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The assessment of local blood flow patterns in patients with peripheral arterial disease is clinically relevant, since these patterns are related to atherosclerotic disease progression and loss of patency in stents placed in peripheral arteries, through mechanisms such as recirculating flow and low wall shear stress (WSS). However, imaging of vascular flow in these patients is technically challenging due to the often complex flow patterns that occur near atherosclerotic lesions. While several flow quantification techniques have been developed that could improve the outcomes of vascular interventions, accurate 2D or 3D blood flow quantification is not yet used in clinical practice. This article provides an overview of several important topics that concern the quantification of blood flow in patients with peripheral arterial disease. The hemodynamic mechanisms involved in the development of atherosclerosis and the current clinical practice in the diagnosis of this disease are discussed, showing the unmet need for improved and validated flow quantification techniques in daily clinical practice. This discussion is followed by a showcase of state-of-the-art blood flow quantification techniques and how these could be used before, during and after treatment of stenotic lesions to improve clinical outcomes. These techniques include novel ultrasound-based methods, Phase-Contrast Magnetic Resonance Imaging (PC-MRI) and Computational Fluid Dynamics (CFD). The last section discusses future perspectives, with advanced (hybrid) imaging techniques and artificial intelligence, including the implementation of these techniques in clinical practice.
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Doença Arterial Periférica , Inteligência Artificial , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Estresse MecânicoRESUMO
Ultrasound contrast agents have been used as vascular reporters for the past 40 years. The ability to enhance vascular features in ultrasound images with engineered lipid-shelled microbubbles has enabled break-throughs such as the detection of tissue perfusion or super-resolution imaging of the microvasculature. However, advances in the field of contrast-enhanced ultra-sound are hindered by experimental variables that are difficult to control in a laboratory setting, such as complex vascular geometries, the lack of ground truth, and tissue nonlinearities. In addition, the demand for large datasets to train deep learning-based computational ultrasound imaging methods calls for the development of a simulation tool that can reproduce the physics of ultrasound wave interactions with tissues and microbubbles. Here, we introduce a physically realistic contrast-enhanced ultrasound simulator (PROTEUS) consisting of four inter-connected modules that account for blood flow dynamics in segmented vascular geometries, intravascular microbubble trajectories, ultrasound wave propagation, and nonlinear microbubble scattering. The first part of this study describes numerical methods that enabled this development. We demonstrate that PROTEUS can generate contrast-enhanced radiofrequency data in various vascular architectures across the range of medical ultrasound frequencies. PROTEUS offers a customizable framework to explore novel ideas in the field of contrast-enhanced ultrasound imaging. It is released as an open-source tool for the scientific community.
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Groundwater monitoring to measure a variety of indicator parameters including dissolved gas concentrations, total dissolved gas pressure (TDGP), and redox indicators is commonly used to evaluate the impacts of gas migration (GM) from energy development in shallow aquifer systems. However, these parameters can be challenging to interpret due to complex free-phase gas source architecture, multicomponent partitioning, and biogeochemical reactions. A series of numerical simulations using a gas flow model and a reactive transport model were conducted to delineate the anticipated evolution of indicator parameters following GM in an aquifer under a variety of physical and biogeochemical conditions. The simulations illustrate how multicomponent mass transfer processes and biogeochemical reactions create unexpected spatial and temporal variations in several analytes. The results indicate that care must be taken when interpreting measured indicator parameters including dissolved hydrocarbon concentrations and TDGP, as the presence of dissolved gases in background groundwater and biogeochemical processes can cause potentially misleading conclusions about the impact of GM. Based on the consideration of multicomponent gas partitioning in this study, it is suggested that dissolved background gases such as N2 and Ar can provide valuable insights on the presence, longevity and fate of free-phase natural gas in aquifer systems. Overall, these results contribute to developing a better understanding of indicators for GM in groundwater, which will aid the planning of future monitoring networks and subsequent data interpretation.
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There is a considerable interest in understanding transient human upper airway aerodynamics, especially in view of assessing the effects of various ventilation therapies. Experimental analyses in a patient-specific manner pose challenges as the upper airway consists of a narrow confined region with complex anatomy. Pressure measurements are feasible, but, for example, PIV experiments require special measures to accommodate for the light refraction by the model. Computational fluid dynamics can bridge the gap between limited experimental data and detailed flow features. This work aims to validate the use of combined lattice Boltzmann method and a large eddy scale model for simulating respiration, and to identify clinical features of the flow and show the clinical potential of the method. Airflow was computationally analyzed during a realistic, transient, breathing profile in an upper airway geometry ranging from nose to trachea, and the resulting pressure calculations were compared against in vitro experiments. Simulations were conducted on meshes containing about 1 billion cells to ensure accuracy and to capture intrinsic flow features. Airway pressures obtained from simulations and in vitro experiments are in good agreement both during inhalation and exhalation. High velocity pharyngeal and laryngeal jets and recirculation in the region of the olfactory cleft are observed. Graphical Abstract The Lattice-Boltzmann Method combined with Large Eddy Simulations was used to compute the aerodynamics in a human upper airway geometry. The left side of this graphical abstract shows the velocity and vorticity (middle figure in bottom row, and right figure of the right bottom figure) profiles at peak exhalation. The simulations were validated against experiments on a 3D-print of the geometry (shown in the top figures on the right hand side). The pressure drop (right bottom corner) shows a good agreement between experiments and simulations.
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Laringe , Traqueia , Humanos , Simulação por Computador , Nariz , Respiração , Cavidade Nasal , Metodologias ComputacionaisRESUMO
Fibrotic tumors, such as pancreatic ductal adenocarcinoma (PDAC), are characterized for high desmoplastic reaction, which results in high intra-tumoral solid stress leading to the compression of blood vessels. These microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of therapeutics. Currently, there is a lack of relevant in vitro models capable of replicating these mechanical characteristics and to test anti-desmoplastic compounds. Here, a multi-layered vascularized 3D PDAC model consisting of primary human pancreatic stellate cells (PSCs) embedded in collagen/fibrinogen (Col/Fib), mimicking tumor tissue within adjunct healthy tissue, is presented to study the fibrosis-induced compression of vasculature in PDAC. It is demonstrated how the mechanical and biological stimulation induce PSC activation, extracellular matrix production and eventually vessel compression. The clinical relevance is confirmed by correlating with patient transcriptomic data. Furthermore, the effects of gradual vessel compression on the fluid dynamics occurring within the channel is evaluated in silico. Finally, it is demonstrated how cancer-associated fibroblast (CAF)-modulatory therapeutics can inhibit the cell-mediated compression of blood vessels in PDAC in vitro, in silico and in vivo. It is envisioned that this 3D model is used to improve the understanding of mechanical characteristics in tumors and for evaluating novel anti-desmoplastic therapeutics.
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Many complications in physiology are associated with a deviation in flow in arteries due to a stenosis. The presence of stenosis may transition the flow to weak turbulence. The degree of stenosis as well as its configuration whether symmetric or non-symmetric to the parent artery influences whether the flow would stay laminar or transition to turbulence. Plenty of research efforts focus on investigating the role of varying degrees of stenosis in the onset of turbulence under steady and pulsatile flow conditions. None of the studies, however, have focused on investigating this under oscillatory flow conditions as flow reversal is a major occurrence in a number of physiologic flows, and is of particular relevance in cerebrospinal fluid flow research. Following up on the previous work in which a [Formula: see text] stenosis was studied, this contribution is a detailed investigation of the role of degrees of stenosis on transition in an oscillatory flow. A cylindrical pipe with [Formula: see text], [Formula: see text] and [Formula: see text] reductions in area in axisymmetric and eccentric configurations is studied for transition with 3 different pulsation frequencies of a purely oscillatory flow. Cycle averaged Reynolds numbers between 1800 and 2100 in steps of 100 are studied for each configuration resulting in 72 simulations each conducted on 76,800 CPU cores of a modern supercomputer. It is found that a higher degree of stenosis and eccentricity causes earlier transition to turbulence in oscillatory flow. The results further demonstrate that a higher frequency of oscillation results in larger hydrodynamic instability in the flow, which is more prominent in smaller degrees of stenosis.
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Modelos Cardiovasculares , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Constrição Patológica , Humanos , Fluxo Pulsátil/fisiologiaRESUMO
The Cerebral Aneurysm Detection and Analysis (CADA) challenge was organized to support the development and benchmarking of algorithms for detecting, analyzing, and risk assessment of cerebral aneurysms in X-ray rotational angiography (3DRA) images. 109 anonymized 3DRA datasets were provided for training, and 22 additional datasets were used to test the algorithmic solutions. Cerebral aneurysm detection was assessed using the F2 score based on recall and precision, and the fit of the delivered bounding box was assessed using the distance to the aneurysm. The segmentation quality was measured using the Jaccard index and a combination of different surface distance measures. Systematic errors were analyzed using volume correlation and bias. Rupture risk assessment was evaluated using the F2 score. 158 participants from 22 countries registered for the CADA challenge. The U-Net-based detection solutions presented by the community show similar accuracy compared to experts (F2 score 0.92), with a small number of missed aneurysms with diameters smaller than 3.5 mm. In addition, the delineation of these structures, based on U-Net variations, is excellent, with a Jaccard score of 0.92. The rupture risk estimation methods achieved an F2 score of 0.71. The performance of the detection and segmentation solutions is equivalent to that of human experts. The best results are obtained in rupture risk estimation by combining different image-based, morphological, and computational fluid dynamic parameters using machine learning methods. Furthermore, we evaluated the best methods pipeline, from detecting and delineating the vessel dilations to estimating the risk of rupture. The chain of these methods achieves an F2-score of 0.70, which is comparable to applying the risk prediction to the ground-truth delineation (0.71).
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Aneurisma Intracraniano , Algoritmos , Angiografia Cerebral/métodos , Humanos , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Raios XRESUMO
BACKGROUND: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. METHODS: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive - C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. RESULTS: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, high D-Dimer, and high hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). CONCLUSION: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, high D-dimer, and high hs-CRP were significantly associated with poor outcomes.
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COVID-19 , Coagulação Sanguínea , Estudos Transversais , Humanos , SARS-CoV-2 , Centros de Atenção TerciáriaRESUMO
Onset of flow transition in a sinusoidally oscillating flow through a rigid, constant area circular pipe with a smooth sinusoidal obstruction in the center of the pipe is studied by performing direct numerical simulations, with resolutions close to the Kolmogorov microscales. The studied pipe is stenosed in the center with a 75% reduction in area in two distinct configurations-one that is symmetric to the axis of the parent pipe and the other that is offset by 0.05 diameters to introduce an eccentricity, which disturbs the flow thereby triggering the onset of flow transition. The critical Reynolds number at which the flow transitions to turbulence for a zero-mean oscillatory flow through a stenosis is shown to be nearly tripled in comparison with studies of pulsating unidirectional flow through the same stenosis. The onset of transition is further explored with three different flow pulsation frequencies resulting in a total of 90 simulations conducted on a supercomputer. It is found that the critical Reynolds number at which the oscillatory flow transitions is not affected by the pulsation frequencies. The locations of flow breakdown and re-stabilization post-stenosis are, however, respectively shifted closer to the stenosis throat with increasing pulsation frequencies. The results show that oscillatory physiological flows, while more stable, exhibit fluctuations due to geometric complexity and have implications in studies of dispersion and solute transport in the cerebrospinal fluid flow and understanding of pathological conditions.
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Reologia , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Constrição Patológica , Análise Numérica Assistida por Computador , PressãoRESUMO
Flows through medical devices as well as in anatomical vessels despite being at moderate Reynolds number may exhibit transitional or even turbulent character. In order to validate numerical methods and codes used for biomedical flow computations, the US Food and Drug Administration (FDA) established an experimental benchmark, which was a pipe with gradual contraction and sudden expansion representing a nozzle. The experimental results for various Reynolds numbers ranging from 500 to 6500 were publicly released. Previous and recent computational investigations of flow in the FDA nozzle found limitations in various CFD approaches and some even questioned the adequacy of the benchmark itself. This communication reports the results of a lattice Boltzmann method (LBM) - based direct numerical simulation (DNS) approach applied to the FDA nozzle benchmark for transitional cases of Reynolds numbers 2000 and 3500. The goal is to evaluate if a simple off the shelf LBM would predict the experimental results without the use of complex models or synthetic turbulence at the inflow. LBM computations with various spatial and temporal resolutions are performed-in the extremities of 45 million to 2.88 billion lattice cells-executed respectively on 32 CPU cores of a desktop to more than 300,000 cores of a modern supercomputer to explore and characterize miniscule flow details and quantify Kolmogorov scales. The LBM simulations transition to turbulence at a Reynolds number 2000 like the FDA's experiments and acceptable agreement in jet breakdown locations, average velocity, shear stress, and pressure is found for both the Reynolds numbers. Graphical Abstract A bisecting plane showing the FDA nozzle and vorticity magnitude at t = 10 s for throat Reynolds numbers of 2000 and 3500.
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Benchmarking/métodos , Simulação por Computador , Equipamentos e Provisões , Estados Unidos , United States Food and Drug AdministrationRESUMO
PURPOSE: Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline. METHODS: 3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods, boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters. RESULTS: A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability. CONCLUSIONS: Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters.
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Angiografia Cerebral/métodos , Circulação Cerebrovascular , Hemodinâmica , Aneurisma Intracraniano/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Velocidade do Fluxo Sanguíneo , Humanos , Imageamento Tridimensional , Aneurisma Intracraniano/fisiopatologia , Artéria Cerebral Média/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Estresse MecânicoRESUMO
Obstruction to the cerebrospinal fluid (CSF) outflow caused by the herniation of cerebellar tonsils as a result of Chiari malformation type I leads to altered CSF hydrodynamics. This contribution explores the minutest characteristics of the CSF hydrodynamics in cervical subarachnoid space (SAS) of a healthy subject and 2 Chiari patients by performing highly resolved direct numerical simulation. The lattice Boltzmann method is used for the simulations because of its scalability on modern supercomputers that allow us to simulate up to approximately 109 cells while resolving the Kolmogorov microscales. The results depict that whereas the complex CSF flow remains largely laminar in the SAS of a healthy subject, constriction of the cranio-vertebral junction in Chiari I patients causes manifold fluctuations in the hydrodynamics of the CSF. These fluctuations resemble a flow that is in a transitional regime rather than laminar or fully developed turbulence. The fluctuations confine near the cranio-vertebral junction and are triggered due to the tonsillar herniation, which perturbs the flow as a result of altered anatomy of the SAS.
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Malformação de Arnold-Chiari/líquido cefalorraquidiano , Malformação de Arnold-Chiari/patologia , Líquido Cefalorraquidiano , Hidrodinâmica , Adulto , Malformação de Arnold-Chiari/fisiopatologia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
PURPOSE: Blood flow in intracranial aneurysms has, until recently, been considered to be disturbed but still laminar. Recent high resolution computational studies have demonstrated, in some situations, however, that the flow may exhibit high frequency fluctuations that resemble weakly turbulent or transitional flow. Due to numerous assumptions required for simplification in computational fluid dynamics (CFD) studies, the occurrence of these events, in vivo, remains unsettled. The detection of these fluctuations in aneurysmal blood flow, i.e., hemodynamics by CFD, poses additional challenges as such phenomena cannot be captured in clinical data acquisition with magnetic resonance (MR) due to inadequate temporal and spatial resolutions. The authors' purpose was to address this issue by comparing results from highly resolved simulations, conventional resolution laminar simulations, and MR measurements, identify the differences, and identify their causes. METHODS: Two aneurysms in the basilar artery, one with disturbed yet laminar flow and the other with transitional flow, were chosen. One set of highly resolved direct numerical simulations using the lattice Boltzmann method (LBM) and another with adequate resolutions under laminar flow assumption were conducted using a commercially available ANSYS Fluent solver. The velocity fields obtained from simulation results were qualitatively and statistically compared against each other and with MR acquisition. RESULTS: Results from LBM, ANSYS Fluent, and MR agree well qualitatively and quantitatively for one of the aneurysms with laminar flow in which fluctuations were <80 Hz. The comparisons for the second aneurysm with high fluctuations of > â¼ 600 Hz showed vivid differences between LBM, ANSYS Fluent, and magnetic resonance imaging. After ensemble averaging and down-sampling to coarser space and time scales, these differences became minimal. CONCLUSIONS: A combination of MR derived data and CFD can be helpful in estimating the hemodynamic environment of intracranial aneurysms. Adequately resolved CFD would suffice gross assessment of hemodynamics, potentially in a clinical setting, and highly resolved CFD could be helpful in a detailed and retrospective understanding of the physiological mechanisms.