Hemodynamic study in a real intracranial aneurysm: an in vitro and in silico approach

Mestrado de dupla diplomação com o Centro Federal de Educação Tecnológica Celso Suckow da Fonseca - Cefet/RJIntracranial aneurysm (IA) is a cerebrovascular disease with high rates of mortality and morbidity when it ruptures. It is known that changes in the intra-aneurysmal hemodynamic load play a significant factor in the development and rupture of IA. However, these factors are not fully understood. In this sense, the main objective of this work is to study the hemodynamic behavior during the blood analogues flow inside an AI and to determine its influence on the evolution of this pathology. To this end, experimental and numerical studies were carried out, using a real AI model obtained using computerized angiography. In the experimental approach, it was necessary, in the initial phase, to develop and manufacture biomodels from medical images of real aneurysms. Two techniques were used to manufacture the biomodels: rapid prototyping and gravity casting. The materials used to obtain the biomodels were of low cost. After manufacture, the biomodels were compared to each other for their transparency and final structure and proved to be suitable for testing flow visualizations. Numerical studies were performed with the aid of the Ansys Fluent software, using computational fluid dynamics (CFD), using the finite volume method. Subsequently, flow tests were performed experimentally and numerically using flow rates calculated from the velocity curve of a patient's doppler test. The experimental and numerical tests, in steady-state, made it possible to visualize the three-dimensional behavior of the flow inside the aneurysm, identifying the vortex zones created throughout the cardiac cycle. Correlating the results obtained in the two analyzes, it was possible to identify that the areas of vortexes are characterized by low speed and with increasing the fluid flow, the vortexes are positioned closer to the wall. These characteristics are associated with the rupture of an intracranial aneurysm. There was also a good qualitative correlation between numerical and experimental results.O aneurisma intracraniano (AI) é uma patologia cerebrovascular com altas taxas de mortalidade e morbidade quando se rompe. Sabe-se que alterações na carga hemodinâmica intra-aneurismática exerce um fator significativo no desenvolvimento e ruptura de AI, porém, esses fatores não estão totalmente compreendidos. Nesse sentido, o objetivo principal deste trabalho é o de estudar o comportamento hemodinâmico durante o escoamento de fluidos análogos do sangue no interior de um AI e determinar a sua influência na evolução da patologia. Para tal, foram realizados estudos experimentais e numéricos, utilizando um modelo de AI real obtido por meio de uma angiografia computadorizada. Na abordagem experimental foi necessário, na fase inicial, desenvolver e fabricar biomodelos a partir de imagens médicas de um aneurisma real. No fabrico dos biomodelos foram utilizadas duas técnicas: a prototipagem rápida e o vazamento por gravidade. Os materiais utilizados para a obtenção dos biomodelos foram de baixo custo. Após a fabricação, os biomodelos foram comparados entre si quanto à sua transparência e estrutura final e verificou-se serem adequados para testes de visualizações do fluxo. Os estudos numéricos foram realizados com recurso ao software Ansys Fluent, utilizando a dinâmica dos fluidos computacional (CFD), através do método dos volumes finitos. Posteriormente, foram realizados testes de escoamento experimentais e numéricos, utilizando caudais determinados a partir da curva de velocidades do ensaio doppler de um paciente. Os testes experimentais e numéricos, em regime permanente, possibilitaram a visualização do comportamento tridimensional do fluxo no interior do aneurisma, identificando as zonas de vórtices criadas ao longo do ciclo cardíaco. Correlacionando os resultados obtidos nas duas análises, foi possível identificar que as áreas de vórtices são caracterizadas por uma baixa velocidade e com o aumento do caudal os vórtices posicionam-se mais próximos da parede. Essas características apresentadas estão associadas com a ruptura de aneurisma intracraniano. Verificou-se, também, uma boa correlação qualitativa entre os resultados numéricos e experimentais

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation

Boundary condition assessment and geometrical accuracy enhancement for computational haemodynamics

Cardiovascular diseases cause over 47 % of all deaths in Europe each year. Computational fluid dynamics provides the research community with a unique opportunity to investigate cardiovascular diseases with the intent of enabling optimised, patient-specific medical therapies. Incorporating physiologically accurate geometries and boundary conditions into computational fluid dynamics simulations can be difficult tasks and are a concern for researchers. This thesis analyses the impact various inlet and outlet boundary conditions can have on the outcome of a simulation. It also presents a novel, semi-automated process that prepares accurate geometrical models for haemodynamic simulations. Firstly, rabbit and human aorta models were used to analyse the impacts of boundary conditions on haemodynamic metrics used for understanding cardiovascular disease pathology. Comparisons were made between traction free, Murray’s Law, three-element Windkessel, and Murray’s Law/in vivo data hybrid outlet boundary conditions. Steady-state, transient, fully-developed and plug-type inlet boundary conditions were also investigated. Results showed that when advanced models such as the three-element Windkessel are unavailable, the Murray’s Law based outlet returns the most physiologically accurate haemodynamics. Results also showed that prescribing a transient simulation and a fully-developed flow at the inlet are not required when the focus is only on the flow within the aorta and around the intercostal branches. Secondly, a sensitivity test was conducted on the simulation of Left Ventricular Assistive Device (LVAD) configurations. The effects of flow ratios between the LVAD and aortic root on haemodynamic metrics were quantified. The general irregular sensitivity of the subclavian and carotid arteries to flow ratios indicates that the perfusion and wall shear stress-based haemodynamic metrics within these arteries cannot be accurately predicted unless the flow ratios are incorporated into the preoperative planning of the optimal LVAD configuration. Finally, a semi-automated reconstruction process combining magnetic resonance angiography and optical coherence tomography data was developed. The process was successful in its ability to create an accurate geometry in a relatively short time. This forms the foundation on which more sophisticated methods can be developed

Trends in Cerebrovascular Surgery and Interventions

This is an open access proceeding book of 9th European-Japanese Cerebrovascular Congress at Milan 2018. Since many experts from Europe and Japan had very important and fruitful discussion on the management of Cerebrovascular diseases, the proceeding book is very attractive for the physician and scientists of the area

In-vitro analysis of haemodynamics in stented arteries.

Cardiovascular diseases (CVD) are the leading cause of death in the developed world. One of the most common management methods for CVD is through vascular implants such as stents to support arterial walls. However, determining the efficacy of stents can be difficult, particularly for high-risk stents, such as those used in the aorta. In-vitro modelling can provide safe insight into the haemodynamics changes within an artery due to specific stenting methods, without intrusive patient monitoring. The in-vitro studies presented in this thesis contribute to research on the haemodynamic changes within arteries using particle image velocimetry (PIV). In-vitro modelling can be used to investigate haemodynamics of arterial geometry and stent implants. However, in-vitro model fidelity is reliant on precise matching of in-vivo conditions. Flow distribution and wall shear stress depend on the Reynolds and Womersley numbers. This thesis reviewed currently published Reynolds and Womersley numbers for 14 major arteries in the human body. The results were presented both in a table and graphically for ease of understanding and future use. The results identified a paucity of information in smaller distal arteries compared to major arteries such as the aorta. Matching Reynolds and Womersley numbers for compliant in-vitro modelling may also be limited by model dimensional tolerances. A method for visualising the range of experimental conditions required for dynamic matching was developed and case studies for the ascending aorta and common carotid artery were presented. The assumed Sylgard 184 silicone would be used for phantom fabrication, and compared three working solutions: water/glycerine, water/glycerine/urea, and water/glycerine/sodium-iodide. To manufacture compliance matched silicone models of the ascending aorta and common carotid arteries, the models were scaled to 1.5x (ascending aorta) and 3x (common carotid) life scale, respectively. Modelling the ascending aorta with the comparatively high viscosity water/glycerine solution will lead to very high pump power demands. However, any of the working fluids considered could be dynamically matched with low pump demand for the common carotid model. The Frozen Elephant Trunk (FET) stent is a hybrid endovascular device that may be implemented in the event of an aneurysm or aortic dissection of the aortic arch or superior descending aorta. However, the FET stent is a high risk stent. In particular, the Type 1B endoleak can lead to intrasaccular flow due to an incomplete distal fit between the stent and artery during systole. Chapter 5 developed an in-vitro modelling technique to enable the investigation of the known failure. Recirculation zones and an asymmetric endoleak were identified distal to the surrogate stent graft. The endoleak developed at the peak of systole and was sustained until the onset of diastole. The endoleak geometry indicated a potential variation in the phantom artery wall thickness or stent alignment. Recirculation was identified on the posterior dorsal line during late systole which may induce an inflammatory response in an artery. The identification of the Type 1B endoleak proved that in-vitro modelling can be used to investigate complex compliance changes and wall motions. The kissing stent (KS) configuration is a low risk, stenting method often used to treat aorto-iliac occlusive disease (AIOD). However, long-term patency reduces by nearly 25% in the first five years potentially due to deleterious flow behaviour. The risk of harmful haemodynamics due to the KS configuration were investigated in-vitro. PIV experimentation identified peak proximal and distal velocity in-vitro was 0.71 m·s-1 and 1.90 m·s-1, respectively. A lumen wall collapse in the sagittal plane occurred during late systole to early diastole proximal the KS configuration. The collapse disturbed the flow proximal to the stented region producing potential recirculation zones and abnormal flow patterns. However, the systolic flow was as normal and undisturbed indicating the KS configuration is safe to use for repairing AIOD. The collapse had not been previously identified and would require further investigation. Thoracic extra-anatomic bypasses (EAB) are grafted stents that may be used to prophylactically revascularize supra-aortic arteries that may require blockage during thoracic endovascular aortic repair (TEVAR) methods. However, prophylactic use of EAB may introduce a risk of failure due to abnormally low or disrupted flow, known as competitive flow, within the bypasses. Competitive flow within the bypasses between supra-aortic arteries has not been captured previously. PIV was used to assess each model configuration for flow abnormalities and potential for flow competition. The investigation found potential for competitive flow in the bypasses when just the left subclavian artery (LSA), the left carotid artery (LCCA), or none of the arteries are blocked. In contrast, when the LSA and LCCA were both blocked, there was no evidence of competitive flow. Flow stagnated at the initiation of systole within the BC bypass in the 2 configurations with an unblocked LCCA, along with notable recirculation zones and reciprocating flow occurring throughout the rest of systolic flow. Flow stagnated in the CS bypass at early systole when only the LCCA was blocked. A large recirculation was identifiable in the CS bypass when just the LSA was blocked, particularly after peak systole. The potential of competitive flow indicated prophylactic used of EAB in the supra-aortic arteries may require location of proximal arteries to limit the number of pathways blood flow can take

Accelerated Simulation Methodologies for Computational Vascular Flow Modelling

Vascular flow modelling can improve our understanding of vascular pathologies and aid in developing safe and effective medical devices. Vascular flow models typically involve solving the nonlinear Navier-Stokes equations in complex anatomies and using physiological boundary conditions, often presenting a multi-physics and multi-scale computational problem to be solved. This leads to highly complex and expensive models that require excessive computational time. This review explores accelerated simulation methodologies, specifically focusing on computational vascular flow modelling. We review reduced order modelling (ROM) techniques like zero-/one-dimensional and modal decomposition-based ROMs and machine learning (ML) methods including ML-augmented ROMs, ML-based ROMs and physics-informed ML models. We discuss the applicability of each method to vascular flow acceleration and the effectiveness of the method in addressing domain-specific challenges. When available, we provide statistics on accuracy and speed-up factors for various applications related to vascular flow simulation acceleration. Our findings indicate that each type of model has strengths and limitations depending on the context. To accelerate real-world vascular flow problems, we propose future research on developing multi-scale acceleration methods capable of handling the significant geometric variability inherent to such problems.</p

Role of Computational Fluid Dynamics in the Analysis of Haemodynamic and Morphological Characteristics of Intracranial Aneurysms

Aneurysmal subarachnoid hemorrhage (SAH) carries a high morbidity and mortality. The current protocols used to treat the unruptured Intracranial Aneurysms (IAs) are inadequate underscoring the need of finding new descriptors. As demonstrated by the studies performed in this manuscript, haemodynamics plays an important role in the aetiopathogenesis of IAs. An evaluation of haemodynamic indices can provide a useful alternative to predict the behavior of an unruptured IA at an early stage. Studies performed by me demonstrate that Computational Fluid Dynamics (CFD) can be used successfully to predict haemodynamic indices where detailed in vivo measurement of haemodynamic flow variables is not possible owing to technical limitations. European Commission funded Project @neurIST was the first project of it’s kind that brought together a number of multidisciplinary professionals from 32 European institutions and made possible development of state-of-the-art tools for personalised risk assessment and treatment IAs using CFD. These tools have been constantly improved and amended in the light of feedback gathered from their controlled exposures conducted world over, as described in the manuscript. However, need of a well-designed Randomized Controlled Trial in this context cannot be overemphasized, before these tools can be accepted by clinicians and patients. In my study on the validation of different concepts used in CFD, I demonstrated that there is no added advantage of complex Womersley-flow-profile over the much simpler plug-flow profile. One of my studies on initiation and rupture of IAs showed that the haemodynamic patterns of IAs during these two phases are significantly different with values of supra-physiological Wall Shear Stress (WSS) being higher in initiation while lower in rupture phase. I also investigated the effects of pharmacological agents on the aetiopathogenesis of IAs and found that heparin induces significant derangements in the haemodynamics of both, pre-aneurysmal as well as ruptured IA. I propose that heparin (and its derivatives) can, on the one hand may facilitate the rupture of existing IAs, on the other hand they may suppress the formation of new IAs. I have also found significant differences in the results using patient-specific vs. Modeled Boundary Conditions and showed that the 1D circulation model adopted by @neurIST performs better than other approaches found in the literature. I also proposed a novel mechanism of increase in Blood Viscosity leading to high WSS as one of the important underlying mechanisms responsible for the increased incidence of IA formation in smokers and hypertensive patients. In my study on patients with pre-existing Coarctation of Aorta (CoA) and Intracranial Aneurysms, I demonstrated that the cerebral flow-rates in CoA patients were significantly higher when compared to average flow-rates in healthy population. It was also seen that the values and the area affected by supraphysiological WSS (>15Pa) were exponentially higher in patients with CoA indicating the possible role of increased haemodynamic WSS secondary to the increased flow-rates playing an important role in the pathogenesis and rupture of IAs in CoA patients

Multiscale Fluid-Structure Interaction Models Development and Applications to the 3D Elements of a Human Cardiovascular System

Cardiovascular diseases (CVD) are the number one cause of death of humans in the United States and worldwide. Accurate, non-invasive, and cheaper diagnosis methods have always been on demand as cardiovascular monitoring increase in prevalence. The primary causes of the various forms of these CVDs are atherosclerosis and aneurysms in the blood vessels. Current noninvasive methods (i.e., statistical/medical) permit fairly accurate detection of the disease once clinical symptoms are suggestive of the existence of hemodynamic disorders. Therefore, the recent surge of hemodynamics models facilitated the prediction of cardiovascular conditions. The hemodynamic modeling of a human circulatory system involves varying levels of complexity which must be accounted for and resolved. Pulse-wave propagation effects and high aspect-ratio segments of the vasculature are represented using a quasi-one-dimensional (1D), non-steady, averaged over the cross-section models. However, these reduced 1D models do not account for the blood flow patterns (recirculation zones), vessel wall shear stresses and quantification of repetitive mechanical stresses which helps to predict a vessel life. Even a whole three-dimensional (3D) modeling of the vasculature is computationally intensive and do not fit the timeline of practical use. Thus the intertwining of a quasi 1D global vasculature model with a specific/risk-prone 3D local vessel ones is imperative. This research forms part of a multiphysics project that aims to improve the detailed understanding of the hemodynamics by investigating a computational model of fluid-structure interaction (FSI) of in vivo blood flow. First idealized computational a 3D FSI artery model is configured and executed in ANSYS Workbench, forming an implicit coupling of the blood flow and vessel walls. Then the thesis focuses on an approach developed to employ commercial tools rather than in-house mathematical models in achieving multiscale simulations. A robust algorithm is constructed to combine stabilization techniques to simultaneously overcome the added-mass effect in 3D FSI simulation and mathematical difficulties such as the assignment of boundary conditions at the interface between the 3D-1D coupling. Applications can be of numerical examples evaluating the change of hemodynamic parameters and diagnosis of an abdominal aneurysm, deep vein thrombosis, and bifurcation areas