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Abstract Thoracic aortic aneurysms (TAAs) are a significant source of morbidity and mortality. Classical risk factors for TAAs are hypertension, atherosclerosis, male gender, smoking, age, high body mass index, family history and chronic obstructive pulmonary disease. In addition, in certain cases of TAAs, i.e., ascending aortic aneurysms (AscAA), genetic factors are highly prominent. Matrix metalloproteinases are in a major role in the destruction of the aortic wall and the imbalance between matrix metalloproteinases, and their inhibitors are involved in the formation of aneurysms. In addition, osteopontin is a potent regulator of matrix metalloproteinases and it is widely expressed in injured arteries. Recently, telomere shortening has been shown to be involved in the development of abdominal aortic aneurysms (AAA). In this aneurysm type, atherosclerosis has a major role. Since atherosclerosis is frequently absent in the case of TAAs, the length of telomeres was measured in the blood samples of TAA patients. The purpose of this thesis was to study the genetic background of TAAs of the ascending aorta and furthermore, the molecular background of this disease. The first study was done with families with TAAs, and dissections and one chromosomal locus (5q13-14) of the studied seven loci showed a significant genetic linkage for TAAs. Two other studies were done exploiting our TAA case-control material. Study II showed elevated levels of osteopontin, matrix metalloproteinase type 2 and 9 in the plasma and tissue samples of TAA patients compared with controls. In the third study, longer blood leukocyte telomeres were found in the DNA samples of TAA patients compared with controls; furthermore, the elevation of telomere lengthening protein telomerase expression was found in the tissue samples of TAA patients. This thesis presents region 5q13-14 as a potential genetic regulator for TAAs in Finnish families. In addition, elevated levels of osteopontin, matrix metalloproteinase type 2 and 9 can be considered as a plasma biomarker for aneurysmal disease. Furthermore, longer blood leukocytes were found to be a significant risk factor for developing TAAs. / Tiivistelmä Rinta-aortan aneurysmat ovat merkittävä sairastumisiin ja kuolemiin johtava tekijä. Perinteisinä riskitekijöinä aneurysmille on pidetty korkeaa verenpainetta, ateroskleroosia, miessukupuolta, tupakointia, ikää, ylipainoa, suvussa esiintyneitä aneurysmatapauksia ja keuhkoahtaumatautia. Näiden lisäksi erityisesti nousevan rinta-aortan alueella esiintyvissä aneurysmissa myös perinnöllisillä tekijöillä on korostunut merkitys. Matriksimetalloproteinaaseilla ja niiden estäjillä on merkittävä rooli, kun aortan seinämää hajotetaan. Tasapainon järkkyminen kyseisten proteiinien keskinäisessä suhteessa voi johtaa aneurysman muodostumiseen. Myös osteopontiinin tiedetään olevan tehokas matriksimetalloproteinaasien säätelijä, ja sitä tuotetaankin yleisesti vahingoittuneessa verisuonessa. Telomeerien lyhentyminen on vastikään yhdistetty vatsa-aortan alueella esiintyviin aneurysmiin, joissa ateroskleroosilla on yleensä merkittävä rooli. Koska ateroskleroosi on vain harvoin nousevan rinta-aortan alueen aneurysmien taustalla, rinta-aortan aneurysmapotilaiden valkosolujen telomeerien suhteelliset pituudet määritettiin. Väitöskirjan ensimmäisessä osatyössä keskityttiin löytämään geneettinen kytkentä rinta-aortan aneurysmien ja jonkin seitsemän tutkitun kromosomialueen välille. Geneettinen kytkentä löydettiin kromosomialueelta 5q13-14. Osatöissä 2 ja 3 hyödynnettiin rinta-aortan aneurysmien potilas- ja verrokkiaineistoja. Osatyö 2 osoitti, että matriksimetalloproteinaasien (2 ja 9) määrät ovat kohonneet rinta-aortan aneurysmapotilaiden näytteissä verrokkeihin verrattuna. Osatyössä 3 telomeerien suhteelliset pituudet veren valkosoluissa olivat pidemmät nousevan rinta-aortan aneurysmapotilaiden näytteissä verrokkihenkilöiden näytteisiin verrattuna. Myös telomeraasin tuotto oli lisääntynyt rinta-aortan aneurysmapotilaiden aorttakudosnäytteissä. Väitöskirjassa esitetään tuloksena kromosomialue 5q13-14 geneettisenä säätelijänä suomalaisissa suvuittain esiintyvissä rinta-aortan aneurysmatapauksissa. Kohonneita matriksimetalloproteinaasien ja osteopontiinin tasoja voidaan lisäksi pitää biomarkkereina rinta-aortan aneurysmien sairastavuudelle. Veren valkosolujen pidemmät telomeerit näyttävät myös olevan yhteydessä rinta-aortan aneurysmien sairastavuuteen.

The aim of this thesis is the problematic of abdominal aortic aneurysm wall stress in relation to a different material behavior of intraluminal thrombus, which is in most cases present in the aneurysmal volume. In this thesis, the influence of neglecting the patient-specific material properties of the intraluminal thrombus, on the aneurysmal wall stress, obtained from finite element stress-strain analysis, is investigated. In terms of solution method selection, a system approach was applied so that the solution method was selected in order to respect a system of essential variables as much as possible. The first part of this thesis is focused on a description of the problematic and the human cardiovascular system with important aspects contributing to development and growth of the abdominal aortic aneurysm. Next, this part of the thesis includes chapters devoted to the intraluminal thrombus in terms of its basic characteristics (anatomy, physiology, pathology), structure and its influence on processes within the abdominal aneurysm. The second part of this work is devoted to the accomplishment of the first and second goal of this thesis, which is analyzing the available literature to obtain mean population stiffness values of the intraluminal thrombus and conducting biaxial experimental tests of provided samples of intraluminal thrombus. The experimental testing was conducted in order to obtain the patient-specific mechanical properties, which are used as the inputs in the finite element analysis. The experimental testing confirmed the stiffness negligibility of the intraluminal thrombus’s outer layer, which is mentioned is several studies, however, the influence of this layer on resulting aneurysmal wall stress has been to this date not tested. The dominant part of this thesis is focused on the third goal of this work, which is a comparison of aneurysmal wall stress obtained from the finite element computation that included mechanical properties of intraluminal thrombus obtained either from the literature analysis of experimental testing. This part includes discerption of idealized geometry model development, which was used to analyze the sensibility of computed stresses on a number of ILT layers representing different material properties. In order to obtain this analysis, a macro was created prescribing each element of the intraluminal thrombus finite element mesh with material properties derived from its distance from the lumen. Next, this chapter contains description of patient-specific geometry models development, material models, and boundary conditions selection. In the end of this part, results of the finite element computations are presented together with their statistical analysis. Within the last part of this thesis, discussion of results and conclusions of this thesis is included. Also, an overview of important aspects entering computational modeling of abdominal aortic aneurysms is presented.

This thesis deals with stress strain analysis of an aortic abdominal aneurysm (AAA) and the influence of its contact with the spine on the extreme wall stress. The influence was tested on the idealized geometry, as well as on ten patient specific geometries obtained from computer tomography (CT-A) scans. Hyperelastic constitutive models were used for the AAA wall and intraluminal thrombus (ILT) tissue description. The prestress algorithm was used for reconstruction of the unloaded geometry to get more trustworthy results against the geometry from CT which was obtained under the blood pressure. Statistical analysis was used for the results evaluation. The maximal increase of peak wall stress was as high as 81 %.

The diploma thesis deals with the assessment of the prediction of brain aneurysm rupture based on its geometrical and material properties. In the first part of the thesis there is a~detailed research study of cardiovascular systems with a focus on the cerebral artery and aneurysm occurring on their bifurcates. The second part of the thesis is focused on the creation of two models of arterial cerebral bifurcation with the presence of aneurysm and on obtaining their geometry in unloaded state. Emphasis is placed on the most realistic constitutive model of the artery wall material based on real data from uniaxial tensile tests and on a suitably chosen blood pressure load. This blood pressure may be step-changed, for example, in bungee jumping. In the work, a calculation of the increase in blood pressure during the step-change is performed, which is subsequently used in calculations of tension in the wall of the cerebral aneurysm. In conclusion, the risk of rupture is evaluated in two model idealized brain aneurysms and a discussion of the credibility of the results is given.

This dissertation thesis concerns with Analysis of Influence of Collagen Organization on Mechanical Properties of Arteries and it is divided into three main parts. Motivation for this dissertation thesis was in a study reviewing effect of material model upon resulting stresses in AAA. The effect was calculated in 70 patient-specific geometries of AAA, which exceeds the number of geometries in other scientific papers by one order. Within this study, two material models were used, i.e. real one and 100× stiffer, and obtained stresses were mutually compared. It was quantified that peak stress difference can be higher than 20 % in 10% of patients and therefore the real material model should be preferred over the artificial one although operation with this model is more demanding. The second part of this thesis deals with an identification of structural parameters (orientation and dispersion of collagen fibres) of porcine aortic tissue by using adjusted Fast Fourier Transform based algorithm. The extracted structural parameters were inserted into two-layer structure-motivated constitutive model Martufi-Gasser. This model was validated and its predictive capabilities were also tested with fine results. The most important information obtained from the digital image processing of ~9000 micrographs is existence of only one family of dispersed collagen fibres which breaks the current dogma present in many scientific papers about two families of collagen fibres. The third part concerns with a proposal of an automated phase-correlation based algorithm for obtaining collagen fibre direction from polarized light microscopy images. The proposed algorithm was verified and validated and it yields histograms of collagen fibre directions with overall number of measured points larger than it would be possible to get from any manual measurement. The limitation of the original proposed algorithm is in 90° period of polarized light intensity, thus the method results in angles in the range of 0°–90. Therefore the end of the thesis is dedicated resolving this problem and obtaining real angles in a span of 0°–180°. To this end, the microscope set-up was changed and the algorithm was adjusted accordingly. The original and the adjusted algorithms are collagen-specific, fast and an operator independent. Despite all the author´s effort put into collagen fibre waviness quantification directly from the histograms, the waviness has not been quantified yet in this way and it remains at the stage of research.

This paper deals with the problem of abdominal aortic aneurysms (AAA), taking into account the possibility of using mechanical tests of aortic tissues for improvement of level of their constitutive models. First part of thesis deals with the introduction into the problem, description of the structure of the wall of the healthy aorta, its main components and the degenerative changes which lead to formation of AAA. This is followed by a brief excursion into constitutive modeling, which focuses closely on the description of the models used to describe the mechanical behavior of soft tissues. The theoretical part is then supplemented by a narrower selection of constitutive models used for modeling aortic wall and intraluminal thrombus, together with published results, which are reviewed and discussed at the end of this section. The main part of this thesis is devoted to tests of mechanical properties of arterial tissues. First, the methodology is presented together with the description of the customizations of the laboratory equipments together with the test rig. In addition, attention is focused on the results of mechanical tests of intraluminal thrombus, where the results of both uniaxial tensile tests and equbiaxial testing are presented. Also the influence of distance ILT from the lumen on the mechanical properties of the thrombus is examined. Another area of interest is the investigation of the effect of elastase on the chnage of mechanical properties of pig aorta. In this case, porcine aortas are experimentally tested only by biaxial testing, and the time of elastase action to alter the mechanical properties is analyzed so that the resulting tissue has a similar stress-strain response as aneurysmal tissue. Finally, the results of experimental measurements, limitations and other possible ways of research are summarized.

The diploma thesis is focused on the creation of the aneurysm finite element model and the making of the aneurysm wall stess-strain analysis using ANSYS software. The model of abdominal aortic aneurysm geometry starts from the CT scan of the particular patient. In the thesis there are compared two chosen constitutive models, each of them appears from different mechanical tests done on human arterial fibre samples. Furthermore, a limiting condition for aneurysm wall structure damage is expressed. On the basis of the results of stress calculation in the aneurysm wall and the limiting condition, the safety coefficient and rupture factors risk are worked out.

This master thesis is focused on stress-strain analysis abdominal aortic aneurysm using ANSYS software. The model of abdominal aortic aneurysm are based on CT scans of five specific patients. The branching arteries are included to the model and one goal of this thesis is decision about their influence of the wall stress. In this thesis was used a hyperelastic materiál model, which is based on mechanical tests done on human arterial samples.

Background: Scoring models are widely established in the intensive care unit (ICU). However, the importance in patients with ruptured abdominal aortic aneurysm (RAAA) remains unclear. Our aim was to analyze scoring systems as predictors of survival in patients undergoing open surgical repair (OSR) for RAAA. Methods: This is a retrospective study in critically ill patients in a surgical ICU at a university hospital. Sixty-eight patients with RAAA were treated between February 2005 and June 2013. Serial measurements of Sequential Organ Failure Assessment score (SOFA), Simplified Acute Physiology Score II (SAPS II) and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) were evaluated with respect to in-hospital mortality. Eleven patients had to be excluded from this study because 6 underwent endovascular repair and 5 died before they could be admitted to the ICU. Results: All patients underwent OSR. The initial, highest, and mean of SOFA and SAPS II scores correlated significant with in-hospital mortality. In contrast, TISS-28 was inferior and showed a smaller area under the receiver operating curve. The cut-off point for SOFA showed the best performance in terms of sensitivity and specificity. An initial SOFA score below 9 predicted an in-hospital mortality of 16.2% (95% CI, 4.3–28.1) and a score above 9 predicted an in-hospital mortality of 73.7% (95% CI, 53.8–93.5, p < 0.01). Trend analysis showed the largest effect on SAPS II. When the score increased or was unchanged within the first 48 h (score >45), the in-hospital mortality rate was 85.7% (95% CI, 67.4–100, p < 0.01) versus 31.6% (95% CI, 10.7–52.5, p = 0.01) when it decreased. On multiple regression analysis, only the mean of the SOFA score showed a significant predictive capacity with regards to mortality (odds ratio 1.77; 95% CI, 1.19–2.64; p < 0.01). Conclusion: SOFA and SAPS II scores were able to predict in-hospital mortality in RAAA within 48 h after OSR. According to cut-off points, an increase or decrease in SOFA and SAPS II scores improved sensitivity and specificity.