The Circle of Willis (CoW) is a ring-like arterial structure forming the major anastomotic connection between arterial supply systems in the brain, and is responsible for the distribution of oxygenated blood throughout the cerebral mass. Among the general population, only approximately 50% have a complete CoW, where absent or hypoplastic vessels are common among a multitude of possible anatomical variations, reducing the degree to which blood may be rerouted. While an individual with one of these variations may under normal circumstances suffer no ill effects, there are certain pathological conditions which can present a risk to the person's health and increase the possibility of suffering an ischaemic stroke when compounded with an anatomical variation. This body of work presents techniques for generating 3D models of the cerebral vasculature using magnetic resonance imaging (MRI) and performing computational fluid dynamics (CFD) simulations in order to simulate the flow patterns throughout a circle of Willis. Incorporated with the simulations is a mathematical model of the cerebral autoregulation mechanism, simulating the ability of the smaller arteries and arterioles in the brain to either constrict or dilate in response to alterations in cerebral blood flow, thereby altering the cerebrovascular resistance of each major brain territory and regulating the amount of blood flow within a physiological range of cerebral perfusion pressure. The CFD simulations have the ability to predict the amount of collateral flow rerouted via the communicating arteries in response to a stenosis or occlusion, and the major objective of this study has been the investigation of how anatomical variations of the circle of Willis affect the capacity to provide this collateral flow. Initial work began with the development of three idealized models of common anatomical variations, created using computer aided design software (CAD) and based on the results of MRI scans. The research then shifted to developing a technique whereby patient specific models of the circle of Willis could be directly segmented from the MRI data. As a result of this shift, an interactive GUI-based tool was developed for the processing of the MRI datasets, allowing for rapid data enhancement and creation of a surface topology representing the arterial wall of the circle of Willis, suitable for a CFD simulation. The results of both sets of simulations illustrate that there exist a number of variables associated with a patients circle of Willis geometry, such as cerebral blood flow and combinations and degrees of stenosis, implying that the initial goal of drawing generalized conclusions was perhaps flawed. Instead, a crucial outcome of this body of work is that the future research should be directed toward extending the physiological complexity of both the geometry and the autoregulation model, with the intention of a patient specific application rather than producing large datasets with which to make broad generalizations.

INTRODUÇÃO: Recentemente, fatores de risco cardiovascular (FRCV) e doenças cardíacas têm sido associados à demência, doença de Alzheimer (DA) e demência vascular (DV). O objetivo deste trabalho é investigar a associação entre doença cardiovascular comprovada anatomicamente e demência, definida por critérios clínicos, neuropatológicos e clinicopatológicos. MÉTODOS: Trata-se de estudo transversal com material do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral. Aterosclerose de artérias carótidas e do polígono de Willis (PW) e hipertrofia miocárdica foram avaliados em material de autópsia e relacionados à prevalência de demência. Dados demográficos e FRCV também foram comparados quanto à presença de demência. Esta foi definida por três critérios: (1) clínico de acordo com escalas cognitivas aplicadas ao informante do falecido; (2) neuropatológico de acordo com critérios aceitos para a classificação de DA e DV; (3) clinicopatológico de acordo com a avaliação cognitiva e com a presença de lesões cerebrais associadas à DA e DV. RESULTADOS: No estudo clínico, foram incluídos 603 indivíduos maiores de 50 anos de idade com avaliação cognitiva e cardiovascular. Demência esteve associada a obstruções críticas (75%) em artérias carótidas, a menor peso cardíaco e a menor espessura da parede ventricular esquerda. Os portadores de demência definida por critérios clínicos eram mais idosos e apresentaram maior proporção de acidente vascular cerebral (AVC) referido pelo informante, sedentarismo, insuficiência cardíaca e menor índice de massa corpórea do que os indivíduos sem demência. No estudo neuropatológico, foram avaliados 183 indivíduos que se dividiram em três grupos: controles (n=124), portadores de DA (n=31) e DV (n=28). Indivíduos com DA apresentaram maior proporção de obstruções75% em artérias carótidas do que controles. Os portadores de DV, além de maior gravidade da aterosclerose carotídea, também apresentaram maior obstrução em artérias do PW do que controles. Quanto aos dados demográficos e FRCV, a idade foi maior em indivíduos com DA e DV em relação a controles e AVC referido foi mais prevalente entre os portadores de DV. No estudo clinicopatológico, foram incluídos 124 controles, 12 portadores de doença cerebral assintomática (DCA) e 47 dementados. Maior gravidade da aterosclerose carotídea e das artérias do PW foi observada em portadores de demência em relação a controles. Quanto aos dados demográficos e FRCV, indivíduos com DCA e demência eram mais idosos do que controles. A escolaridade de portadores de DCA foi maior do que controles e AVC referido foi mais prevalente entre dementados em relação a controles. CONCLUSÕES: Doença cardiovascular, particularmente aterosclerose de artérias carótidas e do PW, estão associados à maior chance de demência. Medidas preventivas que visem retardar a progressão da aterosclerose podem ser eficientes para diminuir a incidência de demência / INTRODUCTION: Recently, cardiovascular risk factors (CVRF) and cardiac diseases have been associated with dementia, Alzheimer disease (AD) and vascular dementia (VD). The aim of this study was to investigate the association between anatomically-proven cardiovascular disease and dementia, defined by clinical, neuropathological and clinicopathological criteria. METHODS: This was a cross-sectional study using material drawn from the Human Brain Bank of the Aging Brain Study Group. Carotid artery and Circle of Willis (CW) atherosclerosis as well as myocardial hypertrophy were evaluated in autopsy material and compared for the prevalence of dementia. Demographics and CVRF were also compared for the presence of dementia. This was defined by three criteria: (1) clinical according to cognitive scales applied to the informant of the deceased individual; (2) neuropathological according to accepted criteria for the classification of AD; (3) clinicopathological according to cognitive evaluation and the presence of AD and VD-associated cerebral lesions. RESULTS: The clinical study included 603 individuals older than 50 years, who underwent cognitive and cardiovascular evaluation. Dementia was found to be associated with a high degree (75%) of obstruction in carotid arteries, lower heart weight and thinner left ventricle wall. Individuals with clinically-defined dementia were older and had more informant-reported strokes, greater physical inactivity and heart failure and lower body mass index than subjects without dementia. The neuropathological study involved 183 individuals who were evaluated and divided into three groups: control group (n=124), AD (n=31) and VD (n=28). Individuals with AD showed a higher degree of obstruction75% in the carotid arteries than controls. Subjects with VD, besides presenting greater severity of carotid atherosclerosis, also had a greater degree of obstruction in the arteries of the CW than controls. Regarding demographics and CVRF, age was higher in individuals with AD and VD compared to controls, while informant-reported stroke was more prevalent among individuals with VD. The clinicopathological study included 124 control individuals, 12 patients with asymptomatic brain disease (ABD) and 47 demented subjects. Greater severity of carotid and CW artery atherosclerosis was observed in individuals with dementia compared to controls. In terms of demographics and CVRF, individuals with ABD were older than control individuals. Years of education were higher in subjects with ABD compared to controls and informant-reported stroke was more prevalent among demented persons than controls. CONCLUSIONS: Cardiovascular disease, particularly carotid artery and CW atherosclerosis, are associated with higher risk for dementia. Preventive measures aimed at slowing the progression of atherosclerosis may be effective in decreasing the incidence of dementia

INTRODUÇÃO: Recentemente, fatores de risco cardiovascular (FRCV) e doenças cardíacas têm sido associados à demência, doença de Alzheimer (DA) e demência vascular (DV). O objetivo deste trabalho é investigar a associação entre doença cardiovascular comprovada anatomicamente e demência, definida por critérios clínicos, neuropatológicos e clinicopatológicos. MÉTODOS: Trata-se de estudo transversal com material do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral. Aterosclerose de artérias carótidas e do polígono de Willis (PW) e hipertrofia miocárdica foram avaliados em material de autópsia e relacionados à prevalência de demência. Dados demográficos e FRCV também foram comparados quanto à presença de demência. Esta foi definida por três critérios: (1) clínico de acordo com escalas cognitivas aplicadas ao informante do falecido; (2) neuropatológico de acordo com critérios aceitos para a classificação de DA e DV; (3) clinicopatológico de acordo com a avaliação cognitiva e com a presença de lesões cerebrais associadas à DA e DV. RESULTADOS: No estudo clínico, foram incluídos 603 indivíduos maiores de 50 anos de idade com avaliação cognitiva e cardiovascular. Demência esteve associada a obstruções críticas (75%) em artérias carótidas, a menor peso cardíaco e a menor espessura da parede ventricular esquerda. Os portadores de demência definida por critérios clínicos eram mais idosos e apresentaram maior proporção de acidente vascular cerebral (AVC) referido pelo informante, sedentarismo, insuficiência cardíaca e menor índice de massa corpórea do que os indivíduos sem demência. No estudo neuropatológico, foram avaliados 183 indivíduos que se dividiram em três grupos: controles (n=124), portadores de DA (n=31) e DV (n=28). Indivíduos com DA apresentaram maior proporção de obstruções75% em artérias carótidas do que controles. Os portadores de DV, além de maior gravidade da aterosclerose carotídea, também apresentaram maior obstrução em artérias do PW do que controles. Quanto aos dados demográficos e FRCV, a idade foi maior em indivíduos com DA e DV em relação a controles e AVC referido foi mais prevalente entre os portadores de DV. No estudo clinicopatológico, foram incluídos 124 controles, 12 portadores de doença cerebral assintomática (DCA) e 47 dementados. Maior gravidade da aterosclerose carotídea e das artérias do PW foi observada em portadores de demência em relação a controles. Quanto aos dados demográficos e FRCV, indivíduos com DCA e demência eram mais idosos do que controles. A escolaridade de portadores de DCA foi maior do que controles e AVC referido foi mais prevalente entre dementados em relação a controles. CONCLUSÕES: Doença cardiovascular, particularmente aterosclerose de artérias carótidas e do PW, estão associados à maior chance de demência. Medidas preventivas que visem retardar a progressão da aterosclerose podem ser eficientes para diminuir a incidência de demência / INTRODUCTION: Recently, cardiovascular risk factors (CVRF) and cardiac diseases have been associated with dementia, Alzheimer disease (AD) and vascular dementia (VD). The aim of this study was to investigate the association between anatomically-proven cardiovascular disease and dementia, defined by clinical, neuropathological and clinicopathological criteria. METHODS: This was a cross-sectional study using material drawn from the Human Brain Bank of the Aging Brain Study Group. Carotid artery and Circle of Willis (CW) atherosclerosis as well as myocardial hypertrophy were evaluated in autopsy material and compared for the prevalence of dementia. Demographics and CVRF were also compared for the presence of dementia. This was defined by three criteria: (1) clinical according to cognitive scales applied to the informant of the deceased individual; (2) neuropathological according to accepted criteria for the classification of AD; (3) clinicopathological according to cognitive evaluation and the presence of AD and VD-associated cerebral lesions. RESULTS: The clinical study included 603 individuals older than 50 years, who underwent cognitive and cardiovascular evaluation. Dementia was found to be associated with a high degree (75%) of obstruction in carotid arteries, lower heart weight and thinner left ventricle wall. Individuals with clinically-defined dementia were older and had more informant-reported strokes, greater physical inactivity and heart failure and lower body mass index than subjects without dementia. The neuropathological study involved 183 individuals who were evaluated and divided into three groups: control group (n=124), AD (n=31) and VD (n=28). Individuals with AD showed a higher degree of obstruction75% in the carotid arteries than controls. Subjects with VD, besides presenting greater severity of carotid atherosclerosis, also had a greater degree of obstruction in the arteries of the CW than controls. Regarding demographics and CVRF, age was higher in individuals with AD and VD compared to controls, while informant-reported stroke was more prevalent among individuals with VD. The clinicopathological study included 124 control individuals, 12 patients with asymptomatic brain disease (ABD) and 47 demented subjects. Greater severity of carotid and CW artery atherosclerosis was observed in individuals with dementia compared to controls. In terms of demographics and CVRF, individuals with ABD were older than control individuals. Years of education were higher in subjects with ABD compared to controls and informant-reported stroke was more prevalent among demented persons than controls. CONCLUSIONS: Cardiovascular disease, particularly carotid artery and CW atherosclerosis, are associated with higher risk for dementia. Preventive measures aimed at slowing the progression of atherosclerosis may be effective in decreasing the incidence of dementia

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-09-15T18:22:21Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) / Made available in DSpace on 2016-09-15T18:22:21Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) Previous issue date: 2016-02-24 / Introdução: Os aneurismas intracranianos trazem consequências importantes para o paciente acometido. A hemorragia subaracnóidea (HSA) possui uma forte correlação com aneurismas saculares e devido a sua gravidade e alta ocorrência de sequelas, o seu estudo merece importância. Uma alteração sensorial que pode esta relacionada à HSA é o déficit olfatório. Dentre os métodos de avaliação do olfato descritos, os quantitativos são ferramentas que podem ser utilizados a fim de garantir resultados mais fidedignos considerando o quadro clínico desses pacientes. Objetivos: Caracterizar o olfato de pacientes pré e pós tratamento cirúrgico para hemorragia subaracnóidea aneurismática. Método: Esta dissertação está composta por dois artigos. O primeiro constou de um artigo de revisão com título Métodos de avaliação do olfato em pacientes vítimas de hemorragia subaracnóidea: revisão sistemática. O segundo é um artigo original intitulado Avaliação do olfato na hemorragia subaracnóidea aneurismática antes e após o tratamento cirúrgico, neste foram estudados 15 adultos com hemorragia subaracnóidea aneurismática, atendidos no Hospital da restauração de Pernambuco, avaliados em três momentos distintos: Após a hemorragia, com uma semana de pós-operatório e com três meses de pós-operatório. A pesquisa foi iniciada após aprovação pelo Comitê de Ética em Pesquisa do hospital. Após a aplicação do Termo de Consentimento Livre e Esclarecido foi realizada a revisão do prontuário, entrevista com o participante e avaliação do olfato por meio de um teste de soluções aquosas, adaptado de outros estudos, construído pela farmácia escola da UFPE. Resultados: O primeiro artigo mostrou heterogeneidade nos métodos utilizados para avaliação do olfato na hemorragia subaracnóidea, como também no momento selecionado para aplicação das avaliações, com evidencias de déficit olfatório nesta população. Nos resultados provenientes do estudo original desta dissertação foi observado maior número de classificações olfatórias normais, além disso, não foi encontrada correlação significativa entre a pontuação olfatória com as seguintes variáveis (Idade, Intervalo em dias entre a hemorragia subaracnóidea e a avaliação olfatória, escolaridade e topografia do aneurisma). Não houve mudança significativa na pontuação olfatória após a cirurgia. Houve diferença estatística significativa na comparação entre a pontuação olfatória com uma semana de pós-operatório e com três meses de pós-operatório. Considerações finais: Os resultados deste estudo mostram a ocorrência de alteração olfatória após a hemorragia subaracnóidea aneurismática, assim como piora na classificação do olfato após a cirurgia. Foi observada melhora no olfato após três meses de pós-operatório, com significância estatística. Sugere-se a continuação de estudos com o tema, como também que façam investigação da percepção subjetiva do olfato visando o esclarecimento dos prejuízos que a alteração olfatória causa na vida dessa população. / Introduction: Intracranial aneurysms bring important consequences for the affected patient. The subarachnoid hemorrhage (HSA) has a strong correlation with saccular aneurysms and due to its gravity and high occurrence of sequels, its study deserves importance. A sensory change can this ASH-related is the olfactory deficit. Among the methods of valuation of smell described, are quantitative tools that can be used to ensure more reliable results considering the clinical picture of these patients.Objectives: Characterize the smell of patients before and after surgical treatment for aneurysmal subarachnoid hemorrhage. Method: This dissertation is composed of two articles. The first consisted of a review article with title Methods of evaluation of smell in victims of subarachnoid hemorrhage patients: a systematic review. The second is an original article entitled Olfactory evaluation in aneurysmal subarachnoid hemorrhage before and after surgery, this 15 were studied adults with aneurysmal subarachnoid hemorrhage, met at the Hospital da Restauração de Pernambuco, evaluated in three different moments: After the bleeding, a week after surgery and three months postoperatively. The search was started after approval by the Research Ethics Committee of the Hospital. After the application of informed consent was held to review the medical records, interview with the participant and evaluation of smell through a test of aqueous solutions, adapted from other studies, built by the Pharmacy School, Federal University of Pernambuco. Results: The first article showed heterogeneity of the methods used to evaluate the smell in aneurysmal subarachnoid hemorrhage and in the methods selected for application of evaluations, with evidence of olfactory deficits in this population. The results from the original study of this dissertation it was observed as many olfactory normal ratings, moreover, was not found significant correlation between olfactory score with the following variables (age, interval in days between the subarachnoid hemorrhage and the olfactory evaluation, education and topography of the aneurysm). There was no significant change in scoring olfactory after surgery. There was a statistically significant difference in the comparison between the olfactory score with a week after surgery and three months postoperatively. Final considerations: The results of this study show the occurrence of olfactory disfunction after aneurysmal subarachnoid hemorrhage, as well as worsens the classification of smell after surgery. Improvement was observed in the nose after three months postoperatively, with statistical significance. It is suggested a continuation of studies with the theme, but also to make the subjective perception of smell to identify the problems that the disfunction olfactory cause in this population´s life.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-25T12:54:13Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Islane Cristina Martins.pdf: 2501962 bytes, checksum: f8da8fe4623e40c91559079d260f0d75 (MD5) / Made available in DSpace on 2017-07-25T12:54:13Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Islane Cristina Martins.pdf: 2501962 bytes, checksum: f8da8fe4623e40c91559079d260f0d75 (MD5) Previous issue date: 2016-08-26 / FACEPE / O círculo arterial cerebral é um polígono anastomótico na base do encéfalo que comunica o sistema carotídeo com o sistema vértebro-basilar e as carótidas entre si. Há muitas variações morfológicas nesse polígono e possíveis diferenças entre os sexos, particularmente no segmento A1 da artéria cerebral anterior e na origem da artéria cerebral posterior (ACP). O objetivo do presente estudo foi analisar comparativamente a frequência de hipoplasia do segmento A1 e do padrão fetal da artéria cerebral posterior no homem e na mulher. Foram analisadas retrospectivamente 848 angiografias por ressonância magnética arterial, em 426 homens e 422 mulheres, respectivamente, que se submeteram ao exame no Centro de Diagnóstico Multimagem. Os exames foram escolhidos aleatoriamente entre 1.000 angiorressonância realizadas entre 2010 e 2016, independente do motivo da solicitação médica. Hipoplasia do segmento A1 foi definido por analise qualitativa, quando havia uma nítida assimetria entre os dois segmentos A1 direito e esquerdo bem como o padrão fetal da artéria cerebral posterior. Para análise de hipoplasia foram medidos os diâmetros dos segmentos A1. Para análise do padrão fetal (diâmetro da ACP na origem da artéria carótida>diâmetro do segmento P1) foram analisadas 1.296 artérias carótidas em 648 indivíduos. Na análise estatística utilizouse o teste exato de Fisher. Os homens 152/326 (46,6%) apresentaram hipoplasia de A1 em comparação com 108/322 (33,5%) das mulheres (p<0,01, OR=1,7; IC95% 1,3-2,4). A hipoplasia de A1 nos homens foi mais frequente a direita (20% vs. 15%, p<0,01). O padrão fetal foi mais comum nas mulheres 151/644 (23,4%) do que em homens, 100/652 (15,3%) (p<0,001, OR=1,7; IC95% 1,3-2,2). As mulheres também apresentam mais padrão fetal bilateral do que os homens (8,0% vs. 3,4%; p<0,01; OR=0,4; IC 0,2-0,8). A hipoplasia do segmento A1 da artéria cerebral anterior é mais frequente nos homens e nas mulheres há uma maior frequência do padrão fetal da artéria cerebral posterior. / The Circle of Willis is an anastomotic polygon encephalon base that communicates the carotid system with vertebrobasilar system and carotid each other. There are lots of morphological variations that polygon and possible differences between genders particularly in the A1 segment of the anterior cerebral artery and the origin of the posterior cerebral artery (PCA) which are risk factors for anatomical brain aneurysms. The purpose of this study was to comparatively analyze the frequency of hypoplasia of the segment A1 and fetal type of cerebral posterior artery in man and woman. It was retrospectively reviewed 648 magnetic resonance angiographies in 326 men and 322 women, respectively. The tests were randomly chosen among about a thousand magnetic resonance angiographic performed between 2010 and 2016 in Multimagem Diagnostic Center, regardless of the medical reason request. Hypoplasia of the A1 segment was defined by qualitative analysis, when there was a clear asymmetry between the two segments A1, right and left. For hypoplasia analysis were also measured diameters of segments A1. For hypoplasia analysis were also measured diameters of segments A1. For analysis of the fetal type (diameter of the ACP origin of the carotid artery> diameter of the P1 segment of the ACP) were analyzed 1,296 carotid arteries (right and left) in 648 individuals. Statistical analysis was performed using Fisher's exact test. In men 152/326 (46.6%) showed hypoplasia A1 compared to 108/322 (33.5%) of women (p <0.01, OR = 1.7; 95% CI, 1.3-2, 4). Hypoplasia A1 was more common in men right (20% vs. 15%, p <0.01). Fetal type was more common in women 151/644 (23.4%) than in men (100/652; 15.3%) (p <0.001, OR = 1.7; 95% CI, 1.3-2, two). Women also have more bilateral fetal rate than men (8.0% vs. 3.4%; p <0.01). In conclusion, hypoplasia of the A1 segment of the anterior cerebral artery is more common in men and in women there is a greater frequency of fetal type of the posterior cerebral artery. Keywords: Circle of Willis

Background The Circle of Willis (CoW) is an arterial anastomotic circle located at the skull base thatmaintains collateral circulation in the brain. Variations in CoW anatomy are commonly presentin the general population. Absent or hypoplastic segments of the CoW have been linked to anincreased stroke risk. Aim To determine whether CoW completeness is related to future ischemic stroke in the elderlypopulation after adjustment for relevant clinical risk factors. Methods Consecutive patients that underwent computed tomography angiography (CTA) of the headbetween 2014-2015 (60 years or older) were included. CoW-integrity was determined on CTAimages. Patient journals were retrospectively examined for ischemic stroke events followingthe CTA. Cox proportional hazard regression analysis was performed to determine hazard forischemic stroke in patients with incomplete CoW. Results 147 patients were included. The median follow-up time was 6.4 years (interquartile range 3.0years). 17 ischemic stroke events occurred during the follow-up period. Age (hazard ratio, HR1.10, p=0.03) and gender (HR 0.25, p=0.04) were statistically significant risk factors forischemic stroke. Complete anterior and posterior CoW was associated with lower strokehazards, however, the association was not statistically significant (HR 0.36, p=0.34 and HR0.67, p=0.45, respectively). Conclusions No significant risk reduction could be observed for either complete posterior or anterior CoW.Sex and age were significant risk factors for ischemic stroke. Further research is necessary toinvestigate how CoW integrity influences stroke risk after adjustment for other risk factors.

<p>UVOD: Vilisov poligon predstavlja najznačajniju rezervu kolateralnog protoka između ekstrakranijalnih arterija koje vaskularizuju mozak i ima sposobnost razvoja kolateranih puteva kod ekstrakranijalne karotidne bolesti. Ova anatomska struktura podložna je varijacijama koje uključuju i prekid kontinuiteta i nekompletnost kolateralizacije. CILJEVI: Cilj je bio da se utvrdi da li nekompletnost Vilisovog poligona utiče na če&scaron;će pojavljivanje neurolo&scaron;ke simptomatologije i ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Takođe cilj je bio i da se utvrdi da li cerebrovaskularna reaktivnost kod pacijenata sa asimptomatskom ekstrakranijalnom karotidnom bolesti zavisi od kompletosti Vilisovog poligona i na koji način hirur&scaron;ki tretman utiče na parametre cerebrovaskularne rezerve kod pacijenata sa kompletnim i nekompletnim Vilisovim poligonom. METOD: U retrospektivnoj studiji analiziran je nalaz MRA kod 211 pacijenata sa ekstrakranijalnom karotidnom bolesti i 102 pacijenta iz kontrolne grupe. U prospektivnoj studiji je kod 98 pacijenata sa asimptomatskom karotidnom bolesti pored MRA nalaza određivana cerebrovaskularna reaktivnost putem određivanja &bdquo;breath hold index&ldquo;-a (BHI) pre i nakon operativnog tretmana. REZULTATI: Nekompletan Vilisov poligon nađen je kod 25% asimptomatskih, 47,5% simptomatskih pacijenata sa karotidnom bolesti i kod 59% kontrolne grupe pacijenata, pri čemu su se razlike pokazale kao statistički značajne. Kod asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom BHI preoperativno iznostio je 0,62 a postoperativno 1,01 na strani lezije. U slučaju nekompletnog Vilisovog poligona preoperativna vrednost BHI iznostila je 0,88 a postoperativna 1,09 na strani lezije. Razlike su se pokazale kao statistički značajne između grupa i pre i posle operativnog tretmana. Porast je bio statistički značajno izraženiji u grupi asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom. Nisu zabeležene major operativne komplikacije (perioeprativni moždani udar,smrtni ishod) a na pojavu hiperperfuzionog sindroma najvi&scaron;e su uticali kompletnost Vilisovog poligona, vrednost BHI i preoperativni tretman hipertenzije. ZAKLJUČCI: Nekompletan Vilisov poligon predstavlja faktor rizika za pojavu neurolo&scaron;ke simptomatologije ili ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Kod asimptomatskih pacijenata nekompletan Vilisov pologon utiče na smanjenu cerebrovaskularnu reaktivnost i veći rizik od moždanog udara. Parametri cerebrovaskularne reaktivnosti signifikantno se pobolj&scaron;avaju nakon operativnog tretmana.</p> / <p>INTRODUCTION: Circle of Willis is the most important reserve of collateral flow between the extracranial arteries that supply the brain and has the ability to develop collateral pathways in extracranial carotid disease. This anatomical structure is subject to variations which include a disruption in the continuity and incompleteness of collateralisation. OBJECTIVES: was to determine whether the incompleteness of the Circle of Willis is more often associated with neurological symptoms and ishemic cerebral lesions in patients with extracranial carotid artery disease. Also, the objective was to determine whether cerebrovascular reactivity in patients with asymptomatic extracranial carotid artery disease depends on the completeness Circle of Willis and how surgical treatment affects the parameters of cerebrovascular reserve in patients with complete and incomplete Circle of Willis. METHODS: This study analyzed the findings of MRA in 211 patients with extracranial carotid artery disease and 102 patients in the control group. In prospective study in 98 patients with asymptomatic carotid artery disease in addition to the MRA findings cerebrovascular reactivity was determined by determining the &quot;breath hold index&quot; -a (BHI) before and after surgical treatment. RESULTS: Incomplete Circle of Willis was found in 25% of asymptomatic, 47.5% of symptomatic patients with carotid artery disease, and 59% of the control group patients, where the difference proved to be statistically significant. In asymptomatic patients with incomplete Circle of Willis BHI values were 0.62 preoperatively and 1.01 postoperatively on the side of the lesion. In the case of incomplete Circle of Willis preoperative BHI values were 0.88 preopertively and 1.09 postoperatively in asymptomatic patients. The differences are shown to be statistically significant between the groups before and after surgical treatment. The increase was significantly more pronounced in the group of asymptomatic patients with incomplete Circle of Willis. There were not recorded major operative complications (perioeprativni stroke, mortality) and the occurrence hyperperfusion syndrome was most affected by completeness of the Circle of Willis, a value BHI and preoperative treatment of hypertension. CONCLUSIONS: Incomplete Circle of Willis is a risk factor for the occurrence of neurological symptoms or ischemic brain lesions in patients with extracranial carotid artery disease. In asymptomatic patients incomplete Circle of Willis affects the reduced cerebrovascular reactivity and a higher risk of stroke. The parameters of cerebrovascular reactivity significantly improved after surgical treatment.</p>

Ischaemic stroke is a major cause of death and disability worldwide. Cerebral autoregulation, which can be impaired during acute stroke, and collateral flow to brain tissue through the circle of Willis, both play a role in preventing tissue infarction. The configuration of the arterial circle varies between individuals. Thus, personalised modelling of the cerebral arterial network, to determine the potential for collateral flow, can be of significant value in the clinical context of stroke. The interaction between autoregulation and collateral flow remains poorly understood. In this study, steady-state physiological models of the cerebral arterial network, including several common variants of the circle of Willis, were coupled to a spatially variable mathematical representation of cerebral autoregulation. The resulting model was used to simulate various arterial occlusions, as well as bilateral and unilateral impairment of autoregulation, in each structural variant. The work identified few circle of Willis variants that present either particularly high-risk or particularly low-risk of cerebral ischaemia. Instead it was found that most variants are dependent upon the bilateral function of autoregulation to facilitate collateral flow and preserve cerebral blood flows. When autoregulation was impaired unilaterally, downstream of an occlusion, blood flows in the contralateral hemisphere were preserved at the expense of the ipsilateral tissue at risk. Arterial network models have in the past been personalised using structural, rather than functional, angiography measurements. This thesis presents a novel model-based method for absolute blood volume flow rate quantification in short arterial segments using dynamic magnetic resonance angiography data. The work also investigated the additional information that can be obtained from such functional angiography. The flow quantification technique was found to accurately estimate flows in shorter arterial segments than an existing technique. However, improvements to noise performance, and strategies for rejection of contaminating signals from overlapping vessels within the imaging plane, are required before the technique can be applied to personalised cerebral arterial network modelling.

<p>The fluid dynamics of blood in the systemic circulation modulates production of nitric oxide (NO), a potent vasodilator. Non-invasive techniques such as the flow-mediated dilation (FMD) test and physiologic phenomena associated with autonomic stress induce hyperemia and subsequently higher levels of wall shear stress (WSS), stimulating endothelial nitric oxide synthase (eNOS) expression. In the current clinical practice, WSS–a key regulator of endothelial function–is commonly estimated assuming a parabolic velocity distribution, despite the evidence that the temporal changes of pulsatile blood flow over the cardiac cycle modulate vasodilation in mammals. This work investigates the effect of cardiovascular stress on local WSS distributions and the potential for near-wall accumulation of nitrite, the vasoactive storage form of NO in the bloodstream. The specific aims of the project are therefore as follows: 1) develop a reduced-order model of the major systemic vasculature at rest, during a flight-or-flight response, and under moderate levels of aerobic exercise; 2) derive a velocity-driven Womersley solution for pulsatile flow to support accurate estimation of pulsatile WSS in the clinical setting; and 3) quantify cumulative transport of nitrite in a multiscale model of bifurcating vasculature utilizing computational fluid dynamics (CFD). Development of these open-source, translatable methods enable accurate quantification of hemodynamics and species transport during cardiovascular stress. Results detailed herein extend our knowledge about regulation of regional blood flow during autonomic stress, suggest a convergent evolutionary theory for having a complete circle of Willis, and potentially clarify reproducibility concerns associated with the FMD test. </p>

Los derrames cerebrales son una de las causas principales de morbilidad y mortalidad en los países desarrollados. Esto ha motivado una búsqueda de configuraciones del sistema vascular que se cree que están asociadas con el desarrollo de enfermedades vasculares. En la primera contribución se ha mejorado un método de segmentación vascular para lograr robustez en la segmentación de imágenes procedentes de diferentes modalidades y centros clínicos, con una validación exhaustiva. Una vez que el sistema vascular está correctamente segmentado, en la segunda contribución se ha propuesto una metodología para caracterizar ampliamente la geometría de la arteria carótida interna (ACI). Esto ha incluido el desarrollo de un método para identificar automáticamente la ACI a partir del árbol vascular segmentado. Finalmente, en la tercera contribución, esta identificación automática se ha generalizado a una colección de arterias incluyendo su conectividad y sus relaciones topológicas. Finalmente, la identificación de las arterias en un conjunto de individuos puede permitir la comparación geométrica de sus árboles arteriales utilizando la metodología introducida para la caracterización de la ACI. / Stroke is among the leading causes of morbidity and mortality in the developed countries. This motivated a search for the configurations of vasculature that is assumed to be associated with the development of vascular diseases. In the first contribution we improve a vascular segmentation method to achieve robustness in segmenting images coming from different imaging modalities and clinical centers and we provide exhaustive segmentation validation. Once the vasculature is successfully segmented, in the second contribution we propose a methodology to extensively characterize the geometry of the internal carotid artery (ICA). This includes the development of a method to automatically identify the ICA from the segmented vascular tree. Finally in the third contribution, this automatic identification is generalized to a collection of vessels including their connectivity and topological relationships. Identifying the corresponding vessels in a population enables comparison of their geometry using the methodology introduced for the characterization of the ICA.