Submitted by EMERSON DE ALBUQUERQUE SEIXAS null (emersondas@cardiol.br) on 2017-01-22T14:38:17Z No. of bitstreams: 1 Tese Doutorado apresentação final 17 Janeiro 2017 para repositório em PDF.pdf: 2272650 bytes, checksum: b1d116841eb237b23afc4bf970606f37 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-01-25T16:50:55Z (GMT) No. of bitstreams: 1 seixas_ea_dr_bot.pdf: 2272650 bytes, checksum: b1d116841eb237b23afc4bf970606f37 (MD5) / Made available in DSpace on 2017-01-25T16:50:55Z (GMT). No. of bitstreams: 1 seixas_ea_dr_bot.pdf: 2272650 bytes, checksum: b1d116841eb237b23afc4bf970606f37 (MD5) Previous issue date: 2016-12-09 / Introdução: as doenças cardiovasculares representam a maior causa de mortalidade nos pacientes renais crônicos antes e após o transplante renal, dentre elas a doença coronariana apresenta destaque especial. Preditores de risco tem sido usados no seu diagnóstico que é desafiador. Poucos trabalhos validaram preditores clínicos de seleção para exames invasivos para o diagnóstico de doença arterial coronariana (DAC) antes do transplante renal. Objetivo: avaliar a frequência e poder discriminatório de preditores clínicos da presença da doença arterial coronariana em pacientes renais crônicos em programa de diálise candidatos ao transplante renal, avaliar a performance da fórmula de Gowdak e colaboradores de risco de doença arterial coronariana e verificar a associação entre doença arterial coronariana e desfechos no grupo estudado. Métodos: foram analisadas as cinecoronariografias de candidatos ao transplante renal de dois centros de transplante renal do estado de São Paulo, realizadas entre março de 2008 e abril de 2013. Foi realizado estudo transversal para verificar o poder preditivo de parâmetros clínicos para a presença de doença coronária significativa (estenose ≥70% em uma ou mais artérias epicárdicas ou ≥ 50% no tronco da coronária esquerda). Adicionalmente, verificou-se o poder discriminatório de um escore clínico de risco previamente estabelecido (que leva em conta presença de diabetes melito (DM), idade e manifestações clínicas de doença cardiovascular). Foi realizado também estudo longitudinal observacional e traçaram-se curvas de sobrevida de acordo com o diagnóstico angiográfico para verificar a associação entre a presença de doença coronária e desfechos. Resultados: foram rastreados 128 pacientes, dos quais, 23 foram excluídos. A prevalência de ateromatose coronária de qualquer grau foi de 60/105 (57%) e ateromatose coronária significativa foi de 30/105 (29%) no total da casuística. Os 105 pacientes restantes realizaram coronariografia, dois foram excluídos por falha de registro dos desfechos, portanto 103 foram incluídos em análise longitudinal. Dos 105 pacientes, em seis, a análise dos dados clínicos se mostrou incompleta. Estes foram excluídos do estudo transversal que foi realizado com 99 pacientes. Análise de regressão logística univariada identificou presença de DM, angina e/ou infarto prévio, clínica de doença arterial periférica e dislipidemia como preditores de DAC. Regressão logística múltipla identificou apenas diabetes e angina e/ou infarto prévio como preditores independentes. O escore clínico previamente desenvolvido apresentou associação estreita com o diagnóstico de DAC, o que valida seu uso nos pacientes estudados. A mortalidade foi menor do que à esperada entre os pacientes em diálise. A presença de DAC foi associada à ocorrência de eventos cardiovasculares, porém não se associou à mortalidade. Conclusão: a DAC foi frequente em pacientes renais crônicos em programa de diálise candidatos ao transplante renal, pode ser identificada por dados clínicos e sua identificação por angiografia pode prever evento cardiovascular. / Introduction: cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a special emphasis. Predictors of risk for coronary artery disease has been used for its diagnosis. Few studies have validated clinical predictors to selection patients for invasive procedures for the diagnosis of coronary artery disease (CAD) before renal transplantation. Objective: this study evaluated the frequency and discriminatory power of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, assessed a previously developed scoring system (Gowdak et al.) for coronary artery disease, and we also checked the association between coronary artery disease and outcomes of the study group. Methods: coronary angiographies conducted between March 2008 and April 2013 from candidates for renal transplantation from two transplant centers in São Paulo state were analyzed. Cross-sectional study was conducted to verify the predictive power of clinical parameters for the presence of significant coronary artery disease (≥70% stenosis in one or more epicardial artery or ≥ 50% in the left main coronary artery). In addition, the discriminating power of a previously established clinical risk score was assessed (which takes account of diabetes mellitus (DM), age and clinical manifestations of cardiovascular disease). It was also conducted observational longitudinal study and drew up survival curves according to the angiographic diagnosis to verify the association between the presence of coronary heart disease and outcomes. Results: we screened 128 patients, of which 23 were excluded. The prevalence of coronary atheromatosis of any grade was 60/105 (57%) and significant coronary atheromatosis was 30/105 (29%) in the total sample. The remaining 105 patients underwent coronary angiography, two were excluded because of recording outcomes failures, so 103 were included in the longitudinal analysis. Of the 105 patients, in six, the analysis of clinical data showed incomplete. These were excluded from the cross-sectional study that was conducted with 99 patients. Univariate logistic regression analysis identified the presence of DM, angina and / or previous infarction, clinical peripheral artery disease and hyperlipidemia as predictors of CAD. Multiple logistic regression identified only diabetes and angina and / or previous infarction as independent predictors. The previously developed scoring system showed a close association with the diagnosis of CAD, which validates its use in the patients studied. Mortality was lower than expected among patients on dialysis. The presence of CAD was associated with cardiovascular events and was not a predictor of mortality. Conclusion: the CAD was frequent in renal failure patients on dialysis candidates to kidney transplantation, can be identified by clinical data and identification by angiography can predict cardiovascular events.

Periodontite crônica e perda dentária tornaram-se ferramentas úteis para estudar a hipótese de que a infecção/inflamação aumenta o risco de doenças cardiovasculares. Tem se demonstrado que a periodontite e suas consequências (perdas dentárias) têm o poder de elevar os marcadores inflamatórios sistêmicos, incluindo a proteína C-reativa, a qual é uma proteína aguda plasmática que é reconhecida como um preditor de infarto e se encontra aumentada em infecções. Com base no entendimento que o processo inflamatório sistêmico é o fator ligante entre as duas condições, o objetivo deste estudo foi analisar a associação entre edentulismo, perda dentária e parâmetros clínicos de periodontite crônica com inflamação sistêmica medida através de níveis de proteína C-reativa. Este estudo transversal controlado faz parte de um macro-projeto do Instituto de Cardiologia do Rio Grande do Sul que num estudo tipo consórcio incluiu 130 pacientes que receberam indicação para realizar cineangiocoronariografia. Os pacientes selecionados foram examinados entre dezembro de 2016 e outubro de 2017 e passaram por exame periodontal completo constando de índice de placa visível (IPV), sangramento à sondagem (SS), perda de inserção (PI), profundidade de sondagem (PS) em todos os dentes presentes nos seis sítios e também coletado o número de dentes perdidos e coleta de exames sanguíneos. A amostra foi dividida em 2 grupos: edêntulos (24,6%) e dentados (75,3%), sendo que maioria era homens (67,7%), com idade média de 63,30(±10,7) brancos (80%), com educação fundamental (70%), sedentários (62%), diabéticos (52%), hipertensos (74%) e com pelo menos um evento cardiovascular anterior (52%). As médias ± desvio-padrão de PS foram de 3,36±1,25; para PIos valores foram de 5,42±1,85; IPV médio de 0,39±0,25; e SS médio de 0,34±0,23, com uma média de 13,44±7,95 dentes. No modelo de regressão logística observou-se o efeito independente da perda dentária após ajustada para fumo e sexo. Conclui-se que a perda dentária está associada a incremento do risco cardíaco medido por inflamação sistêmica. / Chronic periodontitis and tooth loss have become useful tools for studying the hypothesis that infection/inflammation increases the risk of cardiovascular disease. It has been shown that periodontitis and its consequences (tooth loss) have the power to elevate systemic inflammatory markers; one of these markers is C-reactive protein is an acute plasma protein that is recognized as a predictor of myocardial infarction and is increased in infections. Based on the understanding that the systemic inflammatory process is the linking factor between the two conditions the objective of this study was to analyze the association between edentulism, tooth loss and clinical parameters of chronic periodontitis with systemic inflammation measured through C-reactive protein levels. This controlled cross-sectional study is part of a macro-project of the Instituto de Cardiologia do Rio Grande do Sul, which in a consortium-type study included 130 patients who were indicated to perform coronary angiography. The selected patients were examined between December 2016 and October 2017 and underwent complete periodontal examination consisting of visible plaque index (VPI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), in six sites per tooth of all teeth present in addition to blood tests. The sample was divided into 2 groups: edentulous (24,6%) and dentate (75,3%)individuals. The majority were men (67.7%), with mean age of 63.30 (± 10.7) whites (80%), hypertensive (74%) and with at least one previous cardiovascular event (52%). The means and standard deviation of PD were 3.36 ±1.25; for CAL mean values of 5.42 ±1,85; Mean VPI was of 0.39 ± 0.25; and BOP presented 0.34 ± 0.23 as mean, with a mean of 13.44 ± 7.95 teeth present. In logistic regression model, we observed the independent effect of tooth loss after adjustment for smoking and sex. It is concluded that tooth loss is associated with increased cardiac risk as measured by systemic inflammation.

abstract: Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques. / Dissertation/Thesis / Ph.D. Bioengineering 2013

Fundamentos: Este estudo tem o objetivo de comparar os resultados clínicos e angiográficos de pacientes com infarto agudo do miocárdio(IAM) tratados com implante de stent revestido com paclitaxel (SRP) versus stent convencional. Métodos e população do estudo: Um grupo de 30 pacientes com infarto agudo do miocárdio foi tratados com stent revestido com paclitaxel (TaxusTM). Um grupo controle com 30 pacientes foi tratado com stent convencional (Express2 TM).Resultados: Aos 6,9±1,2 meses, não ocorreu morte, reinfarto ou trombose intra-stent. Entretanto, pacientes tratados com stent farmacológico tiveram um risco menor de reintervenção (3.3%% vs. 33.3%; p=0.006). A perda luminal tardia foi de 0.2±0.2 mm no grupo de SRP vs. 0.6±0.6 mm (p=0.03) no controle e a reestenose binária foi de 3.3% (RVP)vs. 33.3%(controle) (p=0.006). O percentual médio de obstrução neointimal em pacientes do grupo farmacológico foi de 4,7%±6,8%. Conclusões: O SRP se mostrou seguro e efetivo aos 7 meses em pacientes com IAM / This study aimed to compare the clinical and angiographic outcomes of patients with acute myocardial infarction (AMI) treated with paclitaxel eluting stent (PES) versus conventional stent implantation. Methods and Study Population: A group of 30 patients admitted with AMI was treated with PES (TaxusTM). A control group comprised 30 patients with a similar bare stent (Express IITM). Results: Baseline and procedural characteristics were similar between the PES and control groups. At 6.9±1.2 months, there were no deaths, re-AMI, or stent thrombosis. However, patients treated with PES had a lower risk of repeat revascularization (3.3%% vs. 33.3%; p=0.006). The angiographic late loss was 0.2±0.2 mm vs. 0.6±0.6 mm (p=0.03) and the binary restenosis rate was 3.3% vs. 33.3% (p=0.006) in the PES vs. controls respectively. The average percent neointimal obstruction in patients treated with PES was 4.7±6.8 %. Conclusions: PES appeared safe and effective at 7 months in patients AMI

Este trabalho descreve o desenvolvimento de um sistema integrado transdutor/bobinas de gradientes de alto desempenho para Imagens por Ressonância Magnética. Este sistema é composto por um transdutor de radiofreqüência tipo sela e um conjunto de 3 bobinas locais assimétricas. No desenho do transdutor foram otimizados os parâmetros: relação sinal ruído e uniformidade do campo magnético por ele gerado. A densidade de corrente de cada bobinas local foi otimizada mediante técnicas numéricas estocásticas para gerar um gradiente de campo magnético uniforme em cada uma das 3 direções do espaço numa região das dimensões do crânio. O conjunto de bobinas de gradientes construído possui um diâmetro livre de 31.5 cm e gera em média 25 mT/m/A por bobina, com indutâncias inferiores a 310 mH. São mostradas as aplicações clínicas desenvolvidas nas áreas de imagens tridimensionais e angiografia, a partir das seqüências de pulsos implementadas e aproveitando o uso do sistema integrado, em um tomógrafo de ressonância magnética de 0.5 Tesla. Imagens de phantom foram adquiridas em menos de 500 ms usando o conjunto integrado e técnicas do tipo Echo Planar Imaging. Aspectos referentes à caracterização e correção de campos magnéticos estáticos e homogêneos são também comentados. As soluções descritas nesta tese têm um amplo conteúdo tecnológico e beiram nas fronteiras da Física Aplicada e a Engenharia Biomédica. / Here we describe the development of a high performance radio-frequency/gradient coil integrated system for Magnetic Resonance Imaging. A saddle radio-frequency coil and a three-axis asymmetric local gradient coil composed this system. Two parameters were optimized in the RF coil design: signal-to-noise ratio and magnetic field uniformity. The current density of each local coil was optimized using stochastic numerical techniques, in order to generate a uniform magnetic field gradient by axis in a region representing a human head. The build gradient coil set has an inner diameter of 31 cm. The average gradient efficient of the three-axis is 25 mT/m/A and the maximum inductance is less than 310 mH. We show the clinical applications performed in three-dimensional and angiography imaging areas in a 0.5 Tesla magnetic resonance tomograph. These applications were optimized to taking advantage from the integrated system. Phantom images were acquired in less than 500 millisecond using echo planar techniques and the integrated set. Some aspects about static and homogeneous magnetic field characterization and correction are also commented. In this work we described solutions with wide technologic content close to the boundaries of the Applied Physics and Biomedical Engineering.

A insuficiência cardíaca congestiva (ICC) é uma condição em que o coração não consegue bombear o sangue de acordo com as necessidades metabólicas dos tecidos. Quando a ICC entra em seu estágio final, já refratária ao tratamento medicamentoso, ou outras opções terapêuticas, o transplante cardíaco constitui-se em medida salvadora destes pacientes. Após o primeiro ano de evolução do procedimento, a doença vascular do enxerto (DVE) é a complicação mais temida nestes pacientes. Esta doença caracteriza-se por aterosclerose acelerada, com acometimento concêntrico do vaso, predominando nos terços médios e distais. Sintomas isquêmicos geralmente não estão presentes devido ao coração denervado destes pacientes. Daí a importância em se ter um método com boa acurácia e que possibilite o diagnóstico da DVE em seus estágios iniciais, que, muitas vezes, não é demonstrado pela cineangiocoronariografia (CINE). O nosso trabalho teve como objetivo avaliar se o diagnóstico da DVE pela tomografia computadorizada por múltiplos detectores (TCMD) foi preditor de eventos maiores, definimos como: morte súbita, infarto, angioplastia, queda da fração de ejeção e retransplante. Em nossa amostra, selecionamos 59 pacientes transplantados que tinham sido submetidos à TCMD por indicação clínica. Encontramos idade média de 49 anos ± 11,36 anos e tempo médio de transplante na realização da TCMD de 82,67 ± 36,38 meses. A prevalência de hipertensão (HAS) foi de 59,32%, dislipidemia (DLP) 57,63% e diabetes mellitus (DM) 33,90%. Em relação à etilogia da ICC dos receptores, em primeiro lugar, tivemos doença isquêmica com 38,98%, seguida por doença chagásica com 33,90% e por miocardiopatia dilatada idiopática com 13,56% da amostra. Desta população, um subgrupo de 41 pacientes, além de ter feito a TCMD, fez também a CINE. A comparação dos dois métodos mostrou sensibilidade de 100%, especificidade de 77,27%, valor preditivo positivo (VPP) de 46,34% e valor preditivo negativo (VPN) de 100%. Os resultados mostraram que a presença de DVE pela tomografia foi preditora de eventos maiores no seguimento destes pacientes com significância estatística p 0,001. Outras variáveis analisadas que também tiveram impacto significativo foram escore de cálcio positivo (p< 0,05), piora da classe funcional na evolução para classe II e III, e os receptores que tinham o diagnóstico prévio de miocardiopatia dilatada. Concluímos que a TCMD é um exame que tem boa acurácia diagnóstica na DVE, podendo a CINE ficar restrita aos casos duvidosos. Além disso, alterações deste exame são preditoras de eventos adversos. O escore de cálcio e a piora da classe funcional também foram preditores de eventos. / Congestive heart failure (CHD) is a condition characterized by the heart inot meeting the body oxygen demands. For end-stage CHD, refractory to medical treatment, heart transplant is a lifesaver treatment, but its late results may suffer a negative impact if there is allograft vasculopathy, the main reason of late adverse outcome in this population. This condition is is characterized by accelarated atherosclerosis with concentric disease predominant at the mid and distal segments of the coronary arteries. Ischemic symptoms seldom happen for the heart is denervated, and thus, it would be highly desirable to possess a test that could accuratelly foretell the presence of such abnormality. Furthermore, a possible gold standard, invasive coronary angiography (ICA) has been show to lack sensivity. The aim of this study was to evaluate if multidetector computed tomography( MDCT) could identify and thus to predict patients at higher risk of presenting late adverse events. Major events were considered as: sudden cardiac death (SCD), Hear attack, angioplasty, left ventricle impairment and retransplant. Consulting medical records we selected 59 heart transplant patients that underwent MDCT at least 7 years by clinical discretion. Mean age at the time of the exam was 49 ± 11.36 years. Mean post heart transplantantion time was 82.67 ± 36.38 months. Hypertension (HAS) prevalence was 59,32%, hyperlipidemia 57,63% and diabetes was 33,90%. Main pre-transplant CHD cause was ischemic heart disease in 38,98%, followed by Chaga\'s disease, 33.90% and idiopathic dilated cardiomyoapthy. We had 41 patients that also underwent ICA. Comparing both methods we found that MDCT had a sensibility of 100%, a specificity of 77,27%, a positive preditive value of 46,34% and a negative preditive value of 100%. The diagnosis of CAV done by MDCT was a predictor of major events at the follow-up (p=0,001). Other predictors that achieved statistical significance were positive calcium score (p<0,05), class functional (p<0,001) and dilated cardimyopathy dilated as the CHD cause (p=0,027). So we conclude that MDCT has a good accuracy on the diagnosis of CAV, and is a predictor of adverse events. Higher than zero calcium score, lower functional class and dilated cardiomyopathy also related to patient\'s follow-up.

Abstract Magnetic resonance imaging (MRI) provides methods to study the microstructure and functional properties of tissues that can be utilized to acquire information about the degenerative processes in the spine. The purpose of the current study was to evaluate the value of diffusion-weighted MRI and quantification of delayed gadolinium enhancement in assessing intervertebral disc degeneration. An experimental degeneration model was used to evaluate the sensitivity of diffusion-weighted MRI and T2 relaxation time measurements in detecting early degenerative changes in the disc. In six pigs, an annular disc lesion was induced surgically, after which the discs were repeatedly MR imaged for up to eight weeks. T2 relaxation time of the lesioned discs decreased postoperatively, whereas apparent diffusion coefficient (ADC) initially increased, but at eight weeks decreased when compared to the control discs. The value of ADC in degeneration of human discs was evaluated by imaging 228 voluntary middle-aged men. ADC values of the three lowest lumbar intervertebral discs were measured and disc degeneration was visually graded. The reduction in ADC between visually normal and moderately degenerated discs was 4%, whereas severely degenerated discs showed 5% higher ADC values than normal discs. T2 signal intensity of the discs was significantly correlated with the ADC values. Because of a considerable overlap between ADC values of normal and degenerated discs the clinical relevance of the ADC measurements of lumbar intervertebral discs remains questionable. A method to quantify delayed enhancement of the nucleus pulposus after intravenous gadolinium contrast agent injection was developed to evaluate the diffusion of small solutes into the disc. Twenty male volunteers were imaged in order to correlate the measured change in the T1 relaxation rate with visually evaluated degenerative changes. The percentual change of T1 relaxation rate for individual discs was up to 126%, and a positive trend was observed between the delayed enhancement and the disc degeneration grades. In order to study the factors that determine the intensity of delayed enhancement, T1 relaxation rate measurements were further correlated with lumbar artery stenosis, bone marrow changes adjacent to endplates, endplate defects, and ADC of the disc. Lumbar artery stenosis and ADC values of the discs were not correlated with enhancement, while disc space narrowing and the presence of degenerative endplate changes had a strong correlation, suggesting an important role for the endplate in maintaining the integrity of the disc.

Les anévrismes intracrâniens présentent des risques importants en raison de leur taux de rupture élevé et des conséquences qui peuvent être fatales comme lors d’hémorragies méningées. Afin d’effectuer une recherche hémodynamique sur l’anévrisme intracrânien in vitro, un fantôme est indispensable. Jusqu’à présent, des fantômes rigides ou simplifiés sont utilisés dans littérature, peu d’entre eux sont suffisamment fidèle à la réalité. Le travail de cette thèse se concentre sur la méthodologie de fabrication des fantômes patient-spécifiques d’anévrismes intracrâniens ainsi que leur mise en œuvre pour différentes utilisations. Ces fantômes possèdent la forme anatomique de l’artère du patient et une paroi élastique. Ils sont fabriqués en appliquant une technique originale de prototypage rapide. Les fantômes sont vérifiés selon plusieurs aspects. Pour effectuer des recherches hémodynamiques sur les fantômes, un banc d’essai compatible avec différentes modalités d’imagerie a été conçu. L’angiographie par résonance magnétique 2D par contraste de phase a été utilisée pour étudier l’hémodynamique des fantômes. Le comportement dynamique de paroi, les trajectoires 3D du flux et son champ de vélocité sont analysés. L’application potentielle dans domaine clinique du fantôme patient-spécifique a été aussi testée dans cette thèse, des simulations d’intervention sur des anévrismes intracrâniens ont été effectuées sur le banc d’essai et les fantômes, les résultats de différentes méthodes ont été analysés et comparés. / Intracranial aneurysms are a hazard to human health because of their high rupture rate and fatal subsequence, such as subarachnoid hemorrhage. In order to carry out a hemodynamic research in vitro on the intracranial aneurysm, a phantom is indispensable. Until now, rigid or simplified phantoms are mainly used in the literature, few among them possess sufficient properties compared with reality. The work of this thesis focuses on the methodology of manufacturing patient-specific phantoms of intracranial aneurysms as well as their implementation for different uses. The phantoms have an anatomical shape of patient’s artery and an elastic wall. They are manufactured by applying an original rapid prototyping technique. The phantoms are examined and verified in different ways. In order to perform a hemodynamic research of the phantoms, a testing platform compatible with different imaging modalities has been designed and established. 2D phase-contrast magnetic resonance angiography was applied in the hemodynamic study of the phantoms. The dynamic behavior of the artery wall, the 3D path-line of flow and the velocity field of flow were analyzed. The potential application in the clinical domain of the patient-specific phantoms was also tested in this thesis, simulations of intervention on intracranial aneurysms were carried out with the testing platform and the phantoms, the results of different treatment strategies were analyzed and compared.

Abstract The purpose of this study was to evaluate the role of diminished arterial blood flow in painful disc degeneration. Diffusion in intervertebral discs of 37 asymptomatic adults measured by magnetic resonance imaging (MRI) and their lumbar arterial blood supply measured by magnetic resonance angiography (MRA) correlated significantly. End plate degeneration in intervertebral discs evaluated with MRI was analysed with reference to disc distress evaluated with computed tomography (CT) discography, and a significant correlation between end plate degeneration and disc degeneration was found among 36 low back pain patients. Intradiscal pain caused by discography did not correlate with end plate degeneration. There were significantly more atheromatous plaques in the abdominal aorta among 29 chronic low back pain patients compared to 52 asymptomatic people, especially in the age group under 50 years. Occlusion of lumbar arteries in MRA correlated significantly with disc degeneration in MRI among 113 sciatica patients. Furthermore, the disc degeneration and the occlusion of lumbar arteries were severe among 41 sciatica patients and 41 asymptomatic people. During a three-year follow-up, the occlusion of lumbar arteries in MRA correlated significantly with physical and mental ability measured by a self-efficacy questionnaire at every assessment point (1,2,3 years). Furthermore, the intensity of back pain at 1 year and leg pain at 2 years correlated with the occlusion of lumbar arteries. Re-stenosis of lumbar arteries within 3 years correlated significantly with medical consultations for low back pain, prolonged low back pain and prolonged sciatica during one year before the baseline assessment.

Ischemic heart disease is currently the leading cause of death globally. Coronary artery bypass grafting (CABG) is considered the best treatment for many patients and its success depends on the long-term patency of the conduits. Greater use of arterial grafts has been advocated because of their higher long-term patency compared to saphenous vein grafts (SVGs). Despite this, SVGs account for up to 80% of all grafts used in CABG. Consequently, the long-term patency of the saphenous vein (SV) is one of the most crucial challenges in cardiovascular surgery. The no-touch (NT) SV in CABG has shown a superior patency rate, slower progression of atherosclerosis, and better clinical outcome compared to conventional veins up to 8.5 years postoperatively. The aim of this thesis was to study the long-term angiographic, echocardiographic, and clinical aspects of CABG patients receiving either NT or conventional vein grafts and to investigate the health-related quality of life (HRQoL) in this patient group. Studies I-II report a randomized trial between NT and conventional veins where 74 patients were followed-up at a mean of 16 years postoperatively. Study III is a prospective cohort trial in which 97 patients with NT vein grafts anastomosed to the left anterior descending artery (LAD) were included and followed-up at a mean of 6 years postoperatively. Study IV included 257 patients in whom HRQoL and graft patency were studied during the same follow-up visit. Overall, NT vein grafts showed a higher patency compared to conventional veins at a mean of 16 years, 83% vs. 64% (p=0.03), which was similar to the patency of the left internal thoracic artery, 88%. The NT group had a better left ventricular ejection fraction compared to the conventional group, 57.9% vs. 49.4% (p=0.011). After a mean of 6 years, the patency rate of NT SVs to the LAD was 95.6% and to non-LAD targets, 93.9%. Graft patency was an independent predictor of HRQoL in CABG patients. These patients reported a function and wellbeing similar to that of the Swedish population and clearly higher health status than those in the same disease group in the general population.