Eoghan M. Cunnane

Computational approaches for analyzing the mechanics of atherosclerotic plaques: A review

Vulnerable and stable atherosclerotic plaques are heterogeneous living materials with peculiar mechanical behaviors depending on geometry, composition, loading and boundary conditions. Computational approaches have the potential to characterize the three-dimensional stress/strain distributions in patient-specific diseased arteries of different types and sclerotic morphologies and to estimate the risk of plaque rupture which is the main trigger of acute cardiovascular events. This review article attempts to summarize a few finite element (FE) studies for different vessel types, and how these studies were performed focusing on the used stress measure, inclusion of residual stress, used imaging modality and material model. In addition to histology the most used imaging modalities are described, the most common nonlinear material models and the limited number of models for plaque rupture used for such studies are provided in more detail. A critical discussion on stress measures and threshold stress values for plaque rupture used within the FE studies emphasizes the need to develop a more location and tissue-specific threshold value, and a more appropriate failure criterion. With this addition future FE studies should also consider more advanced strain-energy functions which then fit better to location and tissue-specific experimental data.

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.

Mechanical, biological and structural characterization of in vitro ruptured human carotid plaque tissue.

Recent experimental studies performed on human carotid plaques have focused on mechanical characterization for the purpose of developing material models for finite-element analysis without quantifying the tissue composition or relating mechanical behaviour to preoperative classification. This study characterizes the mechanical and biological properties of 25 human carotid plaques and also investigates the common features that lead to plaque rupture during mechanical testing by performing circumferential uniaxial tests, Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) on each specimen to relate plaque composition to mechanical behaviour. Mechanical results revealed large variations between plaque specimen behaviour with no correlation to preoperative ultrasound prediction. However, FTIR classification demonstrated a statistically significant relationship between stress and stretch values at rupture and the level of calcification (P=0.002 and P=0.009). Energy-dispersive X-ray spectroscopy was carried out to confirm that the calcium levels observed using FTIR analysis were accurate. This work demonstrates the potential of FTIR as an alternative method to ultrasound forpredicting plaque mechanical behaviour. SEM imaging at the rupture sites of each specimen highlighted voids created by the nodes of calcifications in the tissue structure which could lead to increased vulnerability of the plaque.

On the effect of calcification volume and configuration on the mechanical behaviour of carotid plaque tissue.

Vascular calcification is a complex molecular process that exhibits a number of relatively characteristic morphology patterns in atherosclerotic plaques. Treatment of arterial stenosis by endovascular intervention, involving forceful circumferential expansion of the plaque, can be unpredictable in calcified lesions. The aim of this study was to determine the mechanical stretching mechanisms and define the mechanical limits for circumferentially expanding carotid plaque lesions under the influence of distinct calcification patterns. Mechanical and structural characterisation was performed on 17 human carotid plaques acquired from patients undergoing endarterectomy procedures. The mechanical properties were determined using uniaxial extension tests that stretch the lesions to complete failure along their circumferential axis. Calcification morphology of mechanically ruptured plaque lesions was characterised using high resolution micro computed tomography imaging. Scanning electron microscopy was used to examine the mechanically induced failure sites and to identify the interface boundary conditions between calcified and non-calcified tissue. The mechanical tests produced four distinct trends in mechanical behaviour which corresponded to the calcification patterns that structurally defined each mechanical group. Each calcification pattern produced unique mechanical restraining effects on the plaque tissue stretching properties evidenced by the variation in degree of stretch to failure. Resistance to failure appears to rely on interactions between calcification and non-calcified tissue. Scanning electron microscopy examination revealed structural gradations at interface boundary conditions to facilitate the transfer of stress. This study emphasises the mechanical influence of distinct calcification configurations on plaque expansion properties and highlights the importance of pre-operative lesion characterisation to optimise treatment outcomes.

Preventing Urethral Trauma from Inadvertent Inflation of Catheter Balloon in the Urethra during Catheterization: Evaluation of a Novel Safety Syringe after Correlating Trauma with Urethral Distension and Catheter Balloon Pressure

PURPOSE We investigated urethral diametric strain and threshold maximum inflation pressure for rupture during inadvertent inflation of a catheter anchoring balloon in the urethra. In addition, we evaluated a novel safety device to prevent trauma based on these parameters. MATERIALS AND METHODS Inflation of a urethral catheter anchoring balloon was performed in the bulbar urethra of 21 ex vivo porcine models using 16Fr catheters. Urethral trauma was assessed with retrograde urethrography. Urethral rupture was correlated with internal urethral diametric strain and maximal urethral pressure threshold values in kPa. Urethral catheters were then inflated in the bulbar urethras of 7 fresh male cadavers using a standard syringe and a prototype syringe. The plunger of the standard syringe was depressed until opposing resistance pressure generated by the urethra prevented further inflation of the anchoring balloon. The plunger of the prototype safety syringe was depressed until sterile water in the syringe decanted through an activated safety threshold pressure valve. RESULTS Retrograde urethrography demonstrated that porcine urethral rupture consistently occurred at an internal urethral diametric strain greater than 40% and a maximum inflation pressure greater than 150 kPa. The mean ± SD maximum human urethral threshold inflation pressure required to activate the safety prototype syringe pressure valve was 153 ± 3 kPa. In comparison, maximum inflation pressure was significantly greater using the standard syringe than the activated prototype syringe (mean 452 ± 188 kPa, p <0.001). CONCLUSIONS Internal urethral diametric strain and threshold maximum inflation pressures are important parameters for designing a safer urethral catheter system with lower intrinsic threshold inflation pressures.

Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results.

BackgroundDue to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.MethodsNovel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.ResultsSimulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.ConclusionsLarge differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.

A Review of the Hemodynamic Factors Believed to Contribute to Vascular Access Dysfunction

A vascular access (VA) is used to facilitate hemodialysis in patients that suffer from end-stage renal disease. However, they suffer from high failure rates due to non-maturation and venous stenosis, with intimal hyperplasia (IH) the underlying cause of both conditions. Abnormal hemodynamic profiles, which arise following VA creation, are believed to lead to the development of IH. However, the exact physiological response that initiates this process is unknown. This review evaluates the different hemodynamic parameters that are hypothesised to correlate with the development of IH. Review studies that examine the correlation between hemodynamic parameters and the onset of IH using computational fluid dynamics. These studies are divided into groups depending on the type of analysis conducted; longitudinal studies, patient specific arteriovenous fistula (AVF) studies, arteriovenous graft studies, idealised AVF studies and studies that analyse the bulk flow. Studies that conduct longitudinal analysis identify an overall reduction in wall shear stress (WSS) as the VA matures. This is further associated with outward remodelling and the successful maturation of the VA. The majority of studies that conduct a transversal analysis find that low/oscillating shear is associated with the development of IH. However, a number of studies find a link between high shear and high spatial and temporal WSS gradients and the onset of IH. This review highlights the lack of unanimity between studies and emphasises the fact that the exact physiological response that leads to the development of IH remains unknown. This accentuates the need for a single, precise hypothesis capable of accurately predicting the onset of IH. If computational modelling is to assist in this process, the number of longitudinal studies conducted must increase. This will provide a better understanding of the effect that hemodynamic parameters have on the remodelling process and potentially identify a single/group of parameter/s that can accurately predict the onset of IH.

Mechanical properties and composition of carotid and femoral atherosclerotic plaques: A comparative study

This study compares the mechanical properties of excised carotid and femoral human plaques and also develops a predictor of these properties based on plaque composition. Circumferential planar tension tests were performed on 24 carotid and 16 femoral plaque samples. Composition was characterised using Fourier Transform Infrared spectroscopy. Stretch at failure, strength, and stiffness are significantly higher in the carotid group (P=.012, P<.001 and P=.002, respectively). The ratio of calcified to lipid plaque content demonstrates the strongest correlation with the stretch at failure and strength (R2=.285, P<.001 and R2=.347, P<.001). No composition based parameter correlates significantly with stiffness. The significantly different mechanical properties of the two groups aids in explaining the varying endovascular treatment outcomes clinically observed in these vessels. Furthermore, determining the ratio of calcified to lipid plaque content may be useful in predicting individual plaque mechanical response to endovascular treatment.

The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue.

UNLABELLED The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R(2)=0.885, p<0.001). STATEMENT OF SIGNIFICANCE This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment.

On the influence of wall calcification and intraluminal thrombus on prediction of abdominal aortic aneurysm rupture

Objective: Parameters other than maximum diameter that predict rupture of abdominal aortic aneurysms (AAAs) may be helpful for risk‐benefit analysis in individual patients. The aim of this study was to characterize the biomechanical‐structural characteristics associated with AAA walls to better identify the related mechanistic variables required for an accurate prediction of rupture risk. Methods: Anterior AAA wall (n = 40) and intraluminal thrombus (ILT; n = 114) samples were acquired from 18 patients undergoing open surgical repair. Biomechanical characterization was performed using controlled circumferential stretching tests combined with a speckle‐strain tracking technique to quantify the spatial heterogeneity in deformation and localized strains in the AAA walls containing calcification. After mechanical testing, the accompanying microstructural characteristics of the AAA wall and ILT types were examined using electron microscopy. Results: No significant correlation was found between the AAA diameter and the wall mechanical properties in terms of Cauchy stress (rs = −0.139; P = .596) or stiffness (rs = −0.451; P = .069). Quantification of significant localized peak strains, which were concentrated in the tissue regions surrounding calcification, reveals that peak strains increased by a mean of 174% as a result of calcification and corresponding peak stresses by 18.2%. Four ILT types characteristic of diverse stages in the evolving tissue microstructure were directly associated with distinct mechanical stiffness properties of the ILT and underlying AAA wall. ILT types were independent of geometric factors, including ILT volume and AAA diameter measures (ILT stiffness and AAA diameter [rs = −0.511; P = .074]; ILT stiffness and ILT volume [rs = −0.245; P = .467]). Conclusions: AAA wall stiffness properties are controlled by the load‐bearing capacity of the noncalcified tissue portion, and low stiffness properties represent a highly degraded vulnerable wall. The presence of calcification that is contiguous with the inner wall causes severe tissue overstretching in surrounding tissue areas. The results highlight the use of additional biomechanical measures, detailing the biomechanical‐structural characteristics of AAA tissue, that may be a helpful adjunct to improve the accuracy of rupture prediction. Clinical Relevance: The mechanical‐structural calcification information presented in this study marks a crucial starting point for a risk‐benefit analysis to better predict abdominal aortic aneurysm rupture risk. Calcification plays an integral role in the structural degradation of abdominal aortic aneurysm walls, which is mechanically represented by diminished stiffness properties. This degradative influence coupled with significant straining influences of calcification predisposes surrounding noncalcified tissue to significantly increased stresses, which may help disclose the walls localized site of highest rupture risk. Thus, this information may help assess whether a survival benefit can be achieved from clinical intervention.