Characterization of the Deformation Behavior and Mechanical Response of the Femoro-popliteal Arterial Tract after Stent Placement

The femoro-popliteal (FP) segment is the most commonly diseased artery of the peripheral circulation. Obstructions of these lower-limb arteries are frequent and even with the new generation Nitinol stents (drug-eluting or otherwise), long-term restenosis rates following endovascular procedures range from 15 to 40% and are much higher compared with the long-term outcomes after coronary artery interventions. The major difference between peripheral and coronary arteries concerns their mechanical environments, with the FP arterial segments being subjected to repeated external deformations during leg flexion. It has been widely hypothesized that the high distortion of the tissues due to the un-physiological deformations of the arteries following stent implantation is the main cause for restenosis. However, there is very limited information on the FP artery deformations of patients with Peripheral Arterial Disease (PAD). Furthermore, the effects of endovascular therapy on the deformation behavior of the PAD-afflicted FP arteries are currently unknown. As such, further research on the deformations of the FP arteries is warranted to not only improve existing stent designs, but to also determine the correct interventional procedure. The main objectives of this thesis were to characterize the deformation behavior and mechanical response of the FP arterial tract through clinical and numerical investigations. The former was achieved by, first, investigating the pre-angioplasty deformations of the FP arteries during leg flexion in a pilot study of five patients with PAD and utilizing 3D rotational angiography. The methodology was then adapted to perform a clinical study of 35 patients with PAD, in which X-ray angiography was used to image the FP arteries in straight and flexed positions prior to endovascular therapy and following either Percutaneous Transluminal Angioplasty (PTA) or primary Nitinol stent implantation. The 3D models of the FP arteries were reconstructed from the 2D X-ray angiograms and the deformations of axial deformation and curvature were quantified. Both studies showed that the PAD-afflicted FP arterial segment undergoes significant shortening and an increase in curvature with leg flexion. Comparisons between the pre- and post-treatment deformations, as well as between the different treatment methods, suggested that the choice of the treatment method significantly affects the post-interventional axial deformations of the FP arteries (post-balloon: 7.6% ± 4.9%; post-stent: 3.2% ± 2.9%; P: 0.004). As such, while PTA results in a more flexible artery, stents restrict the arteries’ shortening capabilities. Depending on the anatomical position of the stents, this axial stiffening of the arteries may lead to chronic kinking, which may cause occlusions and, consequently, impact the long-term success of the procedure. As current stent designs were found to conform to the curvature behavior of the FP arterial tract, improvements should be focused on reproducing the native axial stiffness of the artery to reduce the risk of restenosis for patients that will have to undergo stent implantation. The complexities caused by leg flexion are further exacerbated by controversial clinical practices, such as Nitinol stent oversizing. The procedure is frequently performed in peripheral arteries to ensure a desirable acute lumen gain and strong wall apposition, and to prevent stent migration. However, the increased radial force exerted onto the arterial walls by the oversized stents could lead to significant arterial damage and, in turn, restenosis. The contradictory findings between animal and clinical studies, in conjunction with the majority of the numerical studies focusing on balloon-expandable stents, suggests that the efficacy of the procedure remains as an issue to be answered. The mechanical behavior of the FP artery under Nitinol stent oversizing was investigated by creating a validated finite element (FE) framework, which included numerical models of healthy FP arteries with patient-specific geometries and idealized arteries with clinically relevant levels of PAD. Based on the artery model, either only stent implantation or the complete endovascular therapy (PTA + stent implantation) was simulated. Four different stent-to-artery ratios ranging from 1.0 to 1.8 were used in the simulations. For the healthy arteries, additional analyses, in the form of computational fluid dynamics (CFD) analyses and fatigue behavior of the stents, were performed to observe the hemodynamic behavior of the arteries with respect to increased oversizing ratios. For the calcified arteries, three different plaque types were modeled to report the influence of the plaque behaviors on the outcomes of endovascular therapy and stent oversizing. Regardless of the presence of a plaque tissue, results showed that Nitinol stent oversizing was found to produce a marginal lumen gain in ix contrast to a significant increase in arterial stresses. For the lightly and moderately calcified arteries, oversizing was found to be non-critical; whereas for healthy and heavily calcified arteries, the procedure should be avoided due to a risk of tissue failure. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, the studies showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure. In order to predict the possibility of restenosis through mechanical markers that are associated with the effects of leg movement following stent implantation, clinical investigations should be complimented with patient-specific numerical analyses. Combining intra-arterial imaging methodologies with in-vivo arterial deformations, which can be translated to FE simulations as boundary conditions, and building upon the numerical framework that is introduced in the 2nd part of this thesis, it’s possible to generate accurate patient-specific models. These models, evaluated in conjunction with clinical follow-ups, are expected to provide a deeper understanding of the mechanical background of restenosis in peripheral arteries

Finite element analysis of idealised cardiovascular stents : understanding the influence of artery material models on stent stress distribution

Stent fracture (SF) is thought to be a major contributor to in-stent restenosis and other adverse clinical events. It has been linked to angulated vessels and bifurcations, where there is often a hinge-motion movement throughout the cardiac cycle. Finite element (FE) analysis of stented arteries can be utilised to assess stent stresses and predict the likelihood of SF.An idealised tubular stent model was initially created and validated for use as a design- independent representation of stent devices. The stent model was idealised to a cylindrical tube to eliminate the device artifacts and ensure the resulting stent stress analysis was not distorted by highly localised areas of higher stress. The idealised model was based on the 3-point-bend test of a cardiovascular stent, and the FE model created to represent the mechanical behaviour of the device.Human arteries have previously been represented using a variety of mathematical models ranging from simple linear isotropic models to more complex hyperelastic models. As there has been little comparative work to qualify the necessity of using the more complex constitutive models for analysis of stresses in the stent, this study employed a variety of mathematical models used to represent human arteries to allow direct comparison of the sensitivity of model variation. The idealised stent model was used to represent an angulated stented vessel undergoing hinge-motion bending. Six different artery models from the literature were used to define the artery in the FE model and the resulting stent stresses were assessed.The results of the sensitivity study were varied and indicated little sensitivity to the artery model in terms of the stress distribution pattens, however the maximum stress values were more diverse. Overall, the likely location of SF was determined to be on the inside of the hinge-point of the stented bifurcation lesion. The model was determined to be useful as a comparative model to assess different stents devices and materials for those most likely to fracture

Application of engineering methodologies to address patient-specific clinical questions in congenital heart disease

The recent advances in medical imaging and in computer technologies have improved the prediction capabilities of biomechanical models. In order to replicate physiological, pathological or surgically corrected portions of the cardiovascular system, several engineering methodologies and their combinations can be adopted. Specifically, in this thesis, 3D reconstructions of patient-specific implanted devices and cardiovascular anatomies have been realised using both volumetric and biplanar visualisation methods, such as CT, MR, 4D-MR Flow and fluoroscopy. Finite Element techniques have been used to computationally deploy cardiovascular endoprosthesis, such as stents and percutaneous pulmonary valve devices, under patient-specific boundary conditions. To analyse pressure and velocity fields occurring in patient-specific vessel anatomies under patient-specific conditions, Lumped Parameter Networks and Computational Fluid Dynamics simulations have been employed. The above mentioned engineering tools have been here applied to address three clinical topics: 1 - Percutaneous pulmonary valve implantation (PPVI) Nowadays, more than 5,000 patients with pulmonary valve dysfunctions have been treated successfully with a percutaneous device, consisting in a bovine jugular venous valve sewn inside a balloon expandable stent. However, 25% of the treated patients experienced stent fracture. Using a novel methodological patient-specific approach that combines 3D reconstructions of the implanted stent from patients’ biplane fluoroscopy images and FE analyses, I carried out a risk stratification for stent fracture prediction. 2 - Transposition of the Great Arteries (TGA) Patients born with the congenital heart defect TGA need a surgical correction, which however, is associated with long term complications: the enlargement of the aortic root, and the development of a unilateral pulmonary stenosis. These may originate a complex hemodynamics that I tried to investigate by using patient-specific LPN and CFD models. 3 - Aortic Coarctation (CoA) Finally, combinations of FE and CFD-LPN models have been used to plan treatment in a patient with CoA and aberrant right subclavian

Age-associated Arterial Remodelling and Cardiovascular Diseases

Arterial remodelling is a major risk factor for a variety of age-related diseases and represents a potential target for therapeutic development. During ageing, the structural, mechanical and functional changes of arteries predispose individuals to the development of diseases related to vascular abnormalities in vital organs such as the brain, heart, eye and kidney. For example, aortic stiffness increases nonlinearly with advancing age – a few percent prior to 50 years of age but over 70% after 70 years of age. The elevated stiffness in large elastic arteries leads to increased transmission of high pressure to downstream smaller blood vessels, in turn affecting the microcirculation and end-organ functions. Meanwhile, the augmented remodelling of small arteries accelerates central arterial stiffening. This chapter is to provide an overview of age-associated changes in the arterial wall and their contributions to both central and peripheral vascular abnormalities associated with ageing. Therapeutics that specially target the different aspects of arterial remodelling are expected to be more effective than the traditional medications, particularly for the treatment and management of vascular ageing-related diseases.published_or_final_versio

Computational methods in cardiovascular mechanics

The introduction of computational models in cardiovascular sciences has been progressively bringing new and unique tools for the investigation of the physiopathology. Together with the dramatic improvement of imaging and measuring devices on one side, and of computational architectures on the other one, mathematical and numerical models have provided a new, clearly noninvasive, approach for understanding not only basic mechanisms but also patient-specific conditions, and for supporting the design and the development of new therapeutic options. The terminology in silico is, nowadays, commonly accepted for indicating this new source of knowledge added to traditional in vitro and in vivo investigations. The advantages of in silico methodologies are basically the low cost in terms of infrastructures and facilities, the reduced invasiveness and, in general, the intrinsic predictive capabilities based on the use of mathematical models. The disadvantages are generally identified in the distance between the real cases and their virtual counterpart required by the conceptual modeling that can be detrimental for the reliability of numerical simulations.Comment: 54 pages, Book Chapte