RESUMEN
Many scientific reports document that asymptomatic and presymptomatic individuals contribute to the spread of COVID-19, probably during conversations in social interactions. Droplet emission occurs during speech, yet few studies document the flow to provide the transport mechanism. This lack of understanding prevents informed public health guidance for risk reduction and mitigation strategies, e.g., the "6-foot rule." Here we analyze flows during breathing and speaking, including phonetic features, using orders-of-magnitude estimates, numerical simulations, and laboratory experiments. We document the spatiotemporal structure of the expelled airflow. Phonetic characteristics of plosive sounds like "P" lead to enhanced directed transport, including jet-like flows that entrain the surrounding air. We highlight three distinct temporal scaling laws for the transport distance of exhaled material including 1) transport over a short distance (<0.5 m) in a fraction of a second, with large angular variations due to the complexity of speech; 2) a longer distance, â¼1 m, where directed transport is driven by individual vortical puffs corresponding to plosive sounds; and 3) a distance out to about 2 m, or even farther, where sequential plosives in a sentence, corresponding effectively to a train of puffs, create conical, jet-like flows. The latter dictates the long-time transport in a conversation. We believe that this work will inform thinking about the role of ventilation, aerosol transport in disease transmission for humans and other animals, and yield a better understanding of linguistic aerodynamics, i.e., aerophonetics.
Asunto(s)
Infecciones Asintomáticas , Betacoronavirus/fisiología , Infecciones por Coronavirus/transmisión , Neumonía Viral/transmisión , Habla/fisiología , Aerosoles , Movimientos del Aire , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Humanos , Modelos Teóricos , Pandemias/prevención & control , Fonética , Neumonía Viral/prevención & control , Neumonía Viral/virología , Respiración , SARS-CoV-2 , VentilaciónRESUMEN
PURPOSE: To evaluate hemodynamic markers obtained by accelerated GRAPPA (R = 2, 3, 4) and compressed sensing (R = 7.6) 4D flow MRI sequences under complex flow conditions. METHODS: The accelerated 4D flow MRI scans were performed on a pulsatile flow phantom, along with a nonaccelerated fully sampled k-space acquisition. Computational fluid dynamics simulations based on the experimentally measured flow fields were conducted for additional comparison. Voxel-wise comparisons (Bland-Altman analysis, L 2 $$ {L}_2 $$ -norm metric), as well as nonderived quantities (velocity profiles, flow rates, and peak velocities), were used to compare the velocity fields obtained from the different modalities. RESULTS: 4D flow acquisitions and computational fluid dynamics depicted similar hemodynamic patterns. Voxel-wise comparisons between the MRI scans highlighted larger discrepancies at the voxels located near the phantom's boundary walls. A trend for all MR scans to overestimate velocity profiles and peak velocities as compared to computational fluid dynamics was noticed in regions associated with high velocity or acceleration. However, good agreement for the flow rates was observed, and eddy-current correction appeared essential for consistency of the flow rates measurements with respect to the principle of mass conservation. CONCLUSION: GRAPPA (R = 2, 3) and highly accelerated compressed sensing showed good agreement with the fully sampled acquisition. Yet, all 4D flow MRI scans were hampered by artifacts inherent to the phase-contrast acquisition procedure. Computational fluid dynamics simulations are an interesting tool to assess these differences but are sensitive to modeling parameters.
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Hidrodinámica , Imagenología Tridimensional , Artefactos , Velocidad del Flujo Sanguíneo , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Fantasmas de ImagenRESUMEN
The Coulter principle is a widespread technique for sizing red blood cells (RBCs) in hematological analyzers. It is based on the monitoring of the electrical perturbations generated by cells passing through a micro-orifice, in which a concentrated electrical field is imposed by two electrodes. However, artifacts associated with near-wall passages in the sensing region are known to skew the statistics for RBCs sizing. This study presents numerical results that emphasize the link between the cell flow-induced rotation in the detection area and the error in its measured volume. Based on these observations, two methods are developed to identify and reject pulses impaired by cell rotation. In the first strategy, the filtering is allowed by a metric computed directly from the waveform. In the second, a numerical database is employed to train a neural network capable of detecting if the cell has experienced a rotation, given its electrical pulse. Detecting and rejecting rotation-associated pulses are shown to provide results comparable to hydrodynamical focusing, which enforces cells to flow in the center of the orifice, the gold standard implementation of the Coulter principle.
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Eritrocitos , Aprendizaje Automático , Tamaño de la Célula , Impedancia Eléctrica , ElectrodosRESUMEN
Several well-resolved 4D Flow MRI acquisitions of an idealized rigid flow phantom featuring an aneurysm, a curved channel as well as a bifurcation were performed under pulsatile regime. The resulting hemodynamics were processed to remove MRI artifacts. Subsequently, they were compared with CFD predictions computed on the same flow domain, using an in-house high-order low dissipative flow solver. Results show that reaching a good agreement is not straightforward but requires proper treatments of both techniques. Several sources of discrepancies are highlighted and their impact on the final correlation evaluated. While a very poor correlation (r2 = 0.63) is found in the entire domain between raw MRI and CFD data, correlation as high as r2 = 0.97 is found when artifacts are removed by post-processing the MR data and down sampling the CFD results to match the MRI spatial and temporal resolutions. This work demonstrates that, in a well-controlled environment, both PC-MRI and CFD might bring reliable and correlated flow quantities when a proper methodology to reduce the errors is followed.
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Hidrodinámica , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Flujo Sanguíneo Regional , Estrés Mecánico , Sístole/fisiología , Factores de TiempoRESUMEN
Dynamic self-organized structures with long-range order have been observed in emulsions and suspensions of particles under confined flows. Here, experiments on red blood cell suspensions under quasi-2D confined flows and numerical simulations were combined to explore long-distance self-organization as a function of the channel width, red blood cell concentration and flow rate. They reveal and quantitatively describe the existence of red blood cell long-range alignments and heterogeneous cross-stream concentration profiles characterized by red blood cell-enriched bands parallel to the flow. Numerical simulations show that, in addition to the degree of lateral confinement, the key factor for the structural self-organization of a suspension of particles under a confined flow is the deformability of the constituent particles.
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Eritrocitos/citología , Dispositivos Laboratorio en un Chip , Deformación Eritrocítica , Volumen de Eritrocitos , Hematócrito , Humanos , Modelos Biológicos , SuspensionesRESUMEN
Blood viscosity decreases with shear stress, a property essential for an efficient perfusion of the vascular tree. Shear thinning is intimately related to the dynamics and mutual interactions of RBCs, the major component of blood. Because of the lack of knowledge about the behavior of RBCs under physiological conditions, the link between RBC dynamics and blood rheology remains unsettled. We performed experiments and simulations in microcirculatory flow conditions of viscosity, shear rates, and volume fractions, and our study reveals rich RBC dynamics that govern shear thinning. In contrast to the current paradigm, which assumes that RBCs align steadily around the flow direction while their membranes and cytoplasm circulate, we show that RBCs successively tumble, roll, deform into rolling stomatocytes, and, finally, adopt highly deformed polylobed shapes for increasing shear stresses, even for semidilute volume fractions of the microcirculation. Our results suggest that any pathological change in plasma composition, RBC cytosol viscosity, or membrane mechanical properties will affect the onset of these morphological transitions and should play a central role in pathological blood rheology and flow behavior.
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Eritrocitos/fisiología , Técnicas Analíticas Microfluídicas/métodos , Reología/métodos , Velocidad del Flujo Sanguíneo/fisiología , Elasticidad/fisiología , Deformación Eritrocítica/fisiología , Eritrocitos/citología , Pruebas Hematológicas , Humanos , Microcirculación/fisiología , Microscopía/métodos , Plasma , Estrés Mecánico , ViscosidadRESUMEN
A recent study of red blood cells (RBCs) in shear flow [Lanotte et al., Proc. Natl. Acad. Sci. U.S.A. 113, 13289 (2016)PNASA60027-842410.1073/pnas.1608074113] has demonstrated that RBCs first tumble, then roll, transit to a rolling and tumbling stomatocyte, and finally attain polylobed shapes with increasing shear rate, when the viscosity contrast between cytosol and blood plasma is large enough. Using two different simulation techniques, we construct a state diagram of RBC shapes and dynamics in shear flow as a function of shear rate and viscosity contrast, which is also supported by microfluidic experiments. Furthermore, we illustrate the importance of RBC shear elasticity for its dynamics in flow and show that two different kinds of membrane buckling trigger the transition between subsequent RBC states.
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Eritrocitos/fisiología , Modelos Biológicos , Tamaño de la Célula , Simulación por Computador , Citosol/fisiología , Elasticidad , Membrana Eritrocítica/fisiología , Eritrocitos/citología , Técnicas Analíticas Microfluídicas , Plasma/fisiología , Resistencia al CorteRESUMEN
Sickle cell anemia is a blood disorder, known to affect the microcirculation and is characterized by painful vaso-occlusive crises in deep tissues. During the last three decades, many scenarios based on the enhanced adhesive properties of the membrane of sickle red blood cells have been proposed, all related to a final decrease in vessels lumen by cells accumulation on the vascular walls. Up to now, none of these scenarios considered the possible role played by the geometry of the flow on deposition. The question of the exact locations of occlusive events at the microcirculatory scale remains open. Here, using microfluidic devices where both geometry and oxygen levels can be controlled, we show that the flow of a suspension of sickle red blood cells around an acute corner of a triangular pillar or of a bifurcation, leads to the enhanced deposition and aggregation of cells. Thanks to our devices, we follow the growth of these aggregates in time and show that their length does not depend on oxygenation levels; instead, we find that their morphology changes dramatically to filamentous structures when using autologous plasma as a suspending fluid. We finally discuss the possible role played by such aggregates in vaso-occlusive events.
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Anemia de Células Falciformes/sangre , Eritrocitos/patología , Técnicas Analíticas Microfluídicas , Anemia de Células Falciformes/patología , Plaquetas/patología , Agregación Eritrocitaria , Hemoglobinas/metabolismo , Hemólisis , Humanos , Leucocitos/patología , Oxígeno/metabolismoRESUMEN
Intraventricular vector flow mapping (iVFM) seeks to enhance and quantify color Doppler in cardiac imaging. In this study, we propose novel alternatives to the traditional iVFM optimization scheme by utilizing physics-informed neural networks (PINNs) and a physics-guided nnU-Net-based supervised approach. When evaluated on simulated color Doppler images derived from a patient-specific computational fluid dynamics model and in vivo Doppler acquisitions, both approaches demonstrate comparable reconstruction performance to the original iVFM algorithm. The efficiency of PINNs is boosted through dual-stage optimization and pre-optimized weights. On the other hand, the nnU-Net method excels in generalizability and real-time capabilities. Notably, nnU-Net shows superior robustness on sparse and truncated Doppler data while maintaining independence from explicit boundary conditions. Overall, our results highlight the effectiveness of these methods in reconstructing intraventricular vector blood flow. The study also suggests potential applications of PINNs in ultrafast color Doppler imaging and the incorporation of fluid dynamics equations to derive biomarkers for cardiovascular diseases based on blood flow.
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Short-range exposure to airborne virus-laden respiratory droplets is an effective transmission route of respiratory diseases, as exemplified by Coronavirus Disease 2019 (COVID-19). In order to assess the risks associated with this pathway in daily-life settings involving tens to hundreds of individuals, the chasm needs to be bridged between fluid dynamical simulations and population-scale epidemiological models. This is achieved by simulating droplet trajectories at the microscale in numerous ambient flows, coarse-graining their results into spatio-temporal maps of viral concentration around the emitter, and coupling these maps to field-data about pedestrian crowds in different scenarios (streets, train stations, markets, queues, and street cafés). At the individual scale, the results highlight the paramount importance of the velocity of the ambient air flow relative to the emitter's motion. This aerodynamic effect, which disperses infectious aerosols, prevails over all other environmental variables. At the crowd's scale, the method yields a ranking of the scenarios by the risks of new infections, dominated by the street cafés and then the outdoor market. While the effect of light winds on the qualitative ranking is fairly marginal, even the most modest air flows dramatically lower the quantitative rates of new infections.
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COVID-19 , Trastornos Respiratorios , Enfermedades Respiratorias , Humanos , Aerosoles y Gotitas RespiratoriasRESUMEN
Counting and sizing blood cells in hematological analyzers is achieved using the Coulter principle. The cells flow in a micro-aperture in which a strong electrical field is imposed, so that an electrical perturbation, called pulse, is measured each time a cell crosses the orifice. The pulses are expected to contain information on the shape and deformability of Red Blood Cells (RBCs), since recent studies state that RBCs rotate and deform in the micro-orifice. By implementing a dedicated numerical model, the present study sheds light on a variety of cells dynamics, which leads to different associated pulse signatures. Furthermore, simulations provide new insights on how RBCs shapes and mechanical properties affect the measured signals. Those numerical observations are confirmed by experimental assays. Finally, specific features are introduced for assessing the most relevant characteristics from the various pulse signatures and shown to highlight RBCs alterations induced by drugs. In summary, this study paves the way to a characterization of RBC rheology by routine hematological instruments.
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Deformación Eritrocítica , Eritrocitos , ReologíaRESUMEN
The heterogeneous model developed by Berod et al [Int J Numer Method Biomed Eng 38, 2021] for representing the hemodynamic effects of endovascular prostheses is applied to a series of 10 patient specific cerebral aneurysms, 6 being treated by flow diverters, 4 being equipped with WEBs. Two markers correlated with the medical outcome of the treatment are used to assess the potential of the model, namely the saccular mean velocity and the inflow rate at the neck of the aneurysm. The comparison with the corresponding wire-resolved simulations is very favorable in both cases, and the model-based simulations also retrieve the jetting-type flows generated downstream of the struts. Noteworthy, the very same model was used for representing the flow diverters and the WEBs, showing the versatility and robustness of the heterogeneous modeling of the devices.
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Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/cirugía , Hemodinámica , StentsRESUMEN
Two well-established numerical representations of the coagulation cascade either initiated by the intrinsic system (Chatterjee et al., PLOS Computational Biology 2010) or the extrinsic system (Butenas et al., Journal of Biological Chemistry, 2004) were compared with thrombin generation assays under realistic pathological conditions. Biochemical modifications such as the omission of reactions not relevant to the case studied, the modification of reactions related to factor XI activation and auto-activation, the adaptation of initial conditions to the thrombin assay system, and the adjustment of some of the model parameters were necessary to align in vitro and in silico data. The modified models are able to reproduce thrombin generation for a range of factor XII, XI, and VIII deficiencies, with the coagulation cascade initiated either extrinsically or intrinsically. The results emphasize that when existing models are extrapolated to experimental parameters for which they have not been calibrated, careful adjustments are required.
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Aclimatación , Trombina , Bioensayo , Coagulación Sanguínea , Biología ComputacionalRESUMEN
Numerical computations of hemodynamics inside intracranial aneurysms treated by endovascular braided devices such as flow-diverters contribute to understanding and improving such treatment procedures. Nevertheless, these simulations yield high computational and meshing costs due to the heterogeneity of length scales between the dense weave of the fine struts of the device and the arterial volume. Homogeneous strategies developed over the last decade to circumvent this issue substitute local dissipations due to the wires with a global effect in the form of a pressure-drop across the device surface. However, these methods cannot accurately reproduce the flow-patterns encountered near the struts, the latter strongly dictating the intra-saccular flow environment. In this work, a versatile theoretical framework which aims at correctly reproducing the local flow heterogeneities due to the wires while keeping memory consumption, meshing and computational times as low as possible is introduced. This model reproduces the drag forces exerted by the device struts onto the fluid, thus producing local and heterogeneous effects on the flow. Extensive validation for various flow and geometric configurations using an idealized device is performed. To further illustrate the method capabilities, a real patient-specific aneurysm endovascularly treated with a flow-diverter is used, enabling quantitative comparisons with classical approaches for both intra-saccular velocities and computational costs reduction. The proposed heterogeneous model endeavors to bridge the gap between computational fluid dynamics and clinical applications and ushers in a new era of numerical treatment planning with minimally costing computational tools.
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Procedimientos Endovasculares , Aneurisma Intracraneal , Arterias , Hemodinámica , Humanos , Hidrodinámica , Aneurisma Intracraneal/cirugía , StentsRESUMEN
Color Doppler imaging (CDI) is the modality of choice for simultaneous visualization of myocardium and intracavitary flow over a wide scan area. This visualization modality is subject to several sources of error, the main ones being aliasing and clutter. Mitigation of these artifacts is a major concern for better analysis of intracardiac flow. One option to address these issues is through simulations. In this article, we present a numerical framework for generating clinical-like CDI. Synthetic blood vector fields were obtained from a patient-specific computational fluid dynamics CFD model. Realistic texture and clutter artifacts were simulated from real clinical ultrasound cineloops. We simulated several scenarios highlighting the effects of 1) flow acceleration; 2) wall clutter; and 3) transmit wavefronts, on Doppler velocities. As a comparison, an "ideal" color Doppler was also simulated, without these harmful effects. This synthetic dataset is made publicly available and can be used to evaluate the quality of Doppler estimation techniques. Besides, this approach can be seen as a first step toward the generation of comprehensive datasets for training neural networks to improve the quality of Doppler imaging.
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Artefactos , Interpretación de Imagen Asistida por Computador , Velocidad del Flujo Sanguíneo , Corazón/diagnóstico por imagen , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Ultrasonografía DopplerRESUMEN
Objective. Intraventricular vector flow mapping (iVFM) is a velocimetric technique for retrieving two-dimensional velocity vector fields of blood flow in the left ventricular cavity. This method is based on conventional color Doppler imaging, which makesiVFM compatible with the clinical setting. We have generalized theiVFM for a three-dimensional reconstruction (3D-iVFM).Approach.3D-iVFM is able to recover three-component velocity vector fields in a full intraventricular volume by using a clinical echocardiographic triplane mode. The 3D-iVFM problem was written in the spherical (radial, polar, azimuthal) coordinate system associated to the six half-planes produced by the triplane mode. As with the 2D version, the method is based on the mass conservation, and free-slip boundary conditions on the endocardial wall. These mechanical constraints were imposed in a least-squares minimization problem that was solved through the method of Lagrange multipliers. We validated 3D-iVFMin silicoin a patient-specific CFD (computational fluid dynamics) model of cardiac flow and tested its clinical feasibilityin vivoin patients and in one volunteer.Main results.The radial and polar components of the velocity were recovered satisfactorily in the CFD setup (correlation coefficients,r = 0.99 and 0.78). The azimuthal components were estimated with larger errors (r = 0.57) as only six samples were available in this direction. In bothin silicoandin vivoinvestigations, the dynamics of the intraventricular vortex that forms during diastole was deciphered by 3D-iVFM. In particular, the CFD results showed that the mean vorticity can be estimated accurately by 3D-iVFM.Significance. Our results tend to indicate that 3D-iVFM could provide full-volume echocardiographic information on left intraventricular hemodynamics from the clinical modality of triplane color Doppler.
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Ecocardiografía Doppler en Color , Ventrículos Cardíacos , Velocidad del Flujo Sanguíneo , Ecocardiografía Doppler en Color/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Hemodinámica , Humanos , HidrodinámicaRESUMEN
This work assesses the risks of Covid-19 spread in diverse daily-life situations involving crowds of maskless pedestrians, mostly outdoors. More concretely, we develop a method to infer the global number of new infections from patchy observations, by coupling ad hoc spatial models for disease transmission via respiratory droplets to detailed field-data about pedestrian trajectories and head orientations. This allows us to rank the investigated situations by the infection risks that they present; importantly, the obtained hierarchy of risks is very largely conserved across transmission models: Street cafés present the largest average rate of new infections caused by an attendant, followed by busy outdoor markets, and then metro and train stations, whereas the risks incurred while walking on fairly busy streets are comparatively quite low. While our models only approximate the actual transmission risks, their converging predictions lend credence to these findings. In situations with a moving crowd, density is the main factor influencing the estimated infection rate. Finally, our study explores the efficiency of street and venue redesigns in mitigating the viral spread: While the benefits of enforcing one-way foot traffic in (wide) walkways are unclear, changing the geometry of queues substantially affects disease transmission risks.
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A numerical approach is presented to efficiently simulate time-resolved 3D phase-contrast Magnetic resonance Imaging (or 4D Flow MRI) acquisitions under realistic flow conditions. The Navier-Stokes and Bloch equations are simultaneously solved with an Eulerian-Lagrangian formalism. A semi-analytic solution for the Bloch equations as well as a periodic particle seeding strategy are developed to reduce the computational cost. The velocity reconstruction pipeline is first validated by considering a Poiseuille flow configuration. The 4D Flow MRI simulation procedure is then applied to the flow within an in vitro flow phantom typical of the cardiovascular system. The simulated MR velocity images compare favorably to both the flow computed by solving the Navier-Stokes equations and experimental 4D Flow MRI measurements. A practical application is finally presented in which the MRI simulation framework is used to identify the origins of the MRI measurement errors.
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Simulación por Computador , Medios de Contraste/química , Imagenología Tridimensional , Imagen por Resonancia Magnética , Análisis Numérico Asistido por Computador , Algoritmos , Hidrodinámica , Fantasmas de Imagen , Factores de TiempoRESUMEN
Color Doppler by transthoracic echocardiography creates two-dimensional fan-shaped maps of blood velocities in the cardiac cavities. It is a one-component velocimetric technique since it only returns the velocity components parallel to the ultrasound beams. Intraventricular vector flow mapping (iVFM) is a method to recover the blood velocity vectors from the Doppler scalar fields in an echocardiographic three-chamber view. We improved ouriVFM numerical scheme by imposing physical constraints. TheiVFM consisted in minimizing regularized Doppler residuals subject to the condition that two fluid-dynamics constraints were satisfied, namely planar mass conservation, and free-slip boundary conditions. The optimization problem was solved by using the Lagrange multiplier method. A finite-difference discretization of the optimization problem, written in the polar coordinate system centered on the cardiac ultrasound probe, led to a sparse linear system. The single regularization parameter was determined automatically for non-supervision considerations. The physics-constrained method was validated using realistic intracardiac flow data from a patient-specific computational fluid dynamics (CFD) model. The numerical evaluations showed that theiVFM-derived velocity vectors were in very good agreement with the CFD-based original velocities, with relative errors ranged between 0.3% and 12%. We calculated two macroscopic measures of flow in the cardiac region of interest, the mean vorticity and mean stream function, and observed an excellent concordance between physics-constrainediVFM and CFD. The capability of physics-constrainediVFM was finally tested within vivocolor Doppler data acquired in patients routinely examined in the echocardiographic laboratory. The vortex that forms during the rapid filling was deciphered. The physics-constrainediVFM algorithm is ready for pilot clinical studies and is expected to have a significant clinical impact on the assessment of diastolic function.
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Algoritmos , Interpretación de Imagen Asistida por Computador , Velocidad del Flujo Sanguíneo , Ecocardiografía/métodos , Humanos , Hidrodinámica , Interpretación de Imagen Asistida por Computador/métodos , FísicaRESUMEN
In Coulter counters, cells counting and volumetry are achieved by monitoring their electrical print when they flow through a sensing zone. However, the volume measurement may be impaired by the cell dynamics, which may be difficult to control. In this paper, numerical simulations of the dynamics and electrical signature of red blood cells in a Coulter counter are presented, accounting for the deformability of the cells. In particular, a specific numerical pipeline is developed to overcome the challenge of the multi-scale nature of the problem. It consists in segmenting the whole computation of the cell dynamics and electrical response in a series of dedicated computations, with a saving of one order of magnitude in computational time. This numerical pipeline is used with rigid spheres and deformable red blood cells in an industrial Coulter counter geometry, and compared with experimental measurements. The simulations not only reproduce electrical signatures typical of those measured experimentally, but also allow an analysis of the electrical signature in terms of the heterogeneity of the electrical field and dynamics of the particles in the measurement zone. This study provides a methodology for computing the sizing of rigid or deformable particles by Coulter counters, opening the way to a better understanding of cells signatures in such devices.