The Circle of Willis (CoW) is the most effective collateral blood supply to the brain.Reference Alpers, Berry and Paddison 1 - Reference Alpers and Berry 3 Blood flow directed at one side can be recruited to the contralateral side through the anterior Circle. This consists of the proximal anterior cerebral artery segments (A1’s) and the anterior communicating artery. In addition, collateral flow can be recruited from the posterior Circle, which consists of the P1 segments of the posterior cerebral arteries and the posterior communicating arteries.Reference Schomer, Marks and Steinberg 4 Secondary collaterals require time for recruitment and play a less important role in acute ischemiaReference Schomer, Marks and Steinberg 4 ; these include but are not limited to pial collaterals and extracranial-intracranial anastomoses via the ophthalmic or meningeal arteries.
It is well-known that numerous anatomical variations of the CoW exist.Reference Alpers, Berry and Paddison 1 - Reference Alpers and Berry 3 , Reference Hartkamp, van der Grond and de Leeuw 5 A complete Circle only exists in approximately 50% of the population.Reference Alpers, Berry and Paddison 1 , Reference Alpers and Berry 3 , Reference Hartkamp, van der Grond and de Leeuw 5 - Reference Moore and David 7 This has an impact on the capacity to supply blood to an affected vascular territory at times of stress. One iatrogenic source of such stress is cross clamping of the internal carotid artery (ICA) during carotid endarterectomy (CEA).
During CEA, surgeons frequently measure the carotid stump pressure (CSP), which is the residual back-pressure in the ICA following temporary occlusion of the common and external carotid arteries (CCA and ECA). CSP is an established surrogate measure of cerebral collateral circulation during CEAReference Boysen 8 - Reference Moore and Hall 10 as well as some neurointerventional procedures.Reference Tomura, Omachi and Takahashi 11 The CSP reflects the arterial pressure on the side of the CoW ipsilateral to major arterial occlusion, and it is used as an indirect measure of ischemic tolerance. Although other monitoring techniques including transcranial Doppler (TCD), near-infrared spectroscopy (NIRS), or somatosensory evoked potential (SSEP) are also widely used, in one comprehensive study with patients undergoing awake CEA, these performed equally (NIRS) or slightly worse (TCD, SSEP) than CSP.Reference Moritz, Kasprzak, Arlt, Taeger and Metz 12 A low stump pressure of 25 mmHg or less is recognized as a risk for intraoperative stroke.Reference Moore and Hall 10 , Reference Harada, Comerota, Good, Hashemi and Hulihan 13 Correspondingly, on angiography, poor collateral circulation is associated with a greater risk of stroke, both short term in CEA patients, and long term in medically managed patients. 14
Currently there is no patient-specific method to predict the adequacy of the cerebral collateral circulation using computed tomography angiography (CTA) data. The present study examines anatomical measurements of the luminal diameters of the CoW and neck vessels on CTA along with the CSP measured at surgery. This was then used to determine which arterial components of the CoW have the most influence on CSP. These findings will provide clinicians with an additional tool to noninvasively assess the adequacy of cerebral collateral circulation before an intervention, and may help with patient consultation in clinic as well as intraoperative decision-making (e.g. shunt use).
Methods
Angiographic and hemodynamic data were collected according to the Canadian Tri-Council policy statement on ethical conduct for research involving the secondary use of data originally collected for health care purposes. Ninety-two patients were included over a 4.5-year period. CSP was measured either intraoperatively during CEA or intraprocedurally during carotid balloon test occlusion.
CSP Measurement
All patients undergoing CEA had symptomatic high-grade ICA stenosis of at least 70% according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. 15 Carotid surgeries were performed after informed consent and under general endotracheal anaesthesia. During CEA, the carotid exposure is performed to fully expose the CCA, ECA, and ICA. Once all vessels segments are skeletonized and mobilized, the CCA and ECA are cross-clamped temporarily. Systemic mean arterial pressure (MAP) is obtained immediately before cross-clamping. A 25-gauge sterile butterfly needle is then introduced into the lumen of the ICA just proximal to the carotid plaque. The needle is connected to an arterial-line setup with rigid tubing and calibrated pressure transducer. The CSP is allowed to stabilize for a few seconds before recording.
The CSP was also recorded for neurointerventional procedures that required balloon occlusion of the ICA. All patients gave informed consent. A balloon is introduced via a 6-Fr femoral sheath and a 6-Fr guiding catheter. Once the balloon is inflated and contrast injection confirms ICA occlusion, the pressure at the tip of catheter is measured via a calibrated arterial line setup and recorded as the CSP. MAP is obtained via the same catheter immediately before balloon inflation.
Luminal Diameter Measurements
All patients underwent CTA of the head and neck before either CEA or neurointerventional procedure to fully characterize the vasculature of the neck and the CoW. The luminal diameters of 16 vascular segments of the CoW and of the neck were measured on CTA (Figure 1). The measurements were performed on axial source images by an experienced neuroradiologist (AL).
Figure 1 Locations of 16 vascular segments measured on CTA in 92 patients. (Anterior circle) ACoA: anterior communicating artery; cA1: contralateral A1; iA1: ipsilateral A1. (Posterior circle) cPCoA: contralateral posterior communicating artery; cP1: contralateral P1; iPCoA: ipsilateral posterior communicating artery; iP1: ipsilateral P1. (Additional intracranial) BA: basilar artery; cOA: contralateral ophthalmic artery; cIICA, contralateral intracranial internal carotid artery; iIICA: ipsilateral intracranial internal carotid artery; iOA: ipsilateral ophthalmic artery. (Neck segments) cDICA: contralateral distal cervical internal carotid artery; iDICA: ipsilateral distal cervical internal carotid artery; n-CICA: narrowest contralateral internal carotid artery; n-IICA: narrowest ipsilateral internal carotid artery.
Statistical Analysis
Statistical analyses were performed by an independent biostatistician (L. Stitt) using the SAS System (the REG procedure). To ensure reliable arterial diameter measurements, intrarater reliability was assessed in 22 cases using intraclass correlations for test-retest reliability. Next, univariate analysis examining MAP and the 16 arterial segments was performed, with tests for normality, treating CSP as the dependent variable. For multivariate analysis, three models were run, one with all variables forced in, followed by stepwise analysis using both forward and backward methods, with entry and removal at the 0.05 level. Analysis was performed on both the whole group (n=92) as well as on the subgroup (n=27) of individuals with high-grade (>70% NASCET) contralateral ICA stenosis.
Results
CSP was reasonably well distributed with no deviation from normality. The mean CSP was 48.7±15.5 mmHg (mean ± standard deviation). Mean systemic pressure was 89±12 mmHg. Diameter results for individual artery segments are presented in Table 1. Univariate analysis showed that the contralateral A1 was the strongest factor influencing CSP. MAP, the narrowest diameter of the contralateral ICA, and the anterior communicating artery were also significant. On multivariate analysis, variance factors were all below 2. Both forward and backward methods yielded the same result. The final model included contralateral A1, MAP, anterior communicating artery, and contralateral ICA diameter (R 2=.364) (Table 2). A possible interaction of these four main effects was assessed using stepwise methods, leaving the variables as continuous. The interaction of MAP and anterior communicating artery diameter proved to be significant (p=0.041). The final model included the four main effects plus the interaction (R 2=0.394). Results are illustrated in Figure 2.
Figure 2 Vascular segments with statistically significant association with CSP in 92 patients using univariable and stepwise multivariable logistic regression. ACoA: anterior communicating artery; cA1: contralateral A1; n-CICA: narrowest contralateral internal carotid artery.
Table 1 Results of descriptive statistics and univariate and multivariate analyses
NS: not significant; SD: standard deviation.
* All variables left in the model are significant at the 0.0500 level. No other variable met the 0.0500 significance level for entry into the model.
Table 2 Summary of stepwise regression for N=92 circles (R 2=0.3636)
For the subgroup of patients with high-grade (>70% NASCET) contralateral carotid stenosis, stepwise regression with forward and backward elimination also yielded identical results. Three explanatory variables met the entry criteria in the model. These were: MAP, contralateral A1 artery, and ipsilateral posterior communicating artery (Figure 3). These three variables accounted for 62% of the observed variation in CSP (Table 3).
Figure 3 Vascular segments with statistically significant association with CSP in 27 patients with high-grade contralateral carotid stenosis. cA1: contralateral A1; iPCoA: ipsilateral posterior communicating artery.
Table 3 Summary of stepwise regression for subgroup of 27 patients with high-grade contralateral carotid stenosis (R 2=0.6201)
Discussion
The most favourable condition for adequate collateral flow during acute ipsilateral ICA occlusion likely occurs in a patient with a large contralateral A1 and decent (>1 mm diameter) anterior communicating artery. These conditions can reassure clinicians by providing a quantitative estimate of the collateral circulation in the event of cross-clamping of the ipsilateral ICA. On the other hand, in patients with contralateral carotid stenosis (≥70% by NASCET 15 criteria (high-grade stenosis) or CTA vessel diameter measurements ≤1.4 mm),Reference Bartlett, Walters, Symons and Fox 16 the role of the ipsilateral posterior communicating artery is quantitatively much more significant in protecting the hemisphere against hemodynamic ischemia. Quantitative assessment can be obtained by constructing a simple linear equation using the intercept and parameter estimates presented in Tables 2 and 3 to estimate the CSP. The results of our study are in keeping with the simulation study by Alastruey et al.Reference Alastruey, Parker, Peiro, Byrd and Sherwin 17 In their study, the authors constructed a one-dimensional fluid dynamic “circuit” model of the CoW using averaged vessel measurements. Their simulation used conservation of mass and momentum equations while accounting for nonlinear vessel wall compliance, the non-Newtonian behavior of blood, and pulse-wave propagation. Similar to our study, they demonstrated that the anterior circulation plays a greater role than the posterior circulation during acute unilateral carotid occlusion. The model assumed a normal contralateral ICA. It was concluded that ipsilateral carotid occlusion with a contralateral aplastic A1 presents the worst scenario with a reduction of ipsilateral MCA flow rate by almost 40%.
Our study provides insight into the determinants of CSP and cerebral collateral circulation via the CoW. These findings can be used before a planned surgical or endovascular intervention, to assist in preprocedural risk assessment. This has been the practice at our institution. Individuals with anatomically robust Circles appear unlikely to require a shunt during CEA, although further study is needed to confirm this. Individuals with severe contralateral stenosis or occlusion and poor posterior communicating anatomy may be at especially high risk of hemodynamic impairment during carotid clamping. Because stroke outcome is the most meaningful dependent variable after carotid surgery, further study should evaluate the relationship between vessel sizes, intraoperative monitoring, and clinical outcome.
Conclusion
In general, the strongest single vessel predictor of CSP and hence the adequacy of the collateral circulation is the calibre of the contralateral A1 segment of the anterior cerebral artery. A dominant contralateral A1 and a patent anterior communicating artery are required to conduct flow from the opposite hemisphere. In patients with high-grade contralateral ICA stenosis, the posterior circulation exerts a greater influence. These results can be incorporated into preprocedural risk assessment and planning for CEA. Clinical judgement and the use of additional monitoring technologies such as SSEP, electroencephalogram, TCD, and NIRS remain of overall importance in assessing for ischemia during endarterectomy.
Disclosures
BHW received funding from the University of Western Ontario MSc. Medical Biophysics.
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Acknowledgements
The authors thank Larry Stitt for assistance with statistical analysis.
