropriate boundary conditions were applied to each of the models. Six symptomatic patients were considered, generating models from each of their left and right carotid bifurcations (12 in total). Results from their symptomatic bifurcation were compared with their contralateral asymptomatic side. K(delta), a measure of the difference in curvature of the inner and outer plaque surfaces, was found to be significantly higher in symptomatic arteries than in asymptomatic arteries (p<0.05). The location of maximum K(delta) (the plaque shoulders) was also found to be a region of high von Mises stress yet no significant difference was found in maximum von Mises stress between the symptomatic and asymptomatic groups. Results suggest that K(delta) is an important factor in the development of a symptomatic plaque and with further investigation could be a useful indicator of plaque rupture.

Site specific inelasticity of arterial tissue

Understanding the mechanical behaviour of arterial tissue is vital to the development and analysis of medical devices targeting diseased vessels. During angioplasty and stenting, stress softening and permanent deformation of the vessel wall occur during implantation of the device, however little data exists on the inelastic behaviour of cardiovascular tissue and how this varies through the arterial tree. The aim of this study was to characterise the magnitude of stress softening and inelastic deformations due to loading throughout the arterial tree and to investigate the anisotropic inelastic behaviour of the tissue. Cyclic compression tests were used to investigate the differences in inelastic behaviour for carotid, aorta, femoral and coronary arteries harvested from 3-4 month old female pigs, while the anisotropic behaviour of aortic and carotid tissue was determined using cyclic tensile tests in the longitudinal and circumferential directions. The differences in inelastic behaviour were correlated to the ratio of collagen to elastin content of the arteries. It was found that larger inelastic deformations occurred in muscular arteries (coronary), which had a higher collagen to elastin ratio than elastic arteries (aorta), where the smallest inelastic deformations were observed. Lower magnitude inelastic deformations were observed in the circumferential tensile direction than in the longitudinal tensile direction or due to radial compression. This may be as a result of non-collagenous components in the artery becoming more easily damaged than the collagen fibres during loading. Stress softening was also found to be dependent on artery type. In the future, computational models should consider such site dependant, anisotropic inelastic behaviour in order to better predict the outcomes of interventional procedures such as angioplasty and stenting.

Inelasticity of Human Carotid Atherosclerotic Plaque

Little mechanical test data exists regarding the inelastic behavior of atherosclerotic plaques. As a result finite element (FE) models of stenting procedures commonly use hyperelastic material models to describe the soft tissue response thus limiting the accuracy of the model to the expansion stage of stent implantation and leave them unable to predict the lumen gain. In this study, cyclic mechanical tests were performed to characterize the inelastic behavior of fresh human carotid atherosclerotic plaque tissue due to radial compressive loading. Plaques were classified clinically as either mixed (M), calcified (Ca), or echolucent (E). An approximately linear increase in the plastic deformation was observed with increases in the peak applied strain for all plaque types. While calcified plaques generally appeared stiffest, it was observed that the clinical classification of plaques had no significant effect on the magnitude of permanent deformation on unloading. The test data was characterized using a constitutive model that accounts for both permanent deformation and stress softening to describe the compressive plaque behavior on unloading. Material constants are reported for individual plaques as well as mean values for each plaque classification. This data can be considered as a first step in characterizing the inelastic behavior of atherosclerotic plaques and could be used in combination with future mechanical data to improve the predictive capabilities of FE models of angioplasty and stenting procedures particularly in relation to lumen gain.

Prediction of fibre architecture and adaptation in diseased carotid bifurcations

Many studies have used patient-specific finite element models to estimate the stress environment in atherosclerotic plaques, attempting to correlate the magnitude of stress to plaque vulnerability. In complex geometries, few studies have incorporated the anisotropic material response of arterial tissue. This paper presents a fibre remodelling algorithm to predict the fibre architecture, and thus anisotropic material response in four patient-specific models of the carotid bifurcation. The change in fibre architecture during disease progression and its affect on the stress environment in the plaque were predicted. The mean fibre directions were assumed to lie at an angle between the two positive principal strain directions. The angle and the degree of dispersion were assumed to depend on the ratio of principal strain values. Results were compared with experimental observations and other numerical studies. In non-branching regions of each model, the typical double helix arterial fibre pattern was predicted while at the bifurcation and in regions of plaque burden, more complex fibre architectures were found. The predicted change in fibre architecture in the arterial tissue during plaque progression was found to alter the stress environment in the plaque. This suggests that the specimen-specific anisotropic response of the tissue should be taken into account to accurately predict stresses in the plaque. Since determination of the fibre architecture in vivo is a difficult task, the system presented here provides a useful method of estimating the fibre architecture in complex arterial geometries.

A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations.

Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a ‘remodelling metric’ between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover’s distance, a similarity measure between two histograms/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric’s potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present.

Imaging and finite element analysis: a methodology for non-invasive characterization of aortic tissue.

Characterization of the mechanical properties of arterial tissues usually involves an invasive procedure requiring tissue removal. In this work we propose a non-invasive method to perform a biomechanical analysis of cardiovascular aortic tissue. This method is based on combining medical imaging and finite element analysis (FEA). Magnetic resonance imaging (MRI) was chosen since it presents relatively low risks for human health. A finite element model was created from the MRI images and loaded with systolic physiological pressures. By means of an optimization routine, the structural material properties were changed until average strains matched those measured by MRI. The method outlined in this work produced an estimate of the in situ properties of cardiovascular tissue based on non-invasive image datasets and finite element analysis.

Patient Specific Computational Modeling in Cardiovascular Mechanics

Diseases of the cardiovascular system are leading causes of morbidity and mortality worldwide. Computational modeling of cardiovascular mechanics has contributed to the understanding of cardiovascular disease etiology and risk evaluation. Patient specific finite element models of disease sites such as atherosclerotic plaques and aneurysms have provided important insights into their biomechanics, including identification of the characteristics of vulnerable locations.

Mechanical Characterization of Fresh Human Carotid Atherosclerotic Plaque

Quantifying the properties of atherosclerotic plaques is critical to improving our understanding of the pathogenesis of the disease. Furthermore realistic tissue properties are vital in order to obtain legitimate results from finite element models of surgical interventions used to treat cardiovascular disease. The aim of this study is to determine the mechanical properties of fresh human carotid plaques immediately following removal during endarterectomy. A number of studies have reported atherosclerotic plaque properties previously [1–3], however all of these tested cadaveric tissue. This study will further investigate in-patient and inter-patient variability, the relationship between plaque properties and their clinical classification (calcified, mixed or echolucent) and the location of the sample (common, internal, external carotid).Copyright