Coronary fractional flow reserve measurements of a stenosed side branch: a computational study investigating the influence of the bifurcation angle

Background Coronary hemodynamics and physiology specific for bifurcation lesions was not well understood. To investigate the influence of the bifurcation angle on the intracoronary hemodynamics of side branch (SB) lesions computational fluid dynamics simulations were performed. Methods A parametric model representing a left anterior descending—first diagonal coronary bifurcation lesion was created according to the literature. Diameters obeyed fractal branching laws. Proximal and distal main branch (DMB) stenoses were both set at 60 %. We varied the distal bifurcation angles (40°, 55°, and 70°), the flow splits to the DMB and SB (55 %:45 %, 65 %:35 %, and 75 %:25 %), and the SB stenoses (40, 60, and 80 %), resulting in 27 simulations. Fractional flow reserve, defined as the ratio between the mean distal stenosis and mean aortic pressure during maximal hyperemia, was calculated for the DMB and SB (FFRSB) for all simulations. Results The largest differences in FFRSB comparing the largest and smallest bifurcation angles were 0.02 (in cases with 40 % SB stenosis, irrespective of the assumed flow split) and 0.05 (in cases with 60 % SB stenosis, flow split 55 %:45 %). When the SB stenosis was 80 %, the difference in FFRSB between the largest and smallest bifurcation angle was 0.33 (flow split 55 %:45 %). By describing the ΔPSB−QSB relationship using a quadratic curve for cases with 80 % SB stenosis, we found that the curve was steeper (i.e. higher flow resistance) when bifurcation angle increases (ΔP = 0.451*Q + 0.010*Q 2 and ΔP = 0.687*Q + 0.017*Q 2 for 40° and 70° bifurcation angle, respectively). Our analyses revealed complex hemodynamics in all cases with evident counter-rotating helical flow structures. Larger bifurcation angles resulted in more pronounced helical flow structures (i.e. higher helicity intensity), when 60 or 80 % SB stenoses were present. A good correlation (R2 = 0.80) between the SB pressure drop and helicity intensity was also found. Conclusions Our analyses showed that, in bifurcation lesions with 60 % MB stenosis and 80 % SB stenosis, SB pressure drop is higher for larger bifurcation angles suggesting higher flow resistance (i.e. curves describing the ΔPSB−QSB relationship being steeper). When the SB stenosis is mild (40 %) or moderate (60 %), SB resistance is minimally influenced by the bifurcation angle, with differences not being clinically meaningful. Our findings also highlighted the complex interplay between anatomy, pressure drops, and blood flow helicity in bifurcations

Hemodynamics in the Stenosed Carotid Bifurcation with Plaque Ulceration

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in an ensemble of matched model vessel geometries determined that ulceration as small as 2 mm can generate significant disturbances in the downstream flow field in a moderately stenosed carotid artery, which are detectable using the DUS velocity-derived parameter turbulence intensity (TI) measured with a clinical system. Further experimental results showed that distal TI was significantly elevated (P \u3c 0.001) due to proximal plaque ulceration in the mild and moderately stenosed carotid bifurcation (30%, 50%, 60% diameter reduction), and also increased with stenosis severity. Pulsatile computational fluid dynamics (CFD) models, with simulated particle tracking, demonstrated enhanced flow disruption of the stenotic jet and slight elevations in path-dependent shear exposure parameters in a stenosed carotid bifurcation model with ulceration. In addition, CFD models were used to evaluate the DUS index TI using finite volume sampling

Coronary fractional flow reserve measurements of a stenosed side branch: A computational study investigating the influence of the bifurcation angle

Background: Coronary hemodynamics and physiology specific for bifurcation lesions was not well understood. To investigate the influence of the bifurcation angle on the intracoronary hemodynamics of side branch (SB) lesions computational fluid dynamics simulations were performed. Methods: A parametric model representing a left anterior descending-first diagonal coronary bifurcation lesion was created according to the literature. Diameters obeyed fractal branching laws. Proximal and distal main branch (DMB) stenoses were both set at 60%. We varied the distal bifurcation angles (40°, 55°, and 70°), the flow splits to the DMB and SB (55%:45%, 65%:35%, and 75%:25%), and the SB stenoses (40, 60, and 80%), resulting in 27 simulations. Fractional flow reserve, defined as the ratio between the mean distal stenosis and mean aortic pressure during maximal hyperemia, was calculated for the DMB and SB (FFRSB) for all simulations. Results: The largest differences in FFRSB comparing the largest and smallest bifurcation angles were 0.02 (in cases with 40% SB stenosis, irrespective of the assumed flow split) and 0.05 (in cases with 60% SB stenosis, flow split 55%:45%). When the SB stenosis was 80%, the difference in FFRSB between the largest and smallest bifurcation angle was 0.33 (flow split 55%:45%). By describing the PSB-QSB relationship using a quadratic curve for cases with 80% SB stenosis, we found that the curve was steeper (i.e. higher flow resistance) when bifurcation angle increases (P=0.451*Q+0.010*Q 2 and P=0.687*Q+0.017*Q 2 for 40° and 70° bifurcation angle, respectively). Our analyses revealed complex hemodynamics in all cases with evident counter-rotating helical flow structures. Larger bifurcation angles resulted in more pronounced helical flow structures (i.e. higher helicity intensity), when 60 or 80% SB stenoses were present. A good correlation (R2=0.80) between the SB pressure drop and helicity intensity was also found. Conclusions: Our analyses showed that, in bifurcation lesions with 60% MB stenosis and 80% SB stenosis, SB pressure drop is higher for larger bifurcation angles suggesting higher flow resistance (i.e. curves describing the PSB-QSB relationship being steeper). When the SB stenosis is mild (40%) or moderate (60%), SB resistance is minimally influenced by the bifurcation angle, with differences not being clinically meaningful. Our findings also highlighted the complex interplay between anatomy, pressure drops, and blood flow helicity in bifurcations

Developing DNS Tools to Study Channel Flow Over Realistic Plaque Morphology

In a normal coronary artery, the flow is laminar and the velocity is parabolic in nature. Over time, plaques deposit along the artery wall, narrowing the artery and creating an obstruction, a stenosis. As the stenosis grows, the characteristics of the flow change and transition occurs, resulting in turbulent flow distal to the stenosis. To date, direct numerical simulation (DNS) of turbulent flow has been performed in a number of studies to understand how stenosis modifies flow dynamics. However, the effect of the actual shape and size of the obstruction has been disregarded in these DNS studies. An ideal approach is to obtain geometrical information of the stenotic channel using medical imaging methods such as IVUS (Intravascular Ultrasound) and couple them with numerical solvers that simulate the flow in the stenotic channel. The purpose of the present thesis is to demonstrate the feasibility of coupling the IVUS geometry with DNS solver. This preliminary research will provide the necessary tools to achieve the long term goal of developing a framework for the morphological features of the stenosis on the flow modifications in a diseased coronary artery. In the present study, the geometrical information of the stenotic plaque has been provided by the medical imaging team at the Cleveland Clinic Foundation for 42 patients who underwent IVUS. The integration of the geometrical information of the stenotic plaque with the DNS was performed in 3 stages 1) fuzzy logic scheme was used to group the 42 patients into categories, 2) meshing algorithm was generated to interface with the DNS solver, and 3) the existing DNS for channel flow was modified to account for inhomogeneity in the streamwise direction. A plaque classification system was developed using statistical k-means clustering with fuzzy logic. Four distinct morphological categories were found in plaque measurements obtained from the 42 patients. Patients were then assigned a degree of membership to each category based on a fuzzy evaluation system. Flow simulations showed distinct turbulent flow characteristics when comparing the four categories, and similar characteristics within each category. An existing DNS solver that used the fourth-order velocity second-order vorticity formulation of the Navier-Stokes equations was modified to account for inhomogeneity in the streamwise direction. A multigrid method was implemented, using Green\u27s method to compute unknown boundary conditions at the walls in using an influence matrix approach. The inflow is the free stream laminar flow condition; the outflow is computed explicitly with a buffer domain and by parabolizing the Navier Stokes equation. The transitional flow solver was tested using blowing and suction disturbances at the wall to generate the Tollmien-Schlichting waves predicted by linear stability theory. The toolset developed as a part of this thesis demonstrates the feasibility of integrating realistic geometry with DNS. This tool can be used for patient-specific simulation of stenotic flow in coronary and carotid arteries. Additionally, within the field of fluid dynamics, this framework will contribute to the understanding of transition and turbulence in stenotic flows

Investigation of Flow Disturbances and Multi-Directional Wall Shear Stress in the Stenosed Carotid Artery Bifurcation Using Particle Image Velocimetry

Hemodynamics and shear forces are associated with pathological changes in the vascular wall and its function, resulting in the focal development of atherosclerosis. Flow complexities that develop in the presence of established plaques create environments favourable to thrombosis formation and potentially plaque rupture leading to stroke. The carotid artery bifurcation is a common site of atherosclerosis development. Recently, the multi-directional nature of shear stress acting on the endothelial layer has been highlighted as a risk factor for atherogenesis, emphasizing the need for accurate measurements of shear stress magnitude as well direction. In the absence of comprehensive patient specific datasets numerical simulations of hemodynamics are limited by modeling assumptions. The objective of this thesis was to investigate the relative contributions of various factors - including geometry, rheology, pulsatility, and compliance – towards the development of disturbed flow and multi-directional wall shear stress (WSS) parameters related to the development of atherosclerosis An experimental stereoscopic particle image velocimetry (PIV) system was used to measure instantaneous full-field velocity in idealized asymmetrically stenosed carotid artery bifurcation models, enabling the extraction of bulk flow features and turbulence intensity (TI). The velocity data was combined with wall location information segmented from micro computed tomography (CT) to obtain phase-averaged maps of WSS magnitude and direction. A comparison between Newtonian and non-Newtonian blood-analogue fluids demonstrated that the conventional Newtonian viscosity assumption underestimates WSS magnitude while overestimating TI. Studies incorporating varying waveform pulsatility demonstrated that the levels of TI and oscillatory shear index (OSI) depend on the waveform amplitude in addition to the degree of vessel constriction. Local compliance resulted in a dampening of disturbed flow due to volumetric capacity of the upstream vessel, however wall tracking had a negligible effect on WSS prediction. While the degree of stenosis severity was found to have a dominant effect on local hemodynamics, comparable relative differences in metrics of flow and WSS disturbances were found due to viscosity model, waveform pulsatility and local vessel compliance

Image-Based Quantification Workflow for Coronary Morphology: A Tool for Use in Next-Generation Bifurcation Stent Design

Coronary artery disease (CAD) occurs in ~200,000 bifurcation lesions annually. Treatment of CAD near bends and bifurcations is challenging and a preferred strategy for bifurcation lesions has yet to be established. However, a favorable treatment option may be elucidated by a more thorough understanding of vessel morphology as well as local hemodynamic alterations caused by current stenting approaches. Computational modeling of human arteries offers an attractive way to investigate the relationships between geometry, hemodynamics and vascular disease. Recent developments also make it possible to perform analysis on realistic geometries acquired noninvasively. The objective of this work was twofold. The first aim was to build on previous work in this area by quantifying hemodynamic alterations introduced by treatment of an idealized coronary bifurcation using several approaches that involve multiple stents. Each model was created using combined computer aided design techniques and computational fluid dynamics (CFD) analysis tools. Resting and hyperemic blood flow conditions were also studied to determine the severity of local hemodynamic alterations and for comparison to previous results. Indices of time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) were quantified for four idealized computational models. The luminal surface exposed to low TAWSS was similar in the main vessel (MV) for all models. Greatest differences were noted between un-stented versus stented side branch vessels (ex. rest: 1% vs. 35%). Sites of elevated OSI (\u3e0.1) were minimal, except under hyperemia conditions in the MV (10% surface area). Flow disturbances were quantified for each provisional technique used, illustrating how stents protruding in main vessels impact flow profiles. Stents without kissing balloon dilation had abnormal flow disturbances, but showed decreased percentage of area exposed to areas of low WSS. A second aim of this work was to design a robust and unbiased method to quantify vessel morphology and representative trends for three bifurcation sites prone to CAD. Computational models of these sites were generated using computed topography images from 22 patients. Models were used to query geometric characteristics from each bifurcation site including area, length, eccentricity, taper, curvature and bifurcation angles. Post-processing was accomplished by a combination of statistical methods and clustering analysis. Vessel length and area were significantly different within and between bifurcation sites. The left main coronary artery (LCA) bifurcation was significantly different from its two daughter bifurcations (left anterior descending and left circumflex arteries). Specifically vessel area and length were significantly different both between and within bifurcation sites. The daughter bifurcation sites were similar for all characteristics. Vessel area and length proved to be the most useful properties for identifying trends within a particular bifurcation site. The outcome of this work provides a workflow for characterizing coronary bifurcations and a strong foundation for elucidating common parameters from normal, healthy coronary arteries. Collectively these results from idealized and patient-specific coronary bifurcations offer additional insight into the impact of current treatment approaches and characteristics associated with current stenting techniques. Flow disturbances and local hemodynamic changes have been quantified for provisional techniques currently used. These methods and results may ultimately be useful in the design of next-generation bifurcation stents

Development of a haemodynamic model for improving clinical treatment of vascular disease

Atherosclerosis is a chronic artery disease that leads to heart attack and stroke; affecting millions of people worldwide. It tends to develop in locations where disturbed flow patterns occur, such as the carotid artery, left coronary artery and abdominal aorta. The causative factors leading to atherosclerosis still remain relatively poorly understood. Conventional diagnosis of arterial disease relies on a combination of history, clinical examination and clinical imaging derived from CT, MRI, etc. To address some of the important factors related to arterial haemodynamics, Computational Fluid Dynamics (CFD) studies were performed on in-vitro models using physiologically relevant conditions. The flow disturbances in terms of wall shear stress and oscillatory shear index were examined. Based on the current research, new insights from a haemodynamics point of view were provided. This study aims to enrich and complement the current arterial disease research, and contribute to promoting the diagnosis accuracy and efficiency in the future. This thesis is composed by six parts of work. Firstly, a comprehensive literature review was performed to identify the research gaps between the current relevant numerical studies with real clinical application. Secondly, the proposed CFD model was validated with published experimental work using particle image velocimetry (PIV) approach. A downstream impedance model was then developed to improve numerical simulation accuracy for image-based artery bifurcations. The numerical results were correlated with a clinical indicator to provide relevant findings for treating physicians. Lastly, a fully fluid-structure interaction (FSI) modelling over left coronary artery models with different bifurcation angles was conducted. The relationship between the mechanical force (first principle stress), the hemodynamic force (wall shear stress), and the bifurcation angle was analysed. In summary, this thesis developed a new downstream artery impedance model, and converted the numerical simulation results into clinical indicators, which can improve the current simulation accuracy and contribute more meaningful results to assist a better clinical diagnosis. A FSI simulation was performed over left coronary artery bifurcation models. The bifurcation angle influence on atherosclerosis progression was addressed. The left circumflex side bifurcation shoulder was found to be more vulnerable in developing atherosclerosis

Numerical and experimental haemodynamic studies of stenotic coronary arteries

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Biomateriais, Reabilitação e Biomecânica)Cardiovascular diseases remain the most frequent cause of mortality worldwide and constitute a major healthcare challenge. Among them, coronary artery disease causes nearly half of the deaths and, thus it is of great interest to better understand its development and effects. This disease is characterized by the narrowing (stenosis) of coronary arteries due to plaque deposition at the arterial wall, a pathological process known as atherosclerosis. This dissertation aimed to study the hemodynamics in stenotic coronary arteries, in order to get a deeper understanding of the effects of this pathology on the blood flow behavior. For this purpose, both numerical and experimental studies were conducted using idealized models. The numerical research was carried out using Ansys® software by means of computational fluid dynamics which applies the finite volume method. The experimental approach was performed using a high-speed video microscopy system, to visualize and investigate the blood flow in the in vitro stenotic biomodels. Initially, the influence of roughness in flow visualizations was studied, and the best biomodel was the one printed with the lowest resolution having been, therefore, the selected to perform the hemodynamic studies. To compare those results with numerical data, the flow was set to be laminar and stationary and the fluid was considered Newtonian. In general, the numerical and experimental results were in good agreement, not only in the prediction of the flow behavior with the appearance of recirculation zones in the post-stenotic section, but also in the velocity profiles. In a posterior phase, a pulsatile inlet condition was applied to compare the use of laminar and turbulent assumptions, using the SST k- model. The results obtained allowed to conclude that the second one is more appropriate to simulate the blood flow. Subsequently, the main differences in hemodynamics were examined considering blood as a Newtonian and non-Newtonian fluid (Carreau model). For these models, the differences were very slight in terms of velocity fields, but more significant for the wall shear stress measurements, with the Newtonian model predicting lower values. The remaining simulations were performed using the Carreau model and a transient inlet flow, having observed an increase in the velocities and wall shear stress values with the degree of stenosis, which is associated with a greater risk of thrombosis.As doenças cardiovasculares continuam a ser a causa mais frequente de mortalidade em todo o mundo e constituem um grande desafio para a saúde. Entre elas, a doença arterial coronariana causa quase metade das mortes e, portanto, é de enorme interesse entender melhor o seu desenvolvimento e efeitos. Esta doença é caracterizada pelo estreitamento (estenose) das artérias coronárias devido à deposição de placas na parede arterial, um processo patológico conhecido como aterosclerose. Esta dissertação teve como objetivo estudar a hemodinâmica nas artérias coronárias estenóticas, a fim de obter uma compreensão mais profunda dos efeitos desta patologia no comportamento do fluxo sanguíneo. Para tal, foram realizados estudos numéricos e experimentais, utilizando modelos idealizados. A investigação numérica foi realizada no software Ansys®, através da dinâmica computacional dos fluidos, que aplica o método dos volumes finitos. A abordagem experimental foi realizada utilizando um sistema de microscopia de vídeo de alta velocidade, para visualizar e investigar o fluxo sanguíneo nos biomodelos estenóticos in vitro. Inicialmente, estudou-se a influência da rugosidade nas visualizações do escoamento, e o melhor biomodelo foi o impresso com menor resolução tendo sido, portanto, o selecionado para a realização dos estudos hemodinâmicos. Para comparar esses resultados com dados numéricos, o escoamento foi definido como laminar e estacionário e o fluído foi considerado Newtoniano. Em geral, os resultados numéricos e experimentais foram concordantes, não só na previsão do comportamento do fluxo com aparecimento de zonas de recirculação na zona pós-estenótica, mas também nos perfis de velocidade. Numa fase posterior, foi aplicada uma condição de entrada pulsátil para comparar o uso de simulações de natureza laminar e turbulenta, usando o modelo SST k-. Os resultados obtidos permitiram concluir que a segunda é mais apropriado para simular o fluxo sanguíneo. Posteriormente, foram examinadas as principais diferenças hemodinâmicas, considerando o sangue como fluído Newtoniano e não-Newtoniano (modelo de Carreau). Para estes modelos, as diferenças foram muito pequenas nos perfis de velocidade, mas mais significativas nas tensões de corte na parede medidas, com o modelo Newtoniano a prever valores mais baixos. As restantes simulações foram realizadas usando o modelo de Carreau e um escoamento de entrada transiente, tendo-se observado um aumento dos valores das velocidades e da tensão de corte na parede com o grau de estenose, o que está associado a um maior risco de trombose