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The Role of Circle of Willis Anatomy Variations in Cardio-embolic Stroke: A Patient-Specific Simulation Based Study
Abstract
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.
... 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. ...
... Since we used the same 3D patient-specific model with the previous study, 29 the final mesh was chosen to be exactly the same as that used in Ref. 29, which is a tetrahedral type and contains 7.8-8.5 Â 10 6 elements, similar to the number mentioned in Ref. 26. The results of the meshsensitivity test and validation will be presented in Sec. ...
... 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 ...
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.
... A patient-specific vasculature model was created spanning arterial pathway from the aortic arch to the CoW using the open-source software tool Simvascular [17,18]. The model was generated from a contrast enhanced computed tomography (CT ) image, available from a set of CT images as part of the Institutional Review Board (IRB ) approved Screening Technology and Outcome Project in Stroke (STOP-Stroke) database [19]. ...
... arteries (see also our prior works [18,20] ). Arteries from the aortic inlet to the cerebral arteries up until the M1, A1, and P1 segments of the MCA, ACA, and PCA, were segmented using planar 2D segmentation technique built into SimVascular. ...
... 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]. ...
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 results shed several insights into embolus transport and source to destination distribution patterns when the flow is driven by an operating LVAD for varying extent of pulse modulation, and varying thromboembolus sizes. As noted in several of our prior works [36][37][38], the transport of emboli from a source to a destination site is intimately related to the overall state of hemodynamics in the vessels that the emboli travel through. For circulation driven by an operating LVAD, blood flow patterns in the aorta and branching vessels are determined by the impingement of a jet flow emanating from the LVAD outflow graft on the aorta wall. ...
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.
... 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. ...
... The CoW anatomy has significant variations in topology and anastomosis across subjects, commonly with 1 or more communicating vessels missing or hypoplastic. [16][17][18][19] Using a meta-analysis of literature on reported CoW anatomical variations, and a ranking statistics approach outlined in our prior work, 16 5 most frequent variations of the CoW anatomy were considered for this study. These variations involved an absent anterior communicating artery (AcoA), absent left and right P1 connectors, and absent left and right communicating arteries. ...
... The CoW anatomy has significant variations in topology and anastomosis across subjects, commonly with 1 or more communicating vessels missing or hypoplastic. [16][17][18][19] Using a meta-analysis of literature on reported CoW anatomical variations, and a ranking statistics approach outlined in our prior work, 16 5 most frequent variations of the CoW anatomy were considered for this study. These variations involved an absent anterior communicating artery (AcoA), absent left and right P1 connectors, and absent left and right communicating arteries. ...
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]. ...
... The CoW anatomy has significant variations in topology and anastomosis across subjects, with one or more communicating vessels missing or hypoplastic [16][17][18][19]. Using a meta-analysis of literature on reported CoW anatomical variations, and a ranking statistics approach outlined in our prior work [16], 5 most frequent variations of the CoW anatomy were considered for this study. ...
... The CoW anatomy has significant variations in topology and anastomosis across subjects, with one or more communicating vessels missing or hypoplastic [16][17][18][19]. Using a meta-analysis of literature on reported CoW anatomical variations, and a ranking statistics approach outlined in our prior work [16], 5 most frequent variations of the CoW anatomy were considered for this study. These variations involved an absent anterior communicating artery (labelled as AcoA for this study), left and right P1 connectors (labelled as LP1 and RP1 for this study), and left and right communicating arteries (labelled as L.Comm and R.Comm for this study). ...
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. ...
... where w and q are the test functions corresponding to u and p, represents the entire arterial domain used for computation, b denotes the total body force, h denotes the contributions at each Neumann boundary ( ) of the computational domain ( ), D is the symmetricity of the velocity gradient (∇u + ∇u T ), R h is the residual of the momentum equation, τ supg and τ pspg are stabilization parameters that are chosen to be functions of the element size Tezduyar & Osawa, 2000) and h 0D is a factor representing all resistance outflow boundary conditions (Vignon-Clementel et al., 2006. 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). ...
... A ratio α, given by α = R p /(R p + R d ), was assigned the value of 0.91. The initial value of the total capacitance C tot was calculated using the relation C tot = dQ dp , and the parameters R p , R d , and C for all eleven Windkessel outlets were assigned in accordance with a cross-sectional-area rule (Coogan et al., 2013;Les et al., 2010;Mukherjee et al., 2018;Xiao et al., 2014). The optimum parameter values were then iteratively obtained using a conventional procedure (Xiao et al., 2014). ...
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.
... (1) previous studies were unable to describe complex three-dimensional haemodynamic phenomena through one-dimensional analyses (Alastruey et al., 2007;Ryu et al., 2015), (2) a limited coverage of the arterial domain (ICA-to-CoW) was considered in three-dimensional studies (Alnaes et al., 2007;Long et al., 2008;Mukherjee et al., 2018;Zhu et al., 2015a), and (3) the complex physical nature of blood flow was disregarded in CS-correlative clinical or statistical approaches. As suggested in a recent review (Liu et al., 2020), once a large-domain study integrates a three-dimensional simulation and CS, the effects of progressive CS on the flow in the CoW may effectively be captured ( Figure 1). ...
... Here, the distal collateral flow through ophthalmic and superficial temporal arteries was discounted as such re-routing of blood flow may occur only during severe bilateral CS (Yamamoto et al., 2004); only unilateral CS was employed in this study. While progressive unilateral CS causes abnormal flow distribution in vasculatures (Cassot et al., 1995(Cassot et al., , 2000Henderson et al., 2000;Moneta et al., 1993;Mukherjee et al., 2018;Rothwell et al., 1994;Schomer et al., 1994), the present study focused on variant forms of CoW and the role of CoAs in cerebral circulation. ...
... 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. ...
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.
... Few research groups, however, have also attempted to observe embolus transport in the cerebrovascular system. Fabbri et al. (2014) conducted computational studies to observe flow dynamics through an anatomical Circle of Willis (CoW) model, while Mukherjee et al. simulated embolus distribution in CoW models (Mukherjee et al. 2018;Mukherjee et al. 2016a, b). Their studies exclusively simulated emboli with diameters ranging from 100 to 1000 μm and utilized a one-way coupled model with no momentum transfer between particles and blood. ...
... Although some research groups have used mock circulatory flow loops (MCFLs) to replicate flow dynamics within blood pumps or cerebrovascular systems, none have collectively merged them into a single research model with embolus transport and varying flow parameters to determine their individual effects. Furthermore, while several studies have attempted to model embolus transport and distribution in the aorta, none have done so with physiologically accurate emboli, anatomies, CPB hemodynamic properties, or validated their results with experimental studies (Mukherjee et al. 2018;Mukherjee et al. 2016a, b;Mukherjee et al. 2016a, b). To address these shortcomings, an improved experimental MCFL will be developed and used to observe emboli distribution in the aortic arch under varying pump flow rates, fluid viscosities, and embolus sizes and densities. ...
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.
... 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. Nevertheless, none of the studies have established a direct link to VA-ECMO, and the examination of emboli transport was conducted under conditions of normal cardiac output [10,12,13]. ...
... 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]: ...
... The reduced blood flow in AIS is coupled with a series of changes associated with structural remodeling of the cerebral vasculature that results in the vessel geometry quantitatively varying from the healthy vasculature 9,10 . Some of these changes may precede the clinical onset of the ischemic event in patients with atherosclerotic vessels 11 . Therefore, analysis of the brain vessel geometry can predict and potentially prevent AIS, improve prognostication, facilitate studying therapeutic options and guide reperfusion therapies when feasible 12 . ...
... Developing a comprehensive atlas of the cerebral vasculature containing quantitative geometric features, including distal branches of the intracranial vessel network and normal variations at different ages in the healthy population, is essential in understanding the brain's anatomy and physiology. It also enables assessment of compensatory collateral flow in the CoW and the collateral circulation during acute and chronic ischemic conditions, given their vital role in the distribution of CBF, to assist with early diagnosis, optimal reperfusion approach, and patient outcomes prediction 11,12 . ...
Background and Purpose: Altered brain vasculature is a key phenomenon in several neurologic disorders. This paper presents a quantitative assessment of vascular morphology in healthy and diseased adults including changes during aging and the anatomical variations in the Circle of Willis (CoW). Methods: We used our automatic method to segment and extract novel geometric features of the cerebral vasculature from MRA scans of 175 healthy subjects, 45 AIS, and 50 AD patients after spatial registration. This is followed by quantification and statistical analysis of vascular alterations in acute ischemic stroke (AIS) and Alzheimer's disease (AD), the biggest cerebrovascular and neurodegenerative disorders. Results: We determined that the CoW is fully formed in only 35 percent of healthy adults and found significantly increased tortuosity and fractality, with increasing age and with disease -- both AIS and AD. We also found significantly decreased vessel length, volume and number of branches in AIS patients. Lastly, we found that AD cerebral vessels exhibited significantly smaller diameter and more complex branching patterns, compared to age-matched healthy adults. These changes were significantly heightened with progression of AD from early onset to moderate-severe dementia. Conclusion: Altered vessel geometry in AIS patients shows that there is pathological morphology coupled with stroke. In AD due to pathological alterations in the endothelium or amyloid depositions leading to neuronal damage and hypoperfusion, vessel geometry is significantly altered even in mild or early dementia. The specific geometric features and quantitative comparisons demonstrate potential for using vascular morphology as a non-invasive imaging biomarker for neurologic disorders.
... Mukherjee et al. 29 presented systematic parametric experiments on the transport of cardiac emboli of different sizes (100, 500, and 1000 lm) and compositions in four patient-specific geometries, considering six different CoW anatomical variants. They illustrated that the anatomical variations of the CoW affected the distribution of emboli to the six major cerebral arteries. ...
... This phenomenon was not observed in previous studies because of applying constant flow rates as inlet or outlet boundary conditions. 25,27,29 It can also be concluded that in the healthy complete CoW, RMCA transfers 31% of the overall flow to the brain tissue; however, this amount decreased by 5% in the stroke-CoW. ...
The circle of Willis (CoW) is a set of arteries located in the basis of the brain. Prediction of perfusion rates and hemodynamics in the CoW is necessary to understand the relevant vascular diseases and to prescribe effective treatments. In this paper, the effect of ischemic stroke in the CoW is studied, taking into consideration the anatomical variations of the CoW. Moreover, an analysis on the effect of applied boundary conditions is carried out. To do so, a patient-specific model of the CoW is reconstructed from CT (computed tomography) images. Six different cases of boundary conditions are applied to complete and healthy CoW, and the flow rates are investigated. The proper pressure boundary conditions are then imposed to three other variations of the CoW, and the flow rates are compared. The results reveal that the overall inlet flow rate varies from 1.75% to 7.5% in three variations of healthy CoW. Moreover, the changes in flow rates of outlet and inlet branches are indicated in ischemic stroke by considering a spherical clot in the right middle cerebral artery (RMCA). In this case, the RMCA flow reduced by 88.4%, and the internal carotid artery flow decreased by 53.6%. These changes lead to increased flow rates of other inlets to support the brain; however, the overall inlet flow rate falls by 21.5%.
... Cilliers et al.'s (2018) results are in tandem with the other studies examined in this analysis and aligned with the statistical results (Figures 3 and 4).4.3 | Clinical applications of variations of the CoW, particularly the PComABeing familiar with the most common CoW variations and their prevalence can be of vital importance to clinicians. Many authors have suggested an increased risk of ischemic stroke in the presence of CoW variations(Chuang, Liu, Pan, & Lin, 2008;Hoksbergen et al., 2003;Mukherjee, Jani, Narvid, & Shadden, 2018).Chuang et al. (2008), for example, highlight that hypoplasia of the PComA is associated with an increased risk of infarction, particularly in the thalamic region. Understanding the anatomy of common variations and their prevalence can help us predict the likelihood of patients suffering a stroke, and which regions are likely to be affected. ...
... anding the anatomy of common variations and their prevalence can help us predict the likelihood of patients suffering a stroke, and which regions are likely to be affected. In the absence of traditional risk factors for stroke, such as ICA stenosis, it would be feasible to consider whether an anatomical variation is the CoW is the causative factor.Mukherjee et al. (2018) suggest that variant CoW anatomy can have an impact on the trajectory of microemboli, and hence lead to infarctions in distal, more unusual areas of the brain. Therefore, being aware of variations and their frequency can help us understand atypical stroke patterns, and predict their likelihood. If a specific variation, of which the prev ...
The circle of Willis is an anastomotic network of arteries surrounding the base of the brain, providing collateral circulation to prevent ischemia. It has, however, long been established that it exhibits considerable anatomical variation when compared to Thomas Willis' originally described circle. This study aimed primarily to determine an accurate prevalence of the variation of the circle of Willis in the general population and the prevalence of common posterior communicating artery variations. Additional aims were to explain why such a wide range of reported variations exist, and whether different types of studies report significantly different prevalence of variation. A comprehensive literature search identified 764 papers. A three‐phase screening process was undertaken, involving a critical analysis of papers, and a total of 33 papers were selected for analysis and literature review. A descriptive statistics test with bootstrap was performed to estimate the average prevalence of variations. The estimated prevalence of general variation, unilateral, and bilateral posterior communicating artery hypoplasia or aplasia was 68.22 ± 14.32%, 19.45 ± 8.63%, and 22.83 ± 14.58%, respectively. Over half of the population exhibit a circle of Willis with some form of variation. To provide a more accurate estimation for the prevalence of variations, a universal classification system needs to be established, collating all the work from high‐quality studies, to provide a comprehensive database of the circle's variations. Knowing the prevalence of variations and how they can impact neurosurgical approaches or patterns of ischemic pathology can be crucial in providing effective patient care.
... The results illustrated that as the rigidity of emboli increases, higher proportion of them tend to enter to MCAs (larger arteries). Mukheijee et al. [14] performed systematic parametric experimentation on the transport of cardiogenic emboli of different compositions and sizes (100, 500 and 1000 pm) in four patient-specific geometries, considering six different anatomical variations of the CoW. They showed that the CoW anatomical variations affected embolus distribution to the six efferent arteries. ...
... Finally, the overall inlet flow rate lessened to 18%. This phenomenon was not seen in previous studies because they fixed the flow rates in the all inlet or outlet branches [11,12,14]. It was the result of choosing pressure waveforms as boundary conditions. ...
Stroke is the second cause of death in developing countries. Meanwhile, ischemic stroke has the highest prevalence. Simulation and prediction of the stroke are big steps toward better understanding and suggesting the therapies. In this study, the computational simulation of the Circle of Willis (CoW) in the presence of a large-sized clot was presented. Patient-specific geometry of the CoW was reconstructed from CT images. The spherical clot was located in right middle cerebral artery (RMCA) as one of the main outlets of the CoW. Proper pressure boundary conditions were applied to the inlets and outlet not to confine the flow rate alterations and a fluid-structure interaction was used between the blood and clot. The pressure distribution in the CoW was reported and compared to the healthy case. Moreover, the changes on flow rates of outlet and inlet arteries were indicated in the case of ischemic stroke of a large efferent artery.
... 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. ...
... 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. ...
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).
... 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.
... Image-based vascular modeling is used for a variety of purposes including diagnosis, personalized treatment planning and fundamental understanding of disease progression [1][2][3][4]. Specialized software has been developed for such modeling, including SimVascular [5,6], CRIMSON [7] and VMTK [8]. This modeling paradigm uses medical imaging, such as computed tomography (CT) or magnetic resonance (MR) angiography, to construct a patient-specific anatomical model of vessels of interest. ...
Computational modeling of cardiovascular function has become a critical part of diagnosing, treating and understanding cardiovascular disease. Most strategies involve constructing anatomically accurate computer models of cardiovascular structures, which is a multistep, time-consuming process. To improve the model generation process, we herein present SeqSeg (sequential segmentation): a novel deep learning based automatic tracing and segmentation algorithm for constructing image-based vascular models. SeqSeg leverages local U-Net-based inference to sequentially segment vascular structures from medical image volumes. We tested SeqSeg on CT and MR images of aortic and aortofemoral models and compared the predictions to those of benchmark 2D and 3D global nnU-Net models, which have previously shown excellent accuracy for medical image segmentation. We demonstrate that SeqSeg is able to segment more complete vasculature and is able to generalize to vascular structures not annotated in the training data.
... As hemodynamics are an intrinsic factor of vascular disease, there has been a concomitant increase in the number of studies using Computational Fluid Dynamics (CFD) and/or fluid-structure interactions to better understand disease prognosis or treatment outcomes after deployment of the pertinent medical device. For example, the transport of cardiogenic emboli causing ischemic stroke can be evaluated using imaging scans of the entire vascular branching network in each patient [51]. The recent introduction of miniaturized optical coherence tomography allows for high-resolution imaging of medical device features as well as the vascular wall in any given patient [53], which in turn facilitates high-resolution computational studies of the pathology. ...
Presented is a path towards a fast and robust adaptive anisotropic mesh generation method that is designed to help streamline the discretization of complex vascular geometries within the Computational Fluid Dynamics (CFD) modeling process. The proposed method combines multiple software tools into a single pipeline to provide the following: (1) image-to-mesh conversion which satisfies quality, fidelity, and smoothness requirements, (2) the generation of a boundary layer grid over the high fidelity surface, (3) a parallel adaptive anisotropic meshing procedure which satisfies real-time requirements, and (4) robustness, which is satisfied by the pipeline's ability to process segmented images and CAD models. The proposed approach is tested with two brain aneurysm cases and is shown to satisfy all the aforementioned requirements. The next steps are to fully parallelize the remaining components of the pipeline to maximize potential performance and to test its integration within a CFD vascular flow simulation. Just as the parallel anisotropic adaptation procedure was tested within aerospace CFD simulations using CAD models, the method is expected to provide accurate results for CFD vascular flow simulations in real-time when executed on multicore cc-NUMA architectures.
... Image-based vascular modeling is used for a variety of purposes including diagnosis, personalized treatment planning and fundamental understanding of disease progression [1][2][3][4]. Specialized software has been developed for such modeling, including SimVascular [5,6], CRIMSON [7] and VMTK [8]. This modeling paradigm uses medical imaging, such as computed tomography (CT) or magnetic resonance (MR) angiography, to construct a patient-specific anatomical model of vessels of interest. ...
Computational modeling of cardiovascular function has become a critical part of diagnosing, treating and understanding cardiovascular disease. Most strategies involve constructing anatomically accurate computer models of cardiovascular structures, which is a multistep, time-consuming process. To improve the model generation process, we herein present SeqSeg (sequential segmentation): a novel deep learning-based automatic tracing and segmentation algorithm for constructing image-based vascular models. SeqSeg leverages local U-Net-based inference to sequentially segment vascular structures from medical image volumes. We tested SeqSeg on CT and MR images of aortic and aortofemoral models and compared the predictions to those of benchmark 2D and 3D global nnU-Net models, which have previously shown excellent accuracy for medical image segmentation. We demonstrate that SeqSeg is able to segment more complete vasculature and is able to generalize to vascular structures not annotated in the training data.
... 29 By integrating medical data with mathematical principles governing fluid motion, these models enhance our understanding of hemodynamics and aim to improve clinical decision-making. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] However, despite significant advancements, patient-specific in silico models still face limitations in providing precise clinical support. This is due to the complexities inherent in the physics of these mathematical models. ...
Coronary artery disease (CAD) is a condition where the coronary arteries, which supply blood to the heart muscle, become narrowed or blocked. The most common cause of CAD is atherosclerosis, which is a condition in which plaque builds up inside the arteries, causing them to harden and narrow. These are critical conditions due to their high prevalence, adverse impact on health and quality of life, and potential for severe complications. Early detection, prevention, and effective management are essential to mitigate their effects, which delves critically on the understanding of blood flow dynamics (hemodynamics) in these arteries. While fluid dynamics simulations incorporating the deformability of blood vessels have proven to be immensely useful in this context, their outcomes remain far from being amenable for clinical decision making in real-life medical practice because of their limitations in capturing the implications of certain key physiological features such as the stiffnesses of the artery walls and the plaque deposits formed therein. In an effort to circumvent these deficits, here we report the development and deployment of a fluid–structure interaction model that unveils the sensitive dependence of the clinically relevant hemodynamic parameters on the arterial wall and plaque stiffness, bringing in explicit quantitative assessment of the pathophysiology of arterial disease progression. Our results enable direct quantification of the time-averaged wall shear stress, offering clinical insights into the biomechanical environment and the endothelial response that are critical in the initiation and progression of atherosclerotic plaques. In addition, our results pinpoint the alterations in the fractional flow reserve due to changes in the deformability of the arterial walls and plaques, providing a functional assessment of the impact of these plaques on coronary blood flow. Our simulation platform thus helps in a comprehensive assessment of cardiovascular risk, enabling better prediction, prevention, and treatment of atherosclerosis-related conditions—a paradigm that has remained to be elusive in clinical practices thus far.
... Our previous study of healthy human cerebrovasculature and the development of a probabilistic vascular atlas (34) showed that the Circle of Willis is not fully formed in most adult humans, and a significant cerebrovascular variability exists within the population. These variations affect cerebral hemodynamics and even rates of neuronal degradation (53,54) during ischemia and, thereby, response to treatment. Hence, a more developed collateral circulation provides more time (even several days) for therapeutic interventions and impacts clinical outcomes (15,16). ...
Background
Rapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage.
Methods
Employing a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient’s cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion’s presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90 days functional outcome for each patient.
Results
The CNN model achieved a segmentation accuracy of 94% based on the Dice similarity coefficient (DSC). The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90 days outcome prediction accuracy from 0.63 to 0.83.
Conclusion
The fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.
... Particles have also been used to represent thromboemboli that completely dislodge, causing subsequent occlusive disorders. Simulations have been used to predict movement of dislodged thromboemboli from the heart to the brain under hemodynamic forces [83], and to model distal embolization risks due to dislodged emboli during thrombectomy procedures in acute ischemic stroke [84]. In summary, these studies indicate that the discontinuous nature of fragmentation processes combined with microstructural heterogeneity preclude a clear understanding of thrombus stability, and how embolization progresses. ...
From the molecular level up to a blood vessel, thrombosis and hemostasis involves many interconnected biochemical and biophysical processes over a wide range of length and time scales. Computational modeling has gained eminence in offering insights into these processes beyond what can be obtained from in vitro or in vivo experiments, or clinical measurements. The multiscale and multiphysics nature of thrombosis has inspired a wide range of modeling approaches that aim to address how a thrombus forms and dismantles. Here we review recent advances in computational modeling with a focus on platelet-based thrombosis. We attempt to summarize the diverse range of modeling efforts straddling the wide-spectrum of physical phenomena, length scales, and time scales; highlighting key advancements and insights from existing studies. Potential information gleaned from models is discussed, ranging from identification of thrombus-prone regions in patient-specific vasculature, to modeling thrombus deformation and embolization in response to fluid forces. Furthermore, we highlight several limitations of current models, future directions in the field, and opportunities for clinical translation, to illustrate the state-of-the-art. There are a plethora of opportunity areas for which models can be expanded, ranging from topics of thromboinflammation to platelet production and clearance. Through successes demonstrated in existing studies described here, as well as continued advancements in computational methodologies and computer processing speeds and memory, in silico investigations in thrombosis are poised to bring about significant knowledge growth in the years to come.
... The vessel lumen for each of these 24 total models were discretized into a computational grid comprising linear, tetrahedral element, and the maximum edge sizes for each model are listed in Table 2. The edge sizes are informed by mesh refinement and aortic hemodynamic studies reported in several prior works [27,28]. ...
Stroke remains a leading cause of complications and mortality in heart failure patients treated with LVAD circulatory support. Hemodynamics plays a central role in affecting risk and etiology of stroke during LVAD support. Yet, detailed quantitative assessment of hemodynamic variables and their relation to stroke outcomes in patients with an implanted LVAD remains a challenge. We present an in silico hemodynamics analysis in a set of 12 patients on LVAD support; 6 with reported stroke outcomes and 6 without. We conducted patient-specific hemodynamics simulations for models with the LVAD outflow graft reconstructed from cardiac-gated CT images. A pre-implantation baseline flow model was virtually generated for each case by removing the LVAD outflow graft and driving flow from the aortic root. Hemodynamics was characterized using quantitative descriptors for helical flow, vortex generation, and wall shear stress. Our analysis showed higher average values for descriptors of positive helical flow, vortex generation, and wall shear stress, across the 6 cases with stroke outcomes on LVAD support, when compared with cases without stroke. When the descriptors for LVAD-driven flow were compared against estimated baseline flow pre-implantation, extent of positive helicity was higher, and vorticity and wall shear were lower in cases with stroke compared to those without. The study suggests that quantitative analysis of hemodynamics after LVAD implantation; and hemodynamic alterations from a pre-implant flow scenario, can potentially reveal hidden information linked to stroke outcomes during LVAD support. This has broad implications on understanding stroke etiology, LVAD treatment planning, surgical optimization, and efficacy assessment.
... Ultrasound and MRI can be utilised to get direct measurements of the lumen's nonlinear dimensions, which can then be scaled to account for a time-varying pressure waveform (Feiger et al., 2021), (Garber et al., 2021), (Taylor & Steinman, 2010). Inlet and exit profiles, as well as zero traction, were proposed by the majority of 3D blood flow models (Arzani, 2018), (Mukherjee et al., 2018), (Habibi et al., 2020). Because measured and prescribed flow measurements were used, vessel compliance was ignored, and the goal was to compute velocity, field, and WSS, this was sufficient for the majority of simulations. ...
Computational Fluid Dynamics (CFD) plays an important role in assessment of genesis and prognosis of atherosclerosis and as a promising tool for risk stratification. CFD is widely used by a majority of the researchers, although, many experimental studies show that the results obtained by CFD are inconsistent with the physio-pathological manifestations, which is mainly due to inconsistent definition of parameters, limited data availability and extreme complexity and heterogeneous behavior of plaque growth and its rupture. In this review, the results obtained by Computational Fluid Dynamics are summarized and an attempt is made to deduce the broad causes of various errors and possible solutions.
... 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.
... Computational models of hemodynamics have been broadly applied to a wide range of adult and pediatric diseases spanning cerebral and abdominal aortic aneurysms, vascular surgery and endovascular devices, stroke and embolism, the thoracic aorta, and others. [86][87][88][89] Models have also been instrumental in accelerating the medical device design pipeline, allowing for inexpensive design optimization prior to full-scale animal and human studies. [90][91][92][93] Here, we focus primarily on two areas of clinical need in cardiovascular disease: coronary artery disease and pulmonary vascular disease. ...
Physics-based computational models of the cardiovascular system are increasingly used to simulate hemodynamics, tissue mechanics, and physiology in evolving healthy and diseased states. While predictive models using computational fluid dynamics (CFD) originated primarily for use in surgical planning, their application now extends well beyond this purpose. In this review, we describe an increasingly wide range of modeling applications aimed at uncovering fundamental mechanisms of disease progression and development, performing model-guided design, and generating testable hypotheses to drive targeted experiments. Increasingly, models are incorporating multiple physical processes spanning a wide range of time and length scales in the heart and vasculature. With these expanded capabilities, clinical adoption of patient-specific modeling in congenital and acquired cardiovascular disease is also increasing, impacting clinical care and treatment decisions in complex congenital heart disease, coronary artery disease, vascular surgery, pulmonary artery disease, and medical device design. In support of these efforts, we discuss recent advances in modeling methodology, which are most impactful when driven by clinical needs. We describe pivotal recent developments in image processing, fluid–structure interaction, modeling under uncertainty, and reduced order modeling to enable simulations in clinically relevant timeframes. In all these areas, we argue that traditional CFD alone is insufficient to tackle increasingly complex clinical and biological problems across scales and systems. Rather, CFD should be coupled with appropriate multiscale biological, physical, and physiological models needed to produce comprehensive, impactful models of mechanobiological systems and complex clinical scenarios. With this perspective, we finally outline open problems and future challenges in the field.
... Without an efficient functioning of the PComA, the collateral circulation path may be compromised and an ischemic stroke can develop [38]. Chuang YM, et al. [36] point out that a hypoplastic PComA is associated with an increased risk of stroke, especially in the thalamic region Mukherjee D, et al. [39] suggested that the presence of anatomical variants at the level of CoW may have an impact on the trajectory of microemboli and therefore may lead to infarcts in distal, more unusual areas of Our study 63.63% 9.09% -the brain. Patients with bilateral para-median thalamic lesions with no lesions other than in the thalamus were more likely to have hypoplastic P1 segments of PCAs or unilateral or bilateral absences of PComAs. ...
Introduction: The current literature proves that the frequency of anatomical variants of circle of Willis (CoW) has not yet been sufficiently evaluated both in the Romanian population and internationally, and in the North East region of Romania there is no evidence of such research so far.The aim of this study is to identify the frequency and types of anatomical variants of the constituent arteries of the posterior part of the Cov in patients with cerebrovascular diseases diagnosed within the main Neurology hospital in the Northeastern region of Romania, based on macroscopic analysis of arterial specimens obtained at autopsy and the results with data from updated literature.
... 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). ...
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.
... The ICA supplies oxygenated blood to most midline portions of the frontal lobe and superior medial parietal lobe. It is the most important blood supply of the cerebral circulation from the circle of Willis (5). The MCA receives 80% of the carotid blood flow, whereas the ACA receives 20%. ...
The brain is a vital organ that requires a constant blood supply. Stroke occurs when the blood supply to specific parts of the brain is reduced; diabetes is an autonomous risk factor for stroke. The present study aimed to investigate the potential vascular protective effect of gymnemic acid (GM) by assessing the morphological changes of microvasculature, along with VEGFA and angiopoietin-1 (Ang-1) protein expression in the brains of diabetic rats. Rats were divided into five groups, including control, gymnemic control rats (CGM), rats that were rendered diabetic by single injection of 60 mg/kg streptozotocin (STZ), diabetic rats treated with 400 mg/kg GM (STZ + GM) and diabetic rats treated with 4 mg/kg glibenclamide (GL; STZ + GL). After 8 weeks, brain tissues were collected to examine the three-dimensional morphology of the anterior cerebral arteries by vascular corrosion casting. Western blotting was performed to determine VEGFA and Ang-1 expression. Cerebral arteries, arterioles and capillaries were depicted the diameter, thickness and collagen accumulation of the wall, and the results demonstrated narrow diameters, thickened walls and collagen accumulation in the STZ group. After receiving GM, the histopathological changes were similar to that of the control group. Through vascular corrosion casting and microscopy, signs of vessel restoration and improvement were exhibited by increased diameters, and healthy and nourished arterioles and capillaries following treatment with GM. Furthermore, VEGF expression and Ang-1 secretion decreased in the STZ + GM group compared with STZ rats. The results of the present study revealed that GM treatment decreased blood vessel damage in the brain, suggesting that it may be used as a therapeutic target for the treatment of diabetes.
... These methods often do not consider the effect that the unique configuration of the Circle of Willis (CoW) has on flow. The CoW is a unique vascular structure in the brain that has shown to reduce the risk of stroke when more collateral arteries are present [3]. Furthering examining the effect that the CoW has on determining parameters for stroke treatment is important. ...
Purpose:
Complex hemodynamics assessments, as those related to carotid stenosis, are not always easily straightforward due to multifaceted challenges presented by the collateral flow in the Circle of Willis (CoW) and brain flow autoregulation. Advanced computational and benchtop methods to investigate hemodynamics aspects related to such complex flows are often used, however both have limitations and could lead to results which may diverge. In this study we investigated these aspects by performing correlated computational fluid dynamics (CFD) simulations and benchtop experiments in patient specific 3D printed phantoms.
Materials and methods:
To investigate the flow in patients with carotid stenosis, we built two patient specific phantoms which contained the arterial lesion of interest, all main arteries leading to the brain, the CoW and main arteries branching from it. Each phantom was connected to a generic aortic arch. A programmable pump was connected and flow parameters were measured proximal and distal to the lesion and the contralateral arteries. The patient 3D geometry was used to perform a set of CFD simulations where inflow boundary conditions matched the experimental ones. Flow conditions were recorded at the same locations as the experimental setup. Further exploration into the translation from experimental to CFD was also performed by customizing vascular segmentation and physically manipulating arterial compliance properties.
Results:
We initially observed significant differences between the CFD recordings and the experimental setup. Most of the differences were due to changes in phantom geometry when subjected to physiological pressures and simplistic outflow boundary conditions in the CFD simulations which do not account for pulsatility and nonlinear phenomena. Further work confirms the need for dynamic mesh behavior within CFD simulations attempting to computationally mimic 3D-printed benchtop experiments. Additionally, CFD simulation may benefit from considering geometry specific to a 3D-printed vascular phantom.
... Substituting Equation (21) into functions (15) and applying them to Equation (20) give ...
We consider the differential–algebraic system for the blood flow and pressure in the systemic arteries. By the operator splitting method, we transform the system into the hyperbolic one, introduce the bicharacteristics, and perform the time–space nonuniform discretization, obtaining the innovative difference scheme. Our results are illustrated with numerical experiments.
... Furthermore, Mukherjee et al. divided the embolism process into three independent steps, and estimated the risks of embolism from a probabilistic view using FSI simulation (Fig.4a) [75]. They applied the FSI model in 24 cases and concluded that anatomical variations of CoW significantly influenced embolus distribution to the six major cerebral arteries while MCA territory was least sensitive to the influence of anatomical variations [76]. ...
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.
... In view of this large number of variations, it appears that the existence of an effective arterial CW could not always be assumed. According to [16], incompleteness of the CW or poor collateral circulation was significantly related to the embolism risk. ...
We are focusing on the difficult task of predicting final lesion in stroke, a complex disease that leads to divergent imaging patterns related to the occluded artery level and the geometry of the patient’s vascular tree. We propose a framework in which convolutional neural networks are trained only from synthetic perfusion MRI - obtained from an existing physical simulator - and tested on real patients. We incorporate new levels of realism into this simulator, allowing to simulate the vascular tree of a given patient. We demonstrate that our approach is able to predict the final infarct of the tested patients only from simulated data. Among the various simulated databases generated, we show that simulations taking into account the vascular tree information give the best classification performances on the tested patients.
... bi-direction cross-flow and flow separations). Swirling flow patterns were observed in 3D CFD simulations of blood flow in the CoW, and the unsteady pulsatile flow rate imposed as the inflow boundary conditions gave rise to alteration of the flow direction in the communicating arteries 4,25 Additionally, the two types of tubes assembled in the experiment (Tygon and silicone tubes) could contribute in the discrepancies. The Tygon tube has a uniform wall thickness and elasticity, whereas these two parameters of the silicone model cannot be promised to be uniformly manufactured for the entire model, especially at junctions. ...
A one-dimensional (1D) numerical model has been previously developed to investigate the hemodynamics of blood flow in the entire human vascular network. In the current work, an experimental study of water–glycerin mixture flow in a 3D-printed silicone model of an anatomically accurate, complete circle of Willis (CoW) was conducted to investigate the flow characteristics in comparison with the simulated results by the 1D numerical model. In the experiment, the transient flow and pressure waveforms were measured at 13 selected segments within the flow network for comparisons. In the 1D simulation, the initial parameters of the vessel network were obtained by a direct measurement of the tubes in the experimental setup. The results verified that the 1D numerical model is able to capture the main features of the experimental pressure and flow waveforms with good reliability. The mean flow rates measurement results agree with the predictions of the 1D model with an overall difference of less than 1%. Further experiment might be needed to validate the 1D model in capturing pressure waveforms.
Today, the main cause of mortality in the world remains cardiovascular diseases. In this case, the combined pathology of the neck and head arteries, in which atherosclerosis affects the carotid arteries and there is a change in blood flow in the vertebral arteries or in the circle of Willis due to aplasia of the communicating artery, significantly increases the risk of aneurysms formation and their subsequent rupture. Assessing the risk of complications in this type of pathological condition may allow the physician to initiate timely preventive measures in specific clinical cases. The paper presents the results of modelling various variants of combined pathologies in the arteries of the neck and head. The segment under consideration includes sections of the common carotid, external and internal carotid arteries, as well as vessels of the circle of Willis and the basilar artery. The main idea of the study was to create a prognostic model to assess the risks of aneurysm formation in the circle of Willis and atherosclerotic plaque rupture in the carotid arteries. Such a system may be useful for physicians in routine practice when planning treatment tactics in patients with combined pathologies of the arterial channel. Based on the literature analysis, a number of pathologies of the cerebral and carotid arteries, most frequently occurring in various combinations, were identified: stenoses of the ICA (30 % and 70 %) and aplasia (absence) of one of the connecting arteries were considered from the point of view of geometrical features. In addition, the character of blood flow in the basilar artery, which can change its direction in steal-syndrome, was taken into account. Based on the analysis of blood flow and wall shear stress, two degrees of risk of aneurysm formation were distinguished. High risk corresponds to cases for which both of these values were statistically significantly different from the norm. Medium risk corresponds to cases for which only one of the values was statistically significantly different from the norm. For models containing atherosclerotic plaques, data on shear and normal stresses on the surfaces of atherosclerotic plaques were tabulated. The risk of plaque rupture on each side was determined for each case by analysing the result sets 11 combinations of pathological conditions with increased risk were indicated.
The Circle of Willis (CoW) is a ring-like network of blood vessels that perfuses the brain. Flow in the collateral pathways that connect major arterial inputs in the CoW change dynamically in response to vessel narrowing or occlusion. Vasospasm is an involuntary constriction of blood vessels following subarachnoid hemorrhage (SAH), which can lead to stroke. This study investigated interactions between localization of vasospasm in the CoW, vasospasm severity, anatomical variations, and changes in collateral flow directions. Patient-specific computational fluid dynamics (CFD) simulations were created for 25 vasospasm patients. Computed tomographic angiography scans were segmented capturing the anatomical variation and stenosis due to vasospasm. Transcranial Doppler ultrasound measurements of velocity were used to define boundary conditions. Digital subtraction angiography was analyzed to determine the directions and magnitudes of collateral flows as well as vasospasm severity in each vessel. Percent changes in resistance and viscous dissipation were analyzed to quantify vasospasm severity and localization of vasospasm in a specific region of the CoW. Angiographic severity correlated well with percent changes in resistance and viscous dissipation across all cerebral vessels. Changes in flow direction were observed in collateral pathways of some patients with localized vasospasm, while no significant changes in flow direction were observed in others. CFD simulations can be leveraged to quantify the localization and severity of vasospasm in SAH patients. These factors as well as anatomical variation may lead to changes in collateral flow directions. Future work could relate localization and vasospasm severity to clinical outcomes like the development of infarct.
Ischemic stroke, particularly embolic stroke, stands as a significant global contributor to mortality and long-term disabilities. This paper presents a comprehensive simulation of emboli motion through the middle cerebral artery (MCA), a prevalent site for embolic stroke. Our patient-specific computational model integrates major branches of the middle cerebral artery reconstructed from magnetic resonance angiography images, pulsatile flow dynamics, and emboli of varying geometries, sizes, and material properties. The fluid-structure interactions method is employed to simulate deformable emboli motion through the middle cerebral artery, allowing observation of hemodynamic changes in artery branches upon embolus entry. We investigated the impact of embolus presence on shear stress magnitude on artery walls, analyzed the effects of embolus material properties and geometries on embolus trajectory and motion dynamics within the middle cerebral artery. Additionally, we evaluated the non-Newtonian behavior of blood, comparing it with Newtonian blood behavior. Our findings highlight that embolus geometry significantly influences trajectory, motion patterns, and hemodynamics within middle cerebral artery branches. Emboli with visco-hyperelastic material properties experienced higher stresses upon collision with artery walls compared to those with hyperelastic properties. Furthermore, considering blood as a non-Newtonian fluid had notable effects on emboli stresses and trajectories within the artery, particularly during collisions. Notably, the maximum von Mises stress experienced in our study was 21.83 kPa, suggesting a very low probability of emboli breaking during movement, impact, and after coming to a stop. However, in certain situations, the magnitude of shear stress on them exceeded 1 kPa, increasing the likelihood of cracking and disintegration. These results serve as an initial step in anticipating critical clinical conditions arising from arterial embolism in the middle cerebral artery. They provide insights into the biomechanical parameters influencing embolism, contributing to improved clinical decision-making for stroke management.
This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.
Background
Rapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage.
Methods
Employing a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient’s cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion’s presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90-day functional outcome for each patient.
Results
The CNN model achieved a segmentation accuracy of 94%. The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90-day outcome prediction accuracy from 0.63 to 0.83.
Conclusions
The fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.
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.
The Circle of Willis is a redundant network of blood vessels that perfuses the brain. The ring-like anatomy mitigates the negative effects of stroke by activating collateral pathways that help maintain physiological perfusion. Previous studies have investigated the activation of these pathways during embolic stroke and internal carotid artery occlusion. However, the role of collateral pathways during cerebral vasospasm - an involuntary constriction of blood vessels after subarachnoid hemorrhage - is not well-documented. This study presents a novel technique to create patient-specific computational fluid dynamics simulations of the Circle of Willis before and during vasospasm. Computed tomographic angiography scans are segmented to model the vasculature, and transcranial Doppler ultrasound measurements of blood flow velocity are applied as boundary conditions. Bayesian analysis leverages information about the uncertainty in the measurements of vessel diameters and velocities to find an optimized parameter set that satisfies mass conservation and that is applied in the final simulation. With this optimized parameter set, the diameters, velocities, and flow rates fall within typical literature values. Virtual angiograms modeled using passive scalar transport agree closely with clinical angiography. A sensitivity analysis quantifies the changes in collateral flow rates with respect to changes in the inlet and outlet flow rates. This analysis can be applied in the future to a cohort of patients to investigate the relationship between the location and severity of vasospasm, the patient-to-patient anatomical variability in the Circle of Willis, and the activation of collateral pathways.
Background and purpose:
Altered brain vasculature is a key phenomenon in several neurologic disorders. This paper presents a quantitative assessment of the anatomical variations in the Circle of Willis (CoW) and vascular morphology in healthy aging, acute ischemic stroke (AIS) and Alzheimer's Disease (AD). .
Methods:
We used our novel automatic method to segment and extract geometric features of the cerebral vasculature from MR angiography scans of 175 healthy subjects, which were used to create a probabilistic atlas of cerebrovasculature and to study normal aging and intersubject variations in CoW anatomy. Subsequently, we quantified and analyzed vascular alterations in 45AIS and 50 AD patients, two prominent cerebrovascular and neurodegenerative disorders.
Results:
In the sampled cohort, we determined that the CoW is fully formed in only 35% of healthy adults and found significantly (p < .05) increased tortuosity and fractality, with increasing age and also with disease in both AIS and AD. We also found significantly lower vessel length, volume, and number of branches in AIS patients, as expected. The AD cerebral vessels exhibited significantly smaller diameter and more complex branching patterns, compared to age-matched healthy adults. These changes were significantly heightened (p < .05) among healthy, early onset mild AD, and moderate/severe dementia groups.
Conclusion:
Although our study does not include longitudinal data due to paucity of such datasets, the specific geometric features and quantitative comparisons demonstrate the potential for using vascular morphology as a noninvasive imaging biomarker for neurologic disorders.
Objective
Subarachnoid hemorrhage due to vertebral artery dissection is often fatal; however, its anatomical predictors remain unclear. We conducted a retrospective hospital-based case-control study to evaluate whether variations in the posterior communicating artery are associated with the risk of vertebral artery dissection with subarachnoid hemorrhage.
Materials and methods
We obtained data from patients who underwent computed tomography angiography at our hospital between April 2010 and March 2020. Based on the connection between the anterior and posterior circulation of the arterial circle of Willis, the patients were categorized into a separated group (posterior communicating artery hypoplasia) and a connected group (all others). We evaluated the association between the development of posterior communicating artery and subarachnoid hemorrhage due to vertebral artery dissection using multivariate logistic regression analysis.
Results
Thirty-eight patients had subarachnoid hemorrhage due to vertebral artery dissection and 76 were identified as age- and sex-matched controls. In conditional multivariate logistic regression analysis, the separated group showed a significant association with subarachnoid hemorrhage due to vertebral artery dissection, with an adjusted odds ratio of 2.8 (95% confidence interval, 1.2–6.5; P = 0.021).
Conclusions
The present study demonstrates that posterior communicating artery hypoplasia may be associated with subarachnoid hemorrhage due to vertebral artery dissection. Our results highlight the importance of anatomical variations in the cerebral artery and provide evidence to help develop preventive measures against strokes.
The Golden ratio ('phi' or 'Ф') has been known to us for ages and its use in art and architectural designs has enhanced their exquisiteness. Even some of the astounding creations of nature do follow this principle of Golden or divine proportions. Three centuries ago 'Circle of Willis' at the base of the brain was first described and illustrated by Thomas Willis. Classically it was described as to be circular in shape however, the gross anatomy reveals a slightly different picture. The components of this complex neurovascular structure are so arranged that it appears more like a pentagon than a circle. A regular pentagon, unlike a circle, is a Golden shape that mathematically obeys the laws of Golden proportions. Like most other marvelous structures in nature, the close resemblance of 'Circle of Willis' to a pentagon is more of a conscious effort of nature to establish consonance with aesthetic perception, rather than just a mere coincidence.
During the last years, several kinds of Embolic Protection Devices (EPD) have been developed, with the aim of minimizing complication caused by thrombi generated during Carotid Artery Stenting (CAS). These devices are capable of capturing small particles generated during the intervention, avoiding cerebral stroke and improving the outcomes of the surgery. However, they have associated complications, like the increase on flow resistance associated by their use or the lack of knowledge on their actual filtration efficiency for thrombi of low size. Current work proposes a validated computational methodology in order to predict the hemodynamic features and filtering efficiency of a commercial EPD. It will be observed how Computational Fluid Dynamics predicts pressure drop with fair agreement with the experimental measurements. Finally, this work analyzes the filtration efficiency and the influence of the distribution of injected particles on this parameter. The capabilities of the filter for retaining particles of diameter below the pore size is, additionally, discussed.
Brain anatomy can be explored with ultrasonography at the patient’s bedside. Anatomy of the brain vasculature has been described through several acoustic windows: the temporal, the transorbital, the transforaminal, and the submandibular windows. Each window offers the possibility to image specific parts of major basal intracranial arteries as well as cerebral deep veins and sinuses. In daily clinical practice, bilateral examination of the entire circle of Willis can be easily done through the temporal window. Recognition of the different basal arteries is based on their relationship with typical brain structures such as brain peduncles and the direction of their flow to the ultrasound probe. Beyond simple identification of brain vasculature, transcranial color duplex Doppler (TCCD) may also provide useful information regarding brain structures. Using this acoustic window, clinician can explore the entire circle of Willis but also visualize typical brain structures such as the brainstem, and lateral and third ventricles. Potential clinical implications are the assessment of ventricle enlargement and midline shift, and the follow-up of brain hematomas. Emergent evidence suggests that ultrasonographic assessment of these clinical features is well correlated with CT scan, providing a bedside evaluation of brain anatomy. In this chapter, we describe brain anatomy though the different acoustic windows. Two different parts are developed: the first one deals with brain vasculature description and the second one describes brain structures that are imaged through the transtemporal window.
La anatomía cerebral humana es de gran relevancia para los médicos que manejanos pacientes neurológicos y neuroquirúrgicos. Durante siglos se ha estudiado su composición, lo cual ha permitido reconocer e identificar las alteraciones en el cuerpo humano de forma eficaz partiendo de la fisiología normal y la fisiopatología de la enfermedad. La doctrina de Monro-Kellie refiere que los diversos componentes que se encuentran en la cavidad intracraneal dan lugar a una presión intracraneal, la cual podría variar según diversas situaciones de la vida. Las variaciones anormales de la PIC se dan en su mayoría por efectos de masa provocados por la alteración de uno de los tres componentes intracraneales, se ha observado que el reconocimiento oportuno de estas alteraciones serán determinantes para el pronóstico. Además, el tratamiento dependerá directamente del grado y del sitio de afectación.
In this study, an image-based morphometry toolset quantifying geometric descriptors of the left ventricle, aorta and their coupling is applied to investigate whether morphological information can differentiate between subjects affected by diastolic dysfunction (patient group) and their age-matched controls (control group). The ventriculo-aortic region of 20 total participants (10 per group) were segmented from high-resolution 3D magnetic resonance images, from the left ventricle to the descending aorta. Each geometry was divided into segments in correspondence of anatomical landmarks. The orientation of each segment was estimated by least-squares fitting of the respective centerline segment to a plane. Curvature and torsion of vessels’ centerlines were automatically extracted, and aortic arch was characterized in terms of height and width.
Tilt angle between subsequent best-fit planes in the left ventricle and ascending aorta regions, curvature and cross-sectional area in the descending aorta resulted significantly different between patient and control groups (P-values< 0.05). Aortic volume (P = 0.04) and aortic arch width (P = 0.03) resulted significantly different between the two groups. The observed morphometric differences underlie differences in hemodynamics, by virtue of the influence of geometry on blood flow patterns.
The present exploratory analysis does not determine if aortic geometric changes precede diastolic dysfunction, or vice versa. However, this study (1) underlines differences between healthy and diastolic dysfunction subjects, and (2) provides geometric parameters that might help to determine early aortic geometric alterations and potentially prevent evolution toward advanced diastolic dysfunction.
Introduction:
We investigated circle of Willis (CoW) completeness in relation to the risk of future ischemic stroke in patients without prior cerebrovascular disease.
Methods:
We included 976 patients with atherosclerotic disease, but no previous TIA/stroke, from the Second Manifestations of ARTerial disease (SMART) study. All patients underwent MR angiography of the CoW. Cox regression was used to determine whether anterior CoW completeness (anterior communicating artery or A1 segments) and posterior CoW completeness (posterior communicating arteries or P1 segments) were related to future stroke, and whether CoW completeness influenced the relation between internal carotid artery (ICA) stenosis/occlusion and future stroke.
Results:
Thirty patients (3.1 %) had ischemic stroke after 9.2 ± 3.0 years of follow-up. Twenty-four patients (80 %) had anterior circulation stroke. An incomplete anterior CoW was related to future anterior circulation stroke (HR 2.8 (95 % CI 1.3-6.3); p = 0.01), whereas a one-sided and two-sided incomplete posterior CoW were not (HR 2.2 (95 % CI 0.7-7.1; p = 0.19) and 1.9 (95 % CI 0.6-5.9; p = 0.29), respectively). In stratified analyses, patients with an incomplete anterior CoW had the highest risk of future anterior circulation stroke when they also had a one-sided (HR 7.0 (95 % CI 1.3-38.2; p = 0.02)) or two-sided incomplete posterior CoW (HR 5.4 (95 % CI 1.0-27.8; p = 0.04). CoW completeness did not change the relation between asymptomatic ICA stenosis/occlusion and future ischemic stroke (p = 0.68).
Conclusions:
An incomplete anterior CoW combined with an incomplete posterior CoW is related to future anterior circulation stroke. CoW completeness has no large effect on the relation between asymptomatic ICA stenosis/occlusion and future stroke.
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.
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© 2015 American Heart Association, Inc.
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.
Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe
a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism—in the same way platelets
do—to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale
components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered
intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model,
restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical
strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers
a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.
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
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.
High-resolution unsteady three-dimensional flow simulations in large intracranial arterial networks of a healthy subject and a patient with hydrocephalus have been performed. The large size of the computational domains requires the use of thousands of computer processors and solution of the flow equations with approximately one billion degrees of freedom. We have developed and implemented a two-level domain decomposition method, and a new type of outflow boundary condition to control flow rates at tens of terminal vessels of the arterial network. In this paper, we demonstrate the flow patterns in the normal and abnormal intracranial arterial networks using patient-specific data.
A numerical model based on one-dimensional balance laws and ad hoc zero-dimensional boundary conditions is tested against experimental data. The study concentrates on the circle of Willis, a vital subnetwork of the cerebral vasculature. The main goal is to obtain efficient and reliable numerical tools with predictive capabilities. The flow is assumed to obey the Navier-Stokes equations, while the mechanical reactions of the arterial walls follow a viscoelastic model. Like many previous studies, a dimension reduction is performed through averaging. Unlike most previous work, the resulting model is both calibrated and validated against in vivo data, more precisely transcranial Doppler data of cerebral blood velocity. The network considered has three inflow vessels and six outflow vessels. Inflow conditions come from the data, while outflow conditions are modeled. Parameters in the outflow conditions are calibrated using a subset of the data through ensemble Kalman filtering techniques. The rest of the data is used for validation. The results demonstrate the viability of the proposed approach.
After the occlusion of an internal carotid artery the principal source of collateral flow is through the arteries of the circle of Willis, but the size and patency of these arteries are quite variable. Study of the anatomy of the collateral pathways in patients with internal-carotid-artery occlusion with or without infarction in the watershed area of the deep white matter may identify patterns that afford protection from ischemic infarction.
Using conventional magnetic resonance imaging and three-dimensional phase-contrast magnetic resonance angiography, we evaluated 29 consecutive patients (32 hemispheres at risk) with angiographically proved occlusion of the internal carotid artery. Four collateral pathways to the occluded vessel were evaluated: the proximal segment of the anterior cerebral artery, the posterior communicating artery, the ophthalmic artery, and leptomeningeal collateral vessels from the posterior cerebral artery.
Only features of the ipsilateral posterior communicating artery were related to the risk of watershed infarction. The presence of posterior communicating arteries measuring at least 1 mm in diameter was associated with the absence of watershed infarction (13 hemispheres, no infarcts; P < 0.001). Conversely, there were 4 watershed infarcts in the 6 hemispheres with posterior communicating arteries measuring less than 1 mm in diameter and 10 infarcts in the 13 hemispheres with no detectable flow in the ipsilateral posterior communicating artery.
A small (< 1 mm in diameter) or absent ipsilateral posterior communicating artery is a risk factor for ischemic cerebral infarction in patients with internal-carotid-artery occlusion.
Autopsy studies show a higher prevalence of circle of Willis anomalies in brains with signs of ischemic infarction. Our goal was to examine the collateral function of the circle of Willis in ischemic stroke patients and to assess in a case-control study if a collateral deficient circle of Willis is a risk factor for ischemic stroke in patients with severe internal carotid artery (ICA) occlusive disease.
Our case-control study included 109 patients with an acute ischemic stroke in the anterior circulation and 113 patients with peripheral arterial disease and no known history of cerebral ischemia. The collateral function of the anterior and posterior communicating arteries of the circle of Willis was assessed by means of transcranial color-coded duplex ultrasonography (TCCD) and carotid compression tests.
TCCD was successfully performed in 75 case patients (mean age 64 years, range 41-91 years) and in 100 control patients (mean age 61 years, range 35-89 years). In 26 cases and 19 controls, a >/=70% stenosis or occlusion of the ICA was found. A nonfunctional anterior collateral pathway in the circle of Willis was found in 33% of the cases and in 6% of the controls (p < 0.001). The posterior collateral pathway was nonfunctional in 57% of the cases and in 43% of the controls (p = 0.02). In patients with severe ICA occlusive disease, the odds ratios of a nonfunctional anterior and a nonfunctional posterior collateral pathway were 7.33 (95% confidence interval, CI, = 1.19-76.52) and 3.00 (95% CI = 0.77-12.04), respectively.
Patients who suffer ischemic stroke in the anterior circulation have a higher incidence of collateral deficient circles of Willis than those with atherosclerotic vascular disease without ischemic cerebrovascular disease. The presence of a nonfunctional anterior collateral pathway in the circle of Willis in patients with severe ICA occlusive disease is strongly associated with ischemic stroke.
Volume flow rates in the feeding arteries of the brain are measured to evaluate blood flow dynamics in vascular disease. Although these flow values are thought to be effected by anatomic variations in the circle of Willis, few reports have described the effect. This study reports on the relationship between variations in the circle of Willis and volume flow rates in the bilateral internal carotid and basilar arteries of normal volunteers.
We prospectively examined 125 healthy volunteers by MR imaging. Variations in the circle of Willis were classified as "textbook" type, hypoplasia of the precommunicating segment of the anterior cerebral artery (A1), hypoplasia of the precommunicating segment of the posterior cerebral artery (P1), or "other." Volume flow rates were measured by 2D cine phase-contrast MR imaging. Lumen boundaries and volume flow rates were semiautomatically determined by pulsatility-based segmentation.
Of the 117 subjects (61 men, 56 women; mean age, 23.6 years) considered suitable for flow measurement, 105 showed textbook type, and 6 each showed A1 hypoplasia and P1 hypoplasia. Total flow rates for the 3 variations were 781 +/- 151 mL/min (mean +/- SD), 744 +/- 119, and 763 +/- 129, respectively. Relative contributions by flow rates of the internal carotid arteries and the basilar artery for the 3 variations were 39.8%:38.9%:21.3%, 31.8%:49.1%:19.0%, and 46.6%:41.6%:11.7%, respectively, showing statistically significant differences.
Variations in the circle of Willis correlate significantly with relative contributions by the flow rates of the bilateral internal carotid and basilar arteries.
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.
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.
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.
Background and purpose:
The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement.
Methods:
A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy.
Results:
Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001).
Conclusions:
A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.
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.
Introduction
There is great variability in the normal configuration of the circle of Willis (Alpers, Berry, Paddison).1 Relatively little information is available concerning its structure in cerebral softening due to thrombosis and embolism and in cerebral hemorrhage and aneurysm. The present study was undertaken in order to determine the incidence and nature of the anomalies of the circle of Willis in the various forms of cerebral vascular disorder, particularly in occlusive vascular disease, where the factor of collateral circulation appears to have greater significance than in cerebral or meningeal hemorrhage.
Material and Methods
The basis of the present study is formed by 194 gross brain softenings. Of these 56 were found to be the result of thrombosis; 53 were due to embolism; and the cause of the softening was unidentified in 85 cases. The high incidence of an unidentified source is due to the fact that many of the
Introduction
The present study was undertaken in order to determine the anatomical structures of the circle of Willis,27 with the purpose of learning its normal configuration, the frequency of deficient or incomplete circles, and, if possible, how these findings can be correlated with the clinical problems of vascular disease, such as infarcts, aneurysms, and vascular anomalies.There are many problems in vascular disease of the brain which make desirable an intimate knowledge of variants in the anatomy of the circle of Willis. The state of the circle becomes important in determining the adequacy of the brain circulation in operations for cerebral aneurysm and in ligation of the carotid artery. The possibility of bypassing or shunting effects in occlusion of one of the cerebral vessels and the adequacy of recovery or lack of recovery after vascular occlusion might be explained in part by variations in the anatomy of the circle
Background and purpose:
Treatment of patients with ischemic stroke after endovascular treatment requires in-depth knowledge of complications. The goal of this study was to make endovascular treatment for acute ischemic stroke safer through an in-depth review of the major periprocedural complications observed in the Solitaire FR With Intention for Thrombectomy (SWIFT) trial.
Materials and methods:
The SWIFT data base was searched for major peri-procedural complications defined as symptomatic intracranial hemorrhage within 36 hours, SAH, air emboli, vessel dissection, major groin complications, and emboli to new vascular territories.
Results:
Major peri-procedural complications occurred in 18 of 144 patients (12.5%) as follows: symptomatic intracranial hemorrhage, 4.9%; air emboli, 1.4%; vessel dissection, 4.2%; major groin complications, 2.8%; and emboli to new vascular territories, 0.7%. Rates of symptomatic intracranial bleeding by subtype were PH1, 0.7%; PH2, 0.7% (PH1 indicates hematoma within ischemic field with some mild space-occupying effect but involving ≤ 30% of the infarcted area; PH2, hematoma within ischemic field with space-occupying effect involving >30% of the infarcted area); intracranial hemorrhage remote from ischemic zone, 0%; intraventricular hemorrhage, 0.7%; and SAH, 3.5%. We did not observe any statistically significant associations of peri-procedural complications with age; type of treatment center; duration of stroke symptoms; NIHSS score, IV thrombolytics, atrial fibrillation, site of vessel occlusion; rescue therapy administered after endovascular treatment; or device. Comparing the Merci with the Solitaire FR retrieval device, we observed symptomatic cerebral hemorrhage (10.9% versus 1.1%; P = .013); symptomatic SAH (7.3% versus 1.1%; P = .07), air emboli (1.8% versus 1.1%; P = 1.0), emboli to new vascular territories (1.8% versus 0%; P = .38), vessel dissection (1.8% versus 4.5%; P = .65), and major groin complications (3.6% versus 7.9%; P = .48). Angiographic vasospasm was common but without clinical sequelae.
Conclusions:
Understanding of procedural complications is important for treatment of patients with stroke after endovascular treatment. We observed fewer endovascular complications with the Solitaire FR device treatment compared with Merci device treatment, particularly symptomatic cerebral hemorrhage.
Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.
A very simple model of the flow in the circle of Willis is described in this paper. Disregarding pulsatility and vessel wall elasticity, fluxes in all segments of the circle of Willis and its afferent and efferent vessels are calculated by applying the Poiseuille-Hagen formula. Comparison withe the fluxes calculated numerically from a more sophisticated mathematical model, including pulsatility, vessel wall elasticity and nonlinear effects, revealed only very slight differences. In short, fluxes in the afferent vessels and the segments of the circle of Willis are influenced by any change of resistance within the network, whereas the fluxes in the efferent segments are dominated by the efferent resistance distribution.However, a great advantage of the present simple model is that it offers the possibility of an analytical approach which yields both an easy sensitivity analysis of parameters and an insight into the mechanisms that govern the flow in a network like the circle of Willis. It can be concluded that these mechanisms are similar to the principles of the Wheatstone bridge, known from electrical circuit theory.
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.
Here we analyse the influence of assumptions made on boundary conditions (BCs) extracted from phase-contrast magnetic resonance imaging (PC-MRI) in vivo measured flow data, applied on hemodynamic models of human aorta. This study aims at investigating if the imposition of BCs based on defective information, even when measured and specific-to-the-subject, might lead to misleading numerical representations of the aortic hemodynamics. In detail, we focus on the influence of assumptions regarding velocity profiles at the inlet section of the ascending aorta, incorporating phase flow data within the computational model. The obtained results are compared in terms of disturbed shear and helical bulk flow structures, when the same measured flow rate is prescribed as inlet BC in terms of 3D or 1D (axial) measured or idealized velocity profiles. Our findings clearly indicate that: (1) the imposition of PC-MRI measured axial velocity profiles as inflow BC may capture disturbed shear with sufficient accuracy, without the need to prescribe (and measure) realistic fully 3D velocity profiles; (2) attention should be put in setting idealized or PC-MRI measured axial velocity profiles at the inlet boundaries of aortic computational models when bulk flow features are investigated, because helical flow structures are markedly affected by the BC prescribed at the inflow. We conclude that the plausibility of the assumption of idealized velocity profiles as inlet BCs in personalized computational models can lead to misleading representations of the aortic hemodynamics both in terms of disturbed shear and bulk flow structures.
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.
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 purpose of this study is to report our preliminary experience with the flow-diverter Silk stent for the endovascular treatment of intracranial aneurysms.
This prospective study was approved by the authors' ethical committees. Twenty-nine patients with 34 fusiform or wide-necked unruptured aneurysms were included and treated by Silk stent placement alone by 2 physicians in 3 different centers. Technical issues, immediate findings, delayed complications, clinical follow-up, and imaging follow-up at 3 and 6 months were assessed.
Endovascular treatment was successfully performed in 26 patients (90%). In 3 patients, the stent could not be delivered. Mortality and morbidity rates were of 4% (1 of 26) and 15% (4 of 26), respectively; 1 patient died from a delayed aneurysm rupture related to stent migration, 3 experienced a thromboembolic event, and 1 patient developed progressive visual disturbances related to an increased mass effect. Clinical outcome in 25 patients was unchanged (n=19), improved (n=2), or worsened (=4). Angiographic follow-up in 24 patients (29 aneurysms) showed 20 complete occlusions (69%), 1 neck remnant (3.5%), and 8 incomplete occlusions (27.5%). Significant parent artery stenosis at 6 months occurred in 8 cases (33%).
Despite the potential interest of the Silk flow-diverter stent to treat complex intracranial aneurysms without coils, the delayed complication rate is quite high and leads to use this technique only in selective cases.
The objective of our session at the 2008 International Bio-Fluid Symposium and Workshop was to review the state-of-the-art in image-based modeling of blood flow, and identify future directions. Here we summarize progress in the field of image-based modeling of blood flow and vessel wall dynamics from mid-2005 to early 2009. We first describe the tremendous progress made in the application of image-based modeling techniques to elucidate the role of hemodynamics in vascular pathophysiology, plan treatments for congenital and acquired diseases in individual patients, and design and evaluate endovascular devices. We then review the advances that have been made in improving the methodology for modeling blood flow and vessel wall dynamics in image-based models, and consider issues related to extracting hemodynamic parameters and verification and validation. Finally, the strengths and weaknesses of current work in image-based modeling and the opportunities and threats to the field are described. We believe that with a doubling of our efforts toward the clinical application of image-based modeling tools, the next few years could surpass the tremendous gains made in the last few.
Stroke is often the result of carotid atheroma, which may cause ischemia via progressive arterial narrowing or lead to superimposed thrombus formation and subsequent atheroembolism to the intracerebral vasculature. Revascularization through carotid endarterectomy or carotid artery stenting with embolic protection devices has produced favorable results in appropriately selected patients. In planning the percutaneous approach, an arch aortogram is first acquired to determine arch type and identify the presence of any anatomic variants which may affect the approach to the procedure and catheter selection. Subsequent imaging of the cerebral vasculature is performed to delineate the collateral circulation that is present, including an evaluation of the Circle of Willis. Although Doppler ultrasound, computed tomography (CT), and magnetic resonance angiography (MRA) may be useful in evaluating the presence of carotid or cerebrovascular disease, digital subtraction angiography is required prior to performance of a percutaneous intervention in order to create a procedural "roadmap". Additionally, the comprehensive management of cerebrovascular disease requires a detailed knowledge of the specific clinical syndromes that result from ischemia in each vascular territory. This methodical review of cerebrovascular anatomy and stroke syndromes will provide the operator with the tools to conduct a thorough neurological assessment prior to revascularization, evaluate any periprocedural complications that may arise, and evaluate the patient with suspected stroke.
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.
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 mathematical model of the flow in the circle of Willis has been designed and the effects of (a) the large anatomical variation of the communicating arteries and (b) physiological changes of the resistances of the vertebral arteries have been studied. The influence of the posterior perforating arteries on the flow in the posterior communicating arteries has been investigated as well, with special attention being paid to the possible occurrence of a 'dead point'. In the model, the influence of diameters of the communicating arteries on the flow in the afferent vessels and the segments of the circle turns out to be considerable, especially in the range of the anatomical variation of the diameters. Within this range flow reductions due to an increased resistance of the vertebral artery will be compensated for by the system. Assuming that the values and ratios of the peripheral resistances are within the physiological range, a dead point is not to be expected in the flow in the posterior communicating arteries.
Watershed infarcts are unique ischemic lesions which are situated along the border zones between the territories of the major cerebral arteries. Altogether, they constitute approximately 10% of all brain infarcts. They may be precipitated by several different mechanisms but episodes of severe hypotension are the most frequent cause. It is also clear that showers of microemboli may lodge preferentially in these areas and cause infarcts in the underlying brain. This is the most likely explanation for the watershed infarcts in cases of carotid thrombosis. Finally, there are examples of bilateral progressive watershed infarcts, with small vessel occlusions, in which both episodes of hypotension and sources of microembli are lacking. Clinically, these cases often have a stepwise or evenly progressive course. There is evidence that at least stome of these cases are caused by hematogenous disorders with abnormal platelet aggregation resulting in clogging of the small vessels in the watershed areas of the brain and in many other organs.
Collateral circulatory pathways are considered the primary determinant of cerebral hemodynamics in patients with obstructive lesions of the internal carotid arteries (ICaAs). However, the hemodynamic effects of the diameter of the anterior communicating artery (ACoA) have never been assessed quantitatively in humans.
Two different mathematical models were used to simulate changes affecting blood pressures and flows in cerebral arteries as a function of ACoA diameter and ICaA stenoses or occlusions. Small changes in ACoA diameter were found to have marked hemodynamic effects when they occurred within the range of 0.4 to 1.6 mm, a situation observed in 80% of the cases. Outside this range, changes in ACoA diameter had no effect. Simulated pressure drops through a stenotic ICaA were consistent with those observed. They were found to depend on the degrees of the stenoses in both ICaAs and on ACoA diameter according to a simple equation. Pressure reserve in the middle and anterior cerebral arteries decreased to below the lower limit of autoregulation, despite a normal mean arterial blood pressure, when the arteries were distal to a unique 70% ICaA stenosis associated with a small-diameter ACoA or to a 50% ICaA stenosis associated with a contralateral ICaA occlusion and a large-diameter ACoA. Above these thresholds, the circle of Willis allowed for an almost complete global cerebral blood flow compensation that involved all the afferent and communicating vessels.
ACoA diameter strongly modulates the effects of ICaA lesions on cerebral hemodynamics. Some proposals for endarterectomy indications can be derived from our study.
To test the hypothesis that cerebral vasomotor reactivity (CVMR) is significantly more reduced in patients with hemispheric low-flow infarctions than in brain infarctions due to arterio-arterial embolism, a series of 64 consecutive patients with internal carotid artery occlusions were studied. CVMR was calculated from relative changes of blood flow velocity within the middle cerebral artery (MCA) measured by transcranial Doppler ultrasonography (TCD) during hypo- and hypercapnia. The configuration of the circle of Willis (COW) was also determined by TCD using common carotid artery compression tests. Anterior, posterior or ophthalmic artery collateral flow, and absence or combinations of these, were differentiated. CT scans were categorized as showing either no infarction (group I; n = 20) or territorial (group II; n = 28), or low-flow infarctions (group III; n = 16). As compared to normal, CVMR was significantly reduced but equal in groups I and II, however, even more reduced in group III. CVMR was lowest, and low-flow infarctions were most frequent in patients whose collateral hemispheric blood supply was from the ophthalmic artery as opposed to patients with a complete or nearly complete COW. Our findings indicate that low-flow infarctions in extracranial ICA occlusions represent brain damage due to a critical reduction in cerebral perfusion pressure, as opposed to thromboembolically induced lesions. The configuration of the COW seems to play the key role. Our findings also support the view that the pattern of hemispheric infarction seen on CT indicates the pathogenesis of stroke.
We sought to investigate the relation between collateral flow via different pathways and hemodynamic parameters measured by dynamic susceptibility contrast-enhanced MRI in patients with severe carotid artery disease.
Dynamic susceptibility contrast-enhanced MRI was performed in 66 patients and 33 control subjects. Patients had severe stenosis (>70%, n=12), unilateral occlusion (n=38), or bilateral occlusion (n=16) of the internal carotid artery (ICA). Cerebripetal flow and collateral flow via the circle of Willis were investigated with MR angiography. Collateral flow via the ophthalmic artery was investigated with transcranial Doppler sonography.
Patients with ICA stenosis had well-preserved cerebral perfusion and were in general not dependent on collateral supply. Patients with unilateral ICA occlusion had impaired cerebral perfusion. However, appearance time, peak time, and mean transit time in white matter were less increased in patients with than in patients without collateral flow via the circle of Willis (P<0.05). Furthermore, patients with collateral flow via both anterior and posterior communicating arteries had less increased regional cerebral blood volume than patients with collateral flow via the posterior communicating artery only (P<0.05). Patients with bilateral ICA occlusion had severely compromised hemodynamic status despite recruitment of collateral supply.
In patients with unilateral ICA occlusion, the pattern of collateral supply has significant influence on hemodynamic status. Collateral flow via the anterior communicating artery is a sign of well-preserved hemodynamic status, whereas no collateral flow via the circle of Willis or flow via only the posterior communicating artery is a sign of deteriorated cerebral perfusion.
The anterior communicating artery (AcoA) and posterior communicating arteries (PcoA) of the circle of Willis provide the main route for collateral blood flow in cases of carotid artery obstruction. Transcranial color-coded duplex ultrasonography (TCCD) allows real-time measurement of the collateral function of the AcoA and PcoA. The primary objective of this study was to determine the collateral artery threshold diameters for supplying collateral flow.
In 12 acute stroke patients with a median age of 75 years (51 to 91 years), the collateral integrity of the circle of Willis as assessed by TCCD and carotid compression tests was compared with their postmortem anatomy. The lengths and diameters of the collateral arteries were measured.
TCCD demonstrated absent anterior collateral flow in 3 patients. In 1 of these patients, absence of anterior cross-flow was due to an occluded anterior cerebral artery, which was revealed at autopsy. Absent posterior collateral flow was found in 14 hemispheres. In 2 of these hemispheres, autopsy revealed a fetal configuration of the posterior cerebral artery hampering posterior collateral flow. The median (range) diameters as found at autopsy of the functional (n=19) and nonfunctional (n=16) collateral arteries of the circle of Willis were 1.1 (0.4 to 2.0) and 0.5 (0.3 to 0.7) mm, respectively (P=0.003). PcoA diameters were found to correlate negatively (rho=-0. 50, P=0.01) to the diameters of their accessory P1 segments.
The threshold diameter allowing for cross-flow through the primary collateral arteries of the circle of Willis is between 0. 4 and 0.6 mm.
Transcranial color-coded duplex ultrasonography combined with common carotid artery (CCA) compression can be used to assess the collateral function of the circle of Willis. The aim of this study was to assess the unknown fraction of hemodynamic functional anterior and posterior communicating arteries (AcoA and PcoA, respectively) in an atherosclerotic population with no cerebrovascular symptoms.
In 76 patients with a mean age of 61 (35 to 89) years, the blood flow velocity changes in the precommunicating parts (A1 and P1, respectively) of the anterior and posterior cerebral arteries were measured during CCA compression. The AcoA was defined as functional if blood flow was reversed in the ipsilateral A1 and enhanced in the contralateral A1 during CCA compression. The PcoA was defined as functional if the flow velocity in the P1 was enhanced >20% during ipsilateral CCA compression.
It was possible to assess cross flow through the anterior part of the circle of Willis in 95% of the subjects. Failure of this collateral pathway was caused by a hypofunctional AcoA in 4% and a hypofunctional A1 in 1% of the subjects. Anomalies in the posterior part of the circle of Willis hampering collateral flow from the basilar to the internal carotid artery were found in 45% of the hemispheres. Thirty-eight percent of PcoAs were hypofunctional, and 7% of the posterior cerebral arteries had a persistent fetal anatomy.
We found that in subjects with no cerebrovascular symptoms, the anterior collateral pathway of the circle of Willis was nearly always functional. In contrast, the posterior collateral pathway was nonfunctional in almost half of the total number of hemispheres. Comparing these basic data with data from patients with cerebral ischemic disease might further help to elucidate the importance of the collateral capacity of the circle of Willis.
Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease.
DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment.
All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch).
Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.
The circle of Willis is regarded as the major source of collateral flow in patients with severe carotid artery disease. The purpose of the present study was to assess whether the presence of border zone infarcts is related to the collateral ability of the circle of Willis in symptomatic (transient ischemic attack, minor stroke) and asymptomatic patients with unilateral occlusion of the internal carotid artery (ICA).
Fifty-one patients (35 symptomatic, 16 asymptomatic) and 53 control subjects were investigated. Patients had unilateral occlusion of the ICA and contralateral ICA stenosis between 0% and 69%. The directions of flow, on the side of the ICA occlusion, and the size of the component vessels in the circle of Willis were investigated with MR angiography.
On average, 92% of the patients without border zone infarcts (n=26) had willisian collateral flow compared with 60% of patients with border zone infarcts (n=25; P<0.05). This increase in collateral flow was caused by the high prevalence of collateral flow via the posterior communicating artery in patients without border zone infarcts (50% versus 12%; P<0.05). No statistically significant relation was found between the pattern of collateral flow via the circle of Willis and the presence of clinical symptoms. Nevertheless, asymptomatic patients with ICA occlusion demonstrated an increased diameter of the anterior communicating artery (P<0.05).
In patients with unilateral ICA occlusion, the presence of collateral flow via the posterior communicating artery in the circle of Willis is associated with a low prevalence of border zone infarcts. Asymptomatic patients with an ICA occlusion do not have an increased collateral function of the circle of Willis.
The collateral flow to the cerebral hemisphere after carotid cross clamping during carotid endarterectomy is mainly through the circle of Willis, and the circle is incomplete in the majority of cases. A correlation between the status of the circle of Willis and the necessity of shunting was evaluated in 67 carotid endarterectomies with pre-operative four-vessel cerebral angiogram. All carotid endarterectomies were performed with selective shunting, based on the change of consciousness and motor function after carotid test clamping under regional anesthesia. Of the 55 patients with either an anterior or a posterior communicating artery, only four (7.3%) required shunting. Twelve patients had neither anterior nor posterior communicating artery, and 10 (83.3%) showed signs of cerebral ischemia necessitating shunting. Mandatory shunt was significantly higher in patients with absence of collaterals (p = 0.00). The rate of intraoperative cerebral ischemia was significantly higher in patients with poor collateral circulation defined by the anatomy of the circle of Willis.
Local hemodynamics are an important factor in atherosclerosis, from the development of early lesions, to the assessment of stroke risk, to determining the ultimate fate of a mature plaque. Until recently, our understanding of arterial fluid dynamics and their relationship to atherosclerosis was limited by the use of idealized or averaged artery models. Recent advances in medical imaging, computerized image processing, and computational fluid dynamics (CFD) now make it possible to computationally reconstruct the time-varying, three-dimensional blood flow patterns in anatomically realistic models. In this paper we review progress, made largely within the last five years, towards the routine use of anatomically realistic CFD models, derived from in vivo medical imaging, to elucidate the role of local hemodynamics in the development and progression of atherosclerosis in large arteries. In addition to describing various image-based CFD studies carried out to date, we review the medical imaging and image processing techniques available to acquire the necessary geometric and functional boundary conditions. Issues related to accuracy, precision, and modeling assumptions are also discussed. © 2002 Biomedical Engineering Society.
PAC2002: 8719Uv, 8757Gg, 8710+e
The collateral circulation plays a pivotal role in the pathophysiology of cerebral ischemia. Current knowledge of the collateral circulation remains sparse, largely because of prior limitations in methods for evaluation of these diminutive routes of cerebral blood flow.
Anatomic descriptions of the collateral circulation often focus on more proximal anastomoses at the circle of Willis, neglecting secondary collateral pathways provided by leptomeningeal vessels. Pathophysiological recruitment of collateral vessels likely depends on the temporal course of numerous compensatory hemodynamic, metabolic, and neural mechanisms. Subsequent endurance of these protective vascular pathways may determine the severity of ischemic injury. Characterization of the collateral circulation with advanced neuroimaging modalities that provide angiographic information and perfusion data may elucidate critical determinants of collateral blood flow. Such information on the status of the collateral circulation may be used to guide therapeutic interventions. Prognostication and risk stratification may also be improved by routine evaluation of collateral blood flow.
Contemporary understanding of the collateral circulation may be greatly enhanced through further refinement of neuroimaging modalities that correlate angiographic findings with perfusion status, providing the basis for future therapeutic and prognostic applications.
Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype.
From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and chi(2) analyses to compare detection by MRI versus CT of watershed infarcts.
Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns.
Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient's baseline. These findings have implications for future clinical practice and research.
Blood flow in the circle of Willis (CoW) is modelled using the 1-D equations of pressure and flow wave propagation in compliant vessels. The model starts at the left ventricle and includes the largest arteries that supply the CoW. Based on published physiological data, it is able to capture the main features of pulse wave propagation along the aorta, at the brachiocephalic bifurcation and throughout the cerebral arteries. The collateral ability of the complete CoW and its most frequent anatomical variations is studied in normal conditions and after occlusion of a carotid or vertebral artery (VA). Our results suggest that the system does not require collateral pathways through the communicating arteries to adequately perfuse the brain of normal subjects. The communicating arteries become important in cases of missing or occluded vessels, the anterior communicating artery (ACoA) being a more critical collateral pathway than the posterior communicating arteries (PCoAs) if an internal carotid artery (ICA) is occluded. Occlusions of the VAs proved to be far less critical than occlusions of the ICAs. The worst scenario in terms of reduction in the mean cerebral outflows is a CoW without the first segment of an anterior cerebral artery combined with an occlusion of the contralateral ICA. Furthermore, in patients without any severe occlusion of a carotid or VA, the direction of flow measured at the communicating arteries corresponds to the side of the CoW with an absent or occluded artery. Finally, we study the effect of partial occlusions of the communicating arteries on the cerebral flows, which again confirms that the ACoA is a more important collateral pathway than the PCoAs if an ICA is occluded.
Wall shear stress (WSS) and pressure are important factors in the development of cerebral aneurysms. We aimed to develop a computational fluid dynamics simulator for flow in the complete circle of Willis to study the impact of variations in vessel radii and bifurcation angles on WSS and pressure on vessel walls.
Blood flow was modeled with Navier-Stokes equations as an incompressible newtonian fluid within rigid vessel walls. A model of the circle of Willis geometry was approximated as a network of tubes around cubic curves. Pulsatile inlet flow rates and constant outlet pressure were used as boundary conditions.
The simulations confirmed that differences in vessel radii and asymmetric branch angles influence WSS magnitude and spatial distribution. High WSS occurred at locations where aneurysms are frequent and in anatomic variants known to be associated with an increased risk for aneurysm development.
Computational fluid dynamics analysis can be applied to the complete circle of Willis and should be used to study the pathophysiology of this complex vascular structure, including risk factors for aneurysm development. Further development of the method should include simulations with flexible vessel walls.
Brains were obtained from 1000 medicolegal autopsy subjects of varying ages. The circle of Wills was examined at the base of the brain. The cerebral vessels were observed with regards to their origin, caliber and typical configuration. Variations were noted and grouped into different categories. Out of 1000 specimens examined, 452 (45.2%) conformed to the typical pattern. In the rest of the specimens (54.8%) there were variations in the circulus arteriosus. The circle was deficient in 32 (3.2%). The anterior cerebral artery was absent in 0.4%; hypoplastic in 1.7%; duplicated in 2.6%; triple in 2.3% and single in 0.9%. The anterior communicating artery was absent in 1.8%, duplicate in 10%, triplicate in 1.2% and plexiform in 0.4%. Multiplication of posterior cerebral artery was observed in 2.4% cases while it was hypoplastic in 10.6% brains. Posterior communicating artery was absent in 1% and hypoplastic in 13.2%. Seventy-four brains (7.4%) had multiple variations. Intracranial saccular aneurysm was present in 10 (1%). These figures are compared with the available literature. Persistence of some embryonic vessel that normally disappear, disappearance of vessels that would normally persist or sprouting of new vessels due to hemodynamic and genetic factors are the usual causes for such anomalies. These variations are discussed with regard to development and other hemodynamic factors.