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Το θέμα της παρούσης εργασίας είναι η μελέτη της μη μόνιμης αιματικής ροής στις στεφανιαίες αρτηρίες της καρδιάς σε φυσιολογική κατάσταση, με στένωση καθώς και με αποκατάσταση της ροής με αναστομωτικό κλάδο. Για τον σκοπό αυτό χρησιμοποιούνται συμπεράσματα από τη διεθνή βιβλιογραφία γύρω από τους παράγοντες που μπορεί να οδηγήσουν στην ανάπτυξη στενώσεων, καθώς και κατευθυντήριες γραμμές για την διαμόρφωση των γεωμετρικών μοντέλων Στο πρώτο κομμάτι γίνεται μία αναφορά στις κυριότερες καρδιαγγειακές παθήσεις, που αποτελούν και την υπ αριθμόν ένα αιτία θανάτου παγκοσμίως. Γίνεται αναφορά στους επεμβατικούς τρόπους αντιμετώπισης της στεφανιαίας νόσου με έμφαση στην αορτοστεφανιαία παράκαμψη (bypass). Ακολουθεί μία σύντομη επισκόπηση της βιβλιογραφίας και εξαγωγή των βασικών συμπερασμάτων που θα αποτελέσουν την βάση για την κριτική των αποτελεσμάτων. Εν συνεχεία επεξηγείται αναλυτικά ο τρόπος με τον οποίο παράγονται τα γεωμετρικά μοντέλα, καθώς και οι περιπτώσεις που αναλύθηκαν. Ακολουθεί ο τρόπος κατασκευής του υπολογιστικού πλέγματος, πάνω στο οποίο επιλύονται οι εξισώσεις Navier- Stokes για ασυμπίεστο ρευστό. Τέλος με βάση τα αποτελέσματα από την εκτέλεση του κώδικα για όλες τις περιπτώσεις γίνεται μία προσπάθεια για εξαγωγή συμπερασμάτων. Εξάγονται με βάση την μελέτη των μοντέλων κάποιες ενδεικτικές κατευθυντήριες γραμμές ως προς το ποιες γεωμετρίες και τρόποι αναστόμωσης τείνουν να ευνοήσουν περισσότερο την ανάπτυξη της αθηρωματικής πλάκας αλλά και ποιες αποκαθιστούν την ροή του αίματος. / The subject of the following thesis is the study of the unsteady blood flow in the coronary arteries of the heart in normal conditions, during stenotic conditions and after restoration of the flow with an anastomotic branch. For this purpose, we use the conclusions from the international literature on the factors that can lead to the further development of stenoses, as well as guidelines on the formation of the geometrical models. In the first part we reference the most significant pathologic conditions of the heart which are the number one leading cause of death world widely. We also mention the invasive techniques with which doctors treat the coronary heart disease, emphasizing on the aorto-coronary bypass technique. Furthermore there is a review on the literature on the subject and extraction of the main conclusions we are going to use in the evaluation of the computational results We continue explaining in detail the way that the geometrical models where produced, as well as the cases which were analyzed. There is also an explanation of the way we constructed the computational grids on which we solve the incompressible Navier – Stokes equations. Finally, based on the computational results we obtain by executing the program for all the different cases we extract the basic conclusions. Based on the study of the models we try to give some basic guidelines regarding which geometries and anastomotic techniques tend to favor the further development of the atherosclerotic plaques , but also which ones restore the blood flow to the normal levels

A endarterectomia de carótida tem um papel bem estabelecido na prevenção de AVC ipsilateral em pacientes com mais de 50% de estenose sintomática da artéria carótida interna. No entanto, o dano cerebral isquêmico contribui significativamente para a morbidade e mortalidade perioperatórias aumentadas na endarterectomia de carótida com clampeamento intra-operatório temporário. Portanto a relação entre a gravidade do dano isquêmico neuronal durante o procedimento e o sistema de auto-regulação do funcionamento da relação oferta/consumo de oxigênio cerebral precisa ser explorado. Esta avaliação poderia ser feita usando-se um marcador sensível de estresse hipóxico, tal como a proteína S-100ß, que é liberada das células da astroglia que sofreram dano estrutural, para o interior da circulação sangüínea quando a permeabilidade da barreira hemato-encefálica está alterada. Isto é especialmente verdadeiro porque uma baixa pressão no coto distal ao clampeamento continua a ser o critério principal para shunt, embora ela possa estar normal em 6% a 30% dos pacientes que subseqüentemente desenvolvem sinais neurológicos, e anormal em 3% a 11% daqueles que não desenvolvem sinais de isquemia. Então, faz sentido investigar outros métodos para detectar dano cerebral isquêmico em endarterectomia de carótida, tais como a taxa de extração de oxigênio cerebral (ECO2) para permitir a otimização de variáveis acessíveis à intervenção médica, como: shunt, parâmetros ventilatórios e parâmetros hemodinâmicos. O objetivo deste trabalho foi avaliar a correlação entre um marcador de dano cerebral isquêmico, a proteína S-100ß sérica, com a fração de extração de oxigênio cerebral (ECO2) e com a pressão arterial de dióxido de carbono (PaCO2) em pacientes submetidos à endarterectomia de carótida para estenose sintomática, com clampeamento temporário. Este estudo transversal avaliou 33 pacientes, estado físico II e III e média de idade de 70 ± 8 anos que foram submetidos à anestesia geral endovenosa e inalatória . PaCO2 (mmHg) e % ECO2 foram medidas antes do clampeamento da carótida (T1), 5 minutos após o clampeamento (T2) e 5 minutos após o desclampeamento (T3) a partir de amostras sangüíneas retiradas da veia jugular interna. S-100ß foi determinada nos seguintes momentos: antes do clampeamento da carótida (T1), imediatamente antes do desclampeamento (T2) e 6 horas após o desclampeamento (T3). O tempo médio de isquemia cerebral foi de 16 minutos [(IQ25-75) 11,05 a 19,00]. Os coeficientes de correlação de Spearman (rs) para a relação entre os níveis de S-100β em 6 horas após a cirurgia e os níveis de ECO2 e PaCO2 durante o período do estudo foram rs = 0,59 (P = 0,00) e rs = -0,36 (P = 0,00) respectivamente. Em conclusão, os presentes achados sugerem que o dano neuronal isquêmico avaliado pela ECO2 durante o período isquêmico podem predizer um aumento de S-100ß. Contudo, futuros estudos são necessários para determinar o impacto clínico de tais achados. / Carotid endarterectomy (CED) is a well established procedure to prevent ipsilateral stroke in patients with more than 50% symptomatic internal carotid artery (ICA) stenosis. However, ischemic brain injury persists as a significant contributing factor to increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. Hence, the relationship between the severity of neuronal ischemic damage during carotid endarterectomy (CED) and the autoregulation system of the functioning brain oxygen supply/consumption ratio needs to be further explored. This appraisal could be made using a sensitive marker of hypoxic stress, such as S-100ß released into de bloodstream when structural damage to astroglial cells alter the permeability of the blood-brain barrier. This methodological resource can be valuable since a low stump pressure is generally the main criterion for shunting, although normal in about 6-30% of patients who subsequently develop neurological signs and abnormal in 3-11% in those without signs of ischemia. Thus, it makes sense to search for additional subsidies to detect ischemic brain damage during carotid endarterectomy, such as the rate of brain oxygen extraction (ECO2). This earlier accessible variable at low cost could help medical decision-making such as shunt or changes in hemodynamic and ventilatory parameters. The aim of this study was, therefore, assess the correlation between a marker of neuronal ischemic damage, serum S-100ß, and brain oxygen extraction fraction (ECO2) and PaCO2 (arterial carbon dioxide tension) in patients undergoing carotid endarterectomy for symptomatic stenosis with temporary clamping. This cross-sectional study assessed 33 patients, physical status II-III, and mean age of 70 ± 8 years, who undergoing intravenous general anesthesia. PaCO2 (mmHg) and %ECO2 were measured prior to carotid clamping (T1), 5 min after carotid clamping (T2) and 5 min after carotid unclamping (T3) with blood drawn from the internal jugular vein. Serum S-100β was determined at T1 - prior to carotid clamping, T2 - immediately before carotid unclamping, and T3 - 6 h after carotid unclamping. The median time of brain ischemia was 16 min [(IQ25-75) 11.05 to 19.00]. Spearman correlation coefficients (rs) for the relationship between S-100ß level at 6 h after surgery and PaCO2 and ECO2 levels during the study period were rs = -0.36 (P < 0.01) and rs = 0.59 (P < 0.01), respectively. To conclude, the present findings suggest that brain ischemic neural damage monitored by ECO2 during the ischemic time may predict an increase in S-100ß. Further studies are warranted to assess the clinical impact of these results.

Highly-trained athletes are accustomed to varied and high-volume based exercise stimuli and eliciting adaptation in individuals already possessing the necessary physiology to compete at the highest level is difficult. Therefore, identifying novel, potent and time efficient methods of achieving cumulative training stress is a continual quest for coaches and exercise scientists. This thesis examined the acute and chronic effects of manipulating exercise and recovery during brief all-out sprint cycling on adaptive responses favouring enhanced endurance capacity. Chapter 3 highlighted that low-volume non-work matched all-out sprint cycling, whether it be interval- (4 x 30 s bouts) or continuous based (1 x 2 min bout) provides a similarly potent stimulus for the acute induction of cell signalling pathways and key growth factors associated with mitochondrial biogenesis and angiogenesis in trained individuals. In line with manipulating recovery and in attempting to identify a novel and potent exercise intervention capable of giving athletes more return on their training investment, Chapters 4-6 investigated the efficacy of combining sprint interval training with post-exercise blood flow restriction (BFR). Firstly, it was demonstrated that BFR potentiates HIF-1α mRNA expression in response to SIT, tentatively suggesting an enhanced stimulus for hypoxia- and/or metabolic-mediated cell signalling associated with mitochondrial biogenesis and angiogenesis over SIT alone. Secondly, four weeks of SIT combined with post-exercise BFR provides a greater training stimulus over SIT alone in trained individuals to enhance VO2max (4.7 v 1.1 % change) and MAP (3.8 v 0.2 % change), but not 15-km TT performance. Finally, in response to four weeks of SIT combined with post-exercise BFR, an international female track sprint cyclist increased her CP and W by 7 and 2 % and VO2max and absolute MAP by 3 and 4 %, respectively. Through a combination of an acute in vivo molecular experiment, a training study and an athlete case study, this thesis has introduced a potentially potent and novel training concept that appears capable of augmenting aerobic capacity.

A endarterectomia de carótida tem um papel bem estabelecido na prevenção de AVC ipsilateral em pacientes com mais de 50% de estenose sintomática da artéria carótida interna. No entanto, o dano cerebral isquêmico contribui significativamente para a morbidade e mortalidade perioperatórias aumentadas na endarterectomia de carótida com clampeamento intra-operatório temporário. Portanto a relação entre a gravidade do dano isquêmico neuronal durante o procedimento e o sistema de auto-regulação do funcionamento da relação oferta/consumo de oxigênio cerebral precisa ser explorado. Esta avaliação poderia ser feita usando-se um marcador sensível de estresse hipóxico, tal como a proteína S-100ß, que é liberada das células da astroglia que sofreram dano estrutural, para o interior da circulação sangüínea quando a permeabilidade da barreira hemato-encefálica está alterada. Isto é especialmente verdadeiro porque uma baixa pressão no coto distal ao clampeamento continua a ser o critério principal para shunt, embora ela possa estar normal em 6% a 30% dos pacientes que subseqüentemente desenvolvem sinais neurológicos, e anormal em 3% a 11% daqueles que não desenvolvem sinais de isquemia. Então, faz sentido investigar outros métodos para detectar dano cerebral isquêmico em endarterectomia de carótida, tais como a taxa de extração de oxigênio cerebral (ECO2) para permitir a otimização de variáveis acessíveis à intervenção médica, como: shunt, parâmetros ventilatórios e parâmetros hemodinâmicos. O objetivo deste trabalho foi avaliar a correlação entre um marcador de dano cerebral isquêmico, a proteína S-100ß sérica, com a fração de extração de oxigênio cerebral (ECO2) e com a pressão arterial de dióxido de carbono (PaCO2) em pacientes submetidos à endarterectomia de carótida para estenose sintomática, com clampeamento temporário. Este estudo transversal avaliou 33 pacientes, estado físico II e III e média de idade de 70 ± 8 anos que foram submetidos à anestesia geral endovenosa e inalatória . PaCO2 (mmHg) e % ECO2 foram medidas antes do clampeamento da carótida (T1), 5 minutos após o clampeamento (T2) e 5 minutos após o desclampeamento (T3) a partir de amostras sangüíneas retiradas da veia jugular interna. S-100ß foi determinada nos seguintes momentos: antes do clampeamento da carótida (T1), imediatamente antes do desclampeamento (T2) e 6 horas após o desclampeamento (T3). O tempo médio de isquemia cerebral foi de 16 minutos [(IQ25-75) 11,05 a 19,00]. Os coeficientes de correlação de Spearman (rs) para a relação entre os níveis de S-100β em 6 horas após a cirurgia e os níveis de ECO2 e PaCO2 durante o período do estudo foram rs = 0,59 (P = 0,00) e rs = -0,36 (P = 0,00) respectivamente. Em conclusão, os presentes achados sugerem que o dano neuronal isquêmico avaliado pela ECO2 durante o período isquêmico podem predizer um aumento de S-100ß. Contudo, futuros estudos são necessários para determinar o impacto clínico de tais achados. / Carotid endarterectomy (CED) is a well established procedure to prevent ipsilateral stroke in patients with more than 50% symptomatic internal carotid artery (ICA) stenosis. However, ischemic brain injury persists as a significant contributing factor to increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. Hence, the relationship between the severity of neuronal ischemic damage during carotid endarterectomy (CED) and the autoregulation system of the functioning brain oxygen supply/consumption ratio needs to be further explored. This appraisal could be made using a sensitive marker of hypoxic stress, such as S-100ß released into de bloodstream when structural damage to astroglial cells alter the permeability of the blood-brain barrier. This methodological resource can be valuable since a low stump pressure is generally the main criterion for shunting, although normal in about 6-30% of patients who subsequently develop neurological signs and abnormal in 3-11% in those without signs of ischemia. Thus, it makes sense to search for additional subsidies to detect ischemic brain damage during carotid endarterectomy, such as the rate of brain oxygen extraction (ECO2). This earlier accessible variable at low cost could help medical decision-making such as shunt or changes in hemodynamic and ventilatory parameters. The aim of this study was, therefore, assess the correlation between a marker of neuronal ischemic damage, serum S-100ß, and brain oxygen extraction fraction (ECO2) and PaCO2 (arterial carbon dioxide tension) in patients undergoing carotid endarterectomy for symptomatic stenosis with temporary clamping. This cross-sectional study assessed 33 patients, physical status II-III, and mean age of 70 ± 8 years, who undergoing intravenous general anesthesia. PaCO2 (mmHg) and %ECO2 were measured prior to carotid clamping (T1), 5 min after carotid clamping (T2) and 5 min after carotid unclamping (T3) with blood drawn from the internal jugular vein. Serum S-100β was determined at T1 - prior to carotid clamping, T2 - immediately before carotid unclamping, and T3 - 6 h after carotid unclamping. The median time of brain ischemia was 16 min [(IQ25-75) 11.05 to 19.00]. Spearman correlation coefficients (rs) for the relationship between S-100ß level at 6 h after surgery and PaCO2 and ECO2 levels during the study period were rs = -0.36 (P < 0.01) and rs = 0.59 (P < 0.01), respectively. To conclude, the present findings suggest that brain ischemic neural damage monitored by ECO2 during the ischemic time may predict an increase in S-100ß. Further studies are warranted to assess the clinical impact of these results.

abstract: The unique anatomical and functional properties of vasculature determine the susceptibility of the spinal cord to ischemia. The spinal cord vascular architecture is designed to withstand major ischemic events by compensating blood supply via important anastomotic channels. One of the important compensatory channels of the arterial basket of the conus medullaris (ABCM). ABCM consists of one or two arteries arising from the anterior spinal artery (ASA) and circumferentially connecting the ASA and the posterior spinal arteries. In addition to compensatory function, the arterial basket can be involved in arteriovenous fistulae and malformations of the conus. The morphometric anatomical analysis of the ABCM was performed with emphasis on vessel diameters and branching patterns. A significant ischemic event that overcomes vascular compensatory capacity causes spinal cord injury (SCI). For example, SCI complicating thoracoabdominal aortic aneurysm repair is associated with ischemic injury. The rate of this devastating complication has been decreased significantly by instituting physiological methods of protection. Traumatic spinal cord injury causes complex changes in spinal cord blood flow (SCBF), which are closely related to a severity of injury. Manipulating physiological parameters such as mean arterial pressure (MAP) and intrathecal pressure (ITP) may be beneficial for patients with a spinal cord injury. It was discovered in a pig model of SCI that the combination of MAP elevation and cerebrospinal fluid drainage (CSFD) significantly and sustainably improved SCBF and spinal cord perfusion pressure. In animal models of SCI, regeneration is usually evaluated histologically, requiring animal sacrifice. Thus, there is a need for a technique to detect changes in SCI noninvasively over time. The study was performed comparing manganese-enhanced magnetic resonance imaging (MEMRI) in hemisection and transection SCI rat models with diffusion tensor imaging (DTI) and histology. MEMERI ratio differed among transection and hemisection groups, correlating to a severity of SCI measured by fraction anisotropy and myelin load. MEMRI is a useful noninvasive tool to assess a degree of neuronal damage after SCI. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2016

O objetivo do estudo foi avaliar, por meio da ultrassonografia bidimensional e da ultrassonografia Doppler, as inter-relações entre a alteração de espessura do coxim digital com os índices vasculares da artéria digital dorsal comum dos membros pélvicos dos bovinos. A avaliação ultrassonográfica Doppler é uma técnica não invasiva de avaliação de índices vasculares, assim como, indiretamente, do volume de sangue do leito vascular. Para isso, foram realizados exames ultrassonográficos da espessura do coxim digital e também avaliação ultrassonográfica Doppler da referida artéria de 13 vacas primíparas da raça Holandesa, em intervalos de 14 dias, durante 126 dias após o parto. Ao longo do experimento o coxim digital apresentou diminuição não significativa de espessura (p=0,1715) e apresentou forte correlação positiva com a média do escore de condição corporal (p=0,03, r=0,71). Ao longo do período avaliado, o fluxo de sangue aumentou significativamente (p<0,0001) e apresentou correlação negativa com os índices que denotam impedância ao deslocamento de sangue, isto é, índice de resistividade (p<0,0001, r=-0,34911) e pulsatilidade (p<0,0001, r=-0,5035). Além disso, realizou-se correlação entre a diferença diária do fluxo de sangue e a diferença da espessura do coxim digital para cada animal e constatou-se uma forte tendência à correlação entre as diferenças das variáveis (p=0,0515, r=-0,5729). Por meio dos resultados encontrados foi possível concluir que o escore de condição corporal teve forte correlação com a espessura do coxim digital, ao longo do estudo. Além disso, o fluxo de sangue, os índices referentes à velocidade de deslocamento das hemácias e o diâmetro da artéria aumentaram ao longo do trabalho. E, também, que a discreta diminuição do coxim digital não foi um fator que influenciou no aumento do fluxo de sangue e nos índices vasculares / The aim of this study was to evaluate, by bidimensional and pused Doppler ultrasound, the interrelationship between the changes of the thickness of digital cushion with vascular indices of the common dorsal digital artery of the hind limbs of cattle. Pused Doppler sonography is a non-invasive tool to assessment the vascular indices, as well as, the blood flow volume in vascular bed. So, were performed ultrasound exams of soft tissue thickness and also the Doppler ultrasonographic evaluation of that artery in thirteen first lactation Holstein cows and followed them up during 126 days in milk. Throughout the experiment the digital cushion showed a slight decrease without significance (p=0,1715), this also was strongly correlated with body condition score (p=0,03, r=0,71). The blood flow volume had significance increase (p<0,0001) and was negatively correlated with both impedance indices, resistance index (P<0,0001 r =-0,34911) and pulsatility index (p <0,0001 r =-0,5035). In addition, a correlation was performed with both daily differences of the blood flow and the thickness of the digital cushion for each animal and it was observed a strong tendency of correlation between the different variables (p=0,0515 r =-0,5729). Therefore, we can conclude that body condition score was strong correlated with the thickness of digital cushion, throughout the study. In addition, the blood flow volume, the velocity indices and the artery diameter increase throughout the days in milk. And, so, the slight decrease in the thickness of digital cushion was not a factor that influenced the increase of blood flow and vascular indices

Orientador: Eunice Oba / Resumo: O objetivo do presente trabalho foi delinear parâmetros hemodinâmicos e avaliar sua relação com os principais hormônios envolvidos na mamogênese de búfalas mestiças Murrah em diferentes estágios fisiológicos. Utilizou-se 24 animais separados de acordo com a categoria (n= 6): bezerras, novilhas, gestantes e lactantes, com idades iniciais de zero, 12, 24 e 48 meses, respectivamente, criadas extensivamente. Realizou-se a cada 28 dias, ultrassonografia Doppler, colheita de sangue e pesagem, durante um ano (bezerras e novilhas) e 10 meses (gestantes e lactantes). Foram determinados os índices de resistividade (IR) e pulsatilidade (IP) e o diâmetro interno (DI) das artérias mamárias pela ultrassonografia. Foram mensuradas as concentrações plasmáticas de progesterona (P4), fator semelhante a insulina tipo I (IGF-I), insulina (IN), hormônio do crescimento (GH) e estradiol (17β-E2). Utilizou-se ANOVA com medidas repetidas, correlação de Spearman e regressão não linear múltipla, considerando nível de significância de 0,05. Nas bezerras e novilhas, houve redução de IR e IP e aumento do DI (P<0,0001) do primeiro ao último mês de avaliação, contudo, não houve diferença estatística para os índices hemodinâmicos entre as artérias mamárias cranial e caudal. Nas bezerras, detectou-se correlação do IR com o IP (r= 0,94; P<0,0001) e com o DI (r= -0,98; P<0,0001) e também, do IP com o DI (r= -0,98; P<0,0001). Nas novilhas o IR também correlacionou-se com o IP (r= 0,99; P<0,000... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to delineate hemodynamic parameters and toevaluate its relationship with key hormones involved in mammogenesis ofcrossbred Murrah buffaloes in different physiological stages. We used 24 animalsdivided according to the category (n= 6): calves, heifers, pregnant and lactatingfemales with early ages of zero, 12, 24 and 48 months, respectively, raisedextensively. Every 28 days, Doppler ultrasound examinations, blood analysis andweighing were held over one year (for calves and heifers) and over 10 months(for pregnant and lactating females). There were determined resistivity index (RI)and pulsatility index (PI) and internal vessel diameter (ID) of the mammaryarteries by ultrasound. Plasma concentrations of progesterone (P4), insulin-likegrowth factor 1 (IGF-I), insulin (IN), growth hormone (GH) and estradiol (17β-E2)were measured. We used repeated measures ANOVA, Spearman correlationand non-linear multiple regression considering 0.05 significance level. In calvesand heifers, a reduction of RI and PI and increased ID (P<0.0001) from first tolast month's assessment, however, there was no statistical difference inhemodynamic indices between the cranial and caudal mammary arteries. Allheifers, RI correlation was detected with PI (r= 0.94; P<0.0001), and ID (r= -0.98;P<0.0001) and also PI with ID (r= -0.98; P<0.0001). In heifers RI also correlatedwith PI (r= 0.99; P<0.0001) and DI (r= -0.95; P<0.0001) and PI with the ID... (Complete abstract click electronic access below) / Doutor

Imagem por ressonância magnética tem sido um dos principais métodos para a aquisição de imagens para diagnósticos na medicina, em especial para a obtenção de medidas do cérebro. Apesar de se mostrar muito eficiente, o método atualmente utilizado para a realização da ressonância em hospitais e centros de diagnósticos, em alguns casos, necessita da aplicação de um contraste de gadolínio intravenoso. Essa injeção do contraste pode mostrar-se um tanto quanto invasivo, podendo em alguns casos resultar em algumas reações indesejadas nos pacientes. Em vista disso, um método que tem sido bastante estudado recentemente e muito promissor é o de Arterial Spin Labeling (ASL). Este método tem como sua principal vantagem o fato de não ser invasivo e de possibilitar a quantificação da perfusão sanguínea cerebral (CBF). No presente trabalho, foi feita uma otimização do contraste na aquisição das fases mais tardias da metodologia de ASL em múltiplas fases. Isso foi feito através de uma modulação do angulo de flip e é particularmente importante para a análise das imagens de pacientes com problemas neurovasculares, principalmente aqueles associados ao retardo nos tempos de trânsito do sangue arterial. Também, foi realizada toda a obtenção e processamento de dados para a avaliação da perfusão sanguínea cerebral utilizando o método proposto. / Magnetic resonance imaging has been one of the major methods to acquire images for medical diagnoses, specially, for obtaining brain images. Although the major method using magnetic resonance used today has high efficiency, in some cases it needs an injection of intravascular contrast agent, like gadolinium. This contrast agent application can be a lot invasive for the patient, in extremes cases resulting to allergic reactions the patient. Therefore, a method that has been studied recently and is very promising is the Arterial Spin Labeling (ASL). This method has the major advantage the feature that it is completely non invasive for the patient and it allows to quantify the perfusion value. In this work, it was implemented an optimization of the contrast in the late phases of ASL multiphase acquisition. It was made using a modulation of the flip angle and it is critical to analyze images from patients with some neurovascular disease, especially those associated with arterial blood transit time delay. Besides that, it was made all data acquisition and data processing for the brain perfusion evaluation using the proposed method.

The study of non-Newtonian flow is presents itself as relevant in bioengineering field, specially for design of devices that conduct blood, as arterial bypass grafts. Improvements in reducing energy dissipation and blood cell damage caused by artificial flows can be achieved by using numerical simulation and optimization methods. Thus, the present work proposes the study of design channels for steady, incompressible non-Newtonian flow, by using Topology Optimization Method based on the density method. The fluid flow is modeled with the Navier-Stokes equations coupled with Carreau-Yasuda constitutive equation for the dynamic viscosity to take into account the effects of the non-Newtonian blood properties. The Topology Optimization Method distributes regions of solid and fluid, given a volume constraint, within a specified domain in order to obtain a geometry and layout that minimizes energy dissipation, shear stress and vorticity by using the material pseudo-density as design variable. To apply this method to fluidic systems design, a fictional porous media based on Darcy equation is introduced. The flow model is implemented in its discrete form by using the Finite Element Method through the OpenSource platform FEniCS, applied to automate the solution of mathematical models based on differential equations. The optimization problem is solved by using the library DOLFIN-adjoint and IPOpt optimizer. Optimized topologies of channels for blood flow, focusing in arterial bypass grafts, are presented to illustrate the proposed method. / O estudo de escoamento de fluidos não-Newtonianos apresenta-se relevante no campo de bioengenharia, em especial no projeto de dispositivos para condução de sangue, como bypass arterial. Melhorias na redução de dissipação de energia e no dano às células sanguíneas causados por fluxos artificiais podem ser obtidas através do uso de técnicas de simulação e otimização numéricas. Deste modo, este trabalho propõe o estudo do projeto de canais para escoamentos incompressíveis em regime permanente de fluidos não-Newtonianos através do Método de Otimização Topológica baseado no método de densidade. O escoamento é modelado com as equações de Navier-Stokes acopladas com a equação constitutiva de Carreau-Yasuda para a viscosidade dinâmica, para que sejam considerados os efeitos das propriedades não-Newtonianas do sangue. O Método de Otimização Topológica distribui regiões de sólido e fluido, dada uma restrição de volume, dentro de um domínio especificado de modo a obter uma geometria e configuração que minimize a dissipação de energia, tensão de cisalhamento e vorticidade, utilizando a pseudo-densidade do material como variável de projeto. Para aplicar este método a sistemas fluidos, um meio poroso fictício, baseado na equação de Darcy, é introduzido. O modelo de escoamento é implementado em sua forma discreta utilizando o Método de Elementos Finitos através da plataforma OpenSource FEniCS, aplicada para automatizar a solução dos modelos matemáticos baseados em equações diferenciais, e o problema de otimização é resolvido utilizando a biblioteca DOLFIN-adjoint e otimizador IPOpt. Topologias otimizadas de canais para fluxo de sangue, com foco em bypass arterial, são apresentadas para ilustrar o método proposto.