Multidetector CT angiography of the Circle of Willis: association of its variants with carotid artery disease and brain ischemia

After Institutional Review Board approval, we retrospectively analysed all brain CT and carotid CTA examinations of patients who (1) underwent carotid endarterectomy in our hospital between January 2013 and November 2015 for >70% symptomatic or >80% asymptomatic ICA stenosis, according to the NASCET criteria [30]; and (2) had adequate CT and CTA to evaluate the CoW. Procedures were in accordance with institutional guidelines. To avoid biases, no patient selection was made.

Reviewing carotid CTAs performed in our institution from January 2014 to November 2017, we identified all subjects with either negative CTA or minor/mild carotid atherosclerosis to provide a sex-matched control group.

All examinations were performed using a 256-slice scanner (Brilliance iCT 256, Philips Healthcare, Best, The Netherlands).

Brain CT was obtained using the following parameters (field of view 200-250 mm, collimation 64×0.625, pitch 0.39, gantry rotation time 400 ms, tube voltage 120 kVp, tube current 120-204 mAs, slice thickness 2 mm, dose-length product 312-626 mGycm).

All CTA examinations were performed from the aortic arch to under the vertex using the following parameters (field of view 180-200 mm, collimation 128×0.625, pitch 0.758, gantry rotation time 330 ms, tube voltage 120 kVp, tube current 76-206 mAs, dose-length product 220-608 mGycm). Bolus tracking technique in the aortic arch was used with 50 ml of iodinated contrast agent (Iomeron 400, Bracco Imaging SpA, Milan, Italy) followed by 40 ml saline bolus, both injected at 5 ml/s through a 18G cannula. Contiguous sections were reconstructed with 0.67-mm slice thickness and 512×512 matrix using hybrid iterative reconstruction technique (iDOSE, Philips Healthcare, Cleveland, OH, USA).

Images were evaluated on a dedicated workstation (IntelliSpace Portal, Philips Healthcare, Best, The Netherlands). Visualization included 3-mm maximum intensity projection slabs parallel and perpendicular to the anterior skull base, providing an overview of the CoW, but final decisions were made on the thin section images.

The presence of any ICA territory infarct at the side of surgery was classified as a positive CT regardless of the infarct’s nature (acute/subacute/chronic or territorial/lacunar/watershed). Conversely, the lack of any detectable infarct in the corresponding ICA territory was regarded as a negative CT result.

In the study group for each side, ICA stenosis was determined according to the NASCET method [30] and categorized using the following four-point score: 0 when <70%, 1 when 70–89%, 2 when 90–99%, and 3 when occluded. The score of the two sides were summed up (range 0–6).

The CoW was evaluated according to three different approaches both in the study and control groups, as follows:

To estimate the inter-observer agreement in defining CoW morphology on CTA, each individual study subject was assessed by two independent radiologists (R1 with 13 years of experience in vascular imaging; R2, with 8 years of experience), unaware of patient characteristics. In case of discrepancy, agreement was reached by consensus. Intra-observer agreement was evaluated for both observers by comparing data of 100 randomly selected patients at two different reading sessions at least 2 months apart.

Continuous variables were expressed as mean±standard deviation (SD), while categorical variables as counts and percentages. Distributions were given according to the three different approaches to classify the CoW; moreover, variants of the anterior part of the CoW were crossed with those of the posterior part. Bivariate association analysis was performed using the ANOVA for continuous variables or using the χ² test for categorical variables. The multiplicity of statistical tests accounts for applying the Bonferroni method. Considering that a statistical test was performed for each of the 11 analysed variables, the threshold for significance was divided by 10 and defined as p≤0.005. All variables that were significantly different between study patients and controls at bivariate analysis were entered into a multivariate logistic regression analysis for ordinal data.

In the χ² test used for brain CT analysis p≤0.05 was considered statistically significant.

Intra- and inter-observer agreement was estimated using the Cohen κ statistics. Cohen’s κ values were interpreted as: 0.81–1.00, excellent; 0.61–0.80, good.

All statistical calculations were performed using SPSS software (SPSS v.23; IBM Corp., Armonk, NY).

From 898 consecutive carotid endarterectomy patients in the study period, we excluded 354 patients (39%) due to poor image quality (24/898, 3%) or missing/incomplete CTA (330/898, 36%). The remaining 544 study subjects were analysed (331 males, mean age 69±8 years, range 44–90 years). Of them, 205 (38%) had symptomatic ICA stenosis, including 59 patients (11%) with previous minor stroke, 25 (5%) with amaurosis fugax and 121 (22%) with TIA. The three study subjects with stenosis of <70% were all symptomatic.

A total of 196 control subjects were analysed (117 males, mean age 66±11 years, range 37–93 years). The indication for CTAs was: (1) false positive ultrasound scan in 58 cases (30%); (2) brachiocephalic/subclavian artery stenosis or aneurysm in 27 (14%); (3) cardiology referral in 29 (14.5%); (4) diagnostic work-up before vascular intervention/surgery in 15 (7.5%); (5) neurology referral in 56 (29%); (6) carotid artery dissection in five (2%); (7) neck tumor in four (2%); and (8) vascular malformation in two (1%).

Further details are reported in Table 1.

The non-visualization of any segment and the hypoplasia of A1 were more frequently reported in cerebrovascular patients as compared to healthy subjects, with some overlap between the two groups, while an opposite trend was demonstrated with respect to AComA and PComA hypoplasia (Table 4).

Comparing our study subjects only with CTA studies on cerebrovascular patients, the prevalence of non-visualized AComA (4%), A1 (4%) and the most commonly compromised PcomA (41%) in our analysis was less frequent (versus 6%-15% and 47%–66%, respectively).

The fact that CTA does not depend on flow velocity (as opposed to 3D TOF MRA) and the higher spatial resolution achieved by 256-slice CT might have contributed to the lower prevalence of non-visualized AComA, A1 and PComA. However, a certain percentage of the non-visualized segments in this study could have been hypoplastic vessels below the CTA detection capability, as in autopsy studies absence was found rarely (0%–3.5%).

Comparing our study group analysis with imaging studies on cerebrovascular patients, we found a higher prevalence of AComA and PcomA hypoplasia (28% and 25%, respectively). The higher detection rate of hypoplastic communicant arteries thanks to the higher spatial resolution of the 256-slice CT relative to the 16-40-row scanners or the MRA techniques used by other investigators might partly account for this difference.

Discontinuity of the CoW in patients with symptomatic ICA stenosis was associated with higher risk of TIA and ischemic stroke [1]. Subjects with high-grade ICA stenosis or occlusion with nil or only one ipsilateral collateral vessel (A1, PComA) had a higher likelihood of stroke when compared to patients with two functional ipsilateral collaterals [5]. This is in agreement with the higher prevalence of brain ischemia found in our patients with severely compromised CoW (p=0.002). We must acknowledge, however, that CT has low sensitivity in the detection of recent ischemia relative to diffusion-weighted magnetic resonance (MR)  imaging but only brain CT was performed for the vast majority of the study group according to institutional protocols with only 11 study subjects having concurrent brain MR imaging and CT.

Most of the previous imaging studies on CoW variants found higher prevalence of hypoplastic or non-visualized segments in cerebrovascular patients [5, 7‐9] in accordance with our study. The anterior part of the CoW is generally considered the most important route for collateral flow in severe ICA stenosis [5‐7, 18, 35]. Kluytman et al. found that the PComA alone had little compensating capacity in ICA occlusion. Best-preserved hemodynamics was reported if both the anterior and posterior parts of the CoW were recruited [35].

The high frequency of compromised circles and the clear difference between the study and control groups strongly suggests that our study subjects have fewer functional segments hindering hemodynamic adaptation. Although the study group and controls were significantly different in terms of five cardiovascular risk factors and coronary artery disease, the multivariate logistic regression analysis showed that ICA stenosis was the only independent predictor of CoW morphology (p<0.001). The higher frequency of ipsilateral A1 hypoplasia/non-visualization was positively associated to ipsilateral ICA stenosis of ≥90% (p<0.001), also implying a correlation between carotid artery disease and hindered collateral recruitment.

Our research group also found significant association between combined incomplete anterior and ipsilateral posterior parts of the CoW and immediate postoperative neurologic complications after carotid endarterectomy without shunt protection (31% vs 5%, p<0.001) [13]. This is in line with another study, in which ≥2 non-visualized segments versus complete CoW were shown to have a statistically significant risk to develop carotid clamping intolerance [11]. In another study, in case of contralateral ICA occlusion, the risk of intraoperative TIA was significantly increased when both parts of the CoW (in particular the posterior part) were incomplete [12].

Three limitations of our study were the lack of comparison with DSA as reference of standard, the possible bias between the study and control groups and the fact that the study group was limited to patients eligible for carotid endarterectomy with either asymptomatic ICA stenosis or symptomatic stenosis with TIA, amaurosis fugax or minor ischemic stroke. DSA and diffusion-weighted MR imaging are not routinely performed as CTA has taken over the role of DSA in the preoperative assessment of the carotid arteries in our institution, moreover it can be easily performed together with brain CT. Further investigations with a well-matched control group including diffusion-weighted MR imaging are needed.

In conclusion, highly variable CoW morphology compared to controls was demonstrated and a likely compromised CoW in relation to ICA stenosis and brain ischemia was observed in a large cohort of carotid endarterectomy subjects.