A finite element model of stress-mediated vascular adaptation: application to abdominal aortic aneurysms

Despite rapid expansion of our knowledge of vascular adaptation, developing patient-specific models of diseased arteries is still an open problem. In this study, we extend existing finite element models of stress-mediated growth and remodelling of arteries to incorporate a medical image-based geometry of a healthy aorta and, then, simulate abdominal aortic aneurysm. Degradation of elastin initiates a local dilatation of the aorta while stress-mediated turnover of collagen and smooth muscle compensates the loss of elastin. Stress distributions and expansion rates during the aneurysm growth are studied for multiple spatial distribution functions of elastin degradation and kinetic parameters. Temporal variations of the degradation function are also investigated with either direct time-dependent degradation or stretch-induced degradation as possible biochemical and biomechanical mechanisms for elastin degradation. The results show that this computational model has the capability to capture the complexities of aneurysm progression due to variations of geometry, extent of damage and stress-mediated turnover as a step towards patient-specific modelling.     

Simulation of transcatheter aortic valve implantation: a patient-specific finite element approach

Until recently, heart valve failure has been treated adopting open-heart surgical techniques and cardiopulmonary bypass. However, over the last decade, minimally invasive procedures have been developed to avoid high risks associated with conventional open-chest valve replacement techniques. Such a recent and innovative procedure represents an optimal field for conducting investigations through virtual computer-based simulations: in fact, nowadays, computational engineering is widely used to unravel many problems in the biomedical field of cardiovascular mechanics and specifically, minimally invasive procedures. In this study, we investigate a balloon-expandable valve and we propose a novel simulation strategy to reproduce its implantation using computational tools. Focusing on the Edwards SAPIEN valve in particular, we simulate both stent crimping and deployment through balloon inflation. The developed procedure enabled us to obtain the entire prosthetic device virtually implanted in a patient-specific aortic root created by processing medical images; hence, it allows evaluation of postoperative prosthesis performance depending on different factors (e.g. device size and prosthesis placement site). Notably, prosthesis positioning in two different cases (distal and proximal) has been examined in terms of coaptation area, average stress on valve leaflets as well as impact on the aortic root wall. The coaptation area is significantly affected by the positioning strategy ( ? 24%, moving from the proximal to distal) as well as the stress distribution on both the leaflets (+13.5%, from proximal to distal) and the aortic wall ( ? 22%, from proximal to distal). No remarkable variations of the stress state on the stent struts have been obtained in the two investigated cases.     

A strain-based finite element model for calcification progression in aortic valves

Calcific aortic valve disease (CAVD) is a serious disease affecting the aging population. A complex interaction between biochemicals, cells, and mechanical cues affects CAVD initiation and progression. In this study, motivated by the progression of calcification in regions of high strain, we developed a finite element method (FEM) based spatial calcification progression model. Several cardiac cycles of transient structural FEM simulations were simulated. After each simulation cycle, calcium deposition was placed in regions of high circumferential strain. Our results show the radial expansion of calcification as spokes starting from the attachment region, agreeing very well with the reported clinical data.     

A novel adaptive algorithm for 3D finite element analysis to model extracortical bone growth

Extracortical bone growth with osseointegration of bone onto the shaft of massive bone tumour implants is an important clinical outcome for long-term implant survival. A new computational algorithm combining geometrical shape changes and bone adaptation in 3D Finite Element simulations has been developed, using a soft tissue envelope mesh, a novel concept of osteoconnectivity, and bone remodelling theory. The effects of varying the initial tissue density, spatial influence function and time step were investigated. The methodology demonstrated good correspondence to radiological results for a segmental prosthesis.     

Intrasac pressure changes and vascular remodeling after endovascular repair of abdominal aortic aneurysms: review and biomechanical model simulation

In this paper, we review existing clinical research data on post-endovascular repair (EVAR) intrasac pressure and relation with abdominal aortic aneurysm (AAA) size changes. Based on the review, we hypothesize that intrasac pressure has a significant impact on post-EVAR AAA size changes, and post-EVAR remodeling depends also on how the pressure has changed over a period of time. The previously developed model of an AAA based on a constrained mixture approach is extended to include vascular adaptation after EVAR using an idealized geometry. Computational simulation shows that the same mechanism of collagen stress-mediated remodeling in AAA expansion induces the aneurysm wall to shrink in a reduced sac-pressure after post-EVAR. Computational simulation suggests that the intrasac pressure of 60 mm?Hg is a critical value. At this value, the AAA remains stable, while values above cause the AAA to expand and values below cause the AAA to shrink. There are, however, variations between individuals due to different cellular sensitivities in stress-mediated adaptation. Computer simulation also indicates that an initial decrease in intrasac pressure helps the AAA shrink even if the pressure increases after some time. The presented study suggests that biomechanics has a major effect on initial adaptation after EVAR and also illustrates the utility of a computational model of vascular growth and remodeling in predicting diameter changes during the progression and after the treatment of AAAs.     

3D reconstruction and manufacture of real abdominal aortic aneurysms: from CT scan to silicone model

Abdominal aortic aneurysm (AAA) can be defined as a permanent and irreversible dilation of the infrarenal aorta. AAAs are often considered to be an aorta with a diameter 1.5 times the normal infrarenal aorta diameter. This paper describes a technique to manufacture realistic silicone AAA models for use with experimental studies. This paper is concerned with the reconstruction and manufacturing process of patient-specific AAAs. 3D reconstruction from computed tomography scan data allows the AAA to be created. Mould sets are then designed for these AAA models utilizing computer aided designcomputer aided manufacture techniques and combined with the injection-moulding method. Silicone rubber forms the basis of the resulting AAA model. Assessment of wall thickness and overall percentage difference from the final silicone model to that of the computer-generated model was performed. In these realistic AAA models, wall thickness was found to vary by an average of 9.21%. The percentage difference in wall thickness recorded can be attributed to the contraction of the casting wax and the expansion of the silicone during model manufacture. This method may be used in conjunction with wall stress studies using the photoelastic method or in fluid dynamic studies using a laser-Doppler anemometry. In conclusion, these patient-specific rubber AAA models can be used in experimental investigations, but should be assessed for wall thickness variability once manufactured.     

A multiscale mechanobiological modelling framework using agent-based models and finite element analysis: application to vascular tissue engineering

Computational models of mechanobiological systems have been widely used to provide insight into these systems and also to predict their behaviour. In this context, vascular tissue engineering benefits from further attention given the challenges involved in developing functional low calibre vascular grafts with long-term patency. In this study, a novel multiscale mechanobiological modelling framework is presented, which takes advantage of lattice-free agent-based models coupled with the finite element method to investigate the dynamics of VSMC growth in vascular tissue engineering scaffolds. The results illustrate the ability of the mechanobiological modelling approach to capture complex multiscale mechanobiological phenomena. Specifically, the framework enabled the study of the influence of scaffold compliance and loading regime in regulating the growth of VSMCs in vascular scaffolds and their role in development of intimal hyperplasia (IH). The model demonstrates that low scaffold compliance compared to host arteries leads to increased luminal ingrowth and IH development. In addition, culture of a tissue-engineered blood vessel under a pulsatile luminal pressure reduced luminal ingrowth and enhanced collagen synthesis within the scaffold compared to non-pulsatile culture. The mechanobiological framework presented provides a robust platform for testing hypotheses in vascular tissue engineering and lends itself to use as an optimisation design tool.     

A new cortical thickness mapping method with application to an in vivo finite element model

Finite element modelling of musculoskeletal systems, with geometrical structures constructed from computed tomography (CT) scans, is a useful and powerful tool for biomechanical studies. The use of CT scans from living human subjects, however, is still limited. Accurate reconstruction of thin cortical bone structures from CT scans of living human subjects is especially problematic, due to low CT resolution that results from mandatory low radiation doses and/or involuntary movements of the subject. In this study, a new method for mapping cortical thickness is described. Using the method, cortical thickness measurements of a coxal (pelvis) bone obtained from CT scans of a cadaver were mapped to the coxal geometry as obtained through CT scans of a live human subject, resulting in accurate cortical thickness while maintaining geometric fidelity of the live subject. The mapping procedure includes shape-preserving parameterisation, mesh movement and interpolation of thickness using a search algorithm. The methodology is applicable to modelling of other bones where accurate cortical thickness is needed and for which such data exist.     

A 3D porous media liver lobule model: the importance of vascular septa and anisotropic permeability for homogeneous perfusion

The hepatic blood circulation is complex, particularly at the microcirculatory level. Previously, 2D liver lobule models using porous media and a 3D model using real sinusoidal geometries have been developed. We extended these models to investigate the role of vascular septa (VS) and anisotropic permeability. The lobule was modelled as a hexagonal prism (with or without VS) and the tissue was treated as a porous medium (isotropic or anisotropic permeability). Models were solved using computational fluid dynamics. VS inclusion resulted in more spatially homogeneous perfusion. Anisotropic permeability resulted in a larger axial velocity component than isotropic permeability. A parameter study revealed that results are most sensitive to the lobule size and radial pressure drop. Our model provides insight into hepatic microhaemodynamics, and suggests that inclusion of VS in the model leads to perfusion patterns that are likely to reflect physiological reality. The model has potential for applications to unphysiological and pathological conditions.     

A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion

American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.     

A methodology to generate structured computational grids from DICOM data: application to a patient-specific abdominal aortic aneurysm (AAA) model

This study presents the generation of a multi-block structured grid on a real abdominal aortic aneurysm (AAA) acquired from Digital Imaging and Communication in Medicine (DICOM) data. With the use of a computed tomography exam (or medical images in standard DICOM format), the shape of a human organ is extracted and a structured computational grid is created. The structured grid generation is done by utilising Floater's and Gopalsamy et al.'s algorithm. The proposed methodology is applied to the AAA case, but it may also be applied to other human organs, enabling the scientist to develop an advanced patient-specific model. More importantly, the proposed methodology provides a precise reconstruction of the human organs, which is required in an AAA, where small variations in the geometry may alter the flow field, the stresses exerted on the walls and finally the rupture risk of the aneurysm.     

Porcine aortic organ culture: A model to study the cellular response to vascular injury

Summary Organ cultures of porcine thoracic aorta were studied to define the characteristics of this system as a model to study the reaction of endothelial cells (ECs) and the underlying smooth muscle cells (SMCs) to injury. Both nonwounded and wounded cultures the latter having had part of the endothelial surface gently denuded with a scalpel blade, were studied over a 7 d period by scanning and transmission electron microscopy. The results showed that the nonwounded ECs underwent a shape change from elongated to polygonal within 24 h in culture. In both nonwounded and wounded explants there was cell proliferation beneath the nondenuded endothelium so that by 7 d several layers of cells were present showing features of the secretory type of SMCs. This proliferation, however, did not occur if the endothelium was totally removed from the aorta. There was also evidence of gaps between the surface ECs, and by 7 d lamellipodia of cells beneath the surface were present in these gaps. Occasionally, elongated cells were seen to be present on the surface of the endothelium. In the wounded organ culture, cell migration and proliferation occurred extending from the wound edge and producing a covering of cells on the denuded area. There were also multilayered cells beneath the surface similar to the nonwounded area. Occasional foam cells were seen in the depth of the multilayered proliferating cells. The results indicate that organ culture of porcine thoracic aorta is a good model to study the reaction of ECs and underlying SMCs to injury. This work was supported by a grant from the Ontario Heart Foundation.     

The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage

Mechanical compression of the cartilage extracellular matrix has a significant effect on the metabolic activity of the chondrocytes. However, the relationship between the stress–strain and fluid-flow fields at the macroscopic “tissue” level and those at the microscopic “cellular” level are not fully understood. Based on the existing experimental data on the deformation behavior and biomechanical properties of articular cartilage and chondrocytes, a multi-scale biphasic finite element model was developed of the chondrocyte as a spheroidal inclusion embedded within the extracellular matrix of a cartilage explant. The mechanical environment at the cellular level was found to be time-varying and inhomogeneous, and the large difference (3 orders of magnitude) in the elastic properties of the chondrocyte and those of the extracellular matrix results in stress concentrations at the cell–matrix border and a nearly two-fold increase in strain and dilatation (volume change) at the cellular level, as compared to the macroscopic level. The presence of a narrow “pericellular matrix” with different properties than that of the chondrocyte or extracellular matrix significantly altered the principal stress and strain magnitudes within the chondrocyte, suggesting a functional biomechanical role for the pericellular matrix. These findings suggest that even under simple compressive loading conditions, chondrocytes are subjected to a complex local mechanical environment consisting of tension, compression, shear, and fluid pressure. Knowledge of the local stress and strain fields in the extracellular matrix is an important step in the interpretation of studies of mechanical signal transduction in cartilage explant culture models.