M.Cur. / The natural progress of an abdominal aortic aneurysm is enlargement and rupture. The incidence of abdominal aortic aneurysms has increased in the past 30 years and up to 50% of the patients with untreated aneurysms will die due to rupture within 5 years. Open surgery is effective in the prevention of rupture and can be performed with a mortality of 2 -5% in most cases. However, patients with aneurysms are generally older and have associated medical co-morbidities, which increase the risk in surgical intervention. In view of these associated risks with open surgery for abdominal aorta aneurysm repair, a less invasive option such as endoluminal stent-grafts, are often preferred. This new, less invasive technique with Parodi as pioneer has several advantages for patients, the greatest being the reduction in peri-operative risks of aneurysm repair. As in all new procedures, this new intervention sets specific requirements for quality peri-operative nursing. Within the legal-ethical framework of nursing there is no room for random nursing, and we as nurses must turn to protocols and standards applicable to quality nursing, and in effect the quality assurance process. Quality nursing care delivery to the patient remains the ideal of each nurse. The endovascular repair of abdominal aortic aneurysms, although less invasive, is still associated with major morbidity and mortality. The potential for complications is a reality. Complications are mainly systemic and/or procedure related. The reality of these complications affects the quality of nursing. Finally, the need to accommodate this problem requires that protocol/standards are established for the nursing of the patient with an endoluminal repair of an abdominal aortic aneurysm by means of an endovascular stent-graft. The following question can be asked in view of the above arguments and problem statement: How must these patients be nursed peri-operatively to ensure quality nursing care? The aim of this study is to compile protocol/standards for quality nursing of patients with an erldovascular stent-graft repair of an abdominal aortic aneurysm in a Coronary Intensive Care Unit in a private hospital in Cape Town.

Le principal objectif de cette thèse est de caractériser l'écoulement dans un anévrisme abdominal aortique (AAA) sous différentes conditions physiologiques et à différents stades de son développement. Cette étude est consacrée aux AAA axisymétriques, modélisés comme une dilatation de profil gaussien et de section circulaire. Ainsi, les résultats s'appliquent surtout aux étapes précoces du développement d'un AAA. Le modèle d'AAA est caractérisé par une hauteur maximale H et une largeur W, l'unité de mesure étant le diamètre d'entrée de l'artère. Pour commencer, la dynamique est étudiée pour les écoulements stationnaires. La stabilité globale de ces écoulements de base est analysée en calculant les valeurs propres et les fonctions propres pour des perturbations de faible amplitude. Pour comprendre les mécanismes d'instabilité, le transfer d'énergie entre l'écoulement de base et les perturbations est calculé. L'écoulement pour des AAA peu profonds (ou de grande longueur) se déstabilise par un mécanisme de ‘lift-up' et les perturbations amplifiées sont stationnaires. Des anévrismes plus localisés (ou plus profonds) deviennent instables pour des nombres de Reynolds plus élevés, sans doute par instabilité elliptique ; dans cette situation, les perturbations sont des modes oscillants. Dans le cas des écoulements pulsés, deux types de profil de débit physiologique ont été considérés dans cette étude, correspondant à une situation de repos ou d'exercice physique. Ces écoulements restent collés aux parois pendant la phase de systole et un écoulement décollé est généralement observé pendant la décélération après le maximum de systole. Dans cette phase, un vortex se forme à l'extrémité aval. Ce vortex s'agrandit au cours du temps et impacte l'extrémité aval de l'AAA, ce qui conduit à de forts gradients de contrainte pariétale, qui ne sont pas observés dans les cas sains. Il a été observé que les conditions d'écoulement varient significativement avec les nombre de Womersley (Wo) et de Reynolds (Re); l'écoulement reste attaché aux parois plus longtemps pour des nombres de Womersley croissants. Le principal effet d'une augmentation de Re est un renforcement du vortex primaire qui se forme après le maximum de systole. Les décollements de l'écoulement, l'impact de vortex au bord aval de l'AAA ou encore de faibles contraintes pariétales oscillantes (des caractéristiques importantes dans les cas d'anévrismes pathologiques) sont observés même pour des anévrismes de faible profondeur. Pour des anévrismes plus développés, des vortex multiples sont observés tout au long du cycle dans la cavité de l'AAA. Une analyse de stabilité de ces écoulements de base pulsés a montré que le maximum des perturbations se développe vers l'extérmité aval des AAA. Cependant, les perturbations ne sont pas complètement confinées dans la cavité de l'AAA et se développent aussi au-delà en aval. On en déduit qu'une fois qu'un AAA s'est développé, les perturbations affectent aussi les artères saines en aval de l'AAA. Enfin, en considérant deux profils équivalents d'AAA, de formes sinusoïdale et gaussienne, la sensibilité des résultats aux détails de la géométrie a pu être établie / The main objective of this thesis is to characterise the flow fields observed in an abdominal aortic aneurysm (AAA) under different physiological conditions during its progressive enlargement. An axisymmetric AAA, modeled as an inflation of Gaussian shape on a vessel of circular cross-section, is considered in the present study. This means that the results are more significant for the early stages of growth of an AAA. The model AAA is characterized by a maximum height H and width W, made dimensionless by the upstream vessel diameter. To begin with, the flow characteristics in AAAs are investigated using steady flows. The global linear stability of the base flows is analysed by determining the eigenfrequencies and eigenfunctions of small-amplitude perturbations. In order to understand the instability mechanisms, the energy transfer between the base flow and the perturbations is computed. The flow in relatively shallow aneurysms (of relatively large width) become unstable by the lift-up mechanism and have a perturbation flow which is characterized by stationary, growing modes. More localized aneurysms (with relatively small width) become unstable at larger Reynolds numbers, presumably by an elliptic instability mechanism; in this case the perturbation flow is characterized by oscillatory modes. For the case of pulsatile flows, two types of physiological flowrate waveforms are considered in our study, corresponding to rest and exercise conditions. The flows are observed to remain attached to the walls during the systolic phase, with flow separation generally observed during the deceleration after the peak systole. During this phase, the vorticity is found to roll-up into a vortex at the proximal end. This vortex enlarges with time and impinges at the downstream end of the AAA, resulting in large spatial gradients of wall shear stress (WSS) along the wall, which are not found in the healthy case. The flow conditions are observed to vary significantly with Womersley (Wo) and Reynolds (Re) numbers, with the flow remaining attached to the walls for longer times, as the Womersley number Wo increases. The principal effect of increasing Re is that the primary vortex formed after peak systole is stronger. Clinically relevant flow characteristics of aneurysmal flow, i.e. detachement of flow and impingement on the distal end, the presence of low oscillatory WSS within the AAA, are observed even for very shallow aneurysms. For deep aneurysms, multiple vortices are observed throughout the cycle within the AAA cavity. Stability analysis of pulsatile base flows reveals that the maximum values of the perturbations are observed near the distal end of the AAA. However, they are not entirely confined to the AAA cavity and extend downstream, implying that once an AAA is formed, the disturbed flow conditions spread even to the undeformed arterial walls downstream of the AAA. Finally, by considering two equivalent AAA shapes modeled by a sinusoidal and a gaussian function, the sensitivity

Abdominal aortic aneurysms (AAA) are a pathological dilation of the aorta greater than 2.5cm and affect more than 4% of the male population and 1% of women aged 60 years or older. Screening is recommended among men and women older than age 65, and is covered by Medicare for patients with a family history and men with a history of smoking. Due to its asymptomatic nature, AAA is usually found incidentally during another radiological investigation. Many factors are associated with AAA development, but it is most commonly found in conjunction with atherosclerosis. There is currently no pharmacological intervention specifically for AAA, though statin therapy has shown some promise. The aneurysm will invariably grow, with an average rate of expansion of less than 0.5cm per year. As the aneurysm grows larger the chance of the rupture increases significantly with this outcome carrying an extremely high rate of mortality. Surgical intervention is recommended once the diameter reaches 5.5cm in men or about 5cm in women. There are two approaches to the repair of the aorta: the open surgical approach and the endovascular approach. The open surgical procedure replaces the affected portion of the aorta with a graft. The endovascular procedure places an endograft within the intact aneurysm, effectively excluding the affected section of vessel. The endovascular method carries a lower perioperative mortality rate than the open procedure, but over time can require additional surgeries to prevent continued aneurysm expansion due to blood flow in the aneurysm sac. Additionally, lifetime surveillance of the endograft is required to monitor its integrity and effectiveness. Lifestyle changes and possible pharmacological interventions in patients with AAA should focus on cardiovascular health changes to improve overall health and minimize risk factors for continued development of the aneurysm. In patients who will require repair particular attention should be paid to individual risks and preferences. The open repair procedure may be preferable in patients with better overall health and a longer life expectancy, while endovascular repair may be beneficial for more elderly or frail patients. Research and technology in this area are developing quickly, particularly for endovascular procedures, and the near future may see important changes in the risk-benefit analysis of AAA surgical interventions.

Cardiovascular disease remains the commonest cause of death worldwide. The majority of deaths are caused by atherosclerotic plaque rupture with resultant myocardial infarction or stroke, or rupture of abdominal aortic aneurysms. Conventional imaging modalities have consistently failed to identify atherosclerotic plaques or aneurysms with high-risk pathological features that are at highest risk of rupture or progression. The development of modern molecular imaging techniques targeted at these features could lead to the identification of such high-risk plaques and aneurysms in vivo and guide the development of novel treatment strategies. The aim of this thesis was to evaluate whether novel molecular modalities have a role in providing new insights into biological disease processes, and identify high-risk plaques and aneurysms. Using positron emission tomography-computed tomography (PET-CT), 18F-fluorodeoxyglucose and 18F-fluoride were utilised as markers of metabolic inflammation and active calcification. Cellular inflammation was assessed using ultrasmall superparamagnetic particles of iron oxide (USPIO) enhanced magnetic resonance imaging (MRI). In a prospective trial, 80 patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-fluoride and 18F-fluorodeoxyglucose PET-CT, and invasive coronary angiography (Chapter 3). Intense 18F-fluoride uptake localised to recently ruptured plaque in patients with acute myocardial infarction. In patients with stable coronary artery disease, 18F-fluoride uptake identified coronary plaques with high-risk features on intravascular ultrasound. 18F-fluoride PET-CT is the first noninvasive imaging method to identify and localise ruptured and high-risk coronary plaques. Aortic vascular uptake of 18F- fluorodeoxyglucose was studied in patients with myocardial infarction and stable angina (Chapter 4). In a separate outcome of 1,003 patients enrolled in the Global Registry of Acute Coronary Events, we further evaluated whether infarct size predicted recurrent coronary events. Patients with myocardial infarction had higher remote atherosclerotic tracer uptake that correlated with the degree of myocardial necrosis, and exceeded that observed in patients with stable coronary disease. The outcome cohort demonstrated that patients with higher degree of myocardial necrosis had the highest risk of early recurrent myocardial infarction. This supports the hypothesis that acute myocardial infarction exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: myocardial infarction begets myocardial infarction. In a prospective imaging cohort, the role inflammation and calcification was assessed in 63 patients with abdominal aortic aneurysms and 19 age and sex matched patients with atherosclerosis (Chapter 5). Compared to non-aneurysmal segments, enhanced inflammation and calcification was observed within the wall of aortic aneurysmal segments. In comparison to matched controls with atherosclerosis, the entire aorta in those with aortic aneurysm appears more highly inflamed, suggesting presence of a global aortopathy rather than a disease confined only to the abdominal region of the aorta. Aortic aneurysms have greater active inflammation and calcification than atherosclerotic controls suggesting a more intense, destructive and transmural pathological process. A subgroup of fifteen patients with aortic aneurysms underwent imaging with both PET-CT with 18F-fluorodeoxyglucose, and T2*- weighted MRI before and 24 h after administration of USPIO (Chapter 6). Whilst there was a moderate correlation between the two tracers, there were distinct differences in the pattern and distribution of uptake suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively. These studies provide novel insights into vascular biological processes involved in the initiation, progression and rupture of atherosclerotic plaques and aortic aneurysms. Future longitudinal studies are needed to establish whether these techniques have a role in improving the clinical management and treatment of patients with coronary artery disease and aortic aneurysms.

Identification of material properties for elastic materials is important in mechanics, material sciences, mechanical engineering and biomedical engineering. Although the principle and techniques have been long established, the application in living biology still faces challenges. The biological materials are in general nonlinear, anisotropic, heterogeneous, and subject-specific. The difficulty is compounded sometimes by the requirement of non-destructiveness in medical applications. Recently, the pointwise identification method (PWIM) was proposed to address some of the needs of soft tissue characterization. PWIM is a non-invasive identification method, designed for thin materials; it can sharply characterize arbitrary heterogeneous property distributions. The primary goal of this thesis is to extend the pointwise identification method , originally developed for membranes which by default is of convex shape in pressurized states, to thin structures of arbitrary geometry. This work consists of four parts. The first part investigates the insensitivity of stress solution to material parameters in thin shell structures. This is an important first step, because PWIM hinges on the static determinacy property of the equilibrium problem of membranes. Before introducing the shell element into PWIM, it is necessary to test to what extent the assumption of static determinacy remains reasonable. It is shown that saccular structure which bending stress is small compared to in-plane stress, can still be treated as a statically determined structure. The second part focuses on developing finite element formulations of forward and inverse shell methods for a hyperelastic material model specifically proposed for cerebral aneuryms tissues. This is a preparatory step for the core development. The third part is the development of pointwise identification method for thin shell structures. Methods for stress solution, strain acquisition, and parameter regression will be discussed in detail. The entire process is demonstrated using an example of a geometrically realistic model of aneurysm. The fourth part is testing the applicability on geometrically realistic cerebral aneurysms. Six models were selected in the study; the emphasis is placed on cerebral aneurysm with concave or saddle surface region for which the use of shell theory is a must. The identification results of all six human cerebral aneurysms successfully demonstrate that the shell PWIM can be applied to realistic cerebral aneurysms. Four types of heterogeneous property distributions are considered in the study. It is found that the method can accurately back out the property distributions in all cases. Fiber directions can also be accurately estimated. The robustness of the method at the presentence of numerical noise is also investigated. It is shown that the shell PWIM still works when small perturbations exist in displacements.

Cerebral aneurysm rupture is a major cause of death and permanent disability. Rupture rate, however, is low; therefore, a physician must weigh the risk of rupture against treatment risk. In order to help physicians determine the rupture risk of any particular case, studies have previously explored morphology as an indicator for mechanical and hemodynamic characteristics of rupture-prone aneurysms. Morphological characteristics of the aneurysms in these studies are often quantified with morphometric indices, or normalized measures of specific geometric traits. This study introduces several novel morphometric indices. These include tissue stretch ratio, which characterizes the amount of deformation which aneurysm tissue may have undergone; neck-to-vessel ratio, which may have hemodynamic implications and is derived from the ratio of the diameter of the ostium to the diameter of the parent vessel; ellipticity index, which may indicate increased wall tension due to an elliptical shape; and non-sphericity index, which may indicate the presence of stress concentrations due to a non-spherical shape. In order to extrapolate these morphological measures, the aneurysm must first be separated from the parent vasculature. A novel method for aneurysm sac isolation is presented, which uses an approximation of the healthy parent vessel to remove all non-aneurysmal portions of a vascular model. This approach results in a more complete extraction of the aneurysm geometry than is possible using previous standard techniques. The repeatability of the isolation process is analyzed, as well as mesh-independence and the agreement of the resulting aneurysm sac model to a known geometry.

An intracranial aneurysm can be a serious, life-threatening condition which may go undetected until the aneurysm ruptures causing hemorrhaging within the brain. The typical treatment method for large aneurysms is by embolization using platinum coils. However, in about 15% of the cases treated by platinum coils, the aneurysm eventually re-opens. The solution to the problem of aneurysm recurrence may be to develop more bio-active materials, including certain polymers, to use as coil implants. In this research, a shape memory polymer (SMP) was investigated as a potential candidate for aneurysm coils. The benefit of a shape memory polymer is that a small diameter fiber can be fed through a micro-catheter and then change its shape into a three-dimensional configuration when heated to body temperature. The SMP was tested to determine its thermo-mechanical properties and the strength of the shape recovery force. In addition, composite specimens containing tantalum filler were produced and tested to determine the mechanical effect of adding this radio-opaque metal. Thermo-mechanical testing showed that the material exhibited a shape recovery force a few degrees above Tg. The effects of the metal filler were small and included depression of Tg and recovery force. SMP coils deployed inside a simulated aneurysm model demonstrated that typical hemodynamic forces would not hinder the shape recovery process. The x-ray absorption capability the tantalum-filled material was characterized using x-ray diffractometry and clinical fluoroscopy. Diffractometry revealed that x-ray absorption increased with tantalum concentration, however, not as the rule of mixtures would predict. Fluoroscopic imaging of the composite coils in a clinical setting verified the radio-opacity of the material.

Background: Abdominal aortic aneurysm (AAA) is a degenerative disease prevailing in men aged 65 years and above. Most AAA patients are asymptomatic until the disease develops to a very severe stage. Systematic screening could detect AAA in an early stage and early treatment is therefore provided to prevent AAA rupture and reduce AAA-related death. Ultrasonography is a recommended tool for AAA screening, which has been widely used in several western countries. Hong Kong currently has not introduced this screening programme yet. The present study attempts to investigate the health related quality of life (HRQOLO) of AAA patients in Hong Kong and then examine whether a systematic screening in elderly men in Hong Kong is cost effective compare with current practice (Non-screening strategy) Methods: Firstly, a questionnaire based study was conducted in a local university-affiliated vascular tertiary referral center targeting on AAA patients. Quality of life data was collected by a face-to-face interview using the Medical Outcomes Study Short-Form-36 Health Survey (SF-36). A controlled group was obtained from a large local population study matched by gender and age to the AAA group. The SF-36 scores were compared between the two groups; a stepwise multivariate regression analysis was conducted to show the association between the disease and the SF-36 scores. Secondly, a cost effectiveness analysis based on a Markov model was conducted to compare the screening strategy against non-screening practice. Incremental cost effectiveness ratios (ICER) was adopted as the rule of decision making. One-way sensitivity analysis and probabilistic analysis were performed to explore the uncertainty around the parameters. Results: 172 out of 252 patients participated the interview, among which 80% were aged 65 years or above, and 85% were males. Around 80% patients were detected incidentally. Comparing with the age and gender matched control group, AAA patients had an impaired HRQOL The disease adversely affected mental health summary of AAA patients. Under the discount rate of 3% on costs and effectiveness, the incremental costs of systematic screening against non-screening is HK$3,710.3; and the incremental life year gained and quality adjusted life year (QALY) gained are 0.024 and 0.014, respectively. The ICER is HK$ 151,070.1 per life year gained and HK$ 268,897.6 per QALY gained, which is cost effective under the threshold of one GDP per capita (HK$285,403) for one QALY gained. Conclusion: The economic evaluation based on the Markov model indicated systematic screening for AAA among elderly men in Hong Kong is cost effective. Government in Hong Kong should consider introducing the screening programme when resource is available. / published_or_final_version / Public Health / Master / Master of Philosophy

Cerebral Cavernous Malformations (CCM) and Intracranial Aneurysms (IA) are cerebrovascular disorders that can lead to a hemorrhagic stroke and other neurological problems. CCMs are characterized by abnormally enlarged capillary cavities while IAs are saccular outpouchings of intracranial arteries. CCM is found in approximately 0.4% to 0.9% of the population, while IA is more common (3-6%). / This dissertation aimed to add to the body of research for CCM and IA and was divided into two parts. Initial work focused on the characterization and identification of the genes involved in CCM; the second phase focused on the identification of a susceptibility gene for IA. / In the first phase, the CCM1, CCM2 and CCM3 genes were characterized in families and in sporadic cases of CCM. In both cohorts, a causative mutation was identified in 71% of the cases. Subsequent MLPA analysis of subjects with no CCM mutations revealed that large genomic deletions and duplications are a common cause of CCM. In addition, investigation of CCM1 point mutations revealed that these were not simple missense mutations but that they rather activated cryptic splice-donor sites and caused aberrant splicing. Furthermore, the genetic predisposition to CCM in sporadic cases with a single lesion was determined to be different from sporadic cases with multiple malformations. Investigation into the loss of heterozygosity demonstrated a plausible mechanism for CCM pathogenesis involving a second somatic hit at the site of the lesion, suggesting that CCM may be caused by a complete loss of CCM protein function. / In the second phase, a genome-wide scan of a large family and subsequent linkage analysis using a monogenic approach identified a susceptibility locus for IA (ANIB4). / As a result of this research, we have greatly contributed to the field of CCM, most specifically to its clinical diagnosis. A greater understanding of the genetics involved in CCM will facilitate and permit better management care for patients. Furthermore, the possibility of identification of a gene with a major effect for IA will give us more insight into which pathways are involved in IA formation.

Abdominal Aortic Aneurysms (AAA) are amongst the top ten most common cause of death in those over 55 years of age. The disease is usually asymptomatic, often being diagnosed incidentally. Once diagnosed, elective repair of an AAA results in excellent long-term survival with a 3-5% operative mortality. However, up to one half of patients present with ruptured aneurysms, a complication that carries an 80% mortality in the community, and of those reaching hospital, a 50% mortality. Clearly early diagnosis and treatment results in improved survival. Screening for AAA, with ultrasound, would detect aneurysms early, prior to rupture. However, debate continues over the cost effectiveness of population based screening programmes. The identification of a sub-population at a higher risk of developing AAA would increase the yield of a screening prograrmne. A number of populations have been examined, none of which have received international acceptance. About 20% of patients with an AAA have a family history of an aneurysm. The disease is also considered to be a disease of Caucasians, both facts suggesting a strong genetic component to the disease. Perhaps a genetically identified sub-population at a high risk of developing an AAA would prove to be an ideal population for screening. This thesis examines the incidence of aneurysms and the family histories of patients with AAA in the Otago region of New Zealand. Almost twenty percent of the population has a family history of AAA. DNA was collected from each of these patients for genetic analysis. The population was divided into familial AAA and non-familial AAA for the purpose of genetic analysis and compared to a control population. AAA is believed to be a disease of Caucasians; a non-Caucasian population with a low incidence of AAA may prove to be a good control population for genetic studies. A literature review demonstrated a higher incidence of AAA in Caucasians than other ethnic groups and within Caucasians a higher incidence in patients of Northern European origin. The incidence was low in Asian communities, even in studies involving of migrant Asian populations. The New Zealand Maori are believed to have originated from South East Asia, therefore could be expected to have a low incidence of AAA and would make an ideal control population for genetic studies. A pilot study was undertaken to examine the incidence of AAA in the New Zealand Maori. The age standardised incidence of AAA proved to be at least equal in Maori to non-Maori, with a more aggressive form of the disease in Maori, manifesting with a younger age at presentation and a higher incidence of ruptured aneurysms at diagnosis. It is well known that at the time of surgery, an AAA