L'anévrisme cérébral est une région fragile de la paroi d'un vaisseau sanguin dans le cerveau, qui peut se rompre et provoquer des saignements importants et des accidents vasculaires cérébraux. La segmentation de l'anévrisme cérébral est une étape primordiale pour l'aide au diagnostic, le traitement et la planification chirurgicale. Malheureusement, la segmentation manuelle prend encore une part importante dans l'angiographie clinique et elle est devenue couteuse en temps de traitement étant donné la gigantesque quantité de données générées par les systèmes d'imagerie médicale. Les méthodes de segmentation automatique d'image constituent un moyen essentiel pour faciliter et accélérer l'examen clinique et pour réduire l'interaction manuelle et la variabilité inter-opérateurs. L'objectif principal de ce travail de thèse est de développer des méthodes automatiques pour la segmentation et la mesure des anévrismes. Le présent travail de thèse est constitué de trois parties principales. La première partie concerne la segmentation des anévrismes géants qui contiennent à la fois la lumière et le thrombus. La méthode consiste d'abord à extraire la lumière et le thrombus en utilisant une procédure en deux étapes, puis à affiner la forme du thrombus à l'aide de la méthode des courbes de niveaux. Dans cette partie, la méthode proposée est également comparée à la segmentation manuelle, démontrant sa bonne précision. La deuxième partie concerne une approche LBM pour la segmentation des vaisseaux dans des images 2D+t et de l'anévrisme cérébral dans les images en 3D. La dernière partie étudie un modèle de segmentation 4D en considérant les images 3D+t comme un hypervolume 4D et en utilisant un réseau LBM D4Q81, dans lequel le temps est considéré de la même manière que les trois autres dimensions pour la définition des directions de mouvement des particules dans la LBM, considérant les données 3D+t comme un hypervolume 4D et en utilisant un réseau LBM D4Q81. Des expériences sont réalisées sur des images synthétiques d'hypercube 4D et d'hypersphere 4D. La valeur de Dice sur l'image de l'hypercube avec et sans bruit montre que la méthode proposée est prometteuse pour la segmentation 4D et le débruitage. / Cerebral aneurysm is a fragile area on the wall of a blood vessel in the brain, which can rupture and cause major bleeding and cerebrovascular accident. The segmentation of cerebral aneurysm is a primordial step for diagnosis assistance, treatment and surgery planning. Unfortunately, manual segmentation is still an important part in clinical angiography but has become a burden given the huge amount of data generated by medical imaging systems. Automatic image segmentation techniques provides an essential way to easy and speed up clinical examinations, reduce the amount of manual interaction and lower inter operator variability. The main purpose of this PhD work is to develop automatic methods for cerebral aneurysm segmentation and measurement. The present work consists of three main parts. The first part deals with giant aneurysm segmentation containing lumen and thrombus. The methodology consists of first extracting the lumen and thrombus using a two-step procedure based on the LBM, and then refining the shape of the thrombus using level set technique. In this part the proposed method is also compared with manual segmentation, demonstrating its good segmentation accuracy. The second part concerns a LBM approach to vessel segmentation in 2D+t images and to cerebral aneurysm segmentation in 3D medical images through introducing a LBM D3Q27 model, which allows achieving a good segmentation and high robustness to noise. The last part investigates a true 4D segmentation model by considering the 3D+t data as a 4D hypervolume and using a D4Q81 lattice in LBM where time is considered in the same manner as for other three dimensions for the definition of particle moving directions in the LBM model.

This thesis is focused on stress in brain aneurysms. It consists of three parts. First part is aimed for gaining information about the topic from scientific resources. Next part consists of analyses of geometry of cerebral aneurysms on the computed wall stress. Analyses are performed on four basic geometrical models and results are being discussed. The risky areas in each investigated shape have been identified as well as the comparisons of stress between those shapes have been performed and the most dangerous shape among investigated shapes has been determined. Third part investigates the influence of surrounding tissue on the brain aneurysm. Conclusion of this thesis is that brain gray tissue has positive yet negligible effect on the computed wall stress.

Objective: To quantify and compare histopathological differences regarding atherosclerosis and granular media calcinosis (GMC) of ascending aortic aneurysms (AAA), which are associated with aortic stenosis (AS) or aortic regurgitation (AR). Additionally, a subanalysis of patients with bicuspid or tricuspid aortic valve (BAV or TAV), which were contained within the AS and AR group, was conducted. Patients and Methods: From 01/2012 till 12/2015 84 ascending aortic tissue samples were obtained and divided into their convex and concave half during aortic surgery. Aortic surgery was indicated due to AAA in association to AS (AS-AAA group: n = 43) or AR (AR-AAA group: n = 41). Both groups contained 19 patients with TAV. Convex and concave halves of all samples were stained with three different histologic dyes: hematoxylin-eosin (HE) was used as general stain for atherosclerosis, von-Kossa (vKossa) stain and alizarin-red (Ared) stain were used as calcinosis specific dyes. HE stained samples were analyzed using a semi-quantitative score, while calcinosis quantification was carried out by a binary, pixel guided contrast analysis via computer software. Results: In the AR-AAA group, atherosclerosis was two and a half times more often detectable in the concave halves of the tissue samples as in the AS-AAA group (AR-AAA concave: 15 (36%) vs. AS-AAA concave: 6 (13%), p ≤ 0,01). Regarding GMC, tissue samples from AS-AAAs showed a 4,2-4,5% higher mean GMC deposit than their AR-AAA counterparts (p ≤ 0,001). Furthermore, BAV patients within the AS-AAA group showed a 2,1-2,4% higher mean deposit of GMC than their TAV peers (p ≤ 0,002). These finding of higher GMC deposition was consistent for BAV patients contained in the AAA-AR group. Conclusion: AR-AAA are, in comparison with AS-AAA, more prone to develop atherosclerosis. Atherosclerosis will most likely present at the concave curvature of the ascending aorta. AS-AAAs present significant higher mean GMC deposits than AR-AAAs. Combined with a bicuspid morphology of the aortic valve, GMC deposition in AAAs is elevated in comparison to AAAs with TAV morphology. Therefore AS-AAAs with BAV have the highest tendency to develop heavy GMC deposition, compromising the biomechanical structure of the aortic wall.

<p><i>Chlamydophila pneumoniae</i> (<i>C. pneumoniae</i>) has been suggested as a stimulator of chronic inflammation in atherosclerosis. <i>C. pneumoniae</i> DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. <i>C. pneumoniae</i> mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. </p><p>Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. <i>C. pneumoniae </i>DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. <i>C. pneumoniae</i> DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for <i>C. pneumoniae</i> in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for <i>C. pneumoniae</i> in atherosclerosis. </p><p>Mice were infected with <i>C. pneumoniae</i> that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for <i>C. pneumoniae</i> metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.</p>

Introduction: Idiopathic dilatation of the right atrium (IDRA) is a rare abnormality usually detected by chance at any time between antenatal and adult life. It is defined as isolated enlargement of the right atrium in the absence of other cardiac lesions causing right atrial dilatation. IDRA can be associated with atrial arrhythmia and systemic embolism. The clinical presentation shows high variability ranging from the lack of any symptoms up to cardiac failure. Methods/Results: We describe 2 children with antenatally diagnosed IDRA, the intrauterine course in 1 case, the postnatal management and its long-term follow-up. There has been no need for surgical intervention so far because of the lack of arrhythmias and no further progression of right atrial diameters. Thrombus formation in the right atrium, which is a potential risk for pulmonary embolism, led us to initiate anticoagulation in our cases to prevent such complications. Furthermore, we suggest one possible pathomechanism of congenital right atrial dilatation. Conclusion: Optimal management of severe IDRA depends on the individual case. Long-term follow-up of these patients is necessary to monitor a possible further progression of right atrial size and occurrence of arrhythmias. As a possible pathomechanism, a functional partial anomalous pulmonary venous insertion may imitate a structural abnormal pulmonary vein connection in some idiopathic cases of congenital right atrial dilatation. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Thoracic aortic aneurysms and dissections (TAAD) have a genetic component with an estimated 20-25% of the patients having a positive family history. An aneurysm often precedes a dissection. Acute aortic dissections are associated with high mortality and morbidity, even when operated on. Complications due to prophylactic surgery are considerably fewer. Therefore, patients at risk for dissection should be identified, followed-up and evaluated for prophylactic intervention. Aims: 1. To establish reference values for ascending (AoA) and descending aortic (AoD) diameters measured by computed tomography. 2. To study the effectiveness of phenotypic cascade screening in families with an inherited form of thoracic aortic aneurysms and dissections (FTAAD) and to address questions that arise when screening for a genetic disorder is applied. 3. To study the agreement of aortic diameters obtained by TTE and MRI and to study aortic stiffness in individuals from families with FTAAD. 4. To perform exome sequencing in order to identify pathogenic sequence variants causing FTAAD, to characterize the phenotype, and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers. Results: Paper I: The diameter of the thoracic aorta increased by 0.17 mm (0.12 – 0.20 mm) per year. The mean sex-related difference in diameter was 1.99 mm (1.28 – 2.60 mm) with men having larger aortas than women. The mean difference in aortic diameter per unit BMI was 0.27 mm (0.14 – 0.44 mm). Upper normal limits for the AoA can be calculated by the formula D (mm)=31+0.16*age and for the AoD by D (mm)=21+0.16*age. Paper II: Of 106 individuals from families with FTAAD but without known thoracic aortic disease, 19 individuals (18%) were identified to have a dilated AoA. The expected number of individuals in this group with an autosomal dominant disease would have been 40 (p&lt;0.0001). In first-degree relatives younger than 40, we found only one individual with a dilated aorta although the expected number of individuals with disease causing mutation would have been 10. Paper III: Of 116 individuals investigated, 21 were identified with thoracic aortic dilatation and 95 individuals with normal thoracic aortic diameter. Aortic stiffness increased with age and diameter. The individuals with aortic dilatation were older than those without (49 vs. 37 years, p=0.001) and showed lower aortic elastic properties. The diameters measured by TTE and MRI correlated strongly (r2=0.93). The mean difference in diameters between the two methods was 0.72 mm (95% CI 0.41-1.02) with TTE giving larger diameters than MRI. Paper IV: From exome sequencing and segregation analysis, a 2-bp deletion in the MYLK gene (c.3272_3273del) was identified to cause FTAAD. The age and the aortic diameter at dissection or rupture varied in the family members. We did not find any differences in aortic diameter, aortic stiffness, or pulse wave velocity between carriers and non-carriers. Conclusions: Thoracic aortic diameter increases with age, and sex and body size are also associated with the diameter. In FTAAD, screening identifies family members with a previously unknown aortic dilatation. However, a normal aortic diameter does not exclude an individual from being a carrier of FTAAD. TTE can be used in follow-up for the ascending aorta. Individuals identified to have a dilated thoracic aorta have increased aortic stiffness compared to individuals with normal thoracic aortic diameter. The MYLK mutation (c.3272_3273del) causes thoracic aortic dissections with variable clinical expression. No differences in aortic stiffness were identified between MYLK mutation carriers and non-carriers.

An estimated 85% of haemorrhagic strokes are secondary to the rupture of an intracranial aneurysm (IA), a localised, blood-filled dilation of the artery wall. The clinically observed rupture of occluded IAs has led to hypothesise that the presence of thrombus may restrict the transport of nutrients, most notably oxygen, to the aneurysmal wall, thus heightening the risk of rupture through the deleterious effects of hypoxia on cellular functionality. The limited research into O2 transport within IAs demonstrate the need for further exploration into the possible detrimental hypoxic conditions as a result of intrasaccular haemodynamics and thrombusformation in untreated, treated and evolving IAs, with the ultimate goal of further understanding disease evolution and developing prognostic decision support models for clinical intervention. Preliminary computational fluid dynamic simulations conducted on a 2Daxisymmetric model of a thrombosed artery highlighted the relative importance of wall-side versus the fluid-side mass transport of oxygen. A sensitivity analysis demonstrated that variations in thrombus thickness, and arterial wall cellular respiration rates have the greatest influence on the oxygen distribution to the portion of wall in direct contact with the thrombus. The results of the coupled flow-mass transport computational fluid dynamic simulations within patient-specific IA show that a reduction in intrasaccular flow as a consequence of stent deployment affects the rate at which oxygenated blood reaches the entirety of the dome. Nonetheless, the distribution ofO2 to the aneurysmal wall itself does not differ from the observed oxygen distribution across the wall when the same IA is left untreated. Conversely, the low velocity recirculations observed in an IA presenting with a very high aspect ratio (i.e a narrow neck and high sack height) limited the transport of oxygen to such an extent as to completely deprive the delivery of oxygen to the fundus. The presence of thrombus within the IA dome results in a dramatic reduction in oxygen delivery to the wall, the extent of which is dependent on the local thrombus thickness. Finally, a novel fluid-solid-growth-mass transport (FSGT) mathematical model is conceived to explore the biochemical role of thrombus on the evolution of an IA. The shear-regulate propagation of a thrombus layer during membrane expansion leads to the gradual decrease in oxygen tension within the wall. Moreover, as a consequence of coupling this oxygen deficiency to fibroblast functionality, the collagen fibre mass density was shown to increase at an insufficient rate to compensate for the transfer in load from the degrading elastinous consitituents to the collagenous constituents, thus resulting in the increased stretch of collagen fibres in order to maintain mechanical equilibrium. Moreover this over-expansion results in the gradual unstable evolution of the IA. The observed obstruction to oxygen delivery as a result of intrasaccular haemodynamics and thrombosis compounds the need for further development of more comprehensive chemo-mechano-biological models of IAs so as to better ascertain the level of rupture risk posed by a hypoxic environment. Refinement to the models proposed within this work would prove invaluable to creating a fully integrated multi-physics, multi-scale in silico framework in aid to patient diagnostics and individual treatment planning of IAs.

Abdominal Aortic Aneurysm (AAA) is a disease that mainly affects elderly men, and ruptured AAA (rAAA) is associated with a mortality of &gt; 80%. AAA seldom gives any symptoms prior to rupture. The aims of this thesis were to investigate different aspects of how to affect mortality from rAAA. In Study I, we identified 849 patients treated for rAAA during 1987-2004, and studied the 30-day survival after surgery, depending on whether they came directly to the treating hospital (one-stop) or were transferred via another hospital (two-stop). A two-stop referral pattern resulted in a 27% lower population-based survival rate for patients 65-74 years of age. However, the consequences would be small even if a one-stop referral pattern could be generally accomplished, due to the huge over-all mortality related to rAAA, hence an argument to find and treat AAA before rupture, e.g. by screening. In Study II, we examined the AAA-prevalence and the risk factors for AAA among 70-year-old men. The screening-detected AAA-prevalence was 2.3%, thus less than half the predicted. The most important risk factor was smoking. In Study III, we compared the screening-detected AAA-prevalence, the attendance rate, and the rate of opportunistic detection of AAA, between almost 8000 65- and 6000 70-year-old men. There was no difference in the screening-detected prevalence; probably due to the fact that almost 40% of the AAAs among the 70-year-old were already known prior to screening, compared to roughly 25% in the 65-year-old. The attendance rate was higher among the 65-year-old men, 85.7% compared 84.0% in the 70-year-old. Thus, there is no benefit of screening for AAA among 70- instead of 65-year-old men. In Study IV, a cost-effectiveness analysis, we found that screening for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management. In conclusion, we found that mortality from rAAA is not affected in any substantial way by different referral patterns and hence centralisation of services for AAA/rAAA is not a solution. A better alternative is to prevent rupture through early detection by screening. Screening 65-year-old men for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management during the last decade. Screening 70- instead of 65-year-old men will not increase the efficacy of screening.

Ce travail de thèse porte sur la simulation du déploiement des prothèses vasculaires de type stent-graft (SG) lors de la réparation endovasculaire (EVAR) des anévrismes de l’aorte abdominale (AAA). Cette étude se présente en trois parties: (i) tests mécaniques en flexion et compression de SG couramment utilisés (corps et jambage de marque Cook) ainsi que la simulation numérique desdits tests, (ii) développement d’un modèle numérique d’anévrisme, (iii) stratégie de simulation du déploiement des SG. La méthode numérique employée est celle des éléments finis. Dans un premier temps, une vérification du modèle éléments finis (MEF) des SG est realisée par comparaison des différents cas de charge avec leur pendant expérimental. Ensuite, le MEF vasculaire (AAA) est lui aussi vérifié lors d’une comparaison des niveaux de contraintes maximales principales dans la paroi avec des valeurs de la littérature. Enfin, le déploiement est abordé tout en intégrant les cathéters. Les tests mécaniques menés sur les SG ont été simulés avec une différence maximale de 5,93%, tout en tenant compte de la pré-charge des stents. Le MEF de la structure vasculaire a montré des contraintes maximales principales éloignées de 4,41% par rapport à un modèle similaire précédemment publié. Quant à la simulation du déploiement, un jeu complet de SG a pu être déployé avec un bon contrôle de la position relative et globale, dans un AAA spécifique pré-déformé, sans toutefois inclure de thrombus intra-luminal (TIL). La paroi du AAA a été modélisée avec une loi de comportement isotropique hyperélastique. Étant donné que la différence maximale tolérée en milieu clinique entre réalité et simulation est de 5%, notre approche semble acceptable et pourrait donner suite à de futurs développements. Cela dit, le petit nombre de SG testés justifie pleinement une vaste campagne de tests mécaniques et simulations supplémentaires à des fins de validation. / This thesis work is concerned with the simulation of the deployment of stent-graft (SG) vascular prostheses in abdominal aortic aneurysms (AAA) during endovascular repair (EVAR). This study is composed of three main parts: (i) mechanical tests in bending and compression of frequently used SG (body and leg from Cook) as well as the numerical simulation of these tests, (ii) development of a numerical AAA model, (iii) strategy of simulation of SG deployment. The finite element method is used. In a first step, a verification of the finite element model (FEM) of SG is performed by comparison of the different load cases with their experimental counterparts. Subsequently, the vascular FEM is also verified in terms of maximal principal constraints in the wall against values available in the literature. Finally, the deployment is investigated while taking the catheters into account. The mechanical tests performed on the SG were simulated with a maximal difference of 5.93%, while accounting for the pre-load in stents. The FEM of the vascular structure showed maximal principal stresses that were 4.41% far from the ones found in the literature for a similar model. Regarding the simulation of SG deployment, a complete set of SG could be deployed with a good control of the relative and global position into a specific and pre-deformed AAA, however, no intra-luminal thrombus (ILT) was included. The AAA wall was modeled with an isotropic hyperelastic constitutive law. In the clinical setting, the maximum tolerated difference between reality and simulation is 5%, therefore, our approach seems acceptable, and could give rise to further developments. However, the small amount of tested SG justifies a wide campaign of additional mechanical tests and simulations for the sake of validation.

Bakgrund: Bröstcancer är den vanligaste cancerformen hos kvinnor i Sverige. Riskfaktorerna är flera och därför har Socialstyrelsen bestämt att hälso- och sjukvården ska erbjuda mammografiscreening för att upptäcka sjukdomen i ett tidigt stadium. Bukaortaaneurysm är en lokal vidgning av kroppspulsådern som främst drabbar män. Sjukdomen är ofta asymtomatisk och kan vara livshotande. Socialstyrelsen har därför bestämt att en engångsundersökning ska erbjudas alla män i 65-års ålder. Syfte: Syftet med examensarbetet var att studera anledningar till utebliven screeningundersökning och om anledningarna skiljer sig åt för mammografi- och bukaortascreening. Metod: Detta examensarbete är en litteraturöversikt som behandlar 15 vetenskapliga artiklar relevanta till arbetets syfte. Resultat: Faktorer som påverkade deltagandet var: ålder, invandring, nära relation till sjukdomen, avstånd, svårigheter att ta sig till klinik/opassande öppettider, utbildning, social status, fysisk och psykisk ohälsa, okunskap/bristande information, rädslor/förnekelse, civilstånd/familj och mottagen påminnelse. Diskussion: Samtliga punkter för icke deltagande stämde inte alltid överens för de båda screeningprogrammen. Efter granskning av inbjudan till screeningprogrammen sågs skillnader i informationen som skulle kunna ha betydelse för de faktorer som studerats i artiklarna. Slutsats: Icke deltagande kan bero på flera faktorer som påverkas av varandra och en liten skillnad mellan män och kvinnor sågs. Inbjudan kan påverka deltagandet i vissa fall. / Background: Breast cancer is the most common form of cancer in women in Sweden and there are several risk factors. Abdominal aortic aneurysm is an expansion of the vessel and men are most likely to suffer. The disease is asymptomatic and life-threatening. The National Board of Health and Welfare has decided to offer mammography screening and aneurysm screening to detect the diseases in an early stage. Aim: The aim with this review was to study reasons for non-participation in screening and if reasons differ from the both screening programme. Method: This bachelor thesis was designed as a review based on 15 articles. Results: Factors that affect the attendance was: age, immigration, close relations to the disease, distance, disable to get to the clinic/unfitting opening hours, education, social status, physical/mental health, unknowledge/less information, fear/denial, civil status/family and reminder letter. Discussion: Factors for non-attendance was not the same for both screening programmes. Inspection of the invitation letter from Jönköping county showed some defects that could affect the factors that has been found in the articles. Conclusion: Non-attendance can depend on several factors that influence each other and small differences was seen between men and women. The invitation letter could affect the participation in some cases.