Introdução: Segmentos coronários com doença aterosclerótica manifesta podem coexistir no mesmo paciente com artérias normais à angiografia. Porém as características desses vasos angiograficamente normais permanecem pouco estudadas. O presente estudo visa a descrição in vivo, através do ultrassom intravascular com histologia virtual, da presença, grau de acometimento e composição da doença coronária aterosclerótica em artérias normais ou quase normais (irregularidades parietais) do ponto de vista angiográfico, em pacientes com doença coronária obstrutiva em outros territórios. Métodos: Pacientes com doença coronária obstrutiva foram selecionados de forma prospectiva e foram submetidos a estudo ultrassonográfico com histologia virtual de múltiplos vasos. Artérias epicárdicas principais foram classificadas em quatro grupos baseado na sua aparência angiográfica: 1) vasos completamente normais, 2) vasos com irregularidades parietais, 3) vasos com pelo menos uma estenose discreta, 4) vasos com pelo menos uma estenose moderada ou importante. Para os vasos com estenoses luminais (grupos 3 e 4 acima), apenas segmentos que não possuíam lesão maior ou igual a 30% (não obstrutivos) foram incluídos na análise. Resultados: Um total de 60 pacientes (154 vasos) foram incluídos no estudo. Vasos angiograficamente normais apresentaram menor carga de placa, menos componente necrótico, menor densidade de lesões e quase nenhuma placa com características de alto risco. Entretanto, em vasos com irregularidades parietais encontramos uma maior carga de placa com elevada densidade de lesões pelo ultrassom intravascular similar a segmentos \"não obstrutivos\" de vasos com estenoses luminais evidentes pela angiografia em outro ponto. Conclusão: Artérias coronárias completamente normais pela angiografia parecem apresentar pouca doença aterosclerótica. Entretanto, vasos com irregularidades parietais estão associados com um maior acometimento aterosclerótico e elevada densidade placas de alto risco, achado este que não pode ser rapidamente obtido com o uso apenas da angiografia coronária / Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone. Descriptors: angiography; atherosclerosis; coronary artery disease; plaque, atherosclerotic; ultrasonography, interventional; coronary vessels.Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone

Předložená diplomová práce se zabývá interakcí mezi proudící krví a krční tepnou, obsahující aterosklerotický plat, za pomoci konečnoprvkové fluid-structure interaction analýzy. První část práce obsahuje souhrn teoretických poznatků, sestávající z kardiovaskulárního systému, cév, souvisejících konstitutivních modelů, reologie krve a úvodu do teorie proudění. Dále je v práci obsažen stručný souhrn současného poznání výpočtového modelování v této oblasti, s důrazem na strukturní a fluid-structure interaction analýzy v oblasti krční tepny, a na použité konstitutivní modely. Experimentální část se soustředí na tvorbu zjednodušeného modelu krční tepny, obsahující aterosklerotický plat, a na tvorbu odpovídajícího modelu krve. Oba modely poté společně vstupují do fluid-structure interaction analýzy, která si klade za cíl pochopit důsledky pulzujícího toku krve na stěnu tepny a na růst aterosklerotického plátu; primárními zkoumanými veličinami jsou první hlavní napětí na stěně tepny, celková deformace stěny tepny, časově zprůměrovaná hodnota smykového napětí na stěně tepny a oscilační smykový index. Všechny výsledky jsou porovnány napříč několika typy analýz, tak aby bylo možné zhodnotit rozdíly a důsledky zvoleného přístupu. Součástí práce je také zjednodušená parametrická studie, která porovnává vliv rostoucího procenta stenózy na vyhodnocované veličiny. V poslední částí práce jsou zhodnoceny výsledky, její limitace a další možnosti výzkumu v této oblasti.

Indiana University-Purdue University Indianapolis (IUPUI) / Coronary artery disease (CAD) is a leading cause of death among Americans and is fueled by underlying metabolic syndrome (MetS). The prevalence and lethality of CAD necessitates rigorous investigations into its underlying mechanisms and to facilitate the development of effective treatment options. Coronary smooth muscle (CSM) phenotypic modulation from quiescent to synthetic, proliferative, and osteogenic phenotypes is a key area of investigation, with underlying mechanisms that remain poorly understood. Using a well-established pre-clinical model of CAD and MetS, the Ossabaw miniature swine, we established for the first time the time course of Ca2+ dysregulation during MetS-induced CAD progression. In particular, we used the fluorescent Ca2+ dye, fura-2, to examine alterations in CSM intracellular Ca2+ regulation during CAD progression, as perturbations in intracellular Ca2+ regulation are implicated in several cellular processes associated with CAD pathology, including CSM contractile responses and proliferative pathways. These studies revealed that the function of several CSM Ca2+ handling proteins is elevated in early CAD, followed by loss of function in severe atherosclerotic plaques. Decreased intracellular Ca2+ regulation occurred concurrently with reductions in CSM proliferation, measured with Ki-67 staining. In particular, alterations in sarcoplasmic reticulum (SR) Ca2+ store together with altered function of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) were associated with induction of proliferation. Organ culture of coronary arterial segments revealed that culture-induced medial thickening was prevented by SERCA inhibition with cyclopiazonic acid (CPA). Activation of SERCA with the small molecule activator, CDN1163, increased CSM proliferation, which was attenuated by treatment with CPA, thus establishing upregulated SERCA function as a proximal inducer of CSM proliferation. Further, we demonstrated that in vitro treatment of CSM from lean Ossabaw swine with the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, increased SERCA function. However, in vivo treatment of Ossabaw swine with MetS with the GLP-1 receptor agonist, AC3174, had no effect on CAD progression and in vitro examination revealed resistance of SERCA to GLP-1 receptor agonism in MetS. These findings further implicate SERCA in CAD progression. Collectively, these are the first data directly linking SERCA dysfunction to CSM proliferation and CAD progression, providing a key mechanistic step in CAD progression.

Fundamentos: A caracterização precisa da interação da placa aterosclerótica no momento do implante do stent é crucial para o entendimento da complacência e da cicatrização vasculares. Objetivamos investigar se a composição da placa avaliada pela tomografia de coerência óptica (OCT), influencia as alterações agudas no procedimento índice do implante do stent e na cicatrização vascular no seguimento tardio. Métodos: Os pacientes tratados com um único tipo de stent eluidor de fármaco (cromo cobalto, eluidor de sirolimus e polímero bioabsorvível) foram incluídos prospectivamente, seguindo um protocolo com etapas de dilatações progressivas do vaso. As imagens de OCT sequenciais foram realizadas no procedimento índice (basal e a cada etapa do protocolo) e no seguimento tardio, co-registradas e analisadas a cada 0,6mm. A avaliação semiquantitativa da placa foi realizada dividindo-se secções transversas em 4 quadrantes, com cada quadrante rotulado de acordo com o seu componente mais prevalente (fibrótico, calcificado, lipídico, normal). A interação stent-vaso avaliada pela OCT foi utilizada como indicador substituto para lesão e cicatrização vasculares após o implante do stent. Resultados: Um total de 22 lesões (1stent/lesão) de 20 pacientes e 2298 seções transversas de OCT foram analisadas no procedimento índice. O reestudo com OCT foi realizado em 17 pacientes e 19 lesões (86%). O componente de placa predominante foi fibrótico (fibrótico = 46.84 ± 16%; lipídico = 17.63 ± 10.72%; calcificado = 4.63 ± 5.9%; normal = 29.16 ± 12.24; não analizável=1.74 ± 5.35%). Houve um aumento nas áreas da luz (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) e do stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001), com um aumento na área do prolapso tecidual (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segmentos com muito tecido fibrocalcificado tiveram áreas luminais menores ao longo das etapas da intervenção. Por outro lado, placas com muito conteúdo lipídico ou vaso normal tiveram maiores ganhos nas medidas das áreas luminais mínimas ao longo das dilatações sequenciais. Além disso, placas com muito tecido fibrocalcificado no momento basal apresentaram menor crescimento neointimal no seguimento tardio, enquanto que o grau de conteúdo lipídico e de vaso normal não tiveram impacto sobre a formação do tecido neointimal. Os indicadores substitutos de lesão vascular após o implante do stent correlacionaram-se significativamente com o crescimento neointimal no seguimento tardio. Conclusões: A composição tecidual das placas subjacentes influencia significativamente o comportamento mecânico agudo e a longo prazo dos vasos coronarianos submetidos ao implante de stent. Além disso, a lesão vascular após o implante do stent está potencialmente ligada ao futuro crescimento neointimal no seguimento tardio / Background Accurate characterization of atherosclerotic plaque interaction during stent deployment is crucial to understand vascular compliance and healing. We sought to determine whether plaque composition assessed by optical coherence tomography (OCT), influences acute changes at index procedure and vascular healing at follow up. Methods Patients treated with a single drug-eluting stent type (cobalt chromium with bioabsorbable polymer eluting sirolimus stent) were prospectively included, following a pre-defined step-by-step progressive vessel dilatation. Sequential OCT imaging were performed at the index procedure (baseline and at each time point of the protocol) and at follow up, co-registered and analyzed every 0.6mm for quantitative measurements. Semi-quantitative plaque assessment was performed at baseline by dividing cross-sections into 4 quadrants, with each quadrant labeled according to its most prevalent component (fibrotic, calcific, lipid). OCT assessments of stent-vessel interactions were used as a surrogate for vessel injury and healing after stent implantation. Results A total of 22 lesions (1stent/lesion) of 20 patients and 2298 OCT crosssections were analyzed at the index procedure. For an average of 19.7 months (591.88 ± 60.52 days), 17 of the patients and 19 lesions (86%) underwent OCT imaging at follow up. The predominant percentage plaque component was fibrotic (fibrotic = 46.84 ± 16%; lipid = 17.63 ± 10.72%; calcific = 4.63 ± 5.9%; normal = 29.16 ± 12.24; non-analyzable = 1.74 ± 5.35%). There was an increase in lumen (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) and stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001) areas, with an increase in tissue prolapse area (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segments with high fibrocalcific content tended to have decreased minimal luminal areas along the intervention time-points. Conversely, plaques with high lipid content had increased minimal luminal areas during sequential dilatations. Moreover, plaques with high fibrocalcific tissue at baseline had significantly smaller neointimal growth at follow-up, whereas the degree of lipid content or normal tri-layered vessel had no impact on neointimal formation. OCT surrogates of vessel injury after coronary stenting significantly correlated with neointimal growth at follow-up. Conclusions: Tissue composition of underlying plaques significantly influences the acute mechanical and the long-term behavior of coronary vessels undergoing stent implantation. In addition, vessel injury after coronary stenting is potentially linked to future neointimal growth at follow-up

As características morfológicas da placa aterosclerótica têm sido sugeridas como componentes auxiliares à estenose, na avaliação de risco de acidente vascular cerebral (AVC), em pacientes com doença aterosclerótica carotídea sintomática. O objetivo desse estudo foi comparar as características da placa aterosclerótica de carótida pelo método de tomografia computadorizada com a análise histológica. Foram incluídos 19 pacientes com doença carotídea sintomática submetidos à TC de placa carotídea antes da realização de endarterectomia carotídea. Uma comparação sistemática entre a TC e a histologia foi realizada para determinar a correspondência entre os componentes da placa seguindo a classificação da \"American Heart Association\". Foi considerada placa vulnerável o tipo VI. A histologia foi realizada 5 (±2) dias após a TC. Os laudos (radiologia e patologia) foram comparados pelo investigador principal. Foi dosada a proteína C-Reativa (PCR) sérica e realizada avaliação do desempenho do PCR para detectar placa vulnerável, considerando como padrão-ouro o resultado da avaliação histológica. Foi avaliada a relação entre PCR e o tempo entre o evento e a cirurgia. Para tipo de placa aterosclerótica, foi encontrada uma acurácia de 84,2% (IC 95%: 82,8% a 85,6%), da tomografia em relação à histologia. A concordância para identificar ruptura de capa fibrosa com acurácia 94,7% (IC 95%: 94,2% a 95,3%), e, para calcificação, com acurácia 89.5% (IC 95%: 88,5% a 90,5%), foi considerada alta, e moderada para identificar hemorragia (68% acurácia). A concordância é moderada entre PCR de alto risco e placa vulnerável, e não há relação entre PCR, placa vulnerável e tempo de cirurgia. A tomografia de placa carotídea é um bom método não invasivo para detecção de vulnerabilidade da placa, identificação de ruptura de capa fibrosa e calcificação. Na nossa amostra, a concordância entre PCR alto risco e vulnerabilidade foi moderada, e não observamos relação entre vulnerabilidade, PCR e tempo entre o evento e a endarterectomia / Plaque morphologic characteristics have been suggested as an auxiliary component to luminal narrowing for assessing the risk of stroke associated with carotid atherosclerotic disease (CAD). The purpose of this study was to evaluate the ability of CT angiography (CTA) to categorize carotid artery atherosclerotic plaques (CAP) features in symptomatic patients submitted to endarterectomy according to the AHA histological classification. Nineteen patients with symptomatic CAD who underwent carotid CTA before endarterectomy were enrolled in a prospective study. A systematic comparison of CTA images with histological sections was performed to determine the CT attenuation associated with each component of the CAP. Histologic examination was performed 5 ± 2 days after the CTA. The neuroradiologist\'s reading of these analyses was compared with the histological slides interpretation performed by the same pathologist according to the CAP features following the AHA classification. The type VI plaque was considered as complicated. The two experts were blinded to each other\"s assessments. We performed C reactive Protein (CRP) and the CRP capacity to detect plaque vulnerability, considering histologic features as gold standard and the relation between CRP and time (event-surgery). There was an overall 84.2% (CI 95%: 82.8% a 85.6%), accuracy agreement in CAP classification between CTA and histological analysis. (Tab.1) The agreement between these two methods for the presence of calcification (Tab.2) in the CAP (accuracy 89.5%), and for categorizing the rupture of fibrous cap (accuracy 94,7), was excellent. (Tab. 3). CTA is not a good method to detect hemorrhage (Tab.4). High-risk CRP had moderate power to predict \"complicated plaque\" (Tab. 4) even as high risk CRP + CTA (Tab.5), There are No relation between CRP, complicated plaque and event to surgery delay. (Tab.6) CTA is a non-invasive tool that may help neurologists to categorize CAP features and potentially predict the risk of ischemic stroke in symptomatic CAD patients, and CRP could not be a good marker to complicated carotid plaque

As características morfológicas da placa aterosclerótica têm sido sugeridas como componentes auxiliares à estenose, na avaliação de risco de acidente vascular cerebral (AVC), em pacientes com doença aterosclerótica carotídea sintomática. O objetivo desse estudo foi comparar as características da placa aterosclerótica de carótida pelo método de tomografia computadorizada com a análise histológica. Foram incluídos 19 pacientes com doença carotídea sintomática submetidos à TC de placa carotídea antes da realização de endarterectomia carotídea. Uma comparação sistemática entre a TC e a histologia foi realizada para determinar a correspondência entre os componentes da placa seguindo a classificação da \"American Heart Association\". Foi considerada placa vulnerável o tipo VI. A histologia foi realizada 5 (±2) dias após a TC. Os laudos (radiologia e patologia) foram comparados pelo investigador principal. Foi dosada a proteína C-Reativa (PCR) sérica e realizada avaliação do desempenho do PCR para detectar placa vulnerável, considerando como padrão-ouro o resultado da avaliação histológica. Foi avaliada a relação entre PCR e o tempo entre o evento e a cirurgia. Para tipo de placa aterosclerótica, foi encontrada uma acurácia de 84,2% (IC 95%: 82,8% a 85,6%), da tomografia em relação à histologia. A concordância para identificar ruptura de capa fibrosa com acurácia 94,7% (IC 95%: 94,2% a 95,3%), e, para calcificação, com acurácia 89.5% (IC 95%: 88,5% a 90,5%), foi considerada alta, e moderada para identificar hemorragia (68% acurácia). A concordância é moderada entre PCR de alto risco e placa vulnerável, e não há relação entre PCR, placa vulnerável e tempo de cirurgia. A tomografia de placa carotídea é um bom método não invasivo para detecção de vulnerabilidade da placa, identificação de ruptura de capa fibrosa e calcificação. Na nossa amostra, a concordância entre PCR alto risco e vulnerabilidade foi moderada, e não observamos relação entre vulnerabilidade, PCR e tempo entre o evento e a endarterectomia / Plaque morphologic characteristics have been suggested as an auxiliary component to luminal narrowing for assessing the risk of stroke associated with carotid atherosclerotic disease (CAD). The purpose of this study was to evaluate the ability of CT angiography (CTA) to categorize carotid artery atherosclerotic plaques (CAP) features in symptomatic patients submitted to endarterectomy according to the AHA histological classification. Nineteen patients with symptomatic CAD who underwent carotid CTA before endarterectomy were enrolled in a prospective study. A systematic comparison of CTA images with histological sections was performed to determine the CT attenuation associated with each component of the CAP. Histologic examination was performed 5 ± 2 days after the CTA. The neuroradiologist\'s reading of these analyses was compared with the histological slides interpretation performed by the same pathologist according to the CAP features following the AHA classification. The type VI plaque was considered as complicated. The two experts were blinded to each other\"s assessments. We performed C reactive Protein (CRP) and the CRP capacity to detect plaque vulnerability, considering histologic features as gold standard and the relation between CRP and time (event-surgery). There was an overall 84.2% (CI 95%: 82.8% a 85.6%), accuracy agreement in CAP classification between CTA and histological analysis. (Tab.1) The agreement between these two methods for the presence of calcification (Tab.2) in the CAP (accuracy 89.5%), and for categorizing the rupture of fibrous cap (accuracy 94,7), was excellent. (Tab. 3). CTA is not a good method to detect hemorrhage (Tab.4). High-risk CRP had moderate power to predict \"complicated plaque\" (Tab. 4) even as high risk CRP + CTA (Tab.5), There are No relation between CRP, complicated plaque and event to surgery delay. (Tab.6) CTA is a non-invasive tool that may help neurologists to categorize CAP features and potentially predict the risk of ischemic stroke in symptomatic CAD patients, and CRP could not be a good marker to complicated carotid plaque

La rupture de plaque athérosclérotique est une complication grave, menant à des conséquences mortelles. En raison de la complexité du processus, les mécanismes de rupture de la plaque sont encore mal connus. Dans cette thèse, l'approche technique innovante pour mesurer la force d'adhérence développée précédemment sera appliquée à des souris. Elle comprend un protocole de délamination à petite échelle pour mesurer la résistance adhésive des plaques d'athérosclérose. Notre équipe à USC a été la première à effectuer ce type de mesures sur des souris. Une autre innovation de notre travail impliquera l'application d'un modèle de zone cohésive pour décrire le comportement de délamination des plaques athérosclérotiques dans une gamme de conditions physiologiques et physiopathologiques, en utilisant un modèle numérique 2D. Bien que l'approche de la zone cohésive ait été largement utilisée pour modéliser la mécanique des fractures, elle a rarement été appliquée pour décrire la rupture des plaques athérosclérotiques. L'étude de la délamination des plaques (Leng.2015) a été conçue pour tester l'utilisation de zones cohésives en mettant en œuvre une loi de séparation de traction spécifique, en supposant les valeurs des paramètres des lois de comportement de la plaque et de la zone cohésive en utilisant des valeurs de la littérature. L'innovation dans notre approche est d'utiliser une simple loi de séparation de la traction pour étudier le comportement des plaques et identifier leurs propriétés. Des résultats expérimentaux de délamination des plaques ont été utilisés dans la définition des lois de traction-séparation de la zone cohésive. / Atherosclerosis is the underlying cause of many cardiovascular diseases. Plaque rupture is a serious complication of advanced atherosclerosis, leading to life-threatening consequences. The mechanisms of atherosclerotic plaque progression and formation have been widely studied. However, due to the complexity of the process, plaque rupture mechanisms are still poorly understood. In this thesis, the innovative technical approach to measure the adhesive strength developed previously, will be applied to mice. It includes a micro-scale peel experiment protocol to measure adhesive strength of mouse atherosclerotic plaques during delamination from the underlying vessel wall. Our team at USC was the first to perform these types of measurements on mice. Another innovation of our work will involve application of a cohesive zone model to describe delamination behavior of atherosclerotic plaques under a range of physiological and pathophysiological conditions, using a 2D numerical model. While the cohesive zone approach has been widely used to model fracture mechanics, it was rarely applied to describe failure of atherosclerotic plaques. The study of plaque delamination (Leng.2015) was designed to test the use of cohesive zones by implementing a specific traction separation law, assuming the parameter values of the behavior laws of the plaque and the cohesive zone using values from the literature. Innovation in our approach is to use a simple traction separation law to study the behavior of plaques and identifying their properties. Experimental results of delamination of the plaques were used in the definition of traction-separation laws of the cohesive zone.

Fundamentos: A caracterização precisa da interação da placa aterosclerótica no momento do implante do stent é crucial para o entendimento da complacência e da cicatrização vasculares. Objetivamos investigar se a composição da placa avaliada pela tomografia de coerência óptica (OCT), influencia as alterações agudas no procedimento índice do implante do stent e na cicatrização vascular no seguimento tardio. Métodos: Os pacientes tratados com um único tipo de stent eluidor de fármaco (cromo cobalto, eluidor de sirolimus e polímero bioabsorvível) foram incluídos prospectivamente, seguindo um protocolo com etapas de dilatações progressivas do vaso. As imagens de OCT sequenciais foram realizadas no procedimento índice (basal e a cada etapa do protocolo) e no seguimento tardio, co-registradas e analisadas a cada 0,6mm. A avaliação semiquantitativa da placa foi realizada dividindo-se secções transversas em 4 quadrantes, com cada quadrante rotulado de acordo com o seu componente mais prevalente (fibrótico, calcificado, lipídico, normal). A interação stent-vaso avaliada pela OCT foi utilizada como indicador substituto para lesão e cicatrização vasculares após o implante do stent. Resultados: Um total de 22 lesões (1stent/lesão) de 20 pacientes e 2298 seções transversas de OCT foram analisadas no procedimento índice. O reestudo com OCT foi realizado em 17 pacientes e 19 lesões (86%). O componente de placa predominante foi fibrótico (fibrótico = 46.84 ± 16%; lipídico = 17.63 ± 10.72%; calcificado = 4.63 ± 5.9%; normal = 29.16 ± 12.24; não analizável=1.74 ± 5.35%). Houve um aumento nas áreas da luz (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) e do stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001), com um aumento na área do prolapso tecidual (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segmentos com muito tecido fibrocalcificado tiveram áreas luminais menores ao longo das etapas da intervenção. Por outro lado, placas com muito conteúdo lipídico ou vaso normal tiveram maiores ganhos nas medidas das áreas luminais mínimas ao longo das dilatações sequenciais. Além disso, placas com muito tecido fibrocalcificado no momento basal apresentaram menor crescimento neointimal no seguimento tardio, enquanto que o grau de conteúdo lipídico e de vaso normal não tiveram impacto sobre a formação do tecido neointimal. Os indicadores substitutos de lesão vascular após o implante do stent correlacionaram-se significativamente com o crescimento neointimal no seguimento tardio. Conclusões: A composição tecidual das placas subjacentes influencia significativamente o comportamento mecânico agudo e a longo prazo dos vasos coronarianos submetidos ao implante de stent. Além disso, a lesão vascular após o implante do stent está potencialmente ligada ao futuro crescimento neointimal no seguimento tardio / Background Accurate characterization of atherosclerotic plaque interaction during stent deployment is crucial to understand vascular compliance and healing. We sought to determine whether plaque composition assessed by optical coherence tomography (OCT), influences acute changes at index procedure and vascular healing at follow up. Methods Patients treated with a single drug-eluting stent type (cobalt chromium with bioabsorbable polymer eluting sirolimus stent) were prospectively included, following a pre-defined step-by-step progressive vessel dilatation. Sequential OCT imaging were performed at the index procedure (baseline and at each time point of the protocol) and at follow up, co-registered and analyzed every 0.6mm for quantitative measurements. Semi-quantitative plaque assessment was performed at baseline by dividing cross-sections into 4 quadrants, with each quadrant labeled according to its most prevalent component (fibrotic, calcific, lipid). OCT assessments of stent-vessel interactions were used as a surrogate for vessel injury and healing after stent implantation. Results A total of 22 lesions (1stent/lesion) of 20 patients and 2298 OCT crosssections were analyzed at the index procedure. For an average of 19.7 months (591.88 ± 60.52 days), 17 of the patients and 19 lesions (86%) underwent OCT imaging at follow up. The predominant percentage plaque component was fibrotic (fibrotic = 46.84 ± 16%; lipid = 17.63 ± 10.72%; calcific = 4.63 ± 5.9%; normal = 29.16 ± 12.24; non-analyzable = 1.74 ± 5.35%). There was an increase in lumen (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) and stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001) areas, with an increase in tissue prolapse area (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segments with high fibrocalcific content tended to have decreased minimal luminal areas along the intervention time-points. Conversely, plaques with high lipid content had increased minimal luminal areas during sequential dilatations. Moreover, plaques with high fibrocalcific tissue at baseline had significantly smaller neointimal growth at follow-up, whereas the degree of lipid content or normal tri-layered vessel had no impact on neointimal formation. OCT surrogates of vessel injury after coronary stenting significantly correlated with neointimal growth at follow-up. Conclusions: Tissue composition of underlying plaques significantly influences the acute mechanical and the long-term behavior of coronary vessels undergoing stent implantation. In addition, vessel injury after coronary stenting is potentially linked to future neointimal growth at follow-up

L’accident vasculaire cérébral (AVC) est une cause principale de décès et de morbidité dans le monde; une bonne partie des AVC est causée par la plaque d’athérosclérose carotidienne. La prévention de l’AVC chez les patients ayant une plaque carotidienne demeure controversée, vu les risques et bénéfices ambigus associés au traitement chirurgical ou médical. Plusieurs méthodes d’imagerie ont été développées afin d’étudier la plaque vulnérable (dont le risque est élevé), mais aucune n’est suffisamment validée ou accessible pour permettre une utilisation comme outil de dépistage. L’élastographie non-invasive vasculaire (NIVE) est une technique nouvelle qui cartographie les déformations (élasticité) de la plaque afin de détecter les plaque vulnérables; cette technique n’est pas encore validée cliniquement. Le but de ce projet est d’évaluer la capacité de NIVE de caractériser la composition de la plaque et sa vulnérabilité in vivo chez des patients ayant des plaques sévères carotidiennes, en utilisant comme étalon de référence, l’imagerie par résonance magnétique (IRM) à haute-résolution. Afin de poursuivre cette étude, une connaissance accrue de l’AVC, l’athérosclérose, la plaque vulnérable, ainsi que des techniques actuelles d’imagerie de la plaque carotidienne, est requise. Trente-et-un sujets ont été examinés par NIVE par ultrasonographie et IRM à haute-résolution. Sur 31 plaques, 9 étaient symptomatiques, 17 contenaient des lipides, et 7 étaient vulnérables selon l’IRM. Les déformations étaient significativement plus petites chez les plaques contenant des lipides, avec une sensibilité élevée et une spécificité modérée. Une association quadratique entre la déformation et la quantité de lipide a été trouvée. Les déformations ne pouvaient pas distinguer les plaques vulnérables ou symptomatiques. En conclusion, NIVE par ultrasonographie est faisable chez des patients ayant des sténoses carotidiennes significatives et peut détecter la présence d’un coeur lipidique. Des études supplémentaires de progression de la plaque avec NIVE sont requises afin d’identifier les plaques vulnérables. / Stroke is a leading cause of death and morbidity worldwide, and a significant proportion of strokes are caused by carotid atherosclerotic plaque rupture. Prevention of stroke in patients with carotid plaque poses a significant challenge to physicians, as risks and benefits of surgical or medical treatments remain equivocal. Many imaging techniques have been developed to identify and study vulnerable (high-risk) atherosclerotic plaques, but none is sufficiently validated or accessible for population screening. Non-invasive vascular elastography (NIVE) is a novel ultrasonic technique that maps carotid plaque strain (elasticity) characteristics to detect its vulnerability; it has not been clinically validated yet. The goal of this project is to evaluate the ability of ultrasound NIVE strain analysis to characterize carotid plaque composition and vulnerability in vivo in patients with significant plaque burden, as determined by the reference standard, high resolution MRI. To undertake this study, a thorough understanding of stroke, atherosclerosis, vulnerable plaque, and current non-invasive carotid plaque imaging techniques is required. Thirty-one subjects underwent NIVE and high-resolution MRI of internal carotid arteries. Of 31 plaques, 9 were symptomatic, 17 contained lipid and 7 were vulnerable on MRI. Strains were significantly lower in plaques containing a lipid core compared to those without lipid, with high sensitivity and moderate specificity. A quadratic fit was found between strain and lipid content. Strains did not discriminate symptomatic patients or vulnerable plaques. In conclusion, ultrasound NIVE is feasible in patients with significant carotid stenosis and can detect the presence of a lipid core. Further studies of plaque progression with NIVE are required to identify vulnerable plaques.

L’accident vasculaire cérébral (AVC) est une cause principale de décès et de morbidité dans le monde; une bonne partie des AVC est causée par la plaque d’athérosclérose carotidienne. La prévention de l’AVC chez les patients ayant une plaque carotidienne demeure controversée, vu les risques et bénéfices ambigus associés au traitement chirurgical ou médical. Plusieurs méthodes d’imagerie ont été développées afin d’étudier la plaque vulnérable (dont le risque est élevé), mais aucune n’est suffisamment validée ou accessible pour permettre une utilisation comme outil de dépistage. L’élastographie non-invasive vasculaire (NIVE) est une technique nouvelle qui cartographie les déformations (élasticité) de la plaque afin de détecter les plaque vulnérables; cette technique n’est pas encore validée cliniquement. Le but de ce projet est d’évaluer la capacité de NIVE de caractériser la composition de la plaque et sa vulnérabilité in vivo chez des patients ayant des plaques sévères carotidiennes, en utilisant comme étalon de référence, l’imagerie par résonance magnétique (IRM) à haute-résolution. Afin de poursuivre cette étude, une connaissance accrue de l’AVC, l’athérosclérose, la plaque vulnérable, ainsi que des techniques actuelles d’imagerie de la plaque carotidienne, est requise. Trente-et-un sujets ont été examinés par NIVE par ultrasonographie et IRM à haute-résolution. Sur 31 plaques, 9 étaient symptomatiques, 17 contenaient des lipides, et 7 étaient vulnérables selon l’IRM. Les déformations étaient significativement plus petites chez les plaques contenant des lipides, avec une sensibilité élevée et une spécificité modérée. Une association quadratique entre la déformation et la quantité de lipide a été trouvée. Les déformations ne pouvaient pas distinguer les plaques vulnérables ou symptomatiques. En conclusion, NIVE par ultrasonographie est faisable chez des patients ayant des sténoses carotidiennes significatives et peut détecter la présence d’un coeur lipidique. Des études supplémentaires de progression de la plaque avec NIVE sont requises afin d’identifier les plaques vulnérables. / Stroke is a leading cause of death and morbidity worldwide, and a significant proportion of strokes are caused by carotid atherosclerotic plaque rupture. Prevention of stroke in patients with carotid plaque poses a significant challenge to physicians, as risks and benefits of surgical or medical treatments remain equivocal. Many imaging techniques have been developed to identify and study vulnerable (high-risk) atherosclerotic plaques, but none is sufficiently validated or accessible for population screening. Non-invasive vascular elastography (NIVE) is a novel ultrasonic technique that maps carotid plaque strain (elasticity) characteristics to detect its vulnerability; it has not been clinically validated yet. The goal of this project is to evaluate the ability of ultrasound NIVE strain analysis to characterize carotid plaque composition and vulnerability in vivo in patients with significant plaque burden, as determined by the reference standard, high resolution MRI. To undertake this study, a thorough understanding of stroke, atherosclerosis, vulnerable plaque, and current non-invasive carotid plaque imaging techniques is required. Thirty-one subjects underwent NIVE and high-resolution MRI of internal carotid arteries. Of 31 plaques, 9 were symptomatic, 17 contained lipid and 7 were vulnerable on MRI. Strains were significantly lower in plaques containing a lipid core compared to those without lipid, with high sensitivity and moderate specificity. A quadratic fit was found between strain and lipid content. Strains did not discriminate symptomatic patients or vulnerable plaques. In conclusion, ultrasound NIVE is feasible in patients with significant carotid stenosis and can detect the presence of a lipid core. Further studies of plaque progression with NIVE are required to identify vulnerable plaques.