Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed

Evolution and rupture of vulnerable plaques: a review of mechanical effects

Atherosclerosis occurs as a result of the buildup and infiltration of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is of critical importance, since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those that rupture (vulnerable) and those that are less likely to rupture (stable). In the last few decades, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces, and structural stress) on the plaque formation and rupture processes. In the literature, physiological experimental studies are limited by the complexity of in vivo experiments to study such effects, whereas the numerical approach often uses simplified models compared with realistic conditions, so that no general agreement of the mechanisms responsible for plaque formation has yet been reached. In addition, in a large number of cases, the presence of plaques in arteries is asymptomatic. The prediction of plaque rupture remains a complex question to elucidate, not only because of the interaction of numerous phenomena involved in this process (biological, chemical, and mechanical) but also because of the large time scale on which plaques develop. The purpose of the present article is to review the current mechanical models used to describe the blood flow in arteries in the presence of plaques, as well as reviewing the literature treating the influence of mechanical effects on plaque formation, development, and rupture. Finally, some directions of research, including those being undertaken by the authors, are described

Towards a Digital Twin of Coronary Stenting: A Suitable and Validated Image-Based Approach for Mimicking Patient-Specific Coronary Arteries

Considering the field of application involving stent deployment simulations, the exploitation of a digital twin of coronary stenting that can reliably mimic the patient-specific clinical reality could lead to improvements in individual treatments. A starting step to pursue this goal is the development of simple, but at the same time, robust and effective computational methods to obtain a good compromise between the accuracy of the description of physical phenomena and computational costs. Specifically, this work proposes an approach for the development of a patient-specific artery model to be used in stenting simulations. The finite element model was generated through a 3D reconstruction based on the clinical imaging (coronary Optical Coherence Tomography (OCT) and angiography) acquired on the pre-treatment patient. From a mechanical point of view, the coronary wall was described with a suitable phenomenological model, which is consistent with more complex constitutive approaches and accounts for the in vivo pressurization and axial pre-stretch. The effectiveness of this artery modeling method was tested by reproducing in silico the stenting procedures of two clinical cases and comparing the computational results with the in vivo lumen area of the stented vessel

Role of biomechanical forces in the natural history of coronary atherosclerosis.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203

Image-Based Quantification Workflow for Coronary Morphology: A Tool for Use in Next-Generation Bifurcation Stent Design

Coronary artery disease (CAD) occurs in ~200,000 bifurcation lesions annually. Treatment of CAD near bends and bifurcations is challenging and a preferred strategy for bifurcation lesions has yet to be established. However, a favorable treatment option may be elucidated by a more thorough understanding of vessel morphology as well as local hemodynamic alterations caused by current stenting approaches. Computational modeling of human arteries offers an attractive way to investigate the relationships between geometry, hemodynamics and vascular disease. Recent developments also make it possible to perform analysis on realistic geometries acquired noninvasively. The objective of this work was twofold. The first aim was to build on previous work in this area by quantifying hemodynamic alterations introduced by treatment of an idealized coronary bifurcation using several approaches that involve multiple stents. Each model was created using combined computer aided design techniques and computational fluid dynamics (CFD) analysis tools. Resting and hyperemic blood flow conditions were also studied to determine the severity of local hemodynamic alterations and for comparison to previous results. Indices of time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) were quantified for four idealized computational models. The luminal surface exposed to low TAWSS was similar in the main vessel (MV) for all models. Greatest differences were noted between un-stented versus stented side branch vessels (ex. rest: 1% vs. 35%). Sites of elevated OSI (\u3e0.1) were minimal, except under hyperemia conditions in the MV (10% surface area). Flow disturbances were quantified for each provisional technique used, illustrating how stents protruding in main vessels impact flow profiles. Stents without kissing balloon dilation had abnormal flow disturbances, but showed decreased percentage of area exposed to areas of low WSS. A second aim of this work was to design a robust and unbiased method to quantify vessel morphology and representative trends for three bifurcation sites prone to CAD. Computational models of these sites were generated using computed topography images from 22 patients. Models were used to query geometric characteristics from each bifurcation site including area, length, eccentricity, taper, curvature and bifurcation angles. Post-processing was accomplished by a combination of statistical methods and clustering analysis. Vessel length and area were significantly different within and between bifurcation sites. The left main coronary artery (LCA) bifurcation was significantly different from its two daughter bifurcations (left anterior descending and left circumflex arteries). Specifically vessel area and length were significantly different both between and within bifurcation sites. The daughter bifurcation sites were similar for all characteristics. Vessel area and length proved to be the most useful properties for identifying trends within a particular bifurcation site. The outcome of this work provides a workflow for characterizing coronary bifurcations and a strong foundation for elucidating common parameters from normal, healthy coronary arteries. Collectively these results from idealized and patient-specific coronary bifurcations offer additional insight into the impact of current treatment approaches and characteristics associated with current stenting techniques. Flow disturbances and local hemodynamic changes have been quantified for provisional techniques currently used. These methods and results may ultimately be useful in the design of next-generation bifurcation stents

Carotid plaque stress analysis by fluid structure interaction based on in-vivo MRI: Implications to plaque vulnerability assessment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University, 2010.Stroke is one of the leading causes of death in the world, resulting mostly from the sudden rupture of atherosclerotic plaques. From a biomechanical view, plaque rupture can be considered as a mechanical failure caused by extremely high plaque stress. In this PhD project, we are aiming to predict 3D plaque stress based on in-vivo MRI by using fluid structure interaction (FSI) method, and provide information for plaque rupture risk assessment. Fluid structure interaction was implemented with ANSYS 11.0, followed by a parameter study on fibrous cap thickness and lipid core size with realistic carotid plaque geometry. Twenty patients with carotid plaques imaged by in-vivo MRI were provided in the project. A framework of reconstructing 3D plaque geometry from in-vivo multispectral MRI was designed. The followed reproducibility study on plaque geometry reconstruction procedure and its effect on plaque stress analysis filled the gap in the literature on imaging based plaque stress modeling. The results demonstrated that current MRI technology can provide sufficient information for plaque structure characterization; however stress analysis result is highly affected by MRI resolution and quality. The application of FSI stress analysis to 4 patients with different plaque burdens has showed that the whole procedure from plaque geometry reconstruction to FSI stress analysis was applicable. In the study, plaque geometries from three patients with recent transient ischemic attack were reconstructed by repairing ruptured fibrous cap. The well correlated relationship between local stress concentrations and plaque rupture sites indicated that extremely high plaque stress could be a factor responsible for plaque rupture. Based on the 20 reconstructed carotid plaques from two groups (symptomatic and asymptomatic), fully coupled fluid structure interaction was performed. It was found that there is a significant difference between symptomatic and asymptomatic patients in plaque stress levels, indicating plaque stress could be used as one of the factors for plaque vulnerability assessment. A corresponding plaque morphological feature study showed that plaque stress is significantly affected by fibrous cap thickness, lipid core size and fibrous cap surface irregularities (curvedness). A procedure was proposed for predicting plaque stress by using fibrous cap thickness and curvedness, which requires much less computational time, and has the potential for clinical routine application. The effects of residual stress on plaque stress analysis and arterial wall material property characterization by using in-vivo MRI data were also discussed for patient specific modeling. As the further development, histological study of plaque sample has been combined with conventional plaque stress analysis by assigning material properties to each computational element, based on the data from histological analysis. This method could bridge the gap between biochemistry and biomechanical study of atherosclerosis plaques. In conclusion, extreme stress distributions in the plaque region can be predicted by modern numerical methods, and used for plaque rupture risk assessment, which will be helpful in clinical practice. The combination of plaque MR imaging analysis, computational modelling, and clinical study/ validation would advance our understandings of plaque rupture, prediction of future rupture, and establish new procedures for patient diagnose, management, and treatment.Financial Support was obtained from British Heart Foundation, Brunel Institute for Bioengineering and Brunel Graduate School

Vortex formation and recirculation zones in left anterior descending artery stenoses: computational fluid dynamics analysis

Flow patterns may affect the potential of thrombus formation following plaque rupture. Computational fluid dynamics (CFD) were employed to assess hemodynamic conditions, and particularly flow recirculation and vortex formation in reconstructed arterial models associated with ST-elevation myocardial infraction (STEMI) or stable coronary stenosis (SCS) in the left anterior descending coronary artery (LAD). Results indicate that in the arterial models associated with STEMI, a 50% diameter stenosis immediately before or after a bifurcation creates a recirculation zone and vortex formation at the orifice of the bifurcation branch, for most of the cardiac cycle, thus allowing the creation of stagnating flow. These flow patterns are not seen in the SCS model with an identical stenosis. Post-stenotic recirculation in the presence of a 90% stenosis was evident at both the STEMI and SCS models. The presence of 90% diameter stenosis resulted in flow reduction in the LAD of 51.5% and 35.9% in the STEMI models and 37.6% in the SCS model, for a 10 mmHg pressure drop. CFD simulations in a reconstructed model of stenotic LAD segments indicate that specific anatomic characteristics create zones of vortices and flow recirculation that promote thrombus formation and potentially myocardial infarction

Study of the relation between blood flow and the age-dependent localisation of early atherosclerosis

Atherosclerosis develops non-uniformly within the arterial system and the distribution of lesions has been observed to change with age. This thesis investigates the concept that the patchiness of the disease is related to local variations in blood flow. Based on the insights from a systematic literature review, a novel study was designed to analyse the relation between haemodynamic factors and age-dependent atherogenesis in the thoracic aorta of rabbits. Arterial geometries were reconstructed by micro-Computed Tomography of vascular corrosion casts, with particular attention to the anatomical accuracy of the dataset. Blood flow was simulated in these geometries using a spectral/hp element method. Distributions of traditional shear-related metrics were calculated and both qualitatively and quantitatively compared to maps of lesion prevalence. In addition, a time-averaged transverse wall shear stress was introduced. A geometric analysis of the dataset of rabbit thoracic aortas revealed a significant change with age in the degree of aortic taper. The geometric changes could explain age-related differences in flow characteristics, in particular in the extent of Dean-type vortical structures into the descending aorta and the strength of a dorsal streak of high shear. The comparative analysis of shear and lesion distributions did not unequivocally support the theory that lesions occur in regions of low shear. The novel haemodynamic metric, in combination with current metrics, enabled an improved identification of zones of multi-directional disturbed flow. In conclusion, this thesis adds to the understanding of the relation between blood flow and early atherosclerosis, and provides tools for use in future studies