Indiana University-Purdue University Indianapolis (IUPUI) / While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called InVascular has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. InVascular integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of InVascular.

Arterial stenosis is a disease characterized by the buildup of a waxy substance inside the artery, which is associated with certain risks. It is difficult to eval- uate the severity of the stenosis, yet the diagnosis can become more accurate using computational fluid dynamics simulations. The present thesis introduces and applies the model of hemodynamics based on the Navier-Stokes equations, implemented in the FEniCS software employing the finite element method. The main focus lies on the prescription of the boundary condition at the outlet of the computational domain. The impact of the outlet boundary condition on medically significant quantities such as the wall shear stress is analyzed in a two- dimensional benchmark case. It appears that the right choice of the boundary condition is fundamental, in particular when vortices occur and propagate across the outlet boundary. The next part of the work is dedicated to the prescrip- tion of the outflow rate in the case of more than one outlet, corresponding to an artery branching inside the computational domain. The physically meaningful flux distribution is derived introducing Murray's law and its extension. Finally, the blood flow is simulated in a three-dimensional geometry of a patient-specific carotid artery. 1

Introdução: A doença aterosclerótica intracraniana é uma das principais causas de acidente vascular cerebral isquêmico (AVCI) no mundo, porém sua prevalência parece estar subestimada na população brasileira pela carência de estudos na área. O objetivo principal deste estudo foi descrever a frequência e gravidade da estenose intracraniana nos pacientes com AVCI ou ataque isquêmico transitório (AIT), utilizando a ultrassonografia transcraniana colorida (UTC). O objetivo secundário foi correlacionar os achados deste exame com a angiotomografia de crânio (AngioTC). Métodos: estudo observacional e prospectivo, onde foram avaliados pacientes consecutivos com o diagnóstico de AVCI ou AIT admitidos no período de fevereiro de 2014 a dezembro de 2014. A avaliação inicial consistiu na coleta de dados demográficos, epidemiológicos e clínicos e em seguida os pacientes foram submetidos ao exame de UTC através das janelas transtemporais e suboccipital, com o intuito de avaliar a presença de estenose intracraniana. Estenose intracraniana foi graduada em moderada (50- 70%), grave (70-99%) e suboclusão/oclusão (>= 99%). Foram considerados sintomáticos os casos em que houve uma associação entre os novos sinais e sintomas e uma nova área de infarto ao exame de neuroimagem no território da artéria envolvida ou quando o quadro neurológico correspondeu ao território da artéria envolvida. Os pacientes que possuíam UTC e AngioTC em sua avaliação foram comparados de forma cega quanto ao grau de estenose intracraniana seguindo a mesma classificação. Resultados: Foram avaliados 271 pacientes com o diagnóstico de AVCI ou AIT agudos (149 homens, com média de idade de 65,8 ± 12,5), 263 (97%) foram submetidos a exame de circulação intracraniana, sendo a ultrassonografia transcraniana colorida realizada em 168 casos (61,9%). Apenas 25 indivíduos (14,9%) foram excluídos devido a janela transtemporal insuficiente. Dentre os 143 pacientes que puderam ser avaliados adequadamente pela ultrassonografia transcraniana, a prevalência de estenose arterial intracraniana foi de 38,5% (55 casos); sendo sintomática em 25,2% dos casos. A média de idade dos pacientes era de 64 ± 11 anos, 26,9 % eram brancos e 29,4% hipertensos. Os pacientes com estenose intracraniana apresentaram maior pontuação na escala do NIH: 10 (IQ 4 - 19) vs 6 (IQ 3 - 13), maiores níveis de pressão arterial sistólica na admissão: 160 (IQ 145-170) vs 140 (IQ 130 - 155) e menores taxas de HDL: 32 (IQ 27 - 39) vs 36 (IQ 30 - 45). Após análise multivariada, o fator de risco independentemente associado à estenose intracraniana foi a hipertesão arterial sistêmica na admissão (p=0,006). Nos 100 pacientes com ambos os exames, a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo da UTC comparada a AngioTC para detecção de estenoses intracranianas moderadas-graves foi de 60%, 73%, 73% e 60%, respectivamente. Conclusões: Encontramos alta frequência de estenose arterial intracraniana entre os pacientes com AVCI agudo e AIT na nossa população, especialmente entre indivíduos portadores de hipertensão arterial sistêmica. A UTC é uma ferramenta não-invasiva que pode ser utilizada para investigação da doença moderada-grave com acurácia moderada quando comparada a AngioTC / Background: Intracranial atherosclerotic disease is a major cause of ischemic stroke in the world, but its prevalence seems to be underestimated in our population by the lack of studies in the area. The aim of this study was to describe the frequency and severity of intracranial stenosis in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA), using the transcranial color-coded sonography (TCCS). The secondary objective was to correlate the TCCS test results with the findings on CT angiography on the same patients. Methods: Prospective observational study that evaluated consecutive patients admitted with a diagnosis of ischemic stroke or TIA during the period February 2014 to December 2014. The initial evaluation consisted of collection of demographic, epidemiological and clinical data and then the patients underwent the examination TCCS through transtemporal and suboccipital windows, in order to assess the presence of intracranial stenosis. Intracranial stenosis was graded moderate (50-70%), severe (70-99%) and subocclusion/occlusion (>= 99%). The cases were considered symptomatic when there was an association between new symptoms and signs and a new infarct area on neuroimaging in the territory of the stenotic artery or when the neurological status corresponded to the territory of that artery. Patients who had TCCS and intracranial angiography in their assessment were blindly compared for the degree of intracranial stenosis following the same classification. Results: We evaluated 271 patients with diagnosis of acute ischemic stroke and TIA (149 men, mean age 65.8 ± 12.5), 263 (97%) underwent examination of intracranial circulation, with the TCCS held in 168 cases (61.9%). Only 25 individuals (14.9%) were excluded due to insufficient transtemporal window. Among the 143 patients who could be evaluated properly by transcranial ultrasound, the prevalence of intracranial arterial stenosis was 38.5% (55 cases); with 25,2% symptomatic cases. The average age of patients was 64 ± 11 years, 26.9% were white and 29.4% hypertensive. Patients with intracranial stenosis had higher scores on the NIHSS: 10 (IR 4-19) vs 6 (IR 3- 13), higher levels of systolic blood pressure at entry: 160 (IR 145-170) vs 140 (IR 130 - 155) and lower HDL rates: 32 (IR 27-39) vs 36 (IR 30-45). After multivariate analysis, the risk factor independently associated with intracranial stenosis was systemic arterial hypertension at admission (p = 0.006). In the 83 patients with both tests, the sensitivity, specificity, positive predictive value and negative predictive value of TCCS compared to CT angiography for detection of intracranial stenosis moderate-severe was 60%, 73%, 73% e 60%, respectively, Conclusions: We found a high frequency of intracranial artery stenosis in patients with acute ischemic stroke and TIA in our population, especially among individuals with hypertension. TCCS is a non-invasive tool that can be used to study moderate-severe disease with moderate accuracy compared to CT angiography

While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called <i>InVascular</i> has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. <i>InVascular</i> integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of <i>InVascular</i>.

Introdução: A doença aterosclerótica intracraniana é uma das principais causas de acidente vascular cerebral isquêmico (AVCI) no mundo, porém sua prevalência parece estar subestimada na população brasileira pela carência de estudos na área. O objetivo principal deste estudo foi descrever a frequência e gravidade da estenose intracraniana nos pacientes com AVCI ou ataque isquêmico transitório (AIT), utilizando a ultrassonografia transcraniana colorida (UTC). O objetivo secundário foi correlacionar os achados deste exame com a angiotomografia de crânio (AngioTC). Métodos: estudo observacional e prospectivo, onde foram avaliados pacientes consecutivos com o diagnóstico de AVCI ou AIT admitidos no período de fevereiro de 2014 a dezembro de 2014. A avaliação inicial consistiu na coleta de dados demográficos, epidemiológicos e clínicos e em seguida os pacientes foram submetidos ao exame de UTC através das janelas transtemporais e suboccipital, com o intuito de avaliar a presença de estenose intracraniana. Estenose intracraniana foi graduada em moderada (50- 70%), grave (70-99%) e suboclusão/oclusão (>= 99%). Foram considerados sintomáticos os casos em que houve uma associação entre os novos sinais e sintomas e uma nova área de infarto ao exame de neuroimagem no território da artéria envolvida ou quando o quadro neurológico correspondeu ao território da artéria envolvida. Os pacientes que possuíam UTC e AngioTC em sua avaliação foram comparados de forma cega quanto ao grau de estenose intracraniana seguindo a mesma classificação. Resultados: Foram avaliados 271 pacientes com o diagnóstico de AVCI ou AIT agudos (149 homens, com média de idade de 65,8 ± 12,5), 263 (97%) foram submetidos a exame de circulação intracraniana, sendo a ultrassonografia transcraniana colorida realizada em 168 casos (61,9%). Apenas 25 indivíduos (14,9%) foram excluídos devido a janela transtemporal insuficiente. Dentre os 143 pacientes que puderam ser avaliados adequadamente pela ultrassonografia transcraniana, a prevalência de estenose arterial intracraniana foi de 38,5% (55 casos); sendo sintomática em 25,2% dos casos. A média de idade dos pacientes era de 64 ± 11 anos, 26,9 % eram brancos e 29,4% hipertensos. Os pacientes com estenose intracraniana apresentaram maior pontuação na escala do NIH: 10 (IQ 4 - 19) vs 6 (IQ 3 - 13), maiores níveis de pressão arterial sistólica na admissão: 160 (IQ 145-170) vs 140 (IQ 130 - 155) e menores taxas de HDL: 32 (IQ 27 - 39) vs 36 (IQ 30 - 45). Após análise multivariada, o fator de risco independentemente associado à estenose intracraniana foi a hipertesão arterial sistêmica na admissão (p=0,006). Nos 100 pacientes com ambos os exames, a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo da UTC comparada a AngioTC para detecção de estenoses intracranianas moderadas-graves foi de 60%, 73%, 73% e 60%, respectivamente. Conclusões: Encontramos alta frequência de estenose arterial intracraniana entre os pacientes com AVCI agudo e AIT na nossa população, especialmente entre indivíduos portadores de hipertensão arterial sistêmica. A UTC é uma ferramenta não-invasiva que pode ser utilizada para investigação da doença moderada-grave com acurácia moderada quando comparada a AngioTC / Background: Intracranial atherosclerotic disease is a major cause of ischemic stroke in the world, but its prevalence seems to be underestimated in our population by the lack of studies in the area. The aim of this study was to describe the frequency and severity of intracranial stenosis in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA), using the transcranial color-coded sonography (TCCS). The secondary objective was to correlate the TCCS test results with the findings on CT angiography on the same patients. Methods: Prospective observational study that evaluated consecutive patients admitted with a diagnosis of ischemic stroke or TIA during the period February 2014 to December 2014. The initial evaluation consisted of collection of demographic, epidemiological and clinical data and then the patients underwent the examination TCCS through transtemporal and suboccipital windows, in order to assess the presence of intracranial stenosis. Intracranial stenosis was graded moderate (50-70%), severe (70-99%) and subocclusion/occlusion (>= 99%). The cases were considered symptomatic when there was an association between new symptoms and signs and a new infarct area on neuroimaging in the territory of the stenotic artery or when the neurological status corresponded to the territory of that artery. Patients who had TCCS and intracranial angiography in their assessment were blindly compared for the degree of intracranial stenosis following the same classification. Results: We evaluated 271 patients with diagnosis of acute ischemic stroke and TIA (149 men, mean age 65.8 ± 12.5), 263 (97%) underwent examination of intracranial circulation, with the TCCS held in 168 cases (61.9%). Only 25 individuals (14.9%) were excluded due to insufficient transtemporal window. Among the 143 patients who could be evaluated properly by transcranial ultrasound, the prevalence of intracranial arterial stenosis was 38.5% (55 cases); with 25,2% symptomatic cases. The average age of patients was 64 ± 11 years, 26.9% were white and 29.4% hypertensive. Patients with intracranial stenosis had higher scores on the NIHSS: 10 (IR 4-19) vs 6 (IR 3- 13), higher levels of systolic blood pressure at entry: 160 (IR 145-170) vs 140 (IR 130 - 155) and lower HDL rates: 32 (IR 27-39) vs 36 (IR 30-45). After multivariate analysis, the risk factor independently associated with intracranial stenosis was systemic arterial hypertension at admission (p = 0.006). In the 83 patients with both tests, the sensitivity, specificity, positive predictive value and negative predictive value of TCCS compared to CT angiography for detection of intracranial stenosis moderate-severe was 60%, 73%, 73% e 60%, respectively, Conclusions: We found a high frequency of intracranial artery stenosis in patients with acute ischemic stroke and TIA in our population, especially among individuals with hypertension. TCCS is a non-invasive tool that can be used to study moderate-severe disease with moderate accuracy compared to CT angiography

Une fistule artérioveineuse (FAV) est un accès vasculaire permanent créé par voie chirurgicale en connectant une veine et une artère chez le patient en hémodialyse. Cet accès vasculaire permet de mettre en place une circulation extracorporelle partielle afin de remplacer les fonctions exocrines des reins. En France, environ 36000 patients sont atteint d’insuffisance rénale chronique en phase terminale, stade de la maladie le plus grave qui nécessite la mise en place d’un traitement de suppléance des reins : l’hémodialyse. La création et présence de la FAV modifient significativement l’hémodynamique dans les vaisseaux sanguins, au niveau local et systémique ainsi qu’à court et à plus long terme. Ces modifications de l’hémodynamiques peuvent induire différents pathologies vasculaires, comme la formation d’anévrysmes et de sténoses. L’objectif de cette étude est de mieux comprendre le comportement mécanique et l’hémodynamique dans les vaisseaux de la FAV. Nous avons étudié numériquement les interactions fluide-structure (IFS) au sein d’une FAV patient-spécifique, dont la géométrie a été reconstruite à partir d’images médicales acquises lors d’un précédent doctorat. Cette FAV a été créée chez le patient en connectant la veine céphalique du patient à l’artère radiale et présente une sténose artérielle réduisant de 80% la lumière du vaisseau. Nous avons imposé le profil de vitesse mesuré sur le patient comme conditions aux limites en entrée et un modèle de Windkessel au niveau des sorties artérielle et veineuse. Nous avons considéré des propriétés mécaniques différentes pour l’artère et la veine et pris en compte le comportement non-Newtonien du sang. Les simulations IFS permettent de calculer l’évolution temporelle des contraintes hémodynamiques et des contraintes internes à la paroi des vaisseaux. Nous nous sommes demandées aussi si des simulations non couplées des équations fluides et solides permettaient d’obtenir des résultats suffisamment précis tout en réduisant significativement le temps de calcul, afin d’envisager son utilisation par les chirurgiens. Dans la deuxième partie de l’étude, nous nous sommes intéressés à l’effet de la présence d’une sténose artérielle sur l’hémodynamique et en particulier à ses traitements endovasculaires. Nous avons dans un premier temps simulé numériquement le traitement de la sténose par angioplastie. En clinique, les sténoses résiduelles après angioplastie sont considérées comme acceptables si elles obstruent moins de 30% de la lumière du vaisseau. Nous avons donc gonflé le ballonnet pour angioplastie avec différentes pressions de manière à obtenir des degrés de sténoses résiduelles compris entre 0 et 30%. Une autre possibilité pour traiter la sténose est de placer un stent après l’angioplastie. Nous avons donc dans un deuxième temps simulé ce traitement numériquement et résolu le problème d’IFS dans la fistule après la pose du stent. Dans ces simulations, la présence du stent a été prise en compte en imposant les propriétés mécaniques équivalentes du vaisseau après la pose du stent à une portion de l’artère. Dans la dernière partie de l’étude nous avons mis en place un dispositif de mesure par PIV (Particle Image Velocimetry). Un moule rigide et transparent de la géométrie a été obtenu par prototypage rapide. Les résultats expérimentaux ont été validés par comparaison avec les résultats des simulations numériques. / An arteriovenous fistula (AVF) is a permanent vascular access created surgically connecting a vein onto an artery. It enables to circulate blood extra-corporeally in order to clean it from metabolic waste products and excess of water for patients with end-stage renal disease undergoing hemodialysis. The hemodynamics results to be significantly altered within the arteriovenous fistula compared to the physiological situation. Several studies have been carried out in order to better understand the consequences of AVF creation, maturation and frequent use, but many clinical questions still lie unanswered. The aim of the present study is to better understand the hemodynamics within the AVF, when the compliance of the vascularwall is taken into account. We also propose to quantify the effect of a stenosis at the afferent artery, the incidence of which has been underestimated for many years. The fluid-structure interactions (FSI) within a patient-specific radio-cephalic arteriovenous fistula are investigated numerically. The considered AVF presents an 80% stenosis at the afferent artery. The patient-specific velocity profile is imposed at the boundary inlet, and a Windkessel model is set at the arterial and venous outlets. The mechanical properties of the vein and the artery are differentiated. The non-Newtonian blood behavior has been taken into account. The FSI simulation advantageously provides the time-evolution of both the hemodynamic and structural stresses, and guarantees the equilibrium of the solution at the interface between the fluid and solid domains. The FSI results show the presence of large zones of blood flow recirculation within the cephalic vein, which might promote neointima formation. Large internal stresses are also observed at the venous wall, which may lead to wall remodeling. The fully-coupled FSI simulation results to be costly in computational time, which can so far limit its clinical use. We have investigated whether uncoupled fluid and structure simulations can provide accurate results and significantly reduce the computational time. The uncoupled simulations have the advantage to run 5 times faster than the fully-coupled FSI. We show that an uncoupled fluid simulation provides informative qualitative maps of the hemodynamic conditions in the AVF. Quantitatively, the maximum error on the hemodynamic parameters is 20%. The uncoupled structural simulation with non-uniform wall properties along the vasculature provides the accurate distribution of internal wall stresses, but only at one instant of time within the cardiac cycle. Although partially inaccurate or incomplete, the results of the uncoupled simulations could still be informative enough to guide clinicians in their decision-making. In the second part of the study we have investigated the effects of the arterial stenosis on the hemodynamics, and simulated its treatment by balloon-angioplasty. Clinically, balloon-angioplasty rarely corrects the stenosis fully and a degree of stenosis remains after treatment. Residual degrees of stenosis below 30% are considered as successful. We have inflated the balloon with different pressures to simulate residual stenoses ranging from 0 to 30%. The arterial stenosis has little impact on the blood flow distribution: the venous flow rate remains unchanged before and after the treatment and thus permits hemodialysis. But an increase in the pressure difference across the stenosis is observed, which could cause the heart work load to increase. To guarantee a pressure drop below 5 mmHg, which is considered as the threshold stenosis pressure difference clinically, we find that the residual stenosis degree must be 20% maximum.