Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI.

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

High-altitude rodents have abundant collaterals that protect against tissue injury after cerebral, coronary and peripheral artery occlusion.

Collateral number/density varies widely in brain and other tissues among strains of Mus musculus mice due to differences in genetic background. Recent studies have shown that prolonged exposure to reduced atmospheric oxygen induces additional collaterals to form, suggesting that natural selection may favor increased collaterals in populations native to high-altitude. High-altitude guinea pigs (Cavia) and deer mice (Peromyscus) were compared with lowland species of Peromyscus, Mus and Rattus (9 species/strains examined). Collateral density, diameter and other morphometrics were measured in brain where, importantly, collateral abundance reflects that in other tissues of the same individual. Guinea pigs and high-altitude deer mice had a greater density of pial collaterals than lowlanders. Consistent with this, guinea pigs and highlander mice evidenced complete and 80% protection against stroke, respectively. They also sustained significantly less ischemia in heart and lower extremities after arterial occlusion. Vessels of the circle of Willis, including the communicating collateral arteries, also exhibited unique features in the highland species. Our findings support the hypothesis that species native to high-altitude have undergone genetic selection for abundant collaterals, suggesting that besides providing protection in obstructive disease, collaterals serve a physiological function to optimize oxygen delivery to meet oxygen demand when oxygen is limiting.

Arterial collateral anatomy predicts the risk for intra-operative changes in somatosensory evoked potentials in patients undergoing carotid endarterectomy: a prospective cohort study.

BACKGROUND: During carotid endarterectomy (CEA), significant amplitude decrement of somatosensory evoked potentials (SEPs) is associated with post-operative neurological deficits. OBJECTIVE: To investigate the association between an incomplete circle of Willis and/or contralateral ICA occlusion and subsequent changes in intra-operatively monitored SEPs. METHODS: We performed a retrospective analysis of a single center, prospective cohort of consecutive patients undergoing CEA over a 42-month period after reviewing the collateral arterial anatomy on pre-operative radiological imaging. The primary endpoint was an intra-operative decline in SEPs > 50% compared to the baseline value during arterial cross-clamping. Univariate and multivariate logistic regression analyses were performed to investigate a potential association between contralateral ICA occlusion, incomplete circle of Willis, and subsequent alteration in SEPs. RESULTS: A total of 140 consecutive patients were included, of which 116 patients (82.9%) had symptomatic carotid stenosis of at least 50% according to the classification used in the North American Carotid Surgery Trial (NASCET) (Stroke 22:711-720, 1991). Six patients (4.3%) showed contralateral ICA occlusion, 22 patients (16%) a missing/hypoplastic anterior communicating artery (Acom) or A1 segment, and 79 patients (56%) a missing ipsilateral posterior communicating artery (Pcom) or P1 segment. ICA occlusion and missing segments of the anterior circulation (missing A1 and/or missing Acom) were associated with the primary endpoint (p = 0.003 and p = 0.022, respectively). CONCLUSION: Contralateral ICA occlusion and missing anterior collaterals of the circle of Willis increase the risk of intra-operative SEP changes during CEA. Pre-operative assessment of collateral arterial anatomy might help identifying patients with an increased intra-operative risk.

Cerebrovacular Reserve Predicts the Cerebral Hyperperfusion Syndrome After Carotid Endarterectomy.

BACKGROUND: Cerebral hyperperfusion syndrome is a rare but potentially severe complication of carotid artery revascularisation that develops under conditions of resistant postoperative hypertension and impaired cerebrovascular autoregulation. OBJECTIVE: Was to determine which preoperative and operative factors affect the development of cerebral hyperperfusion syndrome after carotid endarterectomy. METHODS: This prospective observational study enrolled 93 asymptomatic patients who underwent carotid endarterectomy. Cerebral hyperperfusion was registered in patients who had 100% postoperative increase in mean flow in middle cerebral artery registered by Transcranial Doppler ultrasound. Cerebral hyperperfusion syndrome was diagnosed in patients with cerebral hyperperfusion who postoperatively developed at least one of the symptoms. Pre-operative and operative risk factors for cerebral hyperperfusion syndrome were analysed by multivariate binary logistic regression. RESULTS: Out of 93 operated patients, cerebral hyperperfusion was registered in 23 and cerebral hyperperfusion syndrome in 18 patients. Risk factors for cerebral hyperperfusion syndrome were included in the binary logistic regression model. Incomplete Circle of Willis morphology on 3D TOF magnetic resonance image (p = 0.002), Breath holding index below the 0.69 cut-off (p = 0.006), positive criteria for insufficient collateral flow through circle of Willis registered by TCD (p = 0.03), and poorly controlled hypertension (p = 0.023) showed statistically significant independent predictive value for cerebral hyperperfusion syndrome. The model was statistically significant (p = 0.012) and correctly classified 90.3 % of patients. CONCLUSIONS: Incomplete circle of Willis and insufficient collateral flow, low cerebrovascular reserve, and poorly regulated hypertension are significant predictors of post- carotid endarterectomy hyperperfusion development.

Competitive flow diversion of multiple P1 aneurysms: proposed classification.

We report the case of a patient with subarachnoid hemorrhage and three aneurysms arising from the posterior communicating artery (Pcomm)-P1 complex, treated with endovascular coiling and competitive flow diversion. The largest and likely ruptured Pcomm aneurysm was treated with traditional coiling. Two smaller potentially ruptured aneurysms arose from the distal right posterior cerebral artery (PCA) P1 segment. After a failed attempt to treat with conventional flow diversion across the PCA-P1 segment, the P1 aneurysms were successfully treated with competitive flow diversion distal to the PCA-P1 segment from Pcomm to the P2 segment. Over 12 months, competitive flow diversion redirected flow to the right PCA territory via the internal carotid artery-Pcomm-P2, reducing the size of the PCA-P1 segment and obliterating the P1 aneurysms. Competitive flow diversion treatment should be considered for aneurysms occurring at the circle of Willis when traditional methods are not feasible. Herein, we introduce a novel classification for competitive flow diversion treatment.

Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.

Bihemispheric ischemic strokes secondary to unilateral vessel disease are uncommon. We present the case of a 70-year-old man with multiple acute/subacute bilateral infarcts. The patient was found to have stenosis of the left internal carotid artery secondary to herpes zoster ophthalmicus vasculopathy, with involvement of the left proximal middle and anterior cerebral arteries. Angiographic studies also revealed A1 segment aplasia of the right anterior cerebral artery (ACA), thus indicating dependence on the left-sided circulation for perfusion of the bilateral ACA vascular territory. This case illustrates how A1 segment aplasia, an anatomic variant of the circle of Willis detected by angiographic studies, can contribute to bilateral infarction in the ACA vascular territory.

Repaired coarctation of the aorta, persistent arterial hypertension and the selfish brain.

BACKGROUND: It has been estimated that 20-30% of repaired aortic coarctation (CoA) patients develop hypertension, with significant cardiovascular morbidity and mortality. Vertebral artery hypoplasia (VAH) with an incomplete posterior circle of Willis (ipCoW; VAH + ipCoW) is associated with increased cerebrovascular resistance before the onset of increased sympathetic nerve activity in borderline hypertensive humans, suggesting brainstem hypoperfusion may evoke hypertension to maintain cerebral blood flow: the "selfish brain" hypothesis. We now assess the "selfish brain" in hypertension post-CoA repair. METHODS: Time-of-flight cardiovascular magnetic resonance angiography from 127 repaired CoA patients (34 ± 14 years, 61% male, systolic blood pressure (SBP) 138 ± 19 mmHg, diastolic blood pressure (DBP) 76 ± 11 mmHg) was compared with 33 normotensive controls (42 ± 14 years, 48% male, SBP 124 ± 10 mmHg, DBP 76 ± 8 mmHg). VAH was defined as < 2 mm and ipCoW as hypoplasia of one or both posterior communicating arteries. RESULTS: VAH + ipCoW was more prevalent in repaired CoA than controls (odds ratio: 5.8 [1.6-20.8], p = 0.007), after controlling for age, sex and body mass index (BMI). VAH + ipCoW was an independent predictor of hypertension (odds ratio: 2.5 [1.2-5.2], p = 0.017), after controlling for age, gender and BMI. Repaired CoA subjects with VAH + ipCoW were more likely to have difficult to treat hypertension (odds ratio: 3.3 [1.01-10.7], p = 0.049). Neither age at time of CoA repair nor any specific repair type were significant predictors of VAH + ipCoW in univariate regression analysis. CONCLUSIONS: VAH + ipCoW predicts arterial hypertension and difficult to treat hypertension in repaired CoA. It is unrelated to age at time of repair or repair type. CoA appears to be a marker of wider congenital cerebrovascular problems. Understanding the "selfish brain" in post-CoA repair may help guide management. JOURNAL SUBJECT CODES: High Blood Pressure; Hypertension; Magnetic Resonance Imaging (MRI); Cardiovascular Surgery; Cerebrovascular Malformations.

Fluid-Structure Interaction Simulation of Blood Flow and Cerebral Aneurysm: Effect of Partly Blocked Vessel.

In this study, using fluid-structure interaction (FSI), 3-dimensional blood flow in an aneurysm in the circle of Willis - which is located in the middle cerebral artery (MCA) - has been simulated. The purpose of this study is to evaluate the effect of a partly blocked vessel on an aneurysm. To achieve this purpose, two cases have been investigated using the FSI method: in the first case, an ideal geometry of aneurysm in the MCA has been simulated; in the second case, modeling is performed for an ideal geometry of the aneurysm in the MCA with a partly blocked vessel. All boundary conditions, properties and modeling methods were considered the same for both cases. The only difference between the two cases was that part of the MCA parent artery was blocked in the second case. In order to consider the hyperelastic property of the wall and the non-Newtonian properties of the blood, the Mooney-Rivlin model and the Carreau model have been used, respectively. In the second case, the Von Mises stress in the peak systole is 26% higher than in the first case. With regard to the high amount of Von Mises stress, the risk of rupture of the aneurysm is higher in this case. In the second case, the maximum wall shear stress (WSS) is 12% higher than in the first case. And maximum displacement in the second case is also higher than in the first. So, the risk of growth of the aneurysm is higher in cases with a partly blocked vessel.

Comparison of blood velocity between Transcranial Doppler and numerical method in the patient-specific Circle of Willis with aneurysm.

BACKGROUND: The development of any disturbance in the Circle of Willis (COW) can change the hemodynamics of blood flow and result in damage to the vascular system. Clinical methods such as TCD for diagnosing an aneurysm or growth factors and rupture can measure blood velocity. Several factors influence the accuracy of TCD that can lead to wrong evaluations and affect the treatment planning. OBJECTIVE: In this study, the conformity between CFD and TCD was accomplished for investigating the accuracy of the clinical method (TCD) in different vessels of the Circle of Willis. METHODS: The realistic three-dimensional models have been produced from angiography images. Considering fluid-structure interaction, a domain of the blood flow and vessel wall has been simulated by the ANSYS.CFX software. The velocity in the cerebral arteries has been calculated and compared with the velocity acquired from TCD. RESULTS: According to the findings, there were significant differences between the results obtained from computational fluid dynamics and Doppler test in different vessels of the Circle of Willis. In some areas, differences close to 80 cm/s were also reported. CONCLUSION: According to the results, there are possibilities of errors in carrying out a Doppler test in some arteries and can lead to wrong estimates and ultimately incorrect decisions.

Efficacy and Safety of Willis Covered Stent for Treatment of Complex Vascular Diseases of the Internal Carotid Artery.

BACKGROUND: Willis covered stents are used in clinical practice for some complex cerebrovascular diseases. However, the performance of the Willis covered stent requires further investigation. In this study, we investigate the safety and efficacy of Willis covered stents for the treatment of complex vascular diseases of the internal carotid artery (ICA). METHODS: Thirteen patients with complex ICA diseases treated with the Willis covered stent system at our institution from October 2016 to January 2018 were analyzed retrospectively. Follow-up observation and digital subtraction angiography (DSA) examination were conducted at about 6-10 months after the treatment. RESULTS: The complex vascular diseases of the ICA were successfully treated in 12 patients. The technical success rate was 92.3%. Pathologically, 13 lesions included blood blister-like aneurysm (n = 7), traumatic pseudoaneurysm (n = 1), traumatic carotid artery rupture (n = 1), and aneurysm with arteriovenous fistula (n = 4). Thirteen patients with complex vascular diseases of the ICA were treated with 15 Willis covered stents. The release sites of Willis covered stents were the C7 (n = 2), C6 (n = 1), C5 and/or C4 (n = 9), and the C2 (n = 3) segment of the ICA. DSA performed immediately after stent deployment revealed that complete occlusion of the lesion was achieved in 11 patients and endoleak was observed in 2 patients. Of the 11 patients, postoperative DSA examination indicated that the lesions were occluded completely. Among 2 patients, who had a second stent implantation at the break of the ICA, the traumatic ICA rupture was essentially completely obstructed in 1 patient. The endoleak remained in 1 patient with carotid cavernous sinus fistula because the placement of the second stent system was difficult with his ICA tortuosity. No recurrence of aneurysms, hemorrhagia, and other lesions was observed, and the patients' parent arteries were patent without stenosis. No procedure-related complications or deaths occurred during follow-up. CONCLUSIONS: For the treatment of complex vascular diseases in the ICA, Willis covered stent implantation is safe and effective. However, longer follow-up, large-sample controlled studies, and multicenter studies are needed for further confirmation.

A functional assessment of the circle of Willis before aortic arch surgery using transcranial Doppler.

BACKGROUND: Antegrade selective cerebral perfusion (ASCP) with systemic moderate hypothermia is routinely used as brain protection during aortic arch surgery. Whether ASCP should be delivered unilaterally (u-ASCP) or bilaterally (bi-ASCP) remains controversial. METHODS: We routinely studied the functional anatomy of the circle of Willis (CoW in all patients scheduled for arch surgery using transcranial color-coded Doppler over a decade. On the basis of these data, we classified observed functional variants as being "safe," "moderately safe," or "unsafe" for u-ASCP. RESULTS: From January 2005 to June 2015, 1119 patients underwent aortic arch surgery in our institution. Of these, 636 patients had elective surgery performed with ASCP. Preoperative full functional assessment of the CoW was possible in 61% of patients. A functionally complete CoW was found in only 27%. Of all variants, 72% were classified as being safe for u-ASCP, whereas 18% were moderately safe for u-ASCP, and 10% unsafe. Unsafe variants for bi-ASCP were observed in 0.5% of patients. CONCLUSIONS: The risk of ischemic brain damage due to malperfusion is estimated to be substantially higher during right u-ASCP than during bi-ASCP. Bi-ASCP is therefore highly preferable over u-ASCP if the function of the CoW is unknown. We propose a tailored approach using this full functional assessment preoperatively by applying u-ASCP via the right subclavian artery when considered safely possible, and bi-ASCP when considered a necessity to prevent cerebral malperfusion, and thus thereby try to reduce the embolic stroke risk of ostial instrumentation in bi-ASCP.

Intracerebral steal phenomenon in symptomatic carotid artery disease.

BACKGROUND AND PURPOSE: Intracerebral steal is a paradoxical vasodilatory response that reduces cerebral blood flow (CBF) in hemodynamically compromised brain tissue when blood is rerouted to more healthy areas. The aim of our study was to investigate the presence and extent of steal in patients with steno-occlusive internal carotid artery (ICA) disease, and to assess its relation with collateral blood flow through the circle of Willis (CoW). MATERIALS AND METHODS: Thirty-eight patients with symptomatic steno-occlusive ICA disease underwent MRI examination with arterial spin labeling (ASL) perfusion imaging before and after a vasodilatory challenge. Intracerebral steal was defined as a decline in CBF after acetazolamide. Collateral flow via the CoW was assessed with time-of-flight and flow direction MR angiography (MRA) through the CoW was assessed with 2D phase-contrast MRA's. RESULTS: Eight of 38 patients (21%) had steal in the hemisphere ipsilateral to the symptomatic ICA (mean tissue volume with steal, 6.9 ± 4.1 mL; mean CVR, -11 ± 30%). Cerebrovascular reactivity (CVR) was lower in the middle cerebral artery flow territory of the affected hemisphere in patients with steal compared those without (P = 0.002). Collateral blood flow was impaired in 4 of the 8 patients with steal. These patients had a larger area of steal (P = 0.002). CONCLUSIONS: Intracerebral steal occurs in patients with obstructive ICA disease and can be assesses at brain tissue level with ASL perfusion MRI. Its presence is related to more severely declined CVR in the surrounding brain tissue area and the volume is associated with impaired primary collateral blood flow through the CoW.

Completeness of circle of Willis and white matter hyperintensities in patients with severe internal carotid artery stenosis.

BACKGROUND: We investigated whether completeness of the circle of Willis (CoW) protected patients with severe internal carotid artery (ICA) stenosis against white matter hyperintensities (WMHs). METHODS: We included 115 patients with unilateral ICA stenosis ≥ 70%. The completeness of CoW was assessed and WMHs were rated on a visual scale. The score of deep and periventricular WMHs was compared between patients with complete and incomplete CoW and between the two hemispheres, ipsilateral and contralateral to stenosed ICA. RESULTS: We included 115 patients with severe ICA stenosis, 60 patients had a complete CoW (52.17%) and 55 had an incomplete CoW (47.83%). The patients with incomplete CoW had higher score of deep WMHs (OR = 1.82, 95% CI 1.08-3.06, P = 0.023) and periventricular WMHs (OR = 4.53, 95% CI 2.09-9.81, P = 0.000) than those with complete CoW. In the patients with incomplete CoW, the score of deep WMHs (OR = 4.14, 95% CI 1.33-12.93, P = 0.014) and periventricular WMHs (OR = 5.46, 95% CI 1.16-25.62, P = 0.032) was higher in the hemisphere ipsilateral to stenosed ICA than that in the contralateral hemisphere. In the patients with complete CoW, there was no significant difference in the score of deep WMHs (OR = 2.10, 95% CI 0.37-11.91, P = 0.401) and periventricular WMHs (OR = 2.83, 95% CI 0.99-8.05, P = 0.051) between the ipsilateral and contralateral hemispheres to stenosed ICA. CONCLUSION: The completeness of CoW protected patients with severe ICA stenosis against WMHs.

Incomplete circle of Willis is associated with a higher incidence of neurologic events during carotid eversion endarterectomy without shunting.

OBJECTIVE: A complete circle of Willis (CoW) is considered an important collateral network to maintain blood flow during cross-clamping in carotid endarterectomy (CEA). The aim of this study was to evaluate the impact of an incomplete CoW with isolated middle cerebral artery (iMCA) on immediate neurologic events (INEs) after CEA. METHODS: We prospectively collected the clinical data and outcomes of 902 patients who underwent CEA under general anesthesia between 2013 and 2015. All patients had preoperative computed tomography angiography of the extracranial and intracranial cerebral circulation. Indications were asymptomatic (52%) and symptomatic (48%) carotid artery disease. Patients who had CEA with shunt (n = 35) and those with inadequate intracranial imaging to assess CoW were excluded (n = 322) only. Computed tomography angiography images were reviewed retrospectively and independently by two vascular radiologists who were blinded for treatment outcomes. Imaging assessment included the vertebral and carotid circulation and each segment of the CoW, which was classified as normal, hypoplastic (diameter < 0.8 mm) or absent. The ipsilateral MCA was considered isolated if there was an absence of the anterior and posterior communicating branches from the contralateral carotid or posterior circulations. INE was defined as any transient ischemic attack (TIA) and stroke diagnosed immediately after the procedure. RESULTS: Of the 545 included patients (331 males; mean age, 69 ± 8 years), 12 (2.2%) had a stroke in the postoperative period. There were 20 INEs (8 strokes and 12 TIAs). A complete CoW was rare; it was only detected in 19 patients (3.5%) and an iMCA was found in 34 patients (6.3%). When at least one collateral circulation was complete (in 330 patients), we observed only four INEs (1.2%). Of the 34 patients with an iMCA, 8 (24%) had INE (6 TIAs and 2 strokes). Overall, iMCA was an independent predictor of INEs (odds ratio, 11.12; 95% confidence interval, 3.57-35.87; P < .001). With logistic regression, the model included hypertension, smoking, diabetes, hyperlipidemia, carotid clamping time (minutes), contralateral significant internal carotid artery stenosis of greater than 90%, ipsilateral significant internal carotid artery stenosis of greater than 90%, preoperative symptoms in 6 months, and iMCA; above iMCA only symptomatic patients had significant risk (odds ratio, 3.34; 95% confidence interval, 1.19-9.73; P = .02), whereas all other parameters were not significant. CONCLUSIONS: An iMCA carries more than a 10-fold higher the risk of INEs after CEA with cross-clamping without shunt protection. In these patients, routine shunting is recommended to prevent INEs.

Effect of Cerebral Flow Autoregulation Function on Cerebral Flow Rate Under Continuous Flow Left Ventricular Assist Device Support.

Neurological complications in continuous flow left ventricular assist device (CF-LVAD) patients are the second-leading risk of death after multi-organ failure. They are associated with altered blood flow in the cardiovascular system because of CF-LVAD support. Moreover, an impaired cerebral autoregulation function may also contribute to complications such as hyperperfusion in the cerebral circulation under mechanical circulatory support. The aim of this study is to evaluate the effect of cerebral autoregulatory function on cerebral blood flow rate under CF-LVAD support. A lumped parameter model was used to simulate the cardiovascular system including the heart chambers, heart valves, systemic and pulmonary circulations and cerebral circulation which includes entire Circle of Willis. A baroreflex model was used to regulate the systemic arteriolar and cerebral vascular resistances and a model of the Micromed CF-LVAD was used to simulate the pump dynamics at different operating speeds. Additionally, preserved and impaired cerebral autoregulatory functions were simulated in heart failure and under CF-LVAD support. Cerebral blood flow rate was restored under CF-LVAD support at 10 500 rpm pump operating speed which generated a similar arterial blood pressure and blood flow as in a healthy condition for the impaired cerebral autoregulatory function while the preserved cerebral autoregulatory function regulated the cerebral flow rate within a relatively low range for the applied pump operating speeds. Relatively low or high pump operating speeds may cause underpefusion or hyperperfusion for a failing cardiovascular system with impaired cerebral autoregulatory function under CF-LVAD support which will contribute to the worsening of cerebral complications.

The Role of Circle of Willis Anatomy Variations in Cardio-embolic Stroke: A Patient-Specific Simulation Based Study.

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.

Clinical Significance of the Circle of Willis in Patients with Symptomatic Internal Carotid Artery Occlusion.

BACKGROUND: Despite improvements in medical treatment, many patients experience ischemic stroke owing to internal carotid artery occlusion. We retrospectively evaluated a novel method based on the arterial structure of the circle of Willis (CoW) to identify patients at a high risk of recurrent stroke. METHODS: The study enrolled 104 patients with symptomatic occlusion of the internal carotid artery. CoW integrity was evaluated by a quantitative scoring system based on conventional angiography. Patients were categorized into a good integrity (n = 45) or poor integrity (n = 59) group. Primary endpoint was early neurologic deterioration, recurrent ischemic stroke, or transient ischemic attack. RESULTS: History of ischemic stroke before initial presentation was more prevalent in the poor integrity group (22.2% vs. 47.5%, P = 0.01), and there were no differences between the 2 groups in terms of stroke risk factors. Overall estimated rate of the primary endpoint was 25.6% 2 years after angiography. It was 5.7% in the good integrity group and 39.8% in the poor integrity group (P < 0.001). In a Cox regression analysis, male sex (P = 0.01, hazard ratio = 6.60), use of a tissue plasminogen activator (P = 0.00, hazard ratio = 6.10), and poor integrity of CoW (P = 0.00, hazard ratio = 5.42) were risk factors for the primary endpoint. Patients in the poor integrity group with decreased vascular reserve experienced frequent primary endpoint events compared with patients in the good integrity group (P = 0.00). CONCLUSIONS: Patients with poor integrity of CoW are vulnerable to recurrent ischemic stroke and appear to require more aggressive treatment.

Investigation of circle of Willis variants and hemodynamic parameters in twins using transcranial color-coded Doppler sonography.

Morphological and hemodynamic variations of the circle of Willis (CW) may have an important impact on cerebrovascular events. However, the environmental and genetic influence remains unclear. For this reason we studied the variations and hemodynamic parameters of the CW in twins using transcranial color-coded sonography (TCCS). Sixty-four twins, 19 monozygotic (MZ) and 13 dizygotic (DZ) pairs from the Italian Twin Registry (average age 45.0 ± 13.7 years) underwent TCCS and risk factor assessment. We examined CW morphology and recorded peak systolic velocity (PSV), end-diastolic velocity (EDV) and pulsatility index (PI). Raw heritability was determined for hemodynamic parameters, whereas concordance and discordance rates were calculated for CW morphological variants. A normal CW anatomy was observed in the majority of MZ and DZ twins (76.5% and 92.3%, respectively). The most frequent variant was a missing anterior cerebral artery (ACA). There was no significant difference in the prevalence of most CW variants depending on the zigosity. Concordance rates were low regarding the presence of variant CW anatomy both in MZ and DZ groups (0.14 and 0.00, respectively). Women had a significantly higher PI in vertebral arteries (VA) and in the right ACA (p = 0.01, p = 0.02 and p < 0.01, respectively). An inverse correlation was observed between hemodynamic parameters and age. Morphological variants of the CW do not seem to be heritable; they are most likely determined by environmental factors. In contrast, hemodynamic parameters of the CW are moderately heritable and this might have implications in the management and prevention of cerebrovascular diseases.

Autoregulating Cerebral Tissue Selfishly Exploits Collateral Flow Routes Through the Circle of Willis.

OBJECTIVE: Ischemic stroke is a leading cause of death and disability. Autoregulation and collateral blood flow through the circle of Willis both play a role in preventing tissue infarction. A steady-state model of the cerebral arterial network was used to investigate the interaction of these mechanisms when autoregulation is impaired ipsilateral to an occluded artery. MATERIALS AND METHODS: Twelve structural variants of the circle of Willis were modelled with left internal carotid artery occlusion and coupled with (1) a passive model of the cerebral vascular bed, (2) a steady-state model of an autoregulating cerebral vascular bed, and (3) a model in which the contralateral hemisphere autoregulates and the ipsilateral hemisphere does not. RESULTS: Results showed that if the autoregulatory response is impaired ipsilaterally, then, in the autoregulating hemisphere, cerebral flows are preserved at the expense of those on the ipsilateral side. CONCLUSIONS: Thus, although autoregulation is an essential facilitator of collateral flow through the circle of Willis, contralateral autoregulation can exacerbate flow reductions if not balanced by the same response in the vascular beds on the ipsilateral side. The status of the autoregulatory response in both hemispheres can strongly influence cerebral blood flows and tissue survival and should, therefore, be monitored in stroke.

Aneurysmal Parent Artery-Specific Inflow Conditions for Complete and Incomplete Circle of Willis Configurations.

BACKGROUND AND PURPOSE: Hemodynamics are thought to play a role in intracranial aneurysm growth and rupture. Computational fluid dynamics is frequently performed to assess intra-aneurysmal hemodynamics, using generalized flow waveforms of healthy volunteers as inflow boundary conditions. The purpose of this study was to assess differences in inflow conditions for different aneurysmal parent artery locations and variations of circle of Willis configurations. MATERIALS AND METHODS: In a series of 96 patients with 103 aneurysms, velocity measurements were acquired using 2D phase-contrast MR imaging perpendicular to the aneurysmal parent arteries in the circle of Willis. Circle of Willis configurations were inspected for variations using multiple overlapping thin-slab-acquisition MRAs. Flow rates, velocity magnitudes, and pulsatility indices were calculated for each parent artery location in subgroups of complete and incomplete circle of Willis configurations. RESULTS: Flow rates, velocity magnitudes, and pulsatility indices were significantly different among aneurysmal parent arteries. Incomplete circle of Willis configurations were observed in 24% of the cases. Significantly lower basilar artery flow rates were observed in configurations with hypoplastic P1 segments. Significantly higher A1 flow rates were observed in configurations with a hypoplastic contralateral A1 segment. CONCLUSIONS: Inflow conditions vary substantially between aneurysmal parent arteries and circle of Willis configurations. We have created a collection of parent artery-specific inflow conditions tailored to the patient-specific circle of Willis configuration that can be used in future computational fluid dynamics studies analyzing intra-aneurysmal hemodynamics.