No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Computational Assessment Of The Relation Between Embolism Source And Embolus Distribution To The Circle Of Willis For Improved Understanding Of Stroke Etiology
Abstract
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.
... A. 3D patient-specific model was used in this study. The model employed is consistent with those used in previous studies, [25][26][27][28][29] which were created based on CT scans taken as part of the screening-technology and outcome project in the stroke-database study. 30 We only adopted the patient model referred to as P01 in Refs. ...
... 35 Many previous studies have also been simulated with the assumption of blood as Newtonian. 1,19,[24][25][26][27][28]41,42 Physics of Fluids ARTICLE pubs.aip.org/aip/pof ...
... where P sys is the systolic pressure and P dia is the diastolic pressure. These pressures were typically assumed to be 120 and 80 mm Hg, respectively, as referenced in Ref. 25, resulting in P m ¼ 93.3 mm Hg. The total QðtÞ and total C were initially calculated from the pulsatile inlet waveform and then were evenly distributed to each outlet following the cross-sectional area rule. ...
The circle of Willis (CoW) is a critical, arterial structure that ensures balanced, cerebral-blood supply. The fetal-type posterior cerebral artery (f-PCA) is a CoW variant that can significantly affect hemodynamics and elevate the risk of cerebrovascular diseases. This study used computational fluid dynamics simulations and a patient-specific, three-dimensional model to evaluate the hemodynamic effects of the f-PCA variants on cerebral-blood flow and key hemodynamic indices—such as time-averaged wall-shear stress (TAWSS), oscillatory shear index (OSI), pulsatility index, and resistive index. The fetal ratio (FR) is defined as the ratio of the diameter of the posterior communicating artery (PCoA) to that of the first segment (P1) of the PCA. Our findings indicate that as the FR increases, the contribution of the basilar artery to the second segment (P2) of PCA decreases significantly. Specifically, the flow rate through ipsilateral P1 decreased by 40.0% for FR = 1 and 70.9% for FR = 2, with the internal carotid artery (ICA) compensating for this reduction. Moreover, variations in f-PCA led to significant increases in TAWSS and OSI in key arterial segments (including the ipsilateral P1, PCoA, and the anterior communicating artery), which are associated with a higher risk of aneurysm initiation and growth. Under conditions of unilateral stenosis in the ipsilateral ICA, f-PCA models exhibit a more complex and pronounced impact on blood flow than models without f-PCA, emphasizing the need for detailed hemodynamic assessments in clinical evaluations and preoperative planning to mitigate the risks associated with CoW anatomical variations.
... For this purpose, Total Arterial Resistance (TAR) was estimated using a Mean Arterial Pressure (MAP) of 93.33 mmHg, which assumes that the patient exhibits an average systolic and diastolic blood pressure of 120 and 80 mmHg respectively. A proportion of the TAR was assigned to each vessel outlet based on target flow divisions as outlined in prior work [18,20,23]. For target flow division, 65% of the total CO was assumed to exit the descending aorta [24], flow rates exiting the six cerebral artery outlets were assigned based on measured MR data reported in [25], and the remainder volumetric flow was set to exit the external carotid and subclavian arteries proportional to their cross-sectional areas [26]. ...
... For target flow division, 65% of the total CO was assumed to exit the descending aorta [24], flow rates exiting the six cerebral artery outlets were assigned based on measured MR data reported in [25], and the remainder volumetric flow was set to exit the external carotid and subclavian arteries proportional to their cross-sectional areas [26]. These resistance values were tuned to the targeted flow values through multiple steady-state flow simulations [23,27]. Once obtained, the CO, TAR, MAP, and outlet resistances were kept the same across all models to enable controlled simulations of embolus transport. ...
... Hemodynamics was simulated for three cardiac cycles for each model, and computed velocity and pressure fields for the third cycle were used to conduct embolus transport simulations. Each of these hemodynamic simulations steps are outlined extensively in our previous works [18,20,23]. ...
Deciphering the source of an embolism is a common challenge encountered in stroke treatment. Carotid stenosis is a key source of embolic strokes. Carotid interventions can be indicated when a patient has greater than 50% stenosis in the carotid ipsilateral to the cerebral infarction, which is designated as the symptomatic carotid. However, there are often significant number of cases where carotid emboli travel contralaterally leading to ambiguity regarding which carotid is symptomatic. We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 30 heart-to-brain arterial models with differing combinations of bilateral severe and mild stenosis degrees. We used these models to study source-to-destination transport of thromboemboli released from left/right carotid disease sites, and cardiogenic sources. Across all cases considered, thromboemboli from left and right carotid sources showed non-zero contralateral transport. We also found that cardiogenic thromboemboli do not have an altered hemisphere distribution or distinct transport preference dependent on stenosis degree, thus potentially making the underlying etiology more cryptic. In patients with carotid stenosis or chronic occlusion ipsilateral to the area affected by stroke, we have demonstrated that the presence of contralateral stenosis can cause emboli that travel across the Circle of Willis (CoW) which can potentially lead to ambiguity when deciding which carotid is truly symptomatic.
... However, detailed in silico quantification of spatiotemporally varying embolus-hemodynamics interactions and thromboembolus transport towards the cervical vessels remains sparingly investigated in LVAD driven circulation. Motivated by this knowledge gap, here we demonstrate a patient-specific in silico embolus-hemodynamics model, established extensively in our prior works for stroke [35][36][37][38], for quantitative characterization of embolus distribution towards the cervical vessels post-LVAD implantation. Our goal is to demonstrate key features of thromboembolus source to destination transport trends as function of surgical variables such as varying graft anastomosis and pulse flow modulation, and embolus properties such as size and release locations. ...
... Transport of thromboemboli across the arteries was modelled, by assuming each embolus to be a spherical particle, and modeling their dynamics in the simulated blood flow using a custom modified form of the Maxey-Riley equation [47], that we have developed extensively in a series of prior works [35][36][37][38]. Briefly, this equation incorporates the e↵ects of the drag force, shear-gradient-driven lift forces, fluid stresses for undisturbed flow, added mass and buoyancy forces, alongwith a soft particle-wall collision model to account for embolus interactions with vessel wall. ...
... The simulated thromboembolus distribution shows a strong dependence on embolus size, which is in agreement with observations on embolus transport in arterial flows as indicated in several prior works [35,38,54]. Figure 6 illustrates the variation of thromboembolus distribution towards the cervical vessels from LVAD outflow graft, aortic root, and both sources combined. ...
Left Ventricular Assist Devices (LVADs) are a key treatment option for patients with advanced heart failure, but they carry a significant risk of thromboembolic complications. While improved LVAD design, and systemic anticoagulation regimen, have helped mitigate thromboembolic risks, ischemic stroke due to adverse thromboembolic events remains a major concern with current LVAD therapies. Improved understanding of embolic events, and embolus movement to the brain, is critical to develop techniques to minimize risks of occlusive embolic events such as a stroke after LVAD implantation. Here, we address this need, and devise a quantitative in silico framework to characterize thromboembolus transport and distrbution in hemodynamics driven by an operating LVAD. We conduct systematic numerical experiments to quantify the source-to-destination transport patterns of thromboemboli as a function of: LVAD outflow graft anastomosis, LVAD operating pulse modulation, thromboembolus sizes, and origin locations of emboli. Additionally, we demonstrate how the resulting embolus distribution patterns compare and correlate with descriptors based solely on hemodynamic patterns such as helicity, vorticity, and wall shear stress. Using the concepts of size-dependent embolus-hemodynamics interactions, and two jet flow model for hemodynamics under LVAD operation as established in our prior works, we gain valuable insights on departure of thromboembolus distribution from flow distribution, and establish that our in silico model can generate deep insights into embolus dynamics which is not otherwise available from standard of care imaging and clinical data.
... The study found a strong size-destination relationship for cardiogenic emboli in the carotid and vertebral arteries, influenced significantly by a patient's aortic anatomy. Mukherjee et al. [11] performed an investigation into the complex dynamics of embolic stroke etiology, utilizing a novel computational framework. By combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis, the study revealed size/inertia-dependent trends in embolus distribution to the brain, distinctions in the distribution of cardiogenic versus aortogenic emboli among cerebral arteries, and the left versus right brain preference in emboli transport. ...
... The injections are shown in Fig. 3. Three different diameters of emboli (0.1 mm, 0.5 mm, and 1 mm) with a density of 1100 kg/m 3 were used [11]. ...
... A Lagrangian frame of reference was employed for trajectory computation for spherical particles [10,11,13]. The particle trajectory equation for an individual particle "i" was expressed in a generalized form [28]: ...
... In a series of prior works, we have established a patient-specific in silico flow-embolus interaction model that enables us to quantitatively study the source-destination relationship for the transport of emboli to the brain. [13][14][15][16] We have used this model to demonstrate the transport and distribution of cardiogenic emboli and emboli from aortic arch and illustrate the dependency of embolus distribution on embolus properties, local flow features, and arterial network anatomy. Here, we use our model to conduct a parametric in silico study to understand how emboli from carotid artery sites travel to the 6 cerebral vessels of the CoW as a function of size, CoW anatomy, and laterality of carotid release sites. ...
... These labels and identifiers are used throughout the article. Four patient anatomical geometries, used in our previous works, 14,16 were selected from a set of computed tomography images from an institutional review board approved STOP-Stroke (Screening Technology and Outcome Project in Stroke) database. 20 The STOP-Stroke database comprised 675 patients who were diagnosed with a stroke or a transient ischemic attack, categorized into large vessel occlusion and non-large vessel occlusion cases, with 46% of the stroke cases identified as large vessel occlusion. ...
... Subsequently, a proportion of the total arterial resistance was assigned to each vessel outlet based on target flow divisions as outlined in prior work. 14 Briefly, (1) 65% of total flow was assumed to exit the descending aorta 25 ; ...
Background
Disambiguation of embolus pathogenesis in embolic strokes is often a clinical challenge. One common source of embolic stroke is the carotid arteries, with emboli originating due to plaque buildup or perioperatively during revascularization procedures. Although it is commonly thought that thromboemboli from carotid sources travel to cerebral arteries ipsilaterally, there are existing reports of contralateral embolic events that complicate embolus source destination relationship for carotid sources. Here, we hypothesize that emboli from carotid sources can travel to contralateral hemispheres and that embolus interactions with collateral hemodynamics in the circle of Willis influence this process.
Methods and Results
We use a patient‐specific computational embolus‐hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 4 patient vascular models, 6 circle of Willis anastomosis variants, and 3 different thromboembolus sizes released from left and right carotid artery sites. This led to a total of 144 different experiments, estimating trajectories and distribution of approximately 1.728 million embolus samples. Across all cases considered, emboli from left and right carotid sources showed nonzero contralateral transport ( P value <−0.05). Contralateral movement revealed a size dependence, with smaller emboli traveling more contralaterally. Detailed analysis of embolus dynamics revealed that collateral flow routes in the circle of Willis played a role in routing emboli, and transhemispheric movement occurred through the anterior and posterior communicating arteries in the circle of Willis.
Conclusions
We generated quantitative data demonstrating the complex dynamics of finite size thromboembolus particles as they interact with pulsatile arterial hemodynamics and traverse the vascular network of the circle of Willis. This leads to a nonintuitive source‐destination relationship for emboli originating from carotid artery sites, and emboli from carotid sources can potentially travel to cerebral arteries on contralateral hemispheres.
... It remains challenging to study how emboli released from left/right carotid arteries pass transhemispherically using traditional imaging and animal model studies, and modern in silico techniques can prove to be a viable alternative. In a series of prior works, we have established a patient-specific in silico flow-embolus interaction model that enables us to quantitatively study the source-destination relationship for the transport of emboli to the brain [13][14][15][16]. ...
... These labels and identifiers are used throughout the paper. Four patient anatomical geometries, used in our previous works [14,20], were selected from a set of computed tomography (CT) images from the Institutional Review Board (IRB) approved Screening Technology and Outcome Project in Stroke (STOP-Stroke) database [21]. These patients were selected from the overall database to ensure that: (a) they had a complete CoW anatomy; and (b) the branching vessels at the aortic branch were segregated such that there was no fused vessels or bovine arch anatomy. ...
... An average systolic and diastolic blood pressure of 120 and 80 mmHg was assumed, leading to a mean arterial pressure (MAP) of 93.33 mmHg, which was used to compute a total arterial resistance (TAR) as MAP/CO. Subsequently, a proportion of the TAR was assigned to each vessel outlet based on target flow divisions as outlined in prior work [14]. Briefly: (a) 65% of total flow was assumed to exit the descending aorta [26]; (b) flow rates at the six cerebral artery outlets were assigned based on measured MR data reported in [27]; and (c) the remainder volumetric flow was designated to exit the external carotid and the subclavian artery outlets based on their cross-sectional area [28]. ...
Background: Disambiguation of embolus etiology in embolic strokes is often a clinical challenge. One common source of embolic stroke is the carotid arteries, with emboli originating due to plaque build up, or perioperatively during revascularization procedures. While it is commonly thought that thromboemboli from carotid sources travel to cerebral arteries ipsilaterally, there are existing reports of contralateral embolic events, which complicate embolus source destination relationship for carotid sources. Here, we hypothesize that emboli from carotid sources can travel to contralateral hemispheres, and that embolus interactions with collateral hemodynamics in the Circle of Willis influences this process.
Methods and Results: We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 4 patient vascular models, 6 Circle of Willis anastomosis variants, and 3 diffeent thromboembolus sizes released from left and right carotid sources. This led to a total of 144 different experiments, estimating trajectories and distribution of approximately 1.728 million embolus samples. Across all cases considered, emboli from left and right carotid sources showed non-zero contralateral transport (p value < 0.05). Contralateral movement revealed a size-dependence, with smaller emboli traveling more contralaterally. Detailed analysis of embolus dynamics revealed that collateral flow routes in Circle of Willis played a role in routing emboli, and transhemispheric movement occured through the anterior and posterior communicating arteries in the Circle of Willis.
Conclusions: We generated quantitative data demonstrating the complex dynamics of finite size thromboembolus particles as they interact with pulsatile arterial hemodynamics, and traverse the vascular network of the Circle of Willis. This leads to unintuitive source-destination relationship for emboli originating from carotid artery sites, and emboli from carotid sources can potentially travel to cerebral areries on contalateral hemispheres.
... A set of four models that were identical to those used in previous studies (T. Kang et al., 2021;Mukherjee et al., 2018;Mukherjee et al., 2016) was assessed. In particular, one model was excluded because of its potential string-like occlusive behavior in ICAs. ...
... This formulation was implemented in SimVascular (Updegrove et al., 2017), which has been validated for accurately setting patient-specific boundary conditions (Coogan et al., 2013;Mukherjee et al., 2018;Vignon-Clementel et al., 2006). Furthermore, the capability of a finite element solver with customized preconditioners to describe the flow in large arteries has been verified (Les et al., 2010;Mukherjee et al., 2016). The solver has been specialized with linear basis functions to optimally solve cardiovascular flows with the support of backflow stabilization ( The solver has been shown to solve the complex poststenotic flows during severe CS for non-critical stenoses ( < 85% CS) reasonably well with the use of fine mesh (Kung et al., 2011), even in comparison with a large-eddy simulation turbulence model (Velde, 2018). ...
... The optimum parameter values were then iteratively obtained using a conventional procedure (Xiao et al., 2014). The relation used for obtaining MAP was (P sys + 2P dia )/3, where P sys and P dia are the systolic and diastolic pressures, respectively, and the flow distribution in each artery was identical to that of Mukherjee et al. (2016). Resistance values were iteratively tuned in a steady-state simulation, and capacitance values were tuned to obtain acceptable pulse pressure ranges of 40-50 mmHg for the descending aorta and 30-40 mmHg for other arteries such as the carotid and cerebral arteries (Alastruey et al., 2007;Coogan et al., 2013). ...
Haemodynamic correlations among the pulsatility index (PI), resistive index (RI), time to peak velocity (TPV), and mean Reynolds number (ReMean) were numerically investigated during the progression of carotid stenosis (CS), a highly prevalent condition. Fifteen patient-specific CS cases were modeled in the package, SimVascular, by using computed tomography angiography data for the aortic-cerebral vasculature. Computational fluid domains were solved with a stabilized Petrov–Galerkin scheme under Newtonian and incompressible assumptions. A rigid vessel wall was assumed, and the boundary conditions were pulsatile inflow and three-element lumped Windkessel outlets. During the progression, the increase in the TPV resembled that during aortic stenosis, and the parameter was negatively correlated with PI, RI, and ReMean in the ipsilateral cerebral region. The ReMean was inversely related to PI and RI on the contralateral side. In particular, PI and RI in cerebral arteries showed three second-order regression patterns: ‘constant (Group A)’, ‘moderately decreasing (Group B)’, and ‘decreasing (Group C)’. The patterns were defined using a new parameter, mean ratio (lowest mean index/mean index at 0% CS). This parameter could effectively indicate stenosis-driven tendencies in local haemodynamics. Overall, the haemodynamic indices changed drastically during severe unilateral CS, and they reflected both regional and aortic-cerebral flow characteristics.
... All models displayed anatomical features of (1) a complete CoW and (2) distinctive branching patterns of arterial vessels downstream of the aortic arch. This variety in haemodynamic structure showed different flow distribution types (Mukherjee et al., 2016), ensuring the reliability of the present study ( Figure 1A). ...
... The term h 0D is the contribution to the variational form from all the resistance outflow boundary conditions (Vignon-Clementel et al., 2006. The finite-element solver, with customized preconditioners, was implemented as a part of the SimVascular package (Updegrove et al., 2017), which has been validated for accurately adapting patient-specific boundary conditions (Coogan et al., 2013;Mukherjee et al., 2018;Vignon-Clementel et al., 2006) and describing flows in larger arteries (Les et al., 2010;Mukherjee et al., 2016). Details about the solver are available in Esmaily-Moghadam et al. ...
... All values of C then were iteratively optimized until feasible pressure ranges were achieved using a conventional procedure (Xiao et al., 2014). MAP was calculated as (P sys + 2P dia )/3 with P sys , and P dia as systolic and diastolic pressures, and flow distribution was set to be equivalent to Mukherjee et al. (2016). Iterative tuning of individual resistance values was conducted to obtain desired outflow rates during steady-state simulation, and capacitance values were tuned to match acceptable pulse pressure range of 40-50 mmHg for the descending aorta and its nearest region and 30-40 mmHg for carotid and cerebral arteries (Alastruey et al., 2007;Coogan et al., Figure 2. Specific boundary conditions for each patient model. ...
We investigated the effects of atherosclerosis in the carotid region on cerebral haemodynamics. A total of 15 stenosis cases following NASCET criteria were modelled using patient-specific medical image data and an open-source package, SimVascular. The formulation adopted the stabilised Petrov–Galerkin scheme with Newtonian and incompressible assumptions. The boundary conditions employed pulsatile inflow and three-element lumped Windkessel outlet conditions with a rigid wall assumption. We present transitions in the represented CoW during stenosis progression using three-dimensional aortic-cerebral vasculature for the first time. This was driven by the conserved total cerebral blood flow to 50% carotid stenosis (CS) (P-value, P > 0.05), which deteriorated during subsequent stages of CS (P < 0.01), and the effective collateral capability of the communicating arteries (CoAs) activated from a degree of 75% and above (P < 0.0001). The prevalence of ‘complete’ CoW peaked at 50% CS and then declined. Despite the collateral flow, the ipsilateral hemispheric perfusion was moderately reduced (P < 0.01), and the contralateral perfusion was conserved (P > 0.05), revealing the ineffectiveness of collateral capability of CoW at the extreme stages of CS. We identified bulk cerebral auto-regulation effects of the conventional Windkessel model, demonstrating accurate flow reduction in the stenosed artery.
... 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. ...
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. ...
... There are conflicting arguments in the literature regarding left-right propensity of cardiogenic emboli. Cardiogenic emboli are known to have right brain propensity owning to the fact that the RCCA branches first from the aortic arch [18,[46][47][48]. Gold et al. [47] investigated the role of arch geometry in right-left brain propensity. ...
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).
... Computational tools devised using a combination of image-based modeling, computational fluid dynamics, and discrete particle methods provide a suitable alternative to address these challenges. In prior works, we have employed such methods for understanding the transport of emboli along arteries [1], and embolus distribution to the cerebral arteries for stroke [2]. Here we provide two specific computational case-studies, that further establish the utility and efficacy of these models in addressing the aforementioned challenges, and answering key questions pertaining to stroke and thrombosis. ...
... Once created, the respective computational domains were discretized into meshes comprising linear triangular (for 2D) and tetrahedral (for 3D) elements. The incompressible Navier-Stokes equation for momentum, and the continuity equation, were then solved using a Petrov-Galerkin stabilized finite element formulation [2]. For the patient arterial hemodynamics simulations, inlet flow boundary conditions were assigned based on measured inflow profile at the aortic inlet presented in literature. ...
... Outflow resistor values at all other arterial outlets were chosen by dividing the remainder flow in proportion to their cross-sectional areas. The patient hemodynamics simulations were run for three successive cardiac cycles for convergence, and the final cardiac cycle flow-data was assumed periodic thereafter for subsequent particle transport calculations [2]. For the thrombus case-study hemodynamics simulations, the inflow boundary condition consisted of a specified parabolic velocity profile, and a standard constant pressure outflow boundary condition was employed. ...
... However, patient-specific calibration of cerebral blood flow models remains challenging due to the high anatomical variability of cerebral vasculature and the effects of cerebral autoregulation on cerebral blood flow. Previous CFD studies of cerebral hemodynamics have generally relied on modeling assumption about the flow distribution in the CoW (17,18), thereby significantly limiting the ability to capture the hemodynamic impact of stenosis, in particular the flow compensation in the CoW. ...
... However, one of the challenges in the cerebral vasculature is that the flow in each of the main arteries of the CoW is considerably controlled by the mechanisms of cerebral autoregulation in the distal vascular bed. Previous CFD modeling studies of cerebral blood flow in CAS patients have generally not accounted for these changes in the distal vasculature and instead have relied on idealized assumptions about the flow distribution in the CoW (17,18). Our proposed patient-specific model parameter tuning strategy allows to account for changes in the microvasculature and enables the quantification of collateral flow in the main pathways of the CoW additionally to capturing the pressure gradient over the stenosis. ...
Management of asymptomatic carotid artery stenosis (CAS) relies on measuring the percentage of stenosis. The aim of this study was to investigate the impact of CAS on cerebral hemodynamics using magnetic resonance imaging (MRI)-informed computational fluid dynamics (CFD) and to provide novel hemodynamic metrics that may improve the understanding of stroke risk. CFD analysis was performed in two patients with similar degrees of asymptomatic high-grade CAS. Three-dimensional anatomical-based computational models of cervical and cerebral blood flow were constructed and calibrated patient-specifically using phase-contrast MRI flow and arterial spin labeling perfusion data. Differences in cerebral hemodynamics were assessed in preoperative and postoperative models. Preoperatively, patient 1 demonstrated large flow and pressure reductions in the stenosed internal carotid artery, while patient 2 demonstrated only minor reductions. Patient 1 exhibited a large amount of flow compensation between hemispheres (80.31%), whereas patient 2 exhibited only a small amount of collateral flow (20.05%). There were significant differences in the mean pressure gradient over the stenosis between patients preoperatively (26.3 vs. 1.8 mmHg). Carotid endarterectomy resulted in only minor hemodynamic changes in patient 2. MRI-informed CFD analysis of two patients with similar clinical classifications of stenosis revealed significant differences in hemodynamics which were not apparent from anatomical assessment alone. Moreover, revascularization of CAS might not always result in hemodynamic improvements. Further studies are needed to investigate the clinical impact of hemodynamic differences and how they pertain to stroke risk and clinical management.
... The stabilisation factors τ supg and τ pspg were chosen using the element size (Franca et al., 1992;Tezduyar & Osawa, 2000), and h 0D represents the contribution to the modified form from all resistance outflow boundary conditions (Sun et al., 2019;Vignon-Clementel et al., 2006;Vignon-Clementel et al., 2010). The formulations were embedded in SimVascular (Updegrove et al., 2017), which was employed for the 3D haemodynamic simulations with patient-specific boundary conditions (Coogan et al., 2013;Mukherjee et al., 2018;Vignon-Clementel et al., 2006), and for presenting the complex flow in large artery domains (Les et al., 2010;Mukherjee et al., 2016). ...
... Furthermore, the capability of the finite element solver with customised preconditioners to analyse the blood flow in large arteries has been verified (Les et al., 2010;Mukherjee et al., 2016). The solver has been specialised using linear basis functions to optimally solve cardiovascular flows with the support of backflow stabilisation ...
We investigated differences in haemodynamic forces between carotid arteries that underwent primary closure (PC) or patch angioplasty (PA) using computational fluid dynamics (CFD). A total of 30 subjects were enrolled in this study, consisting of 10 subjects who underwent PC, 10 who underwent PA and 10 healthy subjects. Three-dimensional models of carotid arteries were reconstructed using patient-specific computed tomography angiography images. The conventional Navier-Stokes, continuity equation and constitutive stress-strain law with a stabilized Petrov-Galerkin scheme were solved with Newtonian and incompressible assumptions. The boundary conditions employed patient-specific velocity profiles as the inflow and lumped parameters of the three-element Windkessel model as the outflow with a rigid wall assumption. Thus, the CFD results exhibited good agreement with measurements from the subjects (r = .78). The carotid arteries of the PC group were exposed to abnormal haemodynamic forces related to building atherosclerosis in a smaller (p .05) to healthy arteries. The morphological characteristics of the carotid artery were significantly associated with the area exposed to abnormal haemodynamic forces. We identified that abnormal haemodynamic forces could be avoided by selecting appropriate surgical techniques that produce less bifurcation expansion.
... While patient-specific computational fluid dynamics (CFD) models have been used to study blood flow and hemodynamics in the iliac arteries [36][37][38], the downstream prostate arteries have not been studied. Additionally, Lagrangian particle tracking has been performed along with CFD simulations to create particle destination maps that predict emboli/particles that travel to the brain [39], liver [40], and lungs [41]. However, similar studies have not been performed to guide emboli injection in PAE. ...
... Blood flow was assumed periodic and potential cycle-to-cycle variability due to transitional/turbulent flow effects were not considered. The forces affecting the trajectory of the emboli were assumed to be gravity, Stokesian drag, the force due to stresses from the undisturbed flow [39], and Saffman's lift [50]. Also, it was assumed that when emboli collide with the arterial wall, they conserve 70% of their kinetic energy in the rebound. ...
Benign prostatic hyperplasia (BPH) is a common disease associated with lower urinary tract symptoms and the most frequent benign tumor in men. To reduce BPH therapy complications, prostatic artery embolization (PAE) was developed to replace the surgical options. PAE is a minimally invasive technique in which emboli are injected into the prostate arteries (PA), obstructing the blood flow in the hypervascular nodules. In this work, a personalized PAE treatment strategy was proposed using patient-specific computational fluid dynamics (CFD). First, the hemodynamics environment in the iliac arterial tree considering a large network of bifurcations was studied. The results showed complex blood flow patterns in the iliac arterial network. Subsequently, the transport of embolic particulates during PAE for the standard horizontal and a hypothetical vertical patient positioning was simulated using Lagrangian particle tracking. Emboli with different sizes were released at various locations across the iliac arterial tree. The emboli entering the PA were mapped back to their initial location to create emboli release maps (ERMs). The obtained ERMs during the standard patient positioning for smaller emboli at certain release locations showed distinct regions in which if the emboli were released within these regions, all of them would reach the PA without non-target embolization. During the hypothetical vertical patient positioning, the larger emboli formed a larger coherent region in the ERMs. Our patient-specific model can be used to find the best spatial location for emboli injection and perform the embolization procedure with minimal off-target delivery.
... However, patient-specific calibration of cerebral blood flow CFD models remains challenging. Previous studies have heavily relied on literature data for determining flow splits in the CoW (Xiao et al., 2013;Mukherjee et al., 2016) or used simplistic allometric scaling assumptions to calibrate outflow boundary conditions (Bockman et al., 2012). ...
... Previous CFD modeling studies of cerebral blood flow have relied primarily on assumptions on the flow distribution in the CoW, either based on literature data of healthy vasculatures (Xiao et al., 2013;Mukherjee et al., 2016) or allometric scaling laws (Bockman et al., 2012). However, in situations of cerebrovascular disease, the distribution of flow between the different vessels of the CoW may be substantially different from that given by idealized allometric scaling principles based on healthy data. ...
Cerebral hemodynamics in the presence of cerebrovascular occlusive disease (CVOD) are influenced by the anatomy of the intracranial arteries, the degree of stenosis, the patency of collateral pathways, and the condition of the cerebral microvasculature. Accurate characterization of cerebral hemodynamics is a challenging problem. In this work, we present a strategy to quantify cerebral hemodynamics using computational fluid dynamics (CFD) in combination with arterial spin labeling MRI (ASL). First, we calibrated patient-specific CFD outflow boundary conditions using ASL-derived flow splits in the Circle of Willis. Following, we validated the calibrated CFD model by evaluating the fractional blood supply from the main neck arteries to the vascular territories using Lagrangian particle tracking and comparing the results against vessel-selective ASL (VS-ASL). Finally, the feasibility and capability of our proposed method were demonstrated in two patients with CVOD and a healthy control subject. We showed that the calibrated CFD model accurately reproduced the fractional blood supply to the vascular territories, as obtained from VS-ASL. The two patients revealed significant differences in pressure drop over the stenosis, collateral flow, and resistance of the distal vasculature, despite similar degrees of clinical stenosis severity. Our results demonstrated the advantages of a patient-specific CFD analysis for assessing the hemodynamic impact of stenosis.
... However, patientspecific calibration of cerebral blood flow CFD models remains challenging. Previous studies have heavily relied on literature data for determining flow splits in the CoW [20] [21] or used simplistic allometric scaling assumptions to calibrate outflow boundary conditions [22]. ...
... Previous CFD modeling studies of cerebral blood flow have relied primarily on assumptions on the flow distribution in the CoW, either based on literature data of healthy vasculatures [20] [21] or allometric scaling laws [22]. However, in situations of cerebrovascular disease, the distribution of flow between the different vessels of the CoW may be substantially different from that given by idealized allometric scaling principles based on healthy data. ...
Cerebral hemodynamics in the presence of cerebrovascular occlusive disease (CVOD) are influenced by the anatomy of the intracranial arteries, the degree of stenosis, the patency of collateral pathways, and the condition of the cerebral microvasculature. Accurate characterization of cerebral hemodynamics is a challenging problem. In this work, we present a strategy to quantify cerebral hemodynamics using computational fluid dynamics (CFD) in combination with arterial spin labeling MRI (ASL). First, we calibrated patient-specific CFD outflow boundary conditions using ASL-derived flow splits in the Circle of Willis. Following, we validated the calibrated CFD model by evaluating the fractional blood supply from the main neck arteries to the vascular territories using Lagrangian particle tracking and comparing the results against vessel-selective ASL (VS-ASL). Finally, cerebral hemodynamics were assessed in two patients with CVOD and a healthy control subject. We demonstrated that the calibrated CFD model accurately reproduced the fractional blood supply to the vascular territories, as obtained from VS-ASL. The two patients revealed significant differences in pressure drop over the stenosis, collateral flow, and resistance of the distal vasculature, despite similar degrees of clinical stenosis severity. Our results demonstrated the advantages of a patient-specific CFD analysis for assessing the hemodynamic impact of stenosis.
... Cardiogenic emboli have been observed to have right brain propensity, due to the first vessel branching from the aortic arch being the RCCA. [42][43][44] Other clinical data suggest left hemisphere strokes are more common than right hemisphere strokes, as cardioembolic ischemic strokes in the left middle cerebral artery (MCA) are more frequent due to vessel thickness and geometry. 19,45,46 Differences have also been detected in the number and size of left and right ischemic lesions. ...
... The BCT did experience the most trajectories probably because it branches first from the aortic arch, in agreement with previous work. [42][43][44] However, variations in branching in aortic arch models would allow for future studies to fully understand this relationship between RCCA and LCCA propensity in stroke occurrence and arch geometry. ...
Atrial fibrillation is the most significant contributor to thrombus formation within the heart and is responsible for 45% of all cardio embolic strokes, which account for approximately 15% of acute ischemic strokes cases worldwide. Atrial fibrillation can result in a reduction of normal cardiac output and cycle length of up to 30% and 40%, respectively. A total of 240 embolus analogues were released into a thin-walled, patient-specific aortic arch under normal (60 embolus analogues) and varying atrial fibrillation (180 embolus analogues) pulsatile flow conditions. Under healthy flow conditions (n = 60), the embolus analogues tended to follow the flow rate split through each outlet vessel. There was an increase in clot trajectories along the common carotid arteries under atrial fibrillation flow conditions. A shorter pulse period (0.3 s) displayed the highest percentage of clots travelling to the brain (24%), with a greater percentage of clots travelling through the left common carotid artery (17%). This study provides an experimental insight into the effect varying cardiac output and cycle length can have on the trajectory of a cardiac source blood clots travelling to the cerebral vasculature and possibly causing a stroke.
... Finally, the use of rigid walls can be considered a further limitation, but according to the purpose of the study, the choice is specifically made to enable the integration of the in vitro setup with CFD analysis. Furthermore, with steady flow there is no benefit in applying a compliant wall model, and the rigid wall hypothesis is considered valid in the most advanced computer-based simulations about cerebral embolism 27 while the impact of wall compliance on the embolic distribution along arterial circulation is still unknown. Despite the steady flow assumption seems reasonable because pulse pressure is damped during rapid ventricular pacing of TAVI, 48 further studies should include different hemodynamic conditions resembling the various stages of TAVI implant; at the same, further clinical data quantifying intra-operative aortic hemodynamics are necessary. ...
... In the present study, we limited the use of CFD simulations to the assessment of optimal reversal flow from RSA, although its potentiality in the analysis of cerebral embolism is high as proved by the growing interest for the numerical simulations of particle behavior in complex arterial networks. 3,12,27,28,41 Following such a trend, future developments of the present study will account for a stronger integration of in vitro and in silico tools, based on the implementation of dedicated numerical algorithms able to model inertial dynamics of the particles, which we considered massless, a reasonable hypothesis given the size of the particles (0.5 mm) under investigation. 8 Lastly, the present study uses the weight as the method to evaluate particle destination according to similar previous studies. ...
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.
... 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]. ...
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.
... This approach has been used to study embolus dynamics for scenarios involving key arterial vascular segments in the cerebral vasculature [11,12], for studying embolus transport risks from mechanical circulatory support devices [13], and for studying embolism risks in venous circulation for application in IVC filter assessment [14]. In a series of prior works [15][16][17][18][19], we have developed one of the most extensive computational modeling frameworks for embolus-hemodynamics interactions. In this framework, we model the embolus source to destination mapping across the entire heart-to-brain arterial pathway; and using a Monte-Carlo type sampling approach, we have generated key insights on: (a) size dependent transport patterns of emboli; (b) cardiogenic vs aortogenic vs carotid sources of emboli and how the source manifests in their distribution; and (c) the role of the Circle of Willis anastomosis and flow routing in determining embolus transport. ...
Interactions of particles with unsteady non-linear viscous flows has widespread implications in physiological and biomedical systems. One key application where this plays a fundamental role is in the mechanism and etiology of embolic strokes. Specifically, there is a need to better understand how large occlusive emboli traverse complex vascular geometries, and block a vessel disrupting blood supply. Existing modeling approaches resort to key simplifications in terms of embolic particle shape, size, and their coupling to fluid flow. Here, we devise a novel computational model for resolving embolus-hemodynamics interactions for large non-spherical emboli approaching near occlusive regimes in anatomically real vascular segment. The formulation relies on extending an immersed finite element approach, coupled with a six degree-of-freedom particle dynamics model. The geometric complexities and their manifestation in embolus-flow and embolus-wall interactions are handles using a parametric shape representation, and projection of vessel signed distance fields on the particle boundaries. We illustrate our methodology and algorithmic details, as well as present examples of benchmark cases and convergence of our technique. Thereafter, we demonstrate a parametric study of large emboli for LVO strokes, showing that our methodology can capture the non-linear tumbling dynamics of emboli originating form their interactions with the flow and vessel walls; and resolve near-occlusive scenarios involving lubrication effects around the embolus and flow re-routing to non-occludes branches. This is a key methodological advancement in stroke modeling, as to the best of our knowledge this is the first modeling framework for LVO stroke and occlusion biofluid mechanics. Finally, even though we present our framework from the perspective of LVO strokes, the methodology as developed is broadly generalizable to two-way coupled fluid-particle interaction in unsteady viscous flows for a wide range of applications.
... The anatomy of a healthy aorta has diverse applications, including the investigation of hemodynamics and thrombi transport within the aorta. For instance, it aids in the cardiogenic embolic stroke risk assessment, stroke location prediction, and understanding of stroke etiology and arterial embolism (26,27). Additionally, they are utilized in the context of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute cardiogenic shock patients (28), and in benchmarking numerical studies in cardiovascular settings for boundary conditions (29), as well as exploring the effect of blood rheology modeling in aorta (30). ...
Background
The aorta, a central component of the cardiovascular system, plays a pivotal role in ensuring blood circulation. Despite its importance, there is a notable lack of idealized models for experimental and computational studies.
Objective
This study aims to develop computer-aided design (CAD) models for the idealized human aorta, intended for studying hemodynamics or solid mechanics in both in vitro and in silico settings.
Methods
Various parameters were extracted from comprehensive literature sources to evaluate major anatomical characteristics of the aorta in healthy adults, including variations in aortic arch branches and corresponding dimensions. The idealized models were generated based on averages weighted by the cohort size of each study for several morphological parameters collected and compiled from image-based or cadaveric studies, as well as data from four recruited subjects. The models were used for hemodynamics assessment using particle image velocimetry (PIV) measurements and computational fluid dynamics (CFD) simulations.
Results
Two CAD models for the idealized human aorta were developed, focusing on the healthy population. The CFD simulations, which align closely with the PIV measurements, capture the main global flow features and wall shear stress patterns observed in patient-specific cases, demonstrating the capabilities of the designed models.
Conclusions
The collected statistical data on the aorta and the two idealized aorta models, covering prevalent arch variants known as Normal and Bovine types, are shown to be useful for examining the hemodynamics of the aorta. They also hold promise for applications in designing medical devices where anatomical statistics are needed.
... Lower dimensional fluid mechanics studies (i.e., 0D, 1D and 2D) have previously been used to model the arterial tree leading to the cerebrovasculature, or within the eye, in attempts to understand disease development such as glaucoma 7 , diabetic retinopathy 8 , hyper-and hypotension 9 as well as the effects of spaceflight or ground-based HDT experiments 4,10 . Studies have simulated blood flow within large arterial networks for the purposes of understanding pulse wave velocity propagation and age-related arterial stiffening 11 , arterial particle and embolism transport 12,13 , calculation of the ankle-brachial index 14 , effect of venoarterial extracorporeal membrane oxygenation 15 and demonstration of meshing strategies and computational optimisation 16 . Previous large-scale simulations have also encountered challenges in accurately evaluating localised haemodynamic metrics such as WSS due to computational limitations 11 . ...
We investigated variations in haemodynamics in response to simulated microgravity across a semi-subject-specific three-dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth gravity case and a simulated microgravity case. Under simulated microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates that 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data—specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to simulated microgravity, relative to an upright position in Earth gravity.
... Stroke can arise from multiple mechanisms wherein the local hemodynamic environment plays a pivotal role in embolism [38]. The transport of cardiogenic plaque (i.e., 'red' thrombi) depends on the mechanical properties of the cardio-cerebrovascular system [39]. ...
Extant clinical research has underscored that patients suffering from atrial fibrillation (AF) bear an elevated risk for stroke, predominantly driven by the formation of thrombus in the left atrial appendage (LAA). As such, accurately identifying those at an increased risk of thrombosis becomes paramount to facilitate timely and effective treatment. This study was designed to shed light on the mechanisms underlying thrombus formation in the LAA by employing three-dimensional (3D) left atrium (LA) models of AF patients, which were constructed based on Computed Tomography (CT) imaging. The distinct benefits of Computational Fluid Dynamics (CFD) were leveraged to simulate the blood flow field within the LA, using three distinct blood flow models, both under AF and sinus rhythm (SR) conditions. The potential risk of thrombus formation was evaluated by analyzing the Relative Residence Time (RRT) and Endothelial Cell Activation Potential (ECAP) values. The results gleaned from this study affirm that all three blood flow models align with extant clinical guidelines, thereby enabling an effective prediction of thrombosis risk. However, noteworthy differences emerged when comparing the intricacies of the flow field and thrombosis risk across the three models. The single-phase non-Newtonian blood flow model resulted in comparatively lower residence times for blood within the LA and lower values for the Oscillatory Shear Index (OSI), RRT, and ECAP within the LAA. These findings suggest a reduced thrombosis risk. Conversely, the two-phase non-Newtonian blood flow model exhibited a higher residence time for blood and elevated RRT value within the LAA, suggesting an increased risk for thrombosis.
... 0D, 1D and 2D) have previously been used to model the arterial tree leading to the cerebrovasculature, or within the eye, in attempts to understand disease development such as glaucoma 7 , diabetic retinopathy 8 , hyper-and hypotension 9 as well as the effects of space ight or ground based HDT experiments 4,10 . Studies have simulated blood ow within large arterial networks for the purposes of understanding pulse wave velocity propagation and age-related arterial stiffening 11 , arterial particle and embolism transport 12,13 , calculation of the ankle-brachial index 14 , effect of venoarterial extracorporeal membrane oxygenation 15 and demonstration of meshing strategies and computational optimization 16 . However, no studies have utilised 3D CFD simulations to evaluate the haemodynamics within larger arteries such as the aorta through to the retinal arterioles within the eye, particularly in response to extreme environments such as space ight. ...
We investigated variations in haemodynamics in response to microgravity across a semi-subject specific three dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth-gravity case and a microgravity case. Under microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data – specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to microgravity, relative to an upright position in Earth-gravity.
... Computational models offer the possibility to flexibly address these questions, and to embrace the complexity of the treatment and its many variables without endangering patients. To study the CoW, researchers have produced three dimensional representations of the complete network (19) and its most common anatomical variations (20). The treatment of a 3D problem in computational fluid dynamics (CFD) involves the solution of the Navier-Stokes equations. ...
The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome. In this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments.
... Various numerical methods have previously been used to understand the motion of emboli through the cerebral vasculature. On the large vessel scale, the motion of emboli through various circle of Willis (CoW) variations has been studied using computational fluid dynamics (CFD), neglecting small vessels or embolus-flow interactions 11,12 . On the cellular scale, models including ion channels, cell metabolism and apoptosis have been used to study penumbra and lesion evolution following stroke [13][14][15] . ...
Stroke simulations are needed to run in-silico trials, develop hypotheses for clinical studies and to interpret ultrasound monitoring and radiological imaging. We describe proof-of-concept three-dimensional stroke simulations, carrying out in silico trials to relate lesion volume to embolus diameter and calculate probabilistic lesion overlap maps, building on our previous Monte Carlo method. Simulated emboli were released into an in silico vasculature to simulate 1000 s of strokes. Infarct volume distributions and probabilistic lesion overlap maps were determined. Computer-generated lesions were assessed by clinicians and compared with radiological images. The key result of this study is development of a three-dimensional simulation for embolic stroke and its application to an in silico clinical trial. Probabilistic lesion overlap maps showed that the lesions from small emboli are homogeneously distributed throughout the cerebral vasculature. Mid-sized emboli were preferentially found in posterior cerebral artery (PCA) and posterior region of the middle cerebral artery (MCA) territories. For large emboli, MCA, PCA and anterior cerebral artery (ACA) lesions were comparable to clinical observations, with MCA, PCA then ACA territories identified as the most to least probable regions for lesions to occur. A power law relationship between lesion volume and embolus diameter was found. In conclusion, this article showed proof-of-concept for large in silico trials of embolic stroke including 3D information, identifying that embolus diameter could be determined from infarct volume and that embolus size is critically important to the resting place of emboli. We anticipate this work will form the basis of clinical applications including intraoperative monitoring, determining stroke origins, and in silico trials for complex situations such as multiple embolisation.
... Current evidence indicates that better preservation of cognitive performance might be expected postoperatively when GME is reduced. 18 Despite a threshold of GMEpost volume to avoid the occurrence of postoperative cognitive decline not being established, [37][38][39] our results suggest that the HAR procedure may contribute to reducing such clinical outcomes. These clinical effects on postoperative cognitive performance are being explored in further stages of this clinical trial. ...
Particulate and gaseous microemboli (GME) are side effects of cardiac surgery that interfere with postoperative recovery by causing endothelial dysfunction and vascular blockages. GME sources during surgery are multiple, and cardiopulmonary bypass (CPB) is contributory to this embolic load. Hematic antegrade repriming (HAR) is a novel procedure that combines the benefits of repriming techniques with additional measures, by following a standardized procedure to provide a reproducible hemodilution of 300 ml. To clarify the safety of HAR in terms of embolic load delivery, a prospective and controlled study was conducted, by applying Doppler probes to the extracorporeal circuit, to determine the number and volume of GME released during CPB. A sample of 115 patients (n = 115) was considered for assessment. Both groups were managed under strict normothermia, and similar clinical conditions and protocols, receiving the same open and minimized circuit. Significant differences in GME volume delivery (control group [CG] = 0.28 ml vs. HAR = 0.08 ml; p = 0.004) and high embolic volume exposure (>1 ml) were found between the groups (CG = 30.36% vs. HAR = 4.26%; p = 0.001). The application of HAR did not represent an additional embolic risk and provided a four-fold reduction in the embolic volume delivered to the patient (coefficient, 0.24; 95% CI, 0.08-0.72; p = 0.01), which appears to enhance GME clearance of the oxygenator before CPB initiation.
... Embolic particle transport has been computationally modelled within reconstructed three-dimensional human anatomical models of arterial sections; aortic arches, circle of Willis, bifurcations, carotid and vertebral arteries. 16,24,[61][62][63] Embolus and vessel wall anatomical and biomechanical properties were studied. Mukherjee et al. 62 outlined a momentum balance governing fluid-particle interactions for emboli, where the motion of particles within simulated vasculature is modelled via a modified form of the Maxey-Riley 55 equation. ...
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.
... The origin of emboli during cardiac surgery is difficult to identify [11], but two possible sources of GME are the heart-lung machine [12] and the blood-air contact at the surgical site [13], where air bubbles form in the pulmonary veins, the heart or in the aorta, and then are pushed towards the periphery during the first heartbeats. Air bubbles can be created at different steps of the surgery [1,14], but it is not clearly understood which is the most threatening source. ...
Background
During cardiac surgery, micro-air emboli regularly enter the blood stream and can cause cognitive impairment or stroke. It is not clearly understood whether the most threatening air emboli are generated by the heart-lung machine (HLM) or by the blood-air contact when opening the heart. We performed an in vitro study to assess, for the two sources, air emboli distribution in the arterial tree, especially in the brain region, during cardiac surgery with different cannulation sites.
Methods
A model of the arterial tree was 3D printed and included in a hydraulic circuit, divided such that flow going to the brain was separated from the rest of the circuit. Air micro-emboli were injected either in the HLM (“ECC Bubbles”) or in the mock left ventricle (“Heart Bubbles”) to simulate the two sources. Emboli distribution was measured with an ultrasonic bubble counter. Five repetitions were performed for each combination of injection site and cannulation site, where air bubble counts and volumes were recorded. Air bubbles were separated in three categories based on size.
Results
For both injection sites, it was possible to identify statistically significant differences between cannulation sites. For ECC Bubbles, axillary cannulation led to a higher amount of air bubbles in the brain with medium-sized bubbles. For Heart Bubbles, aortic cannulation showed a significantly bigger embolic load in the brain with large bubbles.
Conclusions
These preliminary in vitro findings showed that air embolic load in the brain may be dependent on the cannulation site, which deserves further in vivo exploration.
... Emerging models can now incorporate wall thickness, fibrosis, and fiber organization to resolve relationships between electrophysiology and wall mechanics [63] and fluid-structure interactions [64]. In the case of stroke, novel multi-scale CFD analyses can calculate the biochemical coagulation cascade, the polymerization of fibrin, and platelet aggregation [65], as well as embolus transport towards the brain [66]. However, full electro-mechanical-chemo-fluidic models that integrate all these factors in patient-specific configurations are still missing. ...
The current paradigm of stroke risk assessment and mitigation in patients with atrial fibrillation (AF) is centred around clinical risk factors which, in the presence of AF, lead to thrombus formation. The mechanisms by which these clinical risk factors lead to thromboembolism, including any role played by atrial fibrosis, are not understood. In patients who had embolic stroke of undetermined source (ESUS), the problem is compounded by the absence of AF in a majority of patients despite long-term monitoring. Atrial fibrosis has emerged as a unifying mechanism that independently provides a substrate for arrhythmia and thrombus formation. Fibrosis-based computational models of AF initiation and maintenance promise to identify therapeutic targets in catheter ablation. In ESUS, fibrosis is also increasingly recognised as a major risk factor, but the underlying mechanism of this correlation is unclear. Simulations have uncovered potential vulnerability to arrhythmia induction in patients who had ESUS. Likewise, computational models of fluid dynamics representing blood flow in the left atrium and left atrium appendage have improved our understanding of thrombus formation, in particular left atrium appendage shapes and blood flow changes influenced by atrial remodelling. Multiscale modelling of blood flow dynamics based on structural fibrotic and morphological changes with associated cellular and tissue electrical remodelling leading to electromechanical abnormalities holds tremendous promise in providing a mechanistic understanding of the clinical problem of thromboembolisation. We present a review of clinical knowledge alongside computational modelling frameworks and conclude with a vision of a future paradigm integrating simulations in formulating personalised treatment plans for each patient.
... [22]. This commercial software package allows for multi-planer reconstruction of images and modelling of vasculatures, and has been used in numerous cardiovascular and neurovascular studies [23][24][25]. Tracing was manually performed by a radiologist (with 2-year experience in MRI image interpretation) who recursively screened the MinIP/MIP images and delineated the centre points along each visible arterial segment. Tracing continued as long as the contrast ratio (CR) between LSA lumen and adjacent tissue was above 1.3. ...
Objectives
The objective of this study was to explore the feasibility of using intracranial T1-weighted vessel wall imaging (VWI) to visualize the lenticulostriate arteries (LSAs) at 3T.
Material and methods
Thirteen healthy volunteers were examined with VWI at 3T and TOF-MRA at 7T during the same day. On the vascular skeletons obtained by manual tracing, the number of stems and branches of LSAs were counted. On the most prominent branch in every hemisphere, the contrast-to-noise ratio (CNR), the full length and the local length (5-15 mm above MCAs) were measured and compared between the two methods. Nine stroke patients with intracranial artery stenosis were also recruited into the study. The branches of LSAs were compared between the symptomatic and asymptomatic side.
Results
The extracted vascular trees were in good agreement between 7T TOF-MRA and 3T VWI. The two acquisitions showed similar numbers of the LSA stems. The number of branches revealed by 3T VWI was slightly lower than 7T TOF. The full lengths were slightly lower by VWI at 3T (p = 0.011, ICC = 0.917). The measured local lengths (5-15 mm from MCAs) showed high coherence between VWI and TOF-MRA (p = 0.098, ICC = 0.970). In stroke patients, 12 plaques were identified on MCA segments, and nine plaques were located on the symptomatic side. The average numbers of LSA visualized by 3T VWI were 4.3±1.3 on the symptomatic side and 5.0±1.1 on the asymptomatic side.
Conclusion
3T VWI is capable of depicting LSAs, particularly the stems and the proximal segments, with comparable image quality to that of 7T TOF-MRA.
Key Points
• T1-weighted intracranial VWI at 3T allows for black-blood MR angiography of lenticulostriate artery.
• 3T intracranial VWI depicts the stems and proximal segments of the lenticulostriate arteries comparable to 7T TOF-MRA.
• It is feasible to assess both large vessel wall lesions and lenticulostriate vasculopathy in one scan.
... Particle-based methods in general have enjoyed prominence in many biological applications. Particularly in cardiovascular applications, particle-based approaches have been used to study blood flow and platelet biomechanics (Yamaguchi et al. 2010), and transport of emboli for predicting stroke risks (Mukherjee et al. 2016), among other applications. Discrete element or particle-based methods offer particular advantages in terms of representing complex geometries and micromechanical features, and handling events like fragmentation, aggregation, growth, and restructuring/remodeling. ...
A hybrid, multiscale, particle–continuum numerical method is developed for resolving the interaction of a realistic thrombus geometry with unsteady hemodynamics typically occurring within large arteries. The method is based on a discrete particle/element description of the thrombus, coupled to blood flow using a fictitious domain finite element method. The efficacy of the discrete element approach in representing thrombi with arbitrary aggregate morphology and microstructure is demonstrated. The various features of the method are illustrated using a series of numerical experiments with a model system consisting of an occlusion embedded in a channel. The results from these numerical experiments establish that this approach can resolve the complex macroscale flow structures emanating from unsteady hemodynamics interacting with a thrombus. Simultaneously, it can also resolve micromechanical features, and microscale intra-thrombus flow and perfusion. Using a staggering algorithm, the method can further capture hemodynamics around time-varying thrombus manifolds. This is established using a numerical simulation of lysis of an idealized clot. The hybrid particle–continuum description of thrombus–hemodynamics interaction mechanics, and the unified treatment of macroscale as well as microscale flow and transport, renders significant advantages to the proposed method in enabling further investigations of physiological interest in thrombosis within patient-specific settings.
... Collagen I Stenosed tube In-vitro pig 1.2-2. Badimon and Badimón (1989) Tunica media Stenosed tubes Ex vivo pig 60 424-50000 10 Mailhac et al. (1994) Injured artery Stenosis In vivo dog 113-233 13000-82000 Strony et al. (1993) Injury artery Stenosis In vivo dog 80 300-53000Folts (1991) Human atheroma U channel Ex vivo pig 60 1690 5 Fernández Ortiz et al. (1994) ePTFE with ECs, collagen, fibronectin Tubes Ex vivo baboon 64 106 60 Dichek (1997) Fogelson (1992) Platelet activation and aggregation Continuum, ADR equations Sorensen et al. (1999a;1999b) Platelet adhesion, aggregation, and activation Continuum, ADR equations In-vitro 100-1000 Fogelson et al. (2003) Coagulation, platelet aggregation Discrete, IBM Goodman et al. (2005) Embolism, platelet adhesion, aggregation, and activation Continuum, ADR equations In-vitro 650-5800 Pivkin et al. (2006) Platelet adhesion, activation and aggregation Discrete, force coupling12-96 Filipovic et al. (2008) Platelet adhesion, activation and aggregation Discrete, DPD model In-vitro 500-1500 Tosenberger et al. (2013) Embolism, platelet adhesion and aggregation Discrete and continuum, DPD-PDE hybrid model In-vivo 3000 Mehrabadi et al. (2015) Platelet margination Continuum, DFEB In-vitro 50-500 Mukherjee et al. (2016) Embolism Discrete, one-way coupled DPM1000-200,000 Figure 1. The platelet adhesion, activation, and aggregation mechanism. ...
The paper reviews the state‐of‐the‐art in computational modeling of thrombus formation and growth and related phenomena including platelet margination, activation, adhesion, and embolization. Presently, there is a high degree of empiricism in the modeling of thrombus formation. Based on the experimentally observed physics, the review gives useful strategies for predicting thrombus formation and growth. These include determining blood components involved in atherosclerosis, effective blood viscosity, tissue properties, and methods proposed for boundary conditions. In addition to the guidelines, ongoing research on the effect of shear stress on platelet margination, activation and adhesion, and platelet‐surface interactions are reviewed. Biotechnol. Bioeng. 2017;114: 2154–2172. © 2017 Wiley Periodicals, Inc.
... Wall shear-gradient effects in the recirculation zone distal to the apex (see Fig. 10b and c), shear rates as high as 2300 sec -1 and vortex shedding in stenotic blood flows can lead to embolization (61,(66)(67)(68). Detachment of platelet aggregates from thrombi formed on the stenosis can occur followed by convection of emboli downstream (69). ...
Shear stresses play a major role in platelet-substrate interactions and thrombus formation and growth in blood flow, where under both pathological and physiological conditions platelet adhesion and accumulation occur. In this study, a shear-dependent continuum model for platelet activation, adhesion and aggregation is presented. The model was first verified under three different shear conditions and at two heparin levels. Three-dimensional simulations were then carried out to evaluate the performance of the model for severely damaged (stripped) aortas with mild and severe stenosis degrees in laminar flow regime. For these cases, linear shear-dependent functions were developed for platelet-surface and platelet-platelet adhesion rates. It was confirmed that the platelet adhesion rate is not only a function of Reynolds number (or wall shear rate) but also the stenosis severity of the vessel. General correlations for adhesion rates of platelets as functions of stenosis and Reynolds number were obtained based on these cases. Finally using the new platelet adhesion rates, the model was applied to different experimental systems and shown to agree well with measured platelet deposition.
... Files can be exported to VTK formats to facilitate visualization of the data in leading open source scientific visualization softwares such as ParaView and VisIt, as well as more custom postprocessing by applying VTK classes and filters, which can be scripted using Python. For example, recent studies have analyzed flow fields produced by SimVascular to compute Lagrangian coherent structures, 3,4,6,55 residence times in aneurysms, 57,58 turbulent kinetic energy, 1,29 particle tracking, 43,46 and to model surface transport processes relevant for thrombosis. 2,21 ...
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.
Local administration of thrombolytics in ischemic stroke could accelerate clot lysis and the ensuing reperfusion while minimizing the side effects of systemic administration. Medical microrobots could be injected into the bloodstream and magnetically navigated to the clot for administering the drugs directly to the target. The magnetic manipulation required to navigate medical microrobots will depend on various parameters such as the microrobots size, the blood velocity, and the imposed magnetic field gradients. Numerical simulation was used to study the motion of magnetically controlled microrobots flowing through representative cerebral bifurcations, for predicting the magnetic gradients required to navigate the microrobots from the injection point until the target location. Upon thorough validation of the model against several independent analytical and experimental results, the model was used to generate maps and a predictive equation providing quantitative information on the required magnetic gradients, for different scenarios. The developed maps and predictive equation are crucial to inform the design, operation and optimization of magnetic navigation systems for healthcare applications.
Neurological complexities resulting from surgery requiring cardiopulmonary bypass (CPB) remain a major concern, encompassing a spectrum of complications including thromboembolic stroke and various cognitive impairments. Surgical manipulation during CPB is considered the primary cause of these neurological complications. This study addresses the overall lack of knowledge concerning CPB hemodynamics within the aorta, employing a combined experimental-computational modeling approach, featuring computational fluid dynamics simulations validated with an in vitro CPB flow loop under steady conditions. Parametric studies were systematically performed, varying parameters associated with CPB techniques (pump flow rate and hemodiluted blood viscosity) and properties related to formed emboli (size and density). This represents the first comprehensive investigation into the individual and combined effects of these factors. Our findings reveal critical insights into the operating conditions of CPB, indicating a positive correlation between pump flow rate and emboli transport into the aortic branches, potentially increasing the risk of stroke. It was also found that larger emboli were more often transported into the aortic branches at higher pump flow rates, while smaller emboli preferred lower flow rates. Further, as blood is commonly diluted during CPB to decrease its viscosity, more emboli were found to enter the aortic branches with greater hemodilution. The combined effects of these parameters are captured using the non-dimensional Stokes number, which was found to positively correlate with emboli transport into the aortic branches. These findings contribute to our understanding of embolic stroke risk factors during CPB and shed light on the complex interplay between CPB parameters.
This article presents a broad overview of the fluid mechanics of the human cardiovascular system. Beginning in the heart, we travel through the main features of our circulation to highlight important functions and diseases where fluid mechanics plays a central role. Of particular focus is the role of computational modelling in uncovering the dynamic flow phenomenon throughout our body, its association with cardiovascular disease mechanisms and progression and its importance in clinical treatment planning. We also emphasize the multiscale nature of the cardiovascular system, and associated challenges. The main aim of this review is to highlight progress and ongoing challenges in our understanding of cardiovascular haemodynamics, as well as the future outlook for translating the current state-of-the-art to widespread clinical application and improved patient outcomes.
Acute ischemic stroke (AIS) is a leading cause of mortality that occurs when an embolus becomes lodged in the cerebral vasculature and obstructs blood flow in the brain. The severity of AIS is determined by the location and how extensively emboli become lodged, which are dictated in large part by the cerebral flow and the dynamics of embolus migration which are difficult to measure in vivo in AIS patients. Computational fluid dynamics (CFD) can be used to predict the patient-specific hemodynamics and embolus migration and lodging in the cerebral vasculature to better understand the underlying mechanics of AIS. To be relied upon, however, the computational simulations must be verified and validated. In this study, a realistic in vitro experimental model and a corresponding computational model of the cerebral vasculature are established that can be used to investigate flow and embolus migration and lodging in the brain. First, the in vitro anatomical model is described, including how the flow distribution in the model is tuned to match physiological measurements from the literature. Measurements of pressure and flow rate for both normal and stroke conditions were acquired and corresponding CFD simulations were performed and compared with the experiments to validate the flow predictions. Overall, the CFD simulations were in relatively close agreement with the experiments, to within ±7% of the mean experimental data with many of the CFD predictions within the uncertainty of the experimental measurement. This work provides an in vitro benchmark data set for flow in a realistic cerebrovascular model and is a first step towards validating a computational model of AIS.
Progression of carotid stenosis (CS) significantly reduces blood flow in the affected arteries and alters both proximal and distal hemodynamics. While conventional studies consider only the stenosis region for analysis, an extended larger arterial domain of aortic–cerebral vasculature is used to avoid artificial modeling of the inlet condition to the carotid region and facilitate automatic flow redistribution during CS progression. The fluid domain was constructed and simulated using an open-source package SimVascular, and three patient models with five stenosis cases each were created using medical images. Newtonian, incompressible, and rigid-wall conditions were assumed because of the high computational burden, and boundary conditions of the lumped Windkessel and pulsatile flow rate were implemented for the outlets and inlet, respectively. We present a novel index called circulation core fraction (CCF) to quantify and visualize the stenosis-driven hemodynamics; the CCF is developed from the benchmark backward-facing step problem and compares the representative recirculation to the total volume. Thus, CCF in the post-stenotic region increases during CS progression regardless of patient-specific features whereas that in the pre-stenotic region exhibits patient-specific nature despite the incremental tendency. Streamlines with custom sources show a helical vortex with recirculation and artery-wise flow streams that vary during CS progression. We also report transitional patterns in both the pulsatility index (PI) contours and Q-criterion, where the PI values shift from high–low–high to high–low–low across the stenosis, and the latter is nearly absent at 0% and 95% but mostly present at 50% and 75% CS.
Acute ischemic stroke (AIS) is a leading cause of mortality that occurs when a blood embolus becomes lodged in the cerebral vasculature and obstructs blood flow in the brain. The severity of AIS is determined by the location and how extensively emboli become lodged, which is dictated in large part by the cerebral flow and the dynamics of embolus migration that are difficult to measure in vivo in AIS patients. Computational fluid dynamics (CFD) can be used to predict the patient-specific hemodynamics and embolus migration and lodging in the cerebral vasculature to better understand the underlying mechanics of AIS. To be relied upon, however, the computational simulations must be verified and validated. In this study, a realistic in vitro experimental model and a corresponding computational model of the cerebral vasculature are established that can be used to investigate flow and embolus migration and lodging in the brain. First, the in vitro anatomical model is described and how the flow distribution in the model is tuned to match physiological measurements from the literature. Measurements of pressure and flow rate for both normal and stroke conditions were acquired and corresponding CFD simulations were performed and compared with the experiments to validate the flow predictions. Overall, the CFD simulations were in relatively close agreement with the experiments, to within ±7% of the mean experimental data with many of the CFD predictions within the uncertainty of the experimental measurement. This work provides an in vitro benchmark data set for flow in a realistic cerebrovascular model and is a first step towards validating an AIS computational model.
The flow features in branching networks are fundamental for the understanding of transport processes in respiratory and cardiovascular systems. Specifically for tumor embolization, the ability to predict the fate of finite-size particles in bifurcating vessels is highly desirable for improving embolization efficacy. Most past studies focused on very dilute regimes in which particles are not expected to interact with each other. In the present study, we use particle tracking velocimetry to investigate the spatial distribution, velocity, acceleration, and dispersion of finite-size particles in a four-generation bifurcating model. We consider a regime especially relevant to vascular embolization: a physiologic range of bulk flow Reynolds number and a suspension of neutrally buoyant particles with a diameter about 10 times smaller than the parent vessel diameter, reaching solid volume fractions up to 2%. We investigate how particles distribute among the distal branches and the influence of the release location. In addition, the effect of particle volume fraction is studied through Lagrangian statistics of the particle trajectories. Our results show the remarkable influence of particle concentration on particle transport in several ways. The particle traveling speed, acceleration, and dispersion are inhibited by the increasing particle volume fraction due to interparticle interactions. Importantly, the particles travel preferentially to the medial branches rather than to the lateral ones despite the uniform distribution of the distal volumetric flow rate. The findings provide insights relevant to the optimization of targeted drug delivery in embolization settings.
Background: Various computational models of the circle of Willis (CoW) have been developed to non-invasively estimate the blood flow and hemodynamic parameters in intracranial arteries for the assessment of clinical risks such as aneurysms, ischemia, and atherosclerotic plaque growth. This review aims to categorize the latest computational models of CoW and summarize the innovative techniques. Summary of Review: In traditional computational models of CoW, the computational complexity increased from zero-dimensional models to one-dimensional and three-dimensional models. The applications extend from estimating certain hemodynamic parameters to simulating local flow field. The innovative techniques include the combination of models with different dimensions, the extension of vascular structure including heart and veins, as well the addition of distal fractality, cerebral autoregulation, and intracranial pressure. There are some nontraditional models based on fluid-solid-interaction, control theory, and in-vitro experiments. In all kinds of models, the in-vivo data and non-Newtonian rheological models of blood have been widely applied to improve the accuracy of hemodynamic simulation. Conclusion: Firstly, the selection of model depends on its application scenario. The balance between computational complexity and physiological accuracy deserves further investigation. Secondly, the improvement of CoW models relies on the large-scale validations and the combination of various innovative modeling techniques.
Purpose
There has been interest in recent work in using computational fluid dynamics with Lagrangian analysis to calculate the trajectory of emboli-like particles in the vasculature. While previous studies have provided an understanding of the hemodynamic factors determining the fates of such particles and their relationship to risk of stroke, most analyses have relied on a particle equation of motion that assumes the particle is “small” e.g., much less than the diameter of the vessel. This work quantifies the limit when a particle can no longer be considered “small”.
Methods
The motion of embolus-like particles are simulated using an overset mesh technique. This allows the fluid stresses on the particle surface to be fully resolved. Consequently, the particles can be of arbitrary size or shape. The trajectory of resolved particles and “small” particles are simulated through a patient-specific carotid artery bifurcation model with particles 500, 1000, and 2000 μm in diameter. The proportions of particles entering the internal carotid artery are treated as the outcome of the particle fate, and statistical comparisons are made to ascertain the importance of non-small particle effects.
Results
For the 2000 μm embolus, the proportion of particles traveling to the internal carotid artery is 74.7 ± 1.3% (mean ± 95% confidence margin) for the “small” particle model and is 85.7 ± 5.4% for a resolved particle model. The difference is statistically significant, , based on the binomial test for the particle outcomes. No statistically discernible differences are found for the smaller diameter particles.
Conclusions
Quantitative differences are observable for the 2000 μm trajectories between the “small” and resolved particle models which is a particle diameter 27% relative to the common carotid artery diameter. A fully resolved particle model ought to be considered for emboli trajectory simulations when the particle size ratio is ≳ 20%.
To reach a predictive understanding of how particles travel through bifurcating vessels is of paramount importance in many biomedical settings, including embolization, thromboembolism, and drug delivery. Here we utilize an in vitro model in which solid particles are injected through a rigid vessel that symmetrically bifurcates in successive branching generations. The geometric proportion and fluid dynamics parameters are relevant to the liver embolization. The volumetric flow field is reconstructed via phase-contrast magnetic resonance imaging, from which the particle trajectories are calculated for a range of size and density using the particle equation of motion. The method is validated by directly tracking the injected particles via optical imaging. The results indicate that, opposite to the common assumption, the particles distribution is fundamentally different from the volumetric flow partition. In fact, the amount of delivered particles vary substantially between adjacent branches even when the flow is uniformly distributed. This is not due to the inertia of the particles, nor to gravity. The particle distribution is rather rooted in their different pathways, which in turn are linked to their release origin along the main vessel cross-section. Therefore, the tree geometry and the associated flow streamlines are the prime determinant of the particle fate, while local changes of volumetric flow rate to selected branches do not generally produce proportional changes of particle delivery.
This study explores the optimal LVAD cannula outflow configuration in a patient-specific replica of the aorta. The volumetric velocity field is measured using phase-contrast magnetic resonance imaging under a physiologically relevant steady flow. The effect of the LVAD outflow graft insertion site and anastomosis angle on the transport of embolic particles to cranial vessels is studied by solving the particle equation of motion for spheres in the range of 0.1-1.0 mm using the measured 3D velocity field. Results show that for a given aorta anatomy, it is possible to design the cannula graft location and terminal curvature so that the probability of embolic transport to the cranial vessels is significantly minimized. This is particularly important since the complex flow pattern in each cannula case affects the embolic trajectories differently, and hence the common assumption that particles distribute by the volumetric flow division does not hold.
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.
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.
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.
Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and pre-existing cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition.
Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery. The burden of pre-existing versus new ischemic lesions was quantified and compared with the results of baseline and postoperative neuropsychological testing.
After surgery, new lesions were identified in 31% of patients, averaging 0.5 lesions per patient (67 mm(3) [0.004%] of brain tissue). Patients with pre-existing lesions were 10× more likely to receive new lesions after surgery than patients without pre-existing lesions. Pre-existing ischemic lesions were observed in 64% of patients, averaging 19.4 lesions (1542 mm(3) [0.1%] of brain tissue). New lesions in the left hemisphere were significantly smaller and more numerous (29 lesions; median volume, 44 mm(3); volume range, 5-404 mm(3)) than those on the right (10 lesions; median volume, 128 mm(3); volume range, 13-1383 mm(3)), which is consistent with a cardioembolic source of particulate emboli. Overall, the incidence of postoperative cognitive decline was 46% and was independent of whether new lesions were present.
New lesions after cardiac surgery added a small (≈4%) contribution to the burden of pre-existing cerebrovascular disease and did not seem to affect cognitive function.
U.K. Clinical Research Network.
11702.
© 2015 American Heart Association, Inc.
Ischaemic stroke is responsible for up to 80 % of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 [Formula: see text] and densities of 800, 1,030 and 1,300 [Formula: see text] were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 [Formula: see text]) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions.
In cardiovascular blood flow simulations a large portion of computational resources is dedicated to solve the linear system of equations. Boundary conditions in these applications are critical for obtaining accurate and physiologically realistic solutions, and pose numerical challenges due to the coupling between flow and pressure. Using an implicit time integration setting can lead to an ill-conditioned tangent matrix that causes deterioration in performance of traditional iterative linear equation solvers (LS). In this paper we present a novel and efficient preconditioner (PC) for this class of problems that exploits the strong coupling between the flow and pressure. We implement this PC in a LS algorithm designed for solving systems of equations governing incompressible flows. Excellent efficiency and stability properties of the proposed method are illustrated on a set of clinically relevant hemodynamics simulations.
Atrial fibrillation (AF) is the most common sustained dysfunction in heart rhythm clinically and has been identified as an independent risk factor for stroke through formation and embolization of thrombi. AF is associated with reduced cardiac output and short and irregular cardiac cycle length. Although the effect of AF on cardiac hemodynamic parameters has been reported, it remains unclear how the hemodynamic perturbations affect the potential embolization of blood clots to the brain that can cause stroke. To understand stroke propensity in AF, we performed computer simulations to describe trajectories of blood clots subject to the aortic flow conditions that represent normal heart rhythm and AF. Quantitative assessment of stroke propensity by blood clot embolism was carried out for a range of clot properties (e.g., 2-6 mm in diameter and 0-0.8 m/s ejection speed) under normal and AF flow conditions. The simulations demonstrate that the trajectory of clot is significantly affected by clot properties as well as hemodynamic waveforms which lead to significant variations in stroke propensity. The predicted maximum difference in stroke propensity in the left common carotid artery was shown to be about 60% between the normal and AF flow conditions examined. The results suggest that the reduced cardiac output and cycle length induced by AF can significantly increase the incidence of carotid embolism. The present simulations motivate further studies on patient-specific risk assessment of stroke in AF.
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.
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.
AIMS: Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data.Methods and ResultsWe performed a systematic review of papers that compare the localisation of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterise the distribution of disease, and they have been compared to a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. CONCLUSIONS: The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis.
The existing model equations governing the accelerated motion of
a spherical particle
are examined and their predictions compared with the results of the numerical
solution of the full Navier–Stokes equations for unsteady, axisymmetric
flow around
a freely
moving sphere injected into an initially stationary or
oscillating fluid. The
comparison for the particle Reynolds number in the range of 2 to 150 and
the particle
to fluid density ratio in the range of 5 to 200 indicates that the existing
equations
deviate considerably from the Navier–Stokes equations. As a result,
we propose a
new equation for the particle motion and demonstrate its superiority to
the existing
equations over a range of Reynolds numbers (from 2 to 150) and particle
to fluid
density ratios (from 5 to 200). The history terms in the new equation account
for
the effects of large relative acceleration or deceleration of the particle
and the initial
relative velocity between the fluid and the particle. We also examine the
temporal
structure of the near wake of the unsteady, axisymmetric flow around a
freely
moving sphere injected into an initially stagnant fluid. As the sphere
decelerates, the
recirculation eddy size grows monotonically even though the instantaneous
Reynolds
number of the sphere decreases.
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.
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
Some stabilized finite element methods for the Stokes problem are reviewed. The Douglas-Wang approach confirms better stability features for high order interpolations. Next, the advective-diffusive model is approximated in the light of various stabilized methods, a global convergence analysis is presented and numerical experiments are performed. Biquadratic elements produce better numerical results under all stabilized methods examined. The design of the stability parameter is confirmed to be a crucial ingredient for simulating the advective-diffusive model, and some improved possibilities are suggested. Combinations of these methodologies are given in the conclusions and will be examined in detail in the sequel to this paper applied to the incompressible Navier-Stokes equations.
A comprehensive finite element framework to enable the conduct of computational vascular research is described. The software system developed provides an integrated set of tools to solve clinically relevant blood flow problems and test hypotheses regarding hemodynamic (blood flow) factors in vascular adaptation and disease. The validity of the computational method was established by comparing the numerical results to an analytic solution for pulsatile flow as well as to published experimental flow data. The application of the finite element method to qualitatively and quantitatively assess the blood flow field in a number of clinically relevant models is described.
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.
This article provides the reader with an overview and up-date of clinical features, specific cardiac disorders and prognosis of cardioembolic stroke. Cardioembolic stroke accounts for 14-30% of ischemic strokes and, in general, is a severe condition; patients with cardioembolic infarction are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of cardioembolic infarction, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke's aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The more common high risk cardioembolic conditions are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy, and mitral rheumatic stenosis. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Holter monitoring. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. In our experience, in-hospital mortality in patients with early embolic recurrence (within the first 7 days) was 77%. Patients with alcohol abuse, hypertension, valvular heart disease, nausea and vomiting, and previous cerebral infarction are at increased risk of early recurrent systemic embolization. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent.
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.
The simulation of blood flow and pressure in arteries requires outflow boundary conditions that incorporate models of downstream domains. We previously described a coupled multidomain method to couple analytical models of the downstream domains with 3D numerical models of the upstream vasculature. This prior work either included pure resistance boundary conditions or impedance boundary conditions based on assumed periodicity of the solution. However, flow and pressure in arteries are not necessarily periodic in time due to heart rate variability, respiration, complex transitional flow or acute physiological changes. We present herein an approach for prescribing lumped parameter outflow boundary conditions that accommodate transient phenomena. We have applied this method to compute haemodynamic quantities in different physiologically relevant cardiovascular models, including patient-specific examples, to study non-periodic flow phenomena often observed in normal subjects and in patients with acquired or congenital cardiovascular disease. The relevance of using boundary conditions that accommodate transient phenomena compared with boundary conditions that assume periodicity of the solution is discussed.
Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and on the effect of the devices on physiologic function. Finally, patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics are presented, followed by a discussion of the challenges and opportunities that lie ahead.
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 …
Embolism of cardiac origin accounts for about one fifth of ischaemic strokes. Strokes due to cardioembolism are in general severe and prone to early recurrence. The risk of long term recurrence and mortality are high after a cardio-embolic stroke. Cardioembolism can be reliably predicted on clinical grounds but is difficult to document. MRI, transcranial doppler, echocardiogram, Holter monitoring, and electrophysiological studies increase our ability to identify the source of cardioembolism. Non-valvular atrial fibrillation is the commonest cause of cardioembolic stroke. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardio-embolism and no contraindications for anticoagulation. Alternatives to oral anticoagulation in this setting include safer and easier to use antithrombotic drugs and definitive treatment of atrial fibrillation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke.
Phase contrast (PC) magnetic resonance imaging was used to obtain velocity measurements in 30 healthy subjects to provide an assessment of hemodynamic parameters in cerebral vessels. We expect a lower coefficient-of-variation (COV) of the volume flow rate (VFR) compared to peak velocity (v peak) measurements and the COV to increase in smaller caliber arteries compared to large arteries.PC velocity maps were processed to calculate v peak and VFR in 26 vessel segments. The mean, standard deviation and COV, of v peak and VFR in each segment were calculated. A bootstrap-style analysis was used to determine the minimum number of subjects required to accurately represent the population. Significance of v peak and VFR asymmetry was assessed in 10 vessel pairs.The bootstrap analysis suggested that averaging more than 20 subjects would give consistent results. When averaged over the subjects, v peak and VFR ranged from 5.2 ± 7.1 cm s−1, 0.41 ± 0.58 ml s−1 (in the anterior communicating artery; mean ± standard deviation) to 73 ± 23 cm s−1, 7.6 ± 1.7 ml s−1 (in the left internal carotid artery), respectively. A tendency for VFR to be higher in the left hemisphere was observed in 88.8% of artery pairs, while the VFR in the right transverse sinus was larger. The VFR COV was larger than v peak COV in 57.7% of segments, while smaller vessels had higher COV.Significance and potential impact: VFR COV was not generally higher than v peak COV. COV was higher in smaller vessels as expected. These summarized values provide a base against which v peak and VFR in various disease states can be compared.
Virtually all engineering applications involve the use of piping, conduits, and channels. In the petroleum industry, piping systems are extensively used in upstream and downstream processes. These piping systems often carry fluids that are corrosive, which leads to wear, cavitation, and cracking. The replacement of damaged piping systems can be quite expensive, both in terms of capital costs and in operational downtime. This motivates the present research on noninvasive healing of cracked piping systems. In this investigation, we propose to develop computational models for characterizing noninvasive repair strategies involving electromagnetically guided particles. The objective is to heal industrial-piping systems noninvasively, fromthe exterior of the system, during operation, resulting in no downtime and minimal relative cost. The particle accumulation at a target location is controlled by external electromagnetic/ mechanical means. There are two primary effects that play a role for guiding the particles to the solid-fluid-interface/wall: mechanical shear caused by the fluid flow, and an electrical or magnetic force. In this work we develop and study a relationship that characterizes contributions of both, and ascertain how this relationship scales with characteristic physical parameters. Characteristic nondimensional parameters that describe system behavior are derived, and their role in design is illustrated. A detailed, fully 3D discreteelement- simulation framework is presented, and illustrated by use of a model problem of magnetically guided particles. The detailed particle behavior is considered to be regulated by three effects: The field strength, the mass-flow rate, and the wall interactions.
This work presents a computer simulation framework based on discrete element method to analyze manufacturing processes that comprise a loosely flowing stream of particles in a carrier fluid being deposited on a target surface. The individual particulate dynamics under the combined action of particle collisions, fluid–particle interactions, particle–surface contact and adhesive interactions is simulated, and aggregated to obtain global system behavior. A model for deposition which incorporates the effect of surface energy, impact velocity and particle size, is developed. The fluid–particle interaction is modeled using appropriate spray nozzle gas velocity distributions and a one-way coupling between the phases. It is found that the particle response times and the release velocity distribution of particles have a combined effect on inter-particle collisions during the flow along the spray. It is also found that resolution of the particulate collisions close to the target surface plays an important role in characterizing the trends in the deposit pattern. Analysis of the deposit pattern using metrics defined from the particle distribution on the target surface is provided to characterize the deposition efficiency, deposit size, and scatter due to collisions
Objectives:
We attempted to determine the propensity for sidedness of cardiogenic emboli associated with atrial fibrillation (AF) by comparing the sides on which microembolic signals (MES) were detected via transcranial Doppler (TCD) monitoring and the location of infarcts on magnetic resonance imaging.
Design:
Patients with AF on Holter monitoring and MES on TCD monitoring were selected from an ischemic stroke registry. Patients with prosthetic valves or cerebral/carotid artery stenosis were excluded.
Results:
By TCD monitoring of 30 patients, 78 MES were detected: 47 on the right and 31 on the left side (60.3% vs. 39.7%, p < 0.01, chi-square test). Among 21 patients who had middle or anterior cerebral artery (MCA/ACA) territory infarcts, 16 had right-side-dominant infarcts and 5 patients had left-side-dominant infarcts (76.2% vs. 23.8%, p < 0.01, chi-square test). The median infarct volume on the right side was 16.2 (3.18-75.4) ml, while that of left side was 1.2 (0.25-5.05) ml (p < 0.01, Mann-Whitney U test).
Conclusion:
This study demonstrated the existence of a right-side propensity of cardiogenic emboli and the larger infarct volume of right-side MCA/ACA stroke in patients with AF. These results can be attributed to anatomical differences between the innominate and the left common carotid artery.
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.
It is shown that a sphere moving through a very viscous liquid with velocity V relative to a uniform simple shear, the translation velocity being parallel to the streamlines and measured relative to the streamline through the centre, experiences a lift force 81·2 the magnitude of the velocity gradient, and μ and v the viscosity and kinematic viscosity, respectively. The relevance of the result to the observations by Segrée & Silberberg (1962) of small spheres in Poiseuille flow is discussed briefly. Comments are also made about the problem of a sphere in a parabolic velocity profile and the functional dependence of the lift upon the parameters is obtained.
Background and purpose:
To evaluate the impact of proximal flow control on efficacy and safety of mechanical thrombectomy in an in vitro middle cerebral artery occlusion.
Methods:
Three independent variables, including clot type, device (Merci Retriever, Solitaire FR, and Trevo devices), and use of a balloon guide catheter, were used to ascertain the impact of proximal flow control on the size and number of distal emboli generated during thrombectomy. Secondary end points were the recanalization rate and amount of flow restored.
Results:
Use of the balloon guide catheter during thrombectomy of the fragile, hard clot significantly reduced the formation of large distal emboli with a diameter >1 mm, regardless of the device used (P<0.01). Applying aspiration via the balloon guide catheter in place of the conventional guide catheter resulted in a significant increase of flow reversal (P<0.0001). Prior to thrombectomy, deployment of the stent-trievers produced immediate flow restoration through the soft and hard clot occlusions, 69.2 ± 27.3 and 45.5 ± 22.8 mL/min, respectively, that was preserved after the balloon inflation because of collateral flow via the posterior communication artery. After deployment but before thrombectomy, no flow was restored when using the Merci Retriever. After thrombectomy, complete flow restoration was achieved in a majority of cases. The Merci Retriever required more thrombectomy attempts to achieve hard clot removal compared with the stent-trievers when the conventional guide catheter was used (1.5 versus 1.1).
Conclusions:
The risk of distal embolization was significantly reduced with the use of the balloon guide catheter.
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.
Local hemodynamics may strongly influence atherothrombosis, which can lead to acute myocardial infarction and stroke. The relationship between hemodynamics and thrombosis during platelet accumulation was studied through an in vitro flow system consisting of a stenosis. Specifically, wall shear rates (WSR) ranging from 0 to 100,000 s(-1) were ascertained through computations and compared with thrombus growth rates found by image analysis for over 5,000 individual observation points per experiment. A positive correlation (P < 0.0001) was found between thrombus accumulation rates and WSR up to 6,000 s(-1), with a decrease in growth rates at WSR >6,000 s(-1) (P < 0.0001). Furthermore, growth rates at pathological shear rates were found to be two to four times greater than for physiological arterial shear rates below 400 s(-1). Platelets did not accumulate for the first minute of perfusion. The initial lag time, before discernible thrombus growth could be found, diminished with shear (P < 0.0001). These studies show the quantitative increase in thrombus growth rates with very high shear rates in stenoses onto a collagen substrate.
A new finite element formulation for convection dominated flows is developed. The basis of the formulation is the streamline upwind concept, which provides an accurate multidimensional generalization of optimal one-dimensional upwind schemes. When implemented as a consistent Petrov-Galerkin weighted residual method, it is shown that the new formulation is not subject to the artificial diffusion criticisms associated with many classical upwind methods.The accuracy of the streamline upwind/Petrov-Galerkin formulation for the linear advection diffusion equation is demonstrated on several numerical examples. The formulation is extended to the incompressible Navier-Stokes equations. An efficient implicit pressure/explicit velocity transient algorithm is developed which accomodates several treatments of the incompressibility constraint and allows for multiple iterations within a time step. The effectiveness of the algorithm is demonstrated on the problem of vortex shedding from a circular cylinder at a Reynolds number of 100.
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.
This study sought to determine whether procedural factors during percutaneous coronary intervention (PCI) are associated with the occurrence of ischemic stroke or transient ischemic attack (PCI-stroke).
Stroke is a devastating complication of PCI. Demographic predictors are nonmodifiable. Whether PCI-stroke is associated with procedural factors, which may be modifiable, is unknown.
We performed a single-center retrospective study of 21,497 PCI hospitalizations between 1994 and 2008. We compared procedural factors from patients who suffered an ischemic stroke or transient ischemic attack related to PCI (n=79) and a control group (n=158), and matched them 2:1 based on a predicted probability of stroke developed from a logistic regression model.
PCI-stroke procedures involved the use of more catheters (median: 3 [quarter (Q) 1, Q3: 3, 4] vs. 3 [Q1, Q3: 2, 3], p<0.001), greater contrast volumes (250 ml vs. 218 ml, p=0.006), and larger guide caliber (median: 7-F [Q1, Q3: 6, 8] vs. 6-F [Q1, Q3: 6, 8], p<0.001). The number of lesions attempted (1.7±0.8 vs. 1.5±0.8, p=0.14) and stents placed (1.4±1.2 vs. 1.2±1.1, p=0.35) were similar between groups, but PCI-stroke patients were more likely to have undergone rotational atherectomy (10% vs. 3%, p=0.029). Overall procedural success was lower in the PCI-stroke group compared with controls (71% vs. 85%, p=0.017). Evaluation of the entire PCI population revealed no difference in the rate of PCI-stroke between radial and femoral approaches (0.4% vs. 0.4%, p=0.78).
Ischemic stroke related to PCI is associated with potentially modifiable technical parameters. Careful procedural planning is warranted, particularly in patients at increased risk.
Based on thrombus location and nature and anatomic features of aorta and cerebral arteries, we hypothesized that cardiogenic embolisms (CE) and aortogenic embolisms (AE) might have different right-left propensity and lesion patterns.
We retrospectively reviewed patients with acute ischemic stroke with high-risk CE sources or moderate-or-severe aortic atherosclerotic plaques on transesophageal echocardiography. Lesion side and patterns on diffusion-weighted imaging were compared between CE and AE.
CE was identified in 123 and AE in 63. In multivariate analysis, right-sided lesions and corticosubcortical infarcts were independently associated with CE, and left-sided lesions and pial infarcts were independently associated with AE.
CE and AE have different radiological characteristics, as shown by the right-left propensity and lesions patterns of cerebral infarcts.
Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
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.
The decline in stroke incidence and mortality in the U.S. over the past 20 years is reaching a plateau, and the number of strokes may actually start to increase as the population ages. However, recent clinical trials have demonstrated that there are numerous opportunities to improve stroke prevention strategies and also opportunities to effectively intervene in and treat acute strokes. For patients with diabetes and for those with prior strokes or transient ischemic attacks, it has become evident that aggressive low-density lipoprotein lowering with statin medications will decrease the risk for total and fatal strokes. Optimal anticoagulation and antiplatelet therapy for primary and secondary stroke prevention in atrial fibrillation is being carefully defined. With numerous novel factor Xa and direct thrombin inhibitor drugs completing phase III clinical trials, it is likely that additional oral anticoagulant drugs will be clinically available for stroke prevention soon. Additionally, a major clinical trial is nearing completion that may resolve the role of carotid stenting and carotid endarterectomy in primary and secondary stroke prevention. There are recent notable advances in the acute treatment of stroke. It is likely that the time window for thrombolysis for appropriate patients with strokes will be increased from 3 to 4.5 h, permitting the inclusion of more patients in this treatment approach. There is ongoing investigation of intra-arterial thrombolysis and of acute intra-arterial thrombus extraction for treatment of selected patients with strokes. Unlike the progress in treatment of ischemic strokes, treatment of hemorrhagic stroke is progressing more slowly.
The observed distribution of cerebral infarcts varies markedly from expectations based on blood-flow volume or Doppler embolus detection. In this study, we used an in vitro model of the cerebral arteries to test whether embolus microspheres encountering the circle of Willis are carried proportionally to volume flow or express a preferred trajectory related to arterial morphology or embolus size.
Our model consisted of a patient-specific silicone replica of the cerebral macrocirculation featuring physiologically realistic pulsatile flow of a blood-mimicking fluid at approximately 1000 mL/min and an input pressure of approximately 150/70 mm Hg. Particles of 200, 500, and 1000 microm diameter with equivalent density to thrombus were introduced to the carotid arteries and counted on exiting the model outlets.
The middle cerebral arteries (MCAs) of the replica attracted a disproportionate number of emboli compared with the anterior cerebral arteries; 98%+/-3% of 1000 microm and 93%+/-2% of 500 microm emboli entered the MCA compared with 82%+/-5% of the flow. The observed distribution of large emboli was consistent with the ratio of MCA:anterior cerebral artery infarcts, approximately 95% of which occur in territories supplied by the MCA. With decreasing embolus size, the distribution of emboli approaches that of the flow (approximately 89% of 200 microm emboli took the MCA).
Embolus trajectory through the cerebral arteries is dependent on embolus size and strongly favors the MCA for large emboli. The 70:30 ratio of MCA:anterior cerebral artery emboli observed by Doppler ultrasound is consistent with the trajectories of small emboli that tend to be asymptomatic.
Background and purpose:
Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify.
Methods:
The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression.
Results:
Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score <or=2) was negatively predicted by LVO (0.33; 0.24 to 0.45; P<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to National Institutes of Health Stroke Scale and age, independently predicted outcome.
Conclusions:
Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.
To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort.
We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age.
Estimated annual occurrence was 10.8/100,000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those <30, whereas male dominance rapidly increased around age of 44. The most frequent risk factors were dyslipidemia (60%), smoking (44%), and hypertension (39%). Males and patients >44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients <45 years of age. Left hemisphere infarcts were more frequent in general. There were 235 (23%) patients with multiple and 126 (13%) with silent infarcts, and 55 (5%) patients had leukoaraiosis.
The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.
Data from 694 patients hospitalized with stroke were entered in a prospective, computer-based registry. Three hundred and sixty-four patients (53 percent) were diagnosed as having thrombosis, 215 (31 percent)as having cerebral embolism 70 (10 percent) as having intracerebral hematoma, and 45 (6 percent) as having subarachnoid hemorrhage from aneurysm or arteriovenous malformations. The 364 patients diagnosed as having thrombosis were divided into 233 (34 percent of all 694 patients) whose thrombosis was thought to involve a large artery and 131 (19 percent) with lacunar infarction. Many of the findings in this study were comparable to those in previous registries based on postmortem data. New observations include the high incidence of lacunes and cerebral emboli, the absence of an identifiable cardiac origin in 37 percent of all emboli, a nonsudden onset in 21 percent of emboli, and the occurrence of vomiting at onset in 51 percent and the absence of headache at onset in 67 percent of hematomas.
In the analysis of arterial branching the classical "cube law' has provided a working model for the relation between the diameter of a blood vessel and the flow which the vessel carries on a long-term basis. The law has shown good agreement with biological data, but questions remain regarding its applicability to all levels of the arterial tree. The present study tests the hypothesis that the cube law may not be valid in the first few generations of the arterial tree, where vessel capacitance and gross anatomy may play important roles. Biological data have shown some support for this hypothesis in the past but the heterogeneity characteristic of past data has not allowed a conclusive test so far. We present new data which have been obtained from the same location on the arterial tree and in sufficient number to make this test possible for the first time. Also, while past tests have been based primarily on correlation of the measured data with an assumed power law, we show here that this can be misleading. The present data allow a simpler test which does not involve correlation and which leads to more direct conclusions. For the vessels surveyed, the results show unequivocally that the relation between diameter and flow is governed by a 'square law' rather than the classical cube law. Coupled with past findings this suggests that the square law may apply at the first few levels of the arterial tree, while the cube law continues from there to perhaps the precapillary levels.
A mechanism for the Fahraeus-Lindqvist phenomenon, responsible for the direction of cerebral emboli to distal arteries, has been modelled. Results indicate that emboli are distributed along a radial concentration gradient that is in part determined by particle size and that this determines the topographical destiny of emboli in the cerebral circulation.
The paper presents a mathematical analysis of the contributions of flow and mass transport to a single reactive event at a blood vessel wall. The intent is to prepare the ground for a comprehensive study of the intertwining of these contributions with the reaction network of the coagulation cascade. We show that in all vessels with local mural activity, or in “large” vessels (d>0.1 mm) with global reactivity, events at the tubular wall can be rigorously described by algebraic equations under steady conditions, or by ordinary differential forms (ODEs) during transient conditions. this opens up important ways for analyzing the combined roles of flow, transport, and coagulation reactions in thrombosis, a task hitherto considered to be completely intractable.
We report extensively on the dependence of transport coefficient kL and mural coagulant concentration Cw on flow, vessel geometry, and reaction kinetics. It is shown that for protein transport, kL varies only weakly with shear rate in large vessels, and not at all in the smaller tubes (d<10−2 mm). For a typical protein, kL∼10−3 cm s−1 within a factor of 3 in most geometries, irrespective of the mural reaction kinetics. Significant reductions in kL (1/10–1/1,000) leading to high-coagulant accumulation are seen mainly in stagnant zones vicinal to abrupt expansions and in small elliptical tubules. This is in accord with known physical observations. More unexpected are the dramatic increases in accumulation which can come about through the intervention of an autocatalytic reaction step, with Cw rising sharply toward infinity as the ratio of reaction to transport coefficient approaches unity. Such self-catalyzed reactions have the ability to act as powerful amplifiers of an otherwise modest influence of flow and transport on coagulant concentration.
The paper considers as well the effect on mass transport of transient conditions occasioned by coagulation initiation or pulsatile flow. During initiation, instantaneous flux varies with diffusivity and bulk concentration, favouring the early adsorption/consumption of proteins with the highest abundance and mobility. This is akin to the ‘Vroman effect’ seen in narrow, stagnant spaces. The effect of flow pulsatility on kL has the potential, after prolonged cycling, of bringing about segregation or accumulation of proteins, with consequences for the coagulation process.
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.
We present epidemiologic, etiologic, and clinical data for 1,000 consecutive patients with a first stroke (cerebral infarction or hemorrhage) admitted to the Centre Hospitalier Universitaire Vaudois since 1982. The patients were evaluated using a standard protocol of tests (computed tomography, Doppler ultrasonography, and electrocardiography in all patients, as well as angiography and specific cardiac investigations in selected patients). Each case was coded prospectively into a computerized registry. We believe that the Lausanne Stroke Registry is the first registry with complete computed tomography and Doppler ultrasonography data on all patients, which allows correlation between clinical findings, presumed etiology, and stroke location. Although the Lausanne Stroke Registry is not population-based, it gives a good estimate of the stroke-related problems in patients admitted to a primary-care center since our hospital is the sole acute-care facility for stroke in the Lausanne area.
Authors' synopsis: Hot-film constant temperature probes, evaluated in regimes of pipe-flow, have been used to explore velocity distributions across diameters at various sites in the aorta of dogs. Velocity profiles at all levels were blunt, with boundary-layers less than 2 mm thick; marked skews occurred in the profiles at certain sites in the proximal aorta. The major factors influencing flow in these regions are discussed, and possible causative factors identified. Fully-developed turbulence occurred in only one case, which is described.
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.
Cardiac embolism is often involved as a mechanism for embolic stroke, and may be implicated in many strokes that have traditionally been considered of unknown origin (cryptogenic strokes). In recent years, significant advancements have been made in understanding and reducing the risk of stroke from long-known cardioembolic sources (atrial fibrillation, intracardiac thrombus or tumor, infective endocarditis). Also, improved cardiac imaging, especially transesophageal echocardiography, has allowed the identification of newer embolic sources of stroke (aortic atheromas, patent foramen ovale, atrial septal aneurysm). This article reviews the current understanding of cardiac embolism as a mechanism for stroke, and the preventive options that are currently adopted to decrease the stroke risk.