UNASSIGNED: This study explores how vascular stenosis and absence affect the regulation of cerebral blood flow in the Circle of Willis (CoW) and the hemodynamic changes downstream of the stenosis.
UNASSIGNED: Forty idealized CoW models were simulated to analyze the impact of vascular absence and internal carotid artery (ICA) stenosis on hemodynamics. Inlet conditions were set using a physiological pressure waveform, and outflow boundaries were modeled using three-element Windkessel models.
UNASSIGNED: The absence of vessels such as RP1, LP1, RA1, or LA1 had a comparable effect on total blood flow to a 40% stenosis of the left internal carotid artery (LICA) across the entire CoW. Specifically, when LP1 and RA1 were absent with a 50% LICA stenosis, the total blood flow closely resembled that of a complete CoW with 75% LICA stenosis. In cases of proximal ICA stenosis, downstream regions showed elevated oscillatory shear index (OSI >0.2) and reduced time-averaged wall shear stress (TAWSS <1 Pa). With increasing stenosis severity, areas of high OSI shifted, and regions of low TAWSS expanded notably. At 75% stenosis, the area with TAWSS <1 Pa downstream significantly increased. Until complete occlusion, the area of low TAWSS and high OSI were maximized.
UNASSIGNED: This study underscores how anatomical variations in the CoW, combined with ICA stenosis, impact both total cerebral blood flow and its distribution among different outlets. Moreover, it highlights the potential for increased atherosclerosis development in affected areas. Particularly notable is the finding the absence of LP1 and RA1 vessels alongside 50% LICA stenosis results in blood flow patterns similar to those seen with 75% LICA stenosis in a complete CoW, emphasizing clinical implications for the patient. Hemodynamic changes, including TAWSS and OSI, are most pronounced downstream of the stenosis especially when the stenosis rate exceeds 75%.

The circle of Willis (COW) refers to the anastomotic arterial network found on the brain base, tasked with provision of collateral circulation aimed at prevention of ischemia. The COW is of immense clinical importance especially with regard to the assessment of neurovascular diseases. Individuals portray significant variations in the COW\'s anatomical configuration. The present study seeks to evaluate the existing anatomical variations of the COW and within the anterior and posterior segments of the COW. Thus, the study seeks to evaluate the different anatomical variations of the COW and its segments and components within the study population. To attain the set objectives, the present study has utilized the angiographic images for studying the COW variants in patients who underwent cerebral angiography during assessment of different types of cerebral anomalies and conditions. Therefore, this study used conventional angiography as an important tool in the evaluation of the different variations in the COW, and is most appropriate for evaluation of smaller anatomical variations owing to its perfect spatial resolution and portrayal of COW anatomy. The study findings indicated the existence between age and sex, and anatomical variations of the COW, particularly with regard to diameters of COW components like basilar artery (BA), P1, and internal carotid arterys (ICAs). Males had bigger BA, P1 and ICA diameters than females, while individuals aged below 40 years had bigger BA, A1, posterior communicating artery, and ICA diameters than those aged above 40 years.

OBJECTIVE: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE.
METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data.
RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (β ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (β ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (β ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (β ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015).
CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient in vivo data on pathological collateral flow during large vessel occlusions are not available. Moreover, there are no flow models that accurately simulate the hemodynamic conditions in the CoW during large vessel occlusions. We used a circulatory loop to generate highly reproducible cerebrovascular-like flows and pressures and used non-invasive flow visualization and high-resolution flow and pressure measurements to acquire detailed, time-dependent hemodynamics inside an anatomical phantom of the CoW. After calibrating a physiological reference case, we induced occlusions in the 1. middle cerebral artery, 2. terminal carotid artery, and 3. basilar artery; and measured the left posterior communicating artery flow. Mean arterial pressure and pulse pressure remained unchanged in the different occlusion cases compared to the physiological reference case, while total cerebral flow decreased by up to 19%. In all three occlusion cases, reversed flow was found in the left posterior communicating artery compared to the reference case with different flow magnitudes and pulsatility index values. The experimental results were compared with clinical findings, demonstrating the capability of this realistic cerebrovascular flow setup. This novel cerebrovascular flow setup opens the possibility for investigating different topics of neurovascular interventions under various clinical conditions in controlled preclinical laboratory studies.

We investigated the reduction in regional brain volume and cerebral blood flow (CBF) with aging and explored potential sex differences in healthy brains. Three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography, and four-dimensional (4D) flow MRI were performed on 129 healthy volunteers aged 22-92 years. The brains of healthy volunteers were segmented into 21 subregions using 3D T1-weighted MRI and CBFs in 16 major intracranial arteries were measured using 4D flow MRI. The cortical gray matter volume decreased linearly with aging, whereas the cerebral white matter volume increased until the 40s and then decreased, and the subcortical gray matter volume changed little with aging. The cortical gray matter volume was significantly associated with the total CBF of the major intracranial arteries distal to the circle of Willis; however, the cerebral white matter and subcortical gray matter volumes were not. Generally, women have higher total CBF than men, particularly in their 40s and younger, despite the smaller intracranial volume and smaller diameters of intracranial arteries than men. This may contribute to the higher incidence of subarachnoid hemorrhage due to cerebral aneurysms and migraine in women.

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BACKGROUND: To evaluate the impact of anatomical variations in the Circle of Willis (CoW) on immediate neurological events (INEs) after carotid endarterectomy (CEA) without shunting in patients with contralateral carotid occlusion (CCO).
METHODS: Single-center retrospective study. Patient\'s demographic and clinical outcomes data were prospectively collected. CoW segments were reviewed retrospectively. Between January 2013 and May 2018, 2090 patients underwent CEA under general anesthesia, CCO was found in 113 (5.4%) patients. CoW segments were classified as normal, hypoplastic (diameter ˂0.8 mm), or absent based on computed tomography angiography. We studied the CoW segments as 2 collateral networks connecting the basilar artery and the ipsilateral middle cerebral artery: a short semicircle (first segment of the ipsilateral posterior cerebral artery [P1] and posterior communicating artery [Pcom] segment) and a long semicircle (contralateral P1, Pcom, and both first segments of the anterior cerebri artery (A1) anterior communicating artery (Acom)). INE was defined as any transient ischemic attack or stroke diagnosed immediately after the procedure.
RESULTS: Out of the 113 patients, 46 underwent endarterectomy with shunting. We further excluded 16 patients from the assessment of the CoW due to unavailability or inadequate quality of computed tomography angiography. Of the 113 patients, 2 had strokes, 1 with shunting that occurred hrs after surgery. Besides the other stroke case, 4 INE were observed, all without the use of a shunt. Of the 51 patients with CoW assessment, 10 (19.6%) had a complete CoW, while 21 (41.2%) patients had only 1 semicircle intact (10 short and 11 long intact semicircles), and none of these patients experienced an INE. A total of 20 (39%) patients had both the long and short semicircles incomplete, of which 4 (7.8%) cases had an INE. In all INE cases, at least 1 of the Pcom was absent or hypoplastic. The absence of both Pcom was a strong predictor of incident INE [odds ratio = 11.10 (confidence interval: 1.04-118.60)] for INE.
CONCLUSIONS: Patients with CCO and insufficient CoW collateral flow support are at an increased risk of INE, including stroke, in the absence of shunt protection during CEA cross-clamping. Shunting should always be considered when the collateral flow between the ipsilateral middle cerebral artery and the basilar artery is compromised in CCO patients.

BACKGROUND: The fetal-type posterior cerebral artery (PCA) is defined as a variant anatomy in which the posterior communicating artery (PCOM) is larger than the hypoplastic or aplastic P1 segment of the PCA. The authors present the novel case of a patient with a duplicated right PCA in parallel with fetal-type and conventional PCAs supplying adjacent components of the PCA cerebral territory.
METHODS: A 59-year-old woman presented with a modified Fisher Scale score 4 subarachnoid hemorrhage. A right irregular PCOM aneurysm that measured 9.5 mm × 4.5 mm × 4.5 mm arose from the base of a variant branch supplying a portion of the PCA, rather than a conventional PCOM, and was found on digital subtraction angiography. Following endovascular coil embolization, the patient was discharged home.
CONCLUSIONS: The fetal-type variant has implications for thromboembolic events. If an embolism occludes the anterior circulation in a patient with a fetal-type PCA, it may result in an infarct in the PCA territory. Awareness of cerebral arterial anatomy, including an atypical collateral supply, informs a treating team\'s latitude in tolerance of which sites must be preserved and which can be safely sacrificed. https://thejns.org/doi/10.3171/CASE23735.

Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.