Article

Inertial Particle Dynamics in Large Artery Flows - Implications for Modeling Arterial Embolisms

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The complexity of inertial particle dynamics through swirling chaotic flow structures characteristic of pulsatile large-artery hemodynamics renders significant challenges in predictive understanding of transport of such particles. This is specifically crucial for arterial embolisms, where knowledge of embolus transport to major vascular beds helps in disease diagnosis and surgical planning. Using a computational framework built upon image-based CFD and discrete particle dynamics modeling, a multi-parameter sampling-based study was conducted on embolic particle dynamics and transport. The results highlighted the strong influence of material properties, embolus size, release instance, and embolus source on embolus distribution to the cerebral, renal and mesenteric, and ilio-femoral vasculature beds. The study also isolated the importance of shear-gradient lift, and elastohydrodynamic contact, in affecting embolic particle transport. Near-wall particle re-suspension due to lift alters aortogenic embolic particle dynamics significantly as compared to cardiogenic. The observations collectively indicated the complex interplay of particle inertia, fluid-particle density ratio, and wall collisions, with chaotic flow structures, which render the overall motion of the particles to be non-trivially dispersive in nature.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... In a series of prior works [7,29,28,30], we have established a detailed computational pipeline for studying embolus transport in 3D patient-specific hemodynamics. Our computational model is composed of: (a) medical image-based modeling of vascular anatomy; (b) fully resolved 3D time-dependent flow simulations; (c) discrete particle method for embolus transport; and (d) a Monte-Carlo type approach for characterizing embolus distribution statistics. ...
... Our computational model is composed of: (a) medical image-based modeling of vascular anatomy; (b) fully resolved 3D time-dependent flow simulations; (c) discrete particle method for embolus transport; and (d) a Monte-Carlo type approach for characterizing embolus distribution statistics. We have addressed mathematical modeling issues pertaining to embolus transport [29,30], described how embolus size and other factors influence embolus distribution to the brain [7,28], characterized differences between cardiogenic and aortogenic emboli in terms of their distribution in the brain [28], and demonstrated that understanding the chaotic advection of emboli through large arteries is necessary for discerning the source-destination relationship for cerebral emboli [30]. In this work, we seek to investigate the link between CoW anatomical variations and transport of emboli. ...
... Our computational model is composed of: (a) medical image-based modeling of vascular anatomy; (b) fully resolved 3D time-dependent flow simulations; (c) discrete particle method for embolus transport; and (d) a Monte-Carlo type approach for characterizing embolus distribution statistics. We have addressed mathematical modeling issues pertaining to embolus transport [29,30], described how embolus size and other factors influence embolus distribution to the brain [7,28], characterized differences between cardiogenic and aortogenic emboli in terms of their distribution in the brain [28], and demonstrated that understanding the chaotic advection of emboli through large arteries is necessary for discerning the source-destination relationship for cerebral emboli [30]. In this work, we seek to investigate the link between CoW anatomical variations and transport of emboli. ...
Preprint
We describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.
... Blood clot trajectories have previously been modeled computationally [10][11][12][13][14][15][16][17][18][19][20][21] and experimentally [20][21][22][23][24][25][26][27]. Choi et al. [10] numerically assessed the trajectories of rigid, spherical particles within an idealized three-dimensional aortic arch model, comprising three branching arteries under AF conditions. ...
... Middle cerebral artery (MCA) occlusion is the most common site for cardioembolic strokes [44]. [16][17][18] and microparticles [10,13,14], which are useful but not representative of clots retrieved from patient cases. They also do not capture the behavior of a clot under physiological flow. ...
... However, their study included 17 release positions compared to our three release positions. Mukherjee et al. [16] also discussed the strong influence of embolus release instance on embolus distribution to the cerebral vasculature. The ability to control the release position of a clot experimentally is extremely difficult and is a limitation to this study. ...
Article
Full-text available
Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). A physiological simulation system designed to analyse the trajectory patterns of bovine embolus analogues (EAs) (n = 720) through four patient specific models, under three flow conditions: steady flow, normal pulsatile flow and AF pulsatile flow. Overall AF flow conditions increased trajectories through the LCCA and RCCA by 25%. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left or anterior positions. Overall, the EA trajectory paths were proportional to the percentage flowrate split of 25 - 31% along the branching vessels. Significantly more EAs travelled through the brachiocephalic trunk experienced than through the LCCA or the left subclavian. Yet of the EAs that travelled towards the cerebral vasculature, there was a greater affiliation towards the left common carotid artery compared to the right common carotid artery (p < 0.05).
... These changes play a key role in the progression of numerous diseases including coronary artery disease, bypass graft failure, cardiomyopathy, pulmonary hypertension, aneurysm growth and rupture, and postoperative remodeling in congenital heart disease [7][8][9][10][11][12]. Mechanical forces and flow disruption resulting in endothelial injury, flow stagnation, and shear-related platelet activation can play a key role in thrombus formation, elevating the risk of stroke, heart attacks, and embolisms [13][14][15]. Early studies of hemodynamics played a key role in explaining the localization of atherosclerotic plaques to bifurcation regions, such as in the carotid sinus where flow separation occurs and wall shear stress is relatively low [16]. ...
... The data structure design is critical for modularity and extensibility during development and deployment. The core modules use external open-source packages including: the Visualization Toolkit (VTK) 9 and Vascular Modeling Toolkit (VMTK) 10 for visualization and modeling, Insight Segmentation and Registration Toolkit (ITK) 11 and Grassroots DICOM (GDCM) 12 for image IO and processing, OpenCASCADE 13 for CAD models, Tetrahedral Mesh Generator (TetGen) 14 and Mmg (Mesh Modification and Generation) 15 for surface and volume meshing. The SV solver uses the finite element method to solve the incompressible, Newtonian form of the Navier-Stokes equations, with FSI based on the coupled momentum method [58][59][60][61]. ...
Article
Patient-specific simulation plays an important role in cardiovascular disease research, diagnosis, surgical planning and medical device design, as well as education in cardiovascular biomechanics. SimVascular is an open-source software package encompassing an entire cardiovascular modeling and simulation pipeline from image segmentation, 3D solid modeling, and mesh generation, to patient-specific simulation and analysis. SimVascular is widely used for cardiovascular basic science and clinical research as well as education, following increased adoption by users and development of a GATEWAY web portal to facilitate educational access. Initial efforts of the project focused on replacing commercial packages with open source alternatives and adding increased functionality for multiscale modeling, fluid structure interaction, and solid modeling operations. In this paper, we introduce a major SimVascular release that includes a new graphical user interface (GUI) designed to improve user experience. Additional improvements include enhanced data/project management, interactive tools to facilitate user interaction, new boundary condition functionality, plug-in mechanism to increase modularity, a new 3D segmentation tool, and new CAD-based solid modeling capabilities. Here, we focus on major changes to the software platform and outline features added in this new release. We also briefly describe our recent experiences using SimVascular in the classroom for bioengineering education.
... Large tangential velocities and shear-force gradients characterize these flows. In certain scenarios, they may even cause a lift force that triggers resuspension of particles from the wall into the flow (Mukherjee & Shadden, 2017). Fig. 1. (a). ...
Article
Full-text available
The transport and deposition of inhaled micron particles is largely determined by their inlet conditions, breathing rate, and the individual airway geometry. In this study, helical air-particle flow is introduced, which significantly affects the particle dynamics with applications to targeted drug delivery. Specifically, helical flow, which reduces axial momentum, can be controlled by varying the swirl number and hence the characteristics of the fluid-particle stream. In case of drug-aerosol delivery, the waste of inhaled drugs in the human upper respiratory tract due to inertial impaction can be mitigated by implementing a controlled helical flow with a modified inhaler. For example, 2 μm-particle deposition was reduced in the oral cavity for a helical fluid-particle stream with 10 l/min inhalation by 39.7% when the swirl number was increased from 0 to 0.6. Considering a 30 l/min inhalation flow rate, the deposition fraction of 2 μm-particles in the oral cavity was reduced by 73.5% as the swirl number increased from 0 to 2. A new non-dimensional parameter called the swirl number threshold (Sth), is also discussed, which is useful in assessing the impact of helical streams in drug-aerosol delivery. All computer experiments were performed with an enhanced version of the open-source computational fluid dynamics toolbox OpenFOAM.
... To our knowledge, it is thus far undetermined to what extent the researcher's choice of aortic inlet boundary condition changes the solution, or how far distal to the inlet the flow is significantly affected by the choice of inlet condition. In addition, it is not always clear how the choice of outlet boundary condition affects the flow solution; most researchers choose between an outflow outlet condition, in which flowrate is specified at each outlet, and a Windkessel model, in which distal resistances and capacitances are modeled [45][46][47][48][49]. It is critical to answer these questions to determine the extent to which the hundreds of published studies with non-patient-specific inlet and outlet conditions are accurate. ...
Article
Full-text available
Background Computational modeling of cardiovascular flow is a growing and useful field, but such simulations usually require the researcher to guess the flow’s inlet and outlet conditions since they are difficult and expensive to measure. It is critical to determine the amount of uncertainty introduced by these assumptions in order to evaluate the degree to which cardiovascular flow simulations are accurate. Our work begins to address this question by examining the sensitivity of flow to several different assumed velocity inlet and outlet conditions in a patient-specific aorta model. Methods We examined the differences between plug flow, parabolic flow, linear shear flows, skewed cubic flow profiles, and Womersley flow at the inlet. Only the shape of the inlet velocity profile was varied—all other parameters were identical among these simulations. Secondary flow in the form of a counter-rotating pair of vortices was also added to parabolic axial flow to study its effect on the solution. In addition, we examined the differences between two-element Windkessel, three element Windkessel and the outflow boundary conditions. In these simulations, only the outlet boundary condition was varied. ResultsThe results show axial and in-plane velocities are considerably different close to the inlet for the cases with different inlet velocity profile shapes. However, the solutions are qualitatively similar beyond 1.75D, where D is the inlet diameter. This trend is also observed in other quantities such as pressure and wall shear stress. Normalized root-mean-square deviation, a measure of axial velocity magnitude differences between the different cases, generally decreases along the streamwise coordinate. The linear shear inlet velocity boundary condition and plug velocity boundary condition solution exhibit the highest time-averaged wall shear stress, approximately \(8\%\) higher than the parabolic inlet velocity boundary condition. Upstream of 1D from the inlet, adding secondary flow has a significant impact on temporal wall shear stress distributions. This is especially observable during diastole, when integrated wall shear stress magnitude varies about \(26\%\) between simulations with and without secondary flow. The results from the outlet boundary condition study show the Windkessel models differ from the outflow boundary condition by as much as \(18\%\) in terms of time-averaged wall shear stress. Furthermore, normalized root-mean-square deviation of axial velocity magnitude, a measure of deviation between Windkessel and the outflow boundary condition, increases along the streamwise coordinate indicating larger variations near outlets. Conclusion It was found that the selection of inlet velocity conditions significantly affects only the flow region close to the inlet of the aorta. Beyond two diameters distal to the inlet, differences in flow solution are small. Although additional studies must be performed to verify this result, the data suggest that it is important to use patient-specific inlet conditions primarily if the researcher is concerned with the details of the flow very close to the inlet. Similarly, the selection of outlet conditions significantly affects the flow in the vicinity of the outlets. Upstream of five diameters proximal to the outlet, deviations between the outlet boundary conditions examined are insignificant. Although the inlet and outlet conditions only affect the flow significantly in their respective neighborhoods, our study indicates that outlet conditions influence a larger percentage of the solution domain.
... Sometimes, the plaque forming a stenosis may be ruptured into particles, known as emboli, which may lodge in an artery downstream. 6 If the broken particles are carried into the brain, it causes neurological disorder or a stroke. Plaque rupture may sometimes form a thrombus that blocks blood flow to the heart causing unstable angina or myocardial infarction. ...
Article
The aim of this paper is to throw some light on the rheological study of pulsatile blood flow in a stenosed tapered arterial segment. Arterial wall is considered to be rigid and flexible separately for improving the similarity to the in vivo situation. The streaming blood is considered to be Newtonian. The governing nonlinear equations of motion are sought using the well‐known stream function‐vorticity method and are solved numerically by finite difference technique. Important rheological parameters, such as axial velocity component, wall shear stress, and flow separation region are estimated in the neighborhood of the stenosis. Effects of stenosis height, vessel tapering, and wall flexibility on the blood flow are investigated properly and are explained in detail through their graphical representations.
Article
Introduction: Pulmonary embolism (PE) is one of the most prevalent diseases amid hospitalized patients taking many people's lives annually. This phenomenon, however, has not been investigated via numerical simulations. Methods: In this study, an image-based model of pulmonary arteries has been constructed from a 44-year-old man's computed tomography images. The fluid-structure interaction method was used to simulate the motion of the blood clot. In this regard, Navier-Stokes equations, as the governing equations, have been solved in an arbitrary Lagrangian-Eulerian (ALE) formulation. Results: According to our results, the velocity of visco-hyperelastic model of the emboli was relatively higher than the emboli with hyperelastic model, despite their similar behavioral pattern. The stresses on the clot were also investigated and showed that the blood clot continuously sustained stresses greater than 165 Pa over an about 0.01 s period, which can cause platelets to leak and make the clot grow or tear apart. Conclusions: It could be concluded that in silico analysis of the cardiovascular diseases initiated from clot motion in blood flow is a valuable tool for a better understanding of these phenomena.
Article
Purpose Arterial shear forces may promote the embolization of clotted blood from the surface of thrombi, displacing particles that may occlude vasculature, with increased risk of physiological complications and mortality. Thromboemboli may also collide in vivo to form metastable aggregates that increase vessel occlusion likelihood. Methods A micromechanical force (MMF) apparatus was modified for aqueous applications to study clot-liquid interfacial phenomena between clotted porcine blood particles suspended in modified continuous phases. The MMF measurement is based on visual observation of particle-particle separation, where Hooke’s Law is applied to calculate separation force. This technique has previously been deployed to study solid–fluid interfacial phenomena in oil and gas pipelines, providing fundamental insight to cohesive and adhesive properties between solids in multiphase flow systems. Results This manuscript introduces distributed inter-particle separation force properties as a function of governing physio-chemical parameters; pre-load (contact) force, contact time, and bulk phase chemical modification. In each experimental campaign, the hysteresis and distributed force properties were analysed, to derive insight as to the governing mechanism of cohesion between particles. Porcine serum, porcine albumin and pharmaceutical agents (alteplase, tranexamic acid and hydrolysed aspirin) reduced the measurement by an order of magnitude from the baseline measurement—the apparatus provides a platform to study how surface-active chemistries impact the solid–fluid interface. Conclusion These results provide new insight to potential mechanisms of macroscopic thromboembolic aggregation via particles cohering in the vascular system—data that can be directly applied to computational simulations to predict particle fate, better informing the mechanistic developments of embolic occlusion.
Article
Particulate corticosteroids have been described to lead to greater pain improvement compared with their non‐particulate counterparts when used in epidural injections. It is hypothesised that filtering may significantly impact their concentration and long‐term efficacy. We investigated if passing particulate suspensions through different commonly‐used filters affects drug dosage. Two particulate corticosteroid formulations, triamcinolone acetonide and methylprednisolone acetate, were mixed at different concentrations with either bupivacaine hydrochloride or 0.9% sodium chloride. Solutions were passed through a 5‐μm and a 0.2‐μm filter. Mass spectroscopy results indicated a complete loss of corticosteroid from the solutions using both filters, and light microscopy imaging demonstrated agglomerate formation, suggesting that filtering interferes with drug dosage. The choice of diluents must also be considered to reduce large agglomerate formation. Clinicians should be aware of the consequences of filtering particulate suspensions and carefully consider the selection of diluent when considering treatment plans.
Article
Introduction Endovascular treatments, such as transcatheter aortic valve implantation (TAVI), carry a risk of embolization due to debris dislodgement during various procedural steps. Although embolic filters are already available and marketed, mechanisms underlying cerebral embolism still need to be elucidated in order to further reduce cerebrovascular events. Methods We propose an experimental framework with an in silico duplicate allowing release of particles at the level of the aortic valve and their subsequent capture in the supra-aortic branches, simulating embolization under constant inflow and controlled hemodynamic conditions. The effect of a simple flow modulation, consisting of an auxiliary constant flow via the right subclavian artery (RSA), on the amount of particle entering the brachiocephalic trunk was investigated. Preliminary computational fluid dynamics (CFD) simulations were performed in order to assess the minimum retrograde flow-rate from RSA required to deviate particles. Results Our results show that a constant reversed auxiliary flow of 0.5 L/min from the RSA under a constant inflow of 4 L/min from the ascending aorta is able to protect the brachiocephalic trunk from particle embolisms. Both computational and experimental results also demonstrate that the distribution of the bulk flow dictates the distribution of the particles along the aortic branches. This effect has also shown to be independent of release location and flow rate. Conclusions The present study confirms that the integration of in vitro experiments and in silico analyses allows designing and benchmarking novel solutions for cerebral embolic protection during TAVI such as the proposed embo-deviation technique based on an auxiliary retrograde flow from the right subclavian artery.
Article
In this article, we present an overview of research on flow in microconfinements with deformable boundaries. The time frame of focus is the last decade (2007–2017). The article is arranged into sections based on the geometry of the problem studied, which fall under five major categories—microchannels, tubes, squeeze flow, cylinder near wall and thin structures (membranes, sheets, etc.). The modelling of various coupled phenomena such as electrokinetics, diffusion and porous flow is discussed, maintaining the study of deformable boundaries as a common underlying theme. The article concludes with a brief discussion about the cross-correlation between the works presented based on the phenomena studied, constitutive models considered and methodologies employed.
Article
We describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.
Article
Full-text available
Roughly one-third of all strokes are caused by an embolus traveling to a cerebral artery and blocking blood flow in the brain. The objective of this study is to gain a detailed understanding of the dynamics of embolic particles within arteries. Patient computed tomography image is used to construct a three-dimensional model of the carotid bifurcation. An idealized carotid bifurcation model of same vessel diameters was also constructed for comparison. Blood flow velocities and embolic particle trajectories are resolved using a coupled Euler– Lagrange approach. Blood is modeled as a Newtonian fluid, discretized using the finite volume method, with physiologically appropriate inflow and outflow boundary conditions. The embolus trajectory is modeled using Lagrangian particle equations accounting for embolus interaction with blood as well as vessel wall. Both one-and two-way fluid–particle coupling are considered, the latter being implemented using momentum sources augmented to the discretized flow equations. It was observed that for small-to-moderate particle sizes (relative to vessel diameters), the estimated particle distribution ratio—with and without the inclusion of two-way fluid– particle momentum exchange—were found to be similar. The maximum observed differences in distribution ratio with and without the coupling were found to be higher for the idealized bifurcation model. Additionally, the distribution was found to be reasonably matching the volumetric flow distribution for the idealized model, while a notable deviation from volumetric flow was observed in the anatomical model. It was also observed from an analysis of particle path lines that particle interaction with helical flow, characteristic of anatomical vasculature models, could play a prominent role in transport of embolic particle. The results indicate therefore that flow helicity could be an important hemodynamic indicator for analysis of embolus particle transport. Additionally, in the presence of helical flow, and vessel curvature, inclusion of two-way momentum exchange was found to have a secondary effect for transporting small to moderate embolus particles—and one-way coupling could be used as a reasonable approximation, thereby causing substantial savings in computational resources.
Article
Full-text available
Recent advances in imaging, modeling, and computing have rapidly expanded our capabilities to model hemodynamics in the large vessels (heart, arteries, and veins). This data encodes a wealth of information that is often under-utilized. Modeling (and measuring) blood flow in the large vessels typically amounts to solving for the time-varying velocity field in a region of interest. Flow in the heart and larger arteries is often complex, and velocity field data provides a starting point for investigating the hemodynamics. This data can be used to perform Lagrangian particle tracking, and other Lagrangian-based postprocessing. As described herein, Lagrangian methods are necessary to understand inherently transient hemodynamic conditions from the fluid mechanics perspective, and to properly understand the biomechanical factors that lead to acute and gradual changes of vascular function and health. The goal of the present paper is to review Lagrangian methods that have been used in post-processing velocity data of cardiovascular flows.
Article
Full-text available
Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their margination properties (migration toward walls) in the microvasculature. To investigate margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
Article
Full-text available
Image-based in silico modeling tools provide detailed velocity and particle deposition data. However, care must be taken when prescribing boundary conditions to model lung physiology in health or disease, such as in emphysema. In this study, the respiratory resistance and compliance were obtained by solving an inverse problem; a 0D global model based on healthy and emphysematous rat experimental data. Multi-scale CFD simulations were performed by solving the 3D Navier-Stokes equations in an MRI-derived rat geometry coupled to a 0D model. Particles with 0.95 μm diameter were tracked and their distribution in the lung was assessed. Seven 3D-0D simulations were performed: healthy, homogeneous, and five heterogeneous emphysema cases. Compliance (C) was significantly higher (p = 0.04) in the emphysematous rats (C = 0.37 ± 0.14 cm(3)/cmH2O) compared to the healthy rats (C = 0.25 ± 0.04 cm(3)/cmH2O), while the resistance remained unchanged (p = 0.83). There were increases in airflow, particle deposition in the 3D model, and particle delivery to the diseased regions for the heterogeneous cases compared to the homogeneous cases. The results highlight the importance of multi-scale numerical simulations to study airflow and particle distribution in healthy and diseased lungs. The effect of particle size and gravity were studied. Once available, these in silico predictions may be compared to experimental deposition data.
Article
Full-text available
The present work investigates the mechanics of particle collisions submerged in a liquid using a simple pendulum experiment. Particle trajectories for different particles in water are measured using a high-speed digital camera and the magnitude of the collision is recorded using a high-frequency-response pressure transducer at the colliding surface. The particle deceleration occurs at distances less than half a particle diameter from the wall. The measured collision impulse increases with impact velocity and particle mass. Comparisons are drawn between the measured pressures and the predictions of basic impact mechanics assuming a perfectly elastic collision. A control-volume model is proposed that accounts for the fluid inertia and viscosity. When a particle approaches a planar surface or another particle, the fluid is squeezed prior to contact reducing the initial kinetic energy and decelerating the particle. The pressure profile is integrated over the surface of the particle to obtain a force that is a function of the initial particle Reynolds number, Re-0, and the ratio of the the densities of the particle and fluid phases, rho(p)/rho(f). The model predicts a critical Stokes number at which the particle reaches the wall with zero velocity. Comparisons between the proposed model and the experimental measurements show qualitative agreement.
Article
Full-text available
Explicit equations are developed for the drag coefficient and for the terminal velocity of falling spherical and nonspherical particles. The goodness of fit of these equations to the reported experimental data is evaluated and is compared with that of other recently proposed equations.Accurate design charts for CD and ut are prepared and displayed for all particle sphericities.
Article
Full-text available
While it is intuitively clear that aortic anatomy and embolus size could be important determinants for cardiogenic embolic stroke risk and stroke location, few data exist confirming or characterizing this hypothesis. The objective of this study is to use medical imaging and computational modeling to better understand if aortic anatomy and embolus size influence predilections for cardiogenic embolic transport, and right versus left hemisphere propensity. Anatomically accurate models of the human aorta and branch arteries to the head were reconstructed from CT angiography of 10 patients. Blood flow was modeled by the Navier-Stokes equations using a well-validated flow solver with physiologic inflow and boundary conditions. Embolic particulate was released from the aortic root and tracked through the common carotid and vertebral arteries for a range of particle sizes. Cardiogenic emboli reaching the carotid and vertebral arteries appeared to have a strong size-destination relationship that varied markedly from expectations based on blood distribution. Observed trends were robust to modeling parameters. A patient's aortic anatomy appeared to significantly influence the probability a cardiogenic particle becomes embolic to the head. Right hemisphere propensity appeared dominant for cardiogenic emboli, which has been confirmed clinically. The predilections discovered through this modeling could represent an important mechanism underlying cardiogenic embolic stroke etiology.
Article
Full-text available
Purpose: Measurements of the viscoelastic properties of a thrombus can be used to assess whether blood clots are likely to become occlusive or to break apart and leak into the blood circulation and block smaller vessels. An accurate method for estimating both the shear elasticity and viscosity of a blood clot in vivo is still lacking, which prompted us to use a novel shear-wave approach to measure the viscoelastic modulus of blood clots. Methods: The shear-wave dispersion ultrasound vibrometry was used to measure both the elasticity and viscosity of blood clots. The experimental system was verified by measuring the viscoelastic modulus of phantoms containing gelatin at different concentrations. Blood-clot experiments were carried out using porcine whole blood with hematocrits ranging from 3% to 40%. The measured values for both clots and gelatin phantoms were compared to those obtained using an embedded-sphere method in order to validate the accuracy of the viscoelastic modulus estimations. Results: The shear elastic modulus increased from 406.9 ± 15.8 (mean ± SD) Pa for 3% gelatin to 1587.2 ± 28.9 Pa for 7% gelatin, while the viscosity increased from 0.12 ± 0.02 Pa s to 0.86 ± 0.05 Pa s, respectively. The shear modulus increased from 196.8 ± 58.4 Pa for 40%-hematocrit clots to 641.4 ± 76.3 Pa for 3%-hematocrit clots, while the viscosity increased from 0.29 ± 0.02 Pa s to 0.42 ± 0.01 Pa s, respectively. Conclusions: The results from the statistical analysis indicated that both the embedded-sphere and shear-wave approaches can provide accurate estimations of the shear elasticity for clots and gelatin phantoms. In contrast, the shear-wave approach as well as other methods of rheological measurements does not provide accurate viscosity estimations for blood clots. However, the measured viscosity range of 0.29-0.42 Pa s is reasonable for blood clots.
Article
Full-text available
We propose new ways of computing the stabilization parameters used in the stabilized finite element methods such as the streamline-upwind/Petrov-Galerkin (SUPG) and pressure-stabilizing/Petrov-Galerkin (PSPG) formulations. The parameters are com- puted based on the element-level matrices and vectors, which automatically take into account the local length scales, advection field and the Reynolds number. We describe how we compute these parameters in the context of first a time-dependent advection- diffusion equation and then the Navier-Stokes equations of unsteady incompressible flows.
Article
Full-text available
Blood flow in the large systemic arteries is modeled using one-dimensional equations derived from the axisymmetric Navier–Stokes equations for flow in compliant and tapering vessels. The arterial tree is truncated after the first few generations of large arteries with the remaining small arteries and arterioles providing outflow boundary conditions for the large arteries. By modeling the small arteries and arterioles as a structured tree, a semi-analytical approach based on a linearized version of the governing equations can be used to derive an expression for the root impedance of the structured tree in the frequency domain. In the time domain, this provides the proper outflow boundary condition. The structured tree is a binary asymmetric tree in which the radii of the daughter vessels are scaled linearly with the radius of the parent vessel. Blood flow and pressure in the large vessels are computed as functions of time and axial distance within each of the arteries. Comparison between the simulations and magnetic resonance measurements in the ascending aorta and nine peripheral locations in one individual shows excellent agreement between the two. 2000 Biomedical Engineering Society. PAC00: 8719Uv
Article
Full-text available
The paper provides an overview of the challenges and progress associated with the task of numerically predicting particle-laden turbulent flows. The review covers the mathematical methods based on turbulence closure models as well as direct numerical simulation (DNS). In addition, the statistical (pdf) approach in deriving the dispersed-phase transport equations is discussed. The review is restricted to incompressible, isothermal flows without phase change or particle-particle collision. Suggestions are made for improving closure modelling of some important correlations.
Article
Full-text available
Flow and pressure waves emanate from the heart and travel through the major arteries where they are damped, dispersed and reflected due to changes in vessel caliber, tissue properties and branch points. As a consequence, solutions to the governing equations of blood flow in the large arteries are highly dependent on the outflow boundary conditions imposed to represent the vascular bed downstream of the modeled domain. The most common outflow boundary conditions for three-dimensional simulations of blood flow are prescribed constant pressure or traction and prescribed velocity profiles. However, in many simulations, the flow distribution and pressure field in the modeled domain are unknown and cannot be prescribed at the outflow boundaries. An alternative approach is to couple the solution at the outflow boundaries of the modeled domain with lumped parameter or one-dimensional models of the downstream domain. We previously described a new approach to prescribe outflow boundary conditions for simulations of blood flow based on the Dirichlet-to-Neumann and variational multiscale methods. This approach, termed the coupled multidomain method, was successfully applied to solve the non-linear one-dimensional equations of blood flow with a variety of models of the downstream domain. This paper describes the extension of this method to three-dimensional finite element modeling of blood flow and pressure in the major arteries. Outflow boundary conditions are derived for any downstream domain where an explicit relationship of pressure as a function of flow rate or velocities can be obtained at the coupling interface. We developed this method in the context of a stabilized, semi-discrete finite element method. Flow rate and pressure distributions are shown for different boundary conditions to illustrate the dramatic influence of alternative boundary conditions on these quantities.
Article
Full-text available
This paper compares numerical predictions of turbulence intensity with in vivo measurement. Magnetic resonance imaging (MRI) was carried out on a 60-year-old female with a restenosed aortic coarctation. Time-resolved three-directional phase-contrast (PC) MRI data was acquired to enable turbulence intensity estimation. A contrast-enhanced MR angiography (MRA) and a time-resolved 2D PCMRI measurement were also performed to acquire data needed to perform subsequent image-based computational fluid dynamics (CFD) modeling. A 3D model of the aortic coarctation and surrounding vasculature was constructed from the MRA data, and physiologic boundary conditions were modeled to match 2D PCMRI and pressure pulse measurements. Blood flow velocity data was subsequently obtained by numerical simulation. Turbulent kinetic energy (TKE) was computed from the resulting CFD data. Results indicate relative agreement (error ≈10%) between the in vivo measurements and the CFD predictions of TKE. The discrepancies in modeled vs. measured TKE values were within expectations due to modeling and measurement errors.
Article
Full-text available
Brownian motion of particles affects many branches of science. We report on the Brownian motion of micrometer-sized beads of glass held in air by an optical tweezer, over a wide range of pressures, and we measured the instantaneous velocity of a Brownian particle. Our results provide direct verification of the energy equipartition theorem for a Brownian particle. For short times, the ballistic regime of Brownian motion was observed, in contrast to the usual diffusive regime. We discuss the applications of these methods toward cooling the center-of-mass motion of a bead in vacuum to the quantum ground motional state.
Article
Full-text available
Abdominal aortic aneurysms (AAAs) affect 5-7% of older Americans. We hypothesize that exercise may slow AAA growth by decreasing inflammatory burden, peripheral resistance, and adverse hemodynamic conditions such as low, oscillatory shear stress. In this study, we use magnetic resonance imaging and computational fluid dynamics to describe hemodynamics in eight AAAs during rest and exercise using patient-specific geometric models, flow waveforms, and pressures as well as appropriately resolved finite-element meshes. We report mean wall shear stress (MWSS) and oscillatory shear index (OSI) at four aortic locations (supraceliac, infrarenal, mid-aneurysm, and suprabifurcation) and turbulent kinetic energy over the entire computational domain on meshes containing more than an order of magnitude more elements than previously reported results (mean: 9.0-million elements; SD: 2.3 M; range: 5.7-12.0 M). MWSS was lowest in the aneurysm during rest 2.5 dyn/cm(2) (SD: 2.1; range: 0.9-6.5), and MWSS increased and OSI decreased at all four locations during exercise. Mild turbulence existed at rest, while moderate aneurysmal turbulence was present during exercise. During both rest and exercise, aortic turbulence was virtually zero superior to the AAA for seven out of eight patients. We postulate that the increased MWSS, decreased OSI, and moderate turbulence present during exercise may attenuate AAA growth.
Article
Full-text available
Case presentation : During cardiac catheterization, a 65-year-old man suddenly complained of nuchal pain, vertigo, and nausea and rapidly became unconscious, presumably from a stroke. The operator was unsure what type of imaging and management should be undertaken in this infrequent clinical setting. He paged the neurologist, asking him to urgently provide a strategy for diagnosis and management. Although the overall rate of stroke after left heart catheterization or percutaneous coronary intervention (PCI) is low, ranging from 0.2% to 0.4% (Tables 1 and 2⇓),1–5 it is the most debilitating complication from the patient’s perspective, associated with a high rate of morbidity and mortality (Figure 1).1–8 In 20 679 consecutive patients who underwent PCI in a large-volume center, stroke occurred in 0.44%.4 Multivariate analysis has shown that the occurrence of stroke was more frequently associated with diabetes mellitus, hypertension, prior stroke, or renal failure and was independently associated with in-hospital death. Patients who suffered a stroke had previously undergone longer cardiac catheterization procedures, using more contrast, were more likely to have had the procedure for urgent reasons, and to have had intraaortic balloon counterpulsation, a procedure that is itself known to increase the risk of stroke.9 Possible explanations for this latter characteristic include the greater propensity for hemodynamic compromise in these patients, which may increase the risk of ischemic stroke, and less meticulous care in advancing the catheter through the aorta during urgent PCI, which increases the risk of embolization by scraping of aortic plaques with subsequent embolization of debris to the brain. Indeed, scraping of aortic plaques occurs in >50% of PCI cases and more frequently with large than with small catheters.10 Cerebral microembolism is thought to be the main mechanism of periprocedural ischemic stroke occurring with PCI. This finding is supported …
Article
Full-text available
We study the velocity correlation function of a selected particle in a suspension of interacting Brownian particles. Experimentally, the velocity correlation function can be observed with diffusing wave spectroscopy. The function has also been determined in computer simulation. We assume a wide separation of time scales between momentum relaxation and diffusive motion. The correlation function is found from linear hydrodynamics by use of the fluctuation-dissipation theorem. We propose a simple approximation based on the single particle result that is valid for a dilute suspension. The approximation is fully determined by the short-time self-diffusion coefficient and the effective mass of the selected particle. We discuss the concept of scaling within the framework of the approximation. We find that the amplitude of the t-3/2 long-time tail is independent of the concentration of the suspension.
Article
Full-text available
We consider some basic principles of fluid-induced lubrication at soft interfaces. In particular, we quantify how a soft substrate changes the geometry of and the forces between surfaces sliding past each other. By considering the model problem of a symmetric nonconforming contact moving tangentially to a thin elastic layer, we determine the normal force in the small and large deflection limit, and show that there is an optimal combination of material and geometric properties which maximizes the normal force. Our results can be generalized to a variety of other geometries which show the same qualitative behavior. Thus, they are relevant in the elastohydrodynamic lubrication of soft elastic and poroelastic gels and shells, and in the context of biolubrication in cartilaginous joints.
Article
Patient-specific cardiovascular simulation has become a paradigm in cardiovascular research and is emerging as a powerful tool in basic, translational and clinical research. In this paper we discuss the recent development of a fully open-source SimVascular software package, which provides a complete pipeline from medical image data segmentation to patient-specific blood flow simulation and analysis. This package serves as a research tool for cardiovascular modeling and simulation, and has contributed to numerous advances in personalized medicine, surgical planning and medical device design. The SimVascular software has recently been refactored and expanded to enhance functionality, usability, efficiency and accuracy of image-based patient-specific modeling tools. Moreover, SimVascular previously required several licensed components that hindered new user adoption and code management and our recent developments have replaced these commercial components to create a fully open source pipeline. These developments foster advances in cardiovascular modeling research, increased collaboration, standardization of methods, and a growing developer community.
Article
Stroke caused by an embolism accounts for about a third of all stroke cases. Understanding the source and cause of the embolism is critical for diagnosis and long-term treatment of such stroke cases. The complex nature of the transport of an embolus within large arteries is a primary hindrance to a clear understanding of embolic stroke etiology. Recent advances in medical image-based computational hemodynamics modeling have rendered increasing utility to such techniques as a probe into the complex flow and transport phenomena in large arteries. In this work we present a novel, patient-specific, computational framework for understanding embolic stroke etiology, by combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis. The framework allows us to explore the important question of how embolism source manifests itself in embolus distribution across the various major cerebral arteries. Our investigations illustrate prominent numerical evidence regarding (i) the size/inertia dependent trends in embolus distribution to the brain, (ii) the relative distribution of cardiogenic versus aortogenic emboli amongst the anterior, middle, and posterior cerebral arteries, (iii) the left versus right brain preference in cardio-emboli and aortic-emboli transport, and (iv) the source-destination relationship for embolisms affecting the brain.
Article
Lubrication flows appear in many applications in engineering, biophysics, and in nature. Separation of surfaces and minimisation of friction and wear is achieved when the lubrication fluid builds up a lift force. In this paper we analyse soft lubricated contacts by treating the solid walls as viscoelastic: soft materials are typically not purely elastic, but dissipate energy under dynamical loading conditions. We present a method for viscoelastic lubrication and focus on three canonical examples, namely Kelvin-Voigt-, Standard Linear-, and Power Law-rheology. It is shown how the solid viscoelasticity affects the lubrication process when the timescale of loading becomes comparable to the rheological timescale. We derive asymptotic relations between lift force and sliding velocity, which give scaling laws that inherit a signature of the rheology. In all cases the lift is found to decrease with respect to purely elastic systems.
Article
Blood flow in arteries is dominated by unsteady flow phenomena. The cardiovascular system is an internal flow loop with multiple branches in which a complex liquid circulates. A nondimensional frequency parameter, the Womersley number, governs the relationship between the unsteady and viscous forces. Normal arterial flow is laminar with secondary flows generated at curves and branches. The arteries are living organs that can adapt to and change with the varying hemodynamic conditions. In certain circumstances, unusual hemodynamic conditions create an abnormal biological response. Velocity profile skewing can create pockets in which the direction of the wall shear stress oscillates. Atherosclerotic disease tends to be localized in these sites and results in a narrowing of the artery lumena stenosis. The stenosis can cause turbulence and reduce flow by means of viscous head losses and flow choking. Very high shear stresses near the throat of the stenosis can activate platelets and thereby induce thrombosis, which can totally block blood flow to the heart or brain. Detection and quantification of stenosis serve as the basis for surgical intervention. In the future, the study of arterial blood flow will lead to the prediction of individual hemodynamic flows in any patient, the development of diagnostic tools to quantify disease, and the design of devices that mimic or alter blood flow. This field is rich with challenging problems in fluid mechanics involving three-dimensional, pulsatile flows at the edge of turbulence.
Article
Purpose: The goals of this study were to investigate the treatment outcomes of acute mesenteric ischemia caused by superior mesenteric artery (SMA) embolism and identify the posttreatment prognostic factors. Methods: The clinical data of 32 episodes of acute SMA embolism in 30 patients, including 2 recurrent cases, between April 2003 and March 2011 were retrospectively reviewed. Results: Median patient age was 74 years (range, 39-89 years), and 50% were male. Conservative treatment, including bowel rest, nasogastric drainage, intravenous fluid therapy, parenteral nutritional support, and anticoagulation therapy, was undertaken in 5 patients with no clinical evidence of bowel gangrene, including 1 with recurrent ischemia. No deaths occurred among patients treated conservatively. A total of 27 patients were treated with open surgical repair (25 embolectomies and 2 bowel resections alone). Among 25 patients treated with embolectomy, 14 required bowel resection. Most bowel resections (94%, 15/16) were limited, with the remaining length of small bowel greater than 150 cm, which could not cause short bowel syndrome. In-hospital mortality of surgery was 30%. No variables were associated with mortality after surgical intervention, including, age, gender, presence of bowel gangrene, and symptom duration. The overall 1-, 3-, and 5-year survival rates after initial successful treatment were 96%, 73%, and 44%, respectively, regardless of treatment type. Conclusions: Prompt diagnosis and treatment before extensive irreversible gangrene is the mainstay in the treatment of SMA embolism. Limited bowel gangrene was not associated with mortality.
Article
From Boussinesq's work it is known that the frictional resistance of a particle in a viscous, inert fluid, depends on its history. This plays an important part in Brownian motion. The general theory of fluctuations in fluid dynamics leads to explicit expressions for the autocorrelation function G(t) for the random force acting on a Brownian particle and the autocorrelation function ϕ(t) for its velocity. It is demonstrated that G(t) contains an inertial term which depends on the velocity distribution in the liquid surrounding the particle. The results obtained lead to the correct value of the diffusivity.
Article
The forces on a small rigid sphere in a nonuniform flow are considered from first principles in order to resolve the errors in Tchen's equation and the subsequent modified versions that have since appeared. Forces from the undisturbed flow and the disturbance flow created by the presence of the sphere are treated separately. Proper account is taken of the effect of spatial variations of the undisturbed flow on both forces. In particular the appropriate Faxen correction for unsteady Stokes flow is derived and included as part of the consistent approximiation for the equation of motion.
Article
Turbulent dispersed multiphase flows are common in many engineering and environmental applications. The stochastic nature of both the carrier-phase turbulence and the dispersed-phase distribution makes the problem of turbulent dispersed multiphase flow far more complex than its single-phase counterpart. In this article we first review the current state-of-the-art experimental and computational techniques for turbulent dispersed multiphase flows, their strengths and limitations, and opportunities for the future. The review then focuses on three important aspects of turbulent dispersed multiphase flows: the preferential concentration of particles, droplets, and bubbles; the effect of turbulence on the coupling between the dispersed and carrier phases; and modulation of carrier-phase turbulence due to the presence of particles and bubbles.
Article
The dynamic deformation of a solid elastic sphere which is immersed in a viscous fluid and in close motion toward another sphere or a plane solid surface is presented. The deformed shape of the solid surfaces and the pressure profile in the fluid layer separating these surfaces are determined simultaneously via asymptotic and numerical techniques. This research provides the first steps in establishing rational criteria for predicting whether a solid particle will stick or rebound subsequent to impact during filtration or coagulation when viscous forces are important.
Article
A 57-year-old man presents with an acute onset of left foot pain, numbness, and partial loss of motor function. Four months ago, he underwent endovascular treatment for disabling claudication, which included placement of overlapping polytetrafluoroethylene-coated stents in the left superficial femoral and popliteal arteries. His popliteal and pedal pulses are absent, and the foot is cool and mottled. Angiography reveals complete occlusion of the stent, with thrombosis extending distally into the popliteal and tibial arteries below the knee. How should his case be managed?
Article
Stabilized methods are proposed and analyzed for a linearized form of the incompressible Navier-Stokes equations. The methods are extended and tested for the nonlinear model. The methods combine the good features of stabilized methods already proposed for the Stokes flow and for advective-diffusive flows. These methods also generalize previous works restricted to low-order interpolations, thus allowing any combination of velocity and continuous pressure interpolations. A careful design of the stability parameters is suggested which considerably simplifies these generalizations.
Article
It was the aim to analyse the impact of age, aortic arch geometry, and size on secondary flow patterns such as helix and vortex flow derived from flow-sensitive magnetic resonance imaging (4D PC-MRI). 62 subjects (age range = 20-80 years) without circumscribed pathologies of the thoracic aorta (ascending aortic (AAo) diameter: 3.2 ± 0.6 cm [range 2.2-5.1]) were examined by 4D PC-MRI after IRB-approval and written informed consent. Blood flow visualisation based on streamlines and time-resolved 3D particle traces was performed. Aortic diameter, shape (gothic, crook-shaped, cubic), angle, and age were correlated with existence and extent of secondary flow patterns (helicity, vortices); statistical modelling was performed. Helical flow was the typical pattern in standard crook-shaped aortic arches. With altered shapes and increasing age, helicity was less common. AAo diameter and age had the highest correlation (r = 0.69 and 0.68, respectively) with number of detected vortices. None of the other arch geometric or demographic variables (for all, P ≥ 0.177) improved statistical modelling. Substantially different secondary flow patterns can be observed in the normal thoracic aorta. Age and the AAo diameter were the parameters correlating best with presence and amount of vortices. Findings underline the importance of age- and geometry-matched control groups for haemodynamic studies. • Secondary blood flow patterns (helices, vortices) are commonly observed in the aorta • Secondary flow patterns predominantly depend on patient age and aortic diameter • Geometric factors show a lesser impact on blood flow patterns than age and diameter • Future analyses of flow patterns should incorporate age- and diameter dependencies.
Article
Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs. Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens. Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05). Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.
Article
Despite improvements in diagnosis and treatment, ischaemic stroke in young adults remains a catastrophic event from the patients' perspective. Stroke can cause death, disability, and hamper quality of life. For the neurologist treating a young adult with suspected ischaemic stroke, the diagnostic challenge is to identify its cause. Contemporary neuroimaging of the brain and its vessels, and a comprehensive cardiac assessment, will enable identification of the most frequent causes of stroke in this age group: cardioembolism and arterial dissection. Specific diagnostic tests for the many other rare causes of ischaemic stroke in young adults (angiography, CSF examination, screening for vasculitis and thrombophilia, genetic testing, and ophthalmological examination) should be guided by suspected clinical findings or by the high prevalence of diseases associated with stroke in some countries.
Article
Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder. Eosinophilia further supports the diagnosis, usually confirmed by biopsy of an affected organ or by the fundoscopic finding of cholesterol crystals in the retinal circulation. Renal and patient prognosis are poor. Treatment is mostly preventive, based on avoidance of further precipitating factors, and symptomatic, aimed to the optimum treatment of hypertension and cardiac and renal failure. Statins, which stabilise atherosclerotic plaques, should be offered to all patients. Steroids might have a role in acute or subacute progressive forms with systemic inflammation.
Article
The effect and modelling of the spatial correlation between particle velocities is investigated in two-phase turbulent flows. A statistical model based on the joint fluid–particle probability distribution function kinetic equation is introduced, which accounts for the modification of the collision probability due to the correlation of the velocities of colliding particles. To study the long-range spatial correlation of the particle velocities, a conditional average, for a given fluid turbulent flow, is introduced. This approach allows us to separate the instantaneous velocity of any particle into two parts: a turbulent contribution, from an underlying continuous velocity field shared by all the particles, and a random contribution obeying the ‘molecular chaos’ assumption.
Article
The demonstration that a significant proportion of patients with renal carcinomas of the clear cell type have tumour cell clumps or aggregates in venous outflow from the kidney has interest from two viewpoints. Firstly, the association of this occurrence with high VEGF-A production by the cancer seems to suggest a novel mode of 'budding' invasion where nests of tumour cells enter the dilated and mechanically fragile new vessels supplying the cancerous growth. Secondly, with the association of fragment occurrence and metastatic development, the entrance of clumps into the circulation indicates that epithelial-mesenchymal transition (EMT) is not an obligatory step for the disseminatory behaviour of all cancers.
Article
Aortic valve calcification is common in the elderly and in patients with congenital bicuspid aortic valve but unlike calcific mitral valve disease it is not a well recognized risk factor for stroke. Although autopsy studies have revealed evidence of systemic embolism in one-third of cases with calcific aortic valves, there is conflicting data from larger clinical studies examining the association between calcific aortic valve and stroke. There are only 8 reported cases of symptomatic stroke from spontaneous cerebral thromboembolism associated with calcific aortic valve in the literature. Computerized tomography (CT) angiography and CT without contrast are modalities of choice to diagnose calcific embolism, while MRI may be useful in delineating the extent of ischemia. Ideal management strategy, the role of antiplatelet therapy, anticoagulation or recommendations for valve replacements are poorly defined. We present a focused literature review on this topic.
Article
By extending traditional particle tracking techniques, we study the dynamics of neutrally buoyant finite-sized particles in a spatiotemporally chaotic flow. We simultaneously measure the flow field and the trajectories of millimeter-scale particles so that the two can be directly compared. While the single-point statistics of the particles are indistinguishable from the flow statistics, the particles often move in directions that are systematically different from the underlying flow. These differences are especially evident when Lagrangian statistics are considered.
Article
In a prospective study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, the 1,273 with infarction were classified into diagnostic subtypes. Diagnosis was based on the clinical history, examination, and laboratory tests including computed tomography, noninvasive vascular imaging, and where safe and relevant, angiography. Five hundred and eight cases (fully 40%) were labeled as infarcts of undetermined cause (IUC), of which 138 (27%) were evaluated with both computed tomography and angiography. The clinical syndrome and computed tomographic and angiographic findings in 91 (65.9%) of these 138 IUC cases were clearly not attributable to large-artery thrombosis and could permit reclassification of the infarct as due to some form of embolism. Failure to define a source of embolus kept them in the category of IUC. Thirty-one cases (22.5%) could be reclassified as due to stenosis or thrombosis of a large artery, and 16 (11.6%) as lacunar infarction. To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses, a stepwise multiple logistic model was used. The most important characteristics were young age, presence of a superficial infarct, prior transient ischemic attack, low weakness score, and presentation with a nonlacunar syndrome. The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis. Continued use of the category IUC may help clarify risk factors and stroke subtypes, allow new mechanisms of ischemic stroke to be uncovered, and prevent classification categories of stroke used in clinical trials from becoming too broad.
Article
Controversy exists regarding whether lacunar infarction is due to embolism or whether it is always due to lipohyalinosis of small penetrating arteries. We hypothesized that emboli can enter penetrating arteries in relation to the blood flow to these arteries and to the diameter of the emboli. We injected agarose spheres of three different mean diameters (31 +/- 4, 68 +/- 14, and 92 +/- 28 microns [n = 50 for each]) into one internal carotid artery of 3 monkeys for each sphere size (total, n = 9 monkeys). After injection of spheres, monkeys were killed, the brains were removed and fixed in formalin, and serial hematoxylin and eosin sections of three coronal sections of the cerebrum were examined by light microscopy. Sphere diameter (n = 25 for each territory and sphere size) and distribution in circumferential and penetrating artery territories were measured with the use of an image analyzer. Corrections were made for shrinkage of spheres during fixation and for the effect of random sampling of 10-microns sections through spheres of different diameter. Mean numbers of spheres for each size were significantly higher in circumferential than penetrating artery territories (P < .05, t test). When correction was made for the volume of brain supplied by each territory, there was no significant difference in the number of spheres in circumferential versus penetrating artery territories for the two smaller sphere sizes. For spheres of mean diameter of 92 microns, significantly more spheres entered circumferential rather than penetrating artery territories (P < .05, t test). The percentage of the total number of spheres that entered penetrating artery territories was 5%, 6%, and 1.4% for beads of 31 +/- 4, 68 +/- 14, and 92 +/- 28 microns mean diameter, respectively. Small emboli can enter penetrating arteries and could therefore produce lacunar infarction. The majority of emboli, however, enter circumferential arteries. The larger the emboli, the more likely that they will enter circumferential arteries rather than penetrating arteries.
Article
Structural analysis of atherosclerotic coronary arteries has suggested that stress concentrations are associated with plaque rupture and that these stress concentrations are critically dependent on the geometry and mechanical properties of the fibrous cap and lipid pool. Recent clinical trials of lipid-lowering therapy have shown a significant reduction in cardiac events associated with plaque rupture perhaps because of the changing composition of subintimal lipid pools. To test the hypothesis that changes in lipid composition can change the mechanical properties of lipid pools, we measured the dynamic shear moduli of combinations of cholesterol monohydrate crystals, phospholipids, and triglycerides similar to those found in atherosclerotic lesions. Increasing the cholesterol monohydrate concentration from 0% to 50% increased the real component of the dynamic shear modulus (storage modulus or stiffness) by 4.5 times at a frequency of 1 Hz (P < .001). All specimens demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.1 to 3 Hz. We conclude that the stiffness of model atherosclerotic plaque lipid pools is related to the concentration of cholesterol monohydrate crystals. Because the relative concentration of cholesterol monohydrate increases during early regression of experimental atherosclerosis, the resultant stiffening of the lipid pool may reduce stresses in plaque caps. However, the magnitude of the contribution of changing lipid stiffness to the reduction of cardiac events seen in clinical studies is unclear.
Article
Nanoparticles are polymeric particles in the nanometer size range whereas microparticles are particles in the micrometre size range. Both types of particle are used as drug carriers into which drugs or antigens may be incorporated in the form of solid solutions or solid dispersions or onto which these materials may be absorbed or chemically bound. These particles have been shown to enhance the delivery of certain drugs across a number of natural and artificial membranes. In addition, the particles were shown to accumulate in areas of the intestine that appear to be the Peyer's patches. Possibly because of the combination of both effects these particles were able to significantly improve the bioavailability of some drugs after peroral administration in comparison with solutions. Recently nanoparticles coated with polysorbate 80 enabled the passage of small peptides and other drugs across the blood-brain barrier and the exhibition of a pharmacological effect after intravenous injection. Without the use of this type of nanoparticles the drugs did not cross this barrier and yielded no effect.
Article
The field of respiratory flow and transport has experienced significant research activity over the past several years. Important contributions to the knowledge base come from pulmonary and critical care medicine, surgery, physiology, environmental health sciences, biophysics, and engineering. Several disciplines within engineering have strong and historical ties to respiration including mechanical, chemical, civil/environmental, aerospace and, of course, biomedical engineering. This review draws from a wide variety of scientific literature that reflects the diverse constituency and audience that respiratory science has developed. The subject areas covered include nasal flow and transport, airway gas flow, alternative modes of ventilation, nonrespiratory gas transport, aerosol transport, airway stability, mucus transport, pulmonary acoustics, surfactant dynamics and delivery, and pleural liquid flow. Within each area are a number of subtopics whose exploration can provide the opportunity of both depth and breadth for the interested reader.
Article
Compression, tension and torsion tests were designed and completed successfully on a brushite and a precipitated hydroxyapatite cement in moist condition. Elastic and strength properties were measured for these three loading cases. For each cement, the full set of strength data was fitted to an isotropic Tsai-Wu criterion and the associated coefficients identified. Since the compressive Young's moduli were about 10% larger than the tensile moduli, the full set of elastic data of each cement was fitted to a conewise linear elastic model. Hysteresis of the stress-strain curves was also observed, indicating dissipation mechanisms within these cement microstructures. A comparison of the measured mechanical properties with human cancellous bone confirmed the indication of brushite as a bone filling material and the potential of the hydroxyapatite cement as a structural biomaterial.
Article
Although recognized as an important feature of atherosclerotic coronary disease, little is known about the frequency and prognostic importance of distal embolization during primary angioplasty for acute myocardial infarction. As part of a randomized trial of thrombolysis vs primary angioplasty, 178 patients with acute myocardial infarction were treated with primary angioplasty. In these patients the occurrence of distal embolization after angioplasty was assessed. Embolization was defined as a distal filling defect with an abrupt 'cutoff' in one of the peripheral coronary artery branches of the infarct-related vessel, distal to the site of angioplasty. We analysed myocardial blush grade, ST-T segment elevation resolution, enzymatic infarct size and left ventricular ejection fraction in patients with and without distal embolization. Clinical information was collected for a mean of 5 years. Distal embolization was present in 27 patients (15.2%). Mean age and gender were not different from patients without distal embolization. Angiographic success (thrombolyis in myocardial infarction flow grade 3 and residual stenosis <50%) after primary angioplasty was less frequently observed in patients with distal embolization (70% vs 90%, P<0.01). Myocardial blush and ST-T segment elevation resolution after angioplasty were reduced when distal embolization was present. Patients with distal embolization had a larger enzymatic infarct size (mean cumulative lactate dehydrogenase measured over 72 h, 1612 vs 847, P<0.05) and a lower left ventricle ejection fraction at discharge (42% vs 51%, P<0.01). Long-term mortality was higher in patients with distal embolization (44% vs 9%, P<0.001). Distal embolization in patients treated with primary angioplasty is visible on the coronary angiogram in 15.2% of patients. It is related to reduced myocardial reperfusion, more extensive myocardial damage and a poor prognosis. Additional pharmacological interventions and/ or mechanical devices should be studied to prevent and/or treat distal embolization.
Article
Stroke associated with percutaneous coronary intervention (PCI) is an infrequent although devastating complication. We investigated the incidence, predictors, and prognostic impact of periprocedural stroke in unselected patients undergoing PCI. A total of 9662 patients who underwent 12 407 PCIs between January 1990 and July 1999 were retrospectively studied. Stroke was diagnosed in 43 patients (0.38% of procedures). Patients with stroke were older (72+/-11 versus 64+/-11 years, P<0.001), had lower left ventricular ejection fraction (42+/-12 versus 46+/-13%, P=0.04) and more diabetes (39.5% versus 27.2%, P=0.07), and experienced a higher rate of intraprocedural complications necessitating emergency use of intra-aortic balloon pump (IABP) (23.3% versus 3.3%, P<0.001). In-hospital mortality (37.2% versus 1.1%, P<0.001) and 1-year mortality (56.1% versus 6.5%, P<0.001) were higher in patients with stroke. Compared with hemorrhagic stroke, patients with ischemic stroke had higher rate of in-hospital major adverse cardiac events (57.1% versus 25%, P=0.037). Multivariate logistic regression analysis identified emergency use of IABP as the strongest predictors for stroke (OR=9.6, CI 3.9 to 23.9, P<0.001), followed by prophylactic use of IABP (OR=5.1), age >80 years (OR=3.2, compared with age <50 years), and vein graft intervention (OR=2.7). Stroke associated with contemporary PCI is associated with substantial increased mortality. Elderly patients who experience intraprocedural complications necessitating the use of IABP are at particularly high risk.
Article
Acute mesenteric ischemia secondary to arterial occlusion (AMI) remains a highly lethal condition. To examine recent trends in management and associated outcomes, we examined our institutional experience over a recent 10-year period. All patients treated for AMI between January 1990 and January 2000 were identified (76 patients, 77 cases) and their medical records examined. At presentation, 64% demonstrated peritonitis and 30% exhibited hypotension. The interval from symptom onset to treatment exceeded 24 h in 63% of cases. Etiology was mesenteric thrombosis in 44 patients (58%) and embolism in 32 patients (42%). Thirty-five patients (46%) had prior conditions placing them at high risk for the development of AMI including chronic mesenteric ischemia (n = 26) and inadequately anticoagulated chronic atrial fibrillation (n = 9). Surgical management consisted of exploration alone in 16 patients, bowel resection alone in 18 patients, and revascularization in 43 patients, including 28 who required concomitant bowel resection. Overall, intestinal necrosis was present in 81% of cases. Perioperative mortality was 62% and long-term parenteral nutrition (TPN) was required in 31% of survivors. Peritonitis (odds ratio [OR] 9.4, 95% confidence interval [CI] 1.6, 54.0; p = 0.012 and bowel necrosis (OR 10.4, CI 1.9, 56.3; p = 0.007) at presentation were independent predictors of death or survival dependent upon TPN. We conclude that AMI remains a highly lethal condition due in large part to advanced presentation and inadequate recognition and treatment of patients at high risk.
Article
Effective myocardial reperfusion after primary percutaneous coronary intervention (PCI) may be limited by distal embolization. We tested the safety, feasibility, and efficacy of the FilterWire-Ex (FW), a distal embolic protection device, as an adjunct to primary PCI. Fifty-three consecutive patients undergoing primary PCI with FW protection were compared with a matched control group treated by primary PCI alone. Successful FW positioning was obtained in 47 patients (89%) without complications. Histological analysis of the content of the last 13 filters showed multiple embolic debris in all cases. FW use was associated with lower postinterventional corrected TIMI frame count (22+/-14 versus 31+/-19; P=0.005) and higher occurrence of grade 3 myocardial blush (66% versus 36%; P=0.006) and early ST-segment elevation resolution (80% versus 54%; P=0.006). At multivariate analysis, FW use was the only independent predictor of early ST-segment elevation resolution and of grade 3 myocardial blush. FW patients showed lower peak creatine kinase-MB release (236+/-172 versus 333+/-219 ng/mL; P=0.013) and greater improvement at 30 days in left ventricular wall motion score index (-0.30+/-0.19 versus -0.18+/-0.26; P=0.008) and ejection fraction (+7+/-4% versus +4+/-7%; P=0.012). FW use during primary PCI is feasible and safe. Distal embolization prevention appears to exert a beneficial effect on markers of myocardial reperfusion and on left ventricular function improvement at 30 days.
Article
To determine the importance of emboli not trapped by carotid angioplasty filtration devices, we examined fragments <100 microm released with ex vivo angioplasty and asked if fragment composition and size correlated with brain injury. Human carotid plaques (21) were excised en bloc, and ex vivo carotid angioplasty was performed. Eight plaques were selected as either highly calcified (4) or highly fibrotic (4) by high-resolution MRI (200 microm3). Fragments were counted by a Coulter counter. Before injection into male Sprague-Dawley rats, fragments from calcified and fibrotic plaques were sized with 60-, 100-, and 200-microm filters. Brain ischemia and infarction were assessed by MRI scans (7-T small-bore magnet) and by immunohistologic staining for HSP70 and NueN. All 5 animals injected with 100- to 200-microm calcified fragments had infarctions. One was lethal. After injection of 60- to 100-microm calcified fragments, 7 of 12 animals had cerebral infarctions, whereas only 1 of 11 had infarctions with fibrous fragments (P<0.02). HSP70 staining showed that ischemia was more common and more extensive than infarction. Ischemia was found in 10 of 12 animals after injection of calcified fragments and in 9 of 11 after injection of fibrous fragments. The mean number of 60- to 100-microm fragments released was 375+/-510; the mean number of 20- to 60-microm fragments was 34 196 (range, 2230 to 186 927). Hundreds of thousands of microemboli can be shed during carotid angioplasty. Fragments from calcified plaques cause greater levels of infarction than fragments from fibrous plaques, although ischemia is common with both fragment types.
Article
Young's modulus and Poisson's ratio of a tissue can be simultaneously obtained using two indentation tests with two different sized indentors in two indentations. Owing to the assumption of infinitesimal deformation of the indentation, the finite deformation effect of indentation on the calculated material parameters was not fully understood in the double indentation approach. However, indentation tests with infinitesimal deformation are not practical for the measurement of real tissues. Accordingly, finite element models were developed to simulate the indentation with different indentor diameters and different deformation ratios to investigate the finite deformation effect of indentation. The results indicated that Young's modulus E increased with the increase in the indentation deformation w, if the finite deformation effect of indentation was not considered. This phenomenon became obvious when Poisson's ratio v approached 0.5 and/or the ratio of indentor radius and tissue thickness a/h increased. The calculated Young's modulus could be different by 23% at 10% deformation in comparison with its real value. The results also demonstrated that the finite deformation effect to indentation on the calculation of Poisson's ratio v was much smaller. After the finite deformation effect of indentation was considered, the error of the calculated Young's modulus could be controlled within 5% (a/h = 1) and 2% (a/h = 2) for deformation up to 10%.