Pulsatile blood flow-split in aortic arch dissection

Abnormalities of the aortic arch, as the most proximal site of the cardiovascular system, are of great interest due to its major role in blood distribution to all downstream members. Wall dissection is one of the disorders that an aorta may suffer due to hypertension or degradation of aortic wall properties. A geometrical change of the aortic arch caused by the dissected wall, and consequently the blood flow path, makes the time-varying flow curves to be different in comparison to the healthy aortic arch. This phenomenon modifies wall shear stress (WSS) history during the cardiac cycle. In the current work, the pulsatile blood flow in a typical Stanford A (DeBakey II) dissected aorta is simulated by CFD technique, STAR-CCM+. The boundary conditions are calculated based on a combination of the impedance boundary condition and the auto-regulation concept in the cardiovascular system.

Automatic segmentation of abdominal aortic aneurysm from medical images based on active shape models and texture models

A semi-automatic segmentation algorithm for abdominal aortic aneurysms (AAA), and based on Active Shape Models (ASM) and texture models, is presented in this work. The texture information is provided by a set of four 3D magnetic resonance (MR) images, composed of axial slices of the abdomen, where lumen, wall and intraluminal thrombus (ILT) are visible. Due to the reduced number of images in the MRI training set, an ASM and a custom texture model based on border intensity statistics are constructed. For the same reason the shape is characterized from 35-computed tomography angiography (CTA) images set so the shape variations are better represented. For the evaluation, leave-one-out experiments have been held over the four MRI set.

Quantitative evaluation of patient-specific conforming hexahedral meshes of abdominal aortic aneurysms and intraluminal thrombus generated from MRI

A novel method for generating patient-specific high quality conforming hexahedral meshes is presented. The meshes are directly obtained from the segmentation of patient magnetic resonance (MR) images of abdominal aortic aneu-rysms (AAA). The MRI permits distinguishing between struc-tures of interest in soft tissue. Being so, the contours of the lumen, the aortic wall and the intraluminal thrombus (ILT) are available and thus the meshes represent the actual anato-my of the patient?s aneurysm, including the layered morpholo-gies of these structures. Most AAAs are located in the lower part of the aorta and the upper section of the iliac arteries, where the inherent tortuosity of the anatomy and the presence of the ILT makes the generation of high-quality elements at the bifurcation is a challenging task. In this work we propose a novel approach for building quadrilateral meshes for each surface of the sectioned geometry, and generating conforming hexahedral meshes by combining the quadrilateral meshes. Conforming hexahedral meshes are created for the wall and the ILT. The resulting elements are evaluated on four patients? datasets using the Scaled Jacobian metric. Hexahedral meshes of 25,000 elements with 94.8% of elements well-suited for FE analysis are generated.

Statistical characterization of soft tissue inelastic parameters and application to the material failure of the aortic ach

Caracterización de los procesos de disipación mecánica basándose en la microestructura de los tejidos blandos. We present a continuous damage model with regularized softening (smeared crack models) for fiber reinforced soft tissues. Material parameters of the continuous model derive from the mesoscopic scale. In the mesoscopic scale continuum is considered as a collagenous fibrilreinforced composite. We want to study the continnumlevel response as a function of the nanoscale properties of the collagen and the adherent forces between the tropocollagen molecules.

High-quality conforming hexahedral meshes of patient-specific abdominal aortic aneurysms including their intraluminal thrombi

In order to perform finite element (FE) analyses of patient-specific abdominal aortic aneurysms, geometries derived from medical images must be meshed with suitable elements. We propose a semi-automatic method for generating conforming hexahedral meshes directly from contours segmented from medical images. Magnetic resonance images are generated using a protocol developed to give the abdominal aorta high contrast against the surrounding soft tissue. These data allow us to distinguish between the different structures of interest. We build novel quadrilateral meshes for each surface of the sectioned geometry and generate conforming hexahedral meshes by combining the quadrilateral meshes. The three-layered morphology of both the arterial wall and thrombus is incorporated using parameters determined from experiments. We demonstrate the quality of our patient-specific meshes using the element Scaled Jacobian. The method efficiently generates high-quality elements suitable for FE analysis, even in the bifurcation region of the aorta into the iliac arteries. For example, hexahedral meshes of up to 125,000 elements are generated in less than 130 s, with 94.8 % of elements well suited for FE analysis. We provide novel input for simulations by independently meshing both the arterial wall and intraluminal thrombus of the aneurysm, and their respective layered morphologies.

A study of the mechanical behaviour of the human aortic artery by means of non-linear finite element models

En la presente tesis desarrollamos una estrategia para la simulación numérica del comportamiento mecánico de la aorta humana usando modelos de elementos finitos no lineales. Prestamos especial atención a tres aspectos claves relacionados con la biomecánica de los tejidos blandos. Primero, el análisis del comportamiento anisótropo característico de los tejidos blandos debido a las familias de fibras de colágeno. Segundo, el análisis del ablandamiento presentado por los vasos sanguíneos cuando estos soportan cargas fuera del rango de funcionamiento fisiológico. Y finalmente, la inclusión de las tensiones residuales en las simulaciones en concordancia con el experimento de apertura de ángulo. El análisis del daño se aborda mediante dos aproximaciones diferentes. En la primera aproximación se presenta una formulación de daño local con regularización. Esta formulación tiene dos ingredientes principales. Por una parte, usa los principios de la teoría de la fisura difusa para garantizar la objetividad de los resultados con diferentes mallas. Por otra parte, usa el modelo bidimensional de Hodge-Petruska para describir el comportamiento mesoscópico de los fibriles. Partiendo de este modelo mesoscópico, las propiedades macroscópicas de las fibras de colágeno son obtenidas a través de un proceso de homogenización. En la segunda aproximación se presenta un modelo de daño no-local enriquecido con el gradiente de la variable de daño. El modelo se construye a partir del enriquecimiento de la función de energía con un término que contiene el gradiente material de la variable de daño no-local. La inclusión de este término asegura una regularización implícita de la implementación por elementos finitos, dando lugar a resultados de las simulaciones que no dependen de la malla. La aplicabilidad de este último modelo a problemas de biomecánica se estudia por medio de una simulación de un procedimiento quirúrgico típico conocido como angioplastia de balón. In the present thesis we develop a framework for the numerical simulation of the mechanical behaviour of the human aorta using non-linear finite element models. Special attention is paid to three key aspects related to the biomechanics of soft tissues. First, the modelling of the characteristic anisotropic behaviour of the softue due to the collagen fibre families. Secondly, the modelling of damage-related softening that blood vessels exhibit when subjected to loads beyond their physiological range. And finally, the inclusion of the residual stresses in the simulations in accordance with the opening-angle experiment The modelling of damage is addressed with two major and different approaches. In the first approach a continuum local damage formulation with regularisation is presented. This formulation has two principal ingredients. On the one hand, it makes use of the principles of the smeared crack theory to avoid the mesh size dependence of the structural response in softening. On the other hand, it uses a Hodge-Petruska bidimensional model to describe the fibrils as staggered arrays of tropocollagen molecules, and from this mesoscopic model the macroscopic material properties of the collagen fibres are obtained using an homogenisation process. In the second approach a non-local gradient-enhanced damage formulation is introduced. The model is built around the enhancement of the free energy function by means of a term that contains the referential gradient of the non-local damage variable. The inclusion of this term ensures an implicit regularisation of the finite element implementation, yielding mesh-objective results of the simulations. The applicability of the later model to biomechanically-related problems is studied by means of the simulation of a typical surgical procedure, namely, the balloon angioplasty.

Influence of rurality, deprivation and distance from clinic on uptake in men invited for abdominal aortic aneurysm screening

Acknowledgements This study received no specific funding. The study involved the analysis of data collected routinely as part of the national AAA screening programme in Scotland.

Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II

Superoxide anion (O2−) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated in the development of hypertension. In previous studies, we found that O2− is produced predominantly in the adventitia of isolated rabbit aorta and acts as a barrier to NO. In the present studies, we characterize the enzyme responsible for O2− production in the adventitia and show that this enzyme is a constitutively active NADPH oxidase with similar composition as the phagocyte NADPH oxidase. Constitutive O2−-generating activity was localized to aortic adventitial fibroblasts and was enhanced by the potent vasoconstrictor angiotensin II. Immunohistochemistry of aortic sections demonstrated the presence of p22phox, gp91phox, p47phox, and p67phox localized exclusively in rabbit aortic adventitia, coincident with the site of staining for O2− production. Furthermore, immunodepletion of p67phox from adventitial fibroblast particulates resulted in the loss of NADPH oxidase activity, which could be restored by the addition of recombinant p67phox. Further study into the regulation of this adventitial source of O2− is important in elucidating the mechanisms regulating the bioactivity of NO and may contribute to our understanding of the pathogenesis of hypertension.

Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study

Objective: To determine the long term relative survival of all patients who had surgery for abdominal aortic aneurysm in Western Australia during 1985-94.

Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells.

In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we hypothesized that endothelial hypoxia may "superinduce" expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-alpha (270% increase over normoxia and TNF-alpha) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-alpha and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.

cAMP- and rapamycin-sensitive regulation of the association of eukaryotic initiation factor 4E and the translational regulator PHAS-I in aortic smooth muscle cells.

Incubating rat aortic smooth muscle cells with either platelet-derived growth factor BB (PDGF) or insulin-like growth factor I (IGF-I) increased the phosphorylation of PHAS-I, an inhibitor of the mRNA cap binding protein, eukaryotic initiation factor (eIF) 4E. Phosphorylation of PHAS-I promoted dissociation of the PHAS-I-eIF-4E complex, an effect that could partly explain the stimulation of protein synthesis by the two growth factors. Increasing cAMP with forskolin decreased PHAS-I phosphorylation and markedly increased the amount of eIF-4E bound to PHAS-I, effects consistent with an action of cAMP to inhibit protein synthesis. Both PDGF and IGF-I activated p70S6K, but only PDGF increased mitogen-activated protein kinase activity. Forskolin decreased by 50% the effect of PDGF on increasing p70S6K, and forskolin abolished the effect of IGF-I on the kinase. The effects of PDGF and IGF-I on increasing PHAS-I phosphorylation, on dissociating the PHAS-I-eIF-4E complex, and on increasing p70S6K were abolished by rapamycin. The results indicate that IGF-I and PDGF increase PHAS-I phosphorylation in smooth muscle cells by the same rapamycin-sensitive pathway that leads to activation of p70S6K.

Identification of endothelin 1 and big endothelin 1 in secretory vesicles isolated from bovine aortic endothelial cells.

Vesicles containing endothelin 1 (ET-1) were isolated from bovine aortic endothelial cells (BAECs) by fractionation of homogenates on sucrose density gradients by ultracentrifugation. The vesicles were localized at the 1.0/1.2 M sucrose interface using a specific anti-ET-1-(16-21) RIA. Identification of ET-1 and big ET-1 in this fraction was confirmed by HPLC analysis combined with RIA. Morphological examination of the ET-1-enriched fraction by electron microscopy identified clusters of vesicles approximately 100 nm in diameter. Immunostaining of ultrathin cryosections prepared from the vesicle fraction for ET-1 or big ET-1 showed clusters of 15-nm gold particles attached to or within vesicles. Immunofluorescence staining of whole BAECs using a specific ET-1-(16-21) IgG purified by affinity chromatography revealed punctate granulation of the cell cytoplasm viewed under light microscopy. This distinct pattern of staining was shown by confocal light microscopy to be intracellular. Immunofluorescence staining of whole cells with a polyclonal antiserum for big ET-1-(22-39) showed a defined perinuclear localization of precursor molecule. Hence, several different approaches have demonstrated that ET-1 and big ET-1 are localized within intracellular vesicles in BAECs, suggesting that these subcellular compartments are an important site for processing of big ET-1 by endothelin-converting enzyme.

Automatic Abdominal Aortic Aneurysm segmentation in MR images

Abdominal Aortic Aneurism is a disease related to a weakening in the aortic wall that can cause a break in the aorta and the death. The detection of an unusual dilatation of a section of the aorta is an indicative of this disease. However, it is difficult to diagnose because it is necessary image diagnosis using computed tomography or magnetic resonance. An automatic diagnosis system would allow to analyze abdominal magnetic resonance images and to warn doctors if any anomaly is detected. We focus our research in magnetic resonance images because of the absence of ionizing radiation. Although there are proposals to identify this disease in magnetic resonance images, they need an intervention from clinicians to be precise and some of them are computationally hard. In this paper we develop a novel approach to analyze magnetic resonance abdominal images and detect the lumen and the aortic wall. The method combines different algorithms in two stages to improve the detection and the segmentation so it can be applied to similar problems with other type of images or structures. In a first stage, we use a spatial fuzzy C-means algorithm with morphological image analysis to detect and segment the lumen; and subsequently, in a second stage, we apply a graph cut algorithm to segment the aortic wall. The obtained results in the analyzed images are pretty successful obtaining an average of 79% of overlapping between the automatic segmentation provided by our method and the aortic wall identified by a medical specialist. The main impact of the proposed method is that it works in a completely automatic way with a low computational cost, which is of great significance for any expert and intelligent system.