articletitle

Correlation of internal carotid artery diameter and carotid flow with asymmetry of the circle of Willis

abstract

Background
The purpose of this study was to clarify the effect of asymmetric COW variants on carotid flow changes, and proposed an easy estimate of the representative carotid flow volume for accurate numerical simulation.
Methods
A total of 210 healthy adults receiving magnetic resonance angiography and carotid duplex sonography were included. Three anterior cerebral artery asymmetry (AA) groups were defined based on the diameter ratio difference (DRD) of bilateral A1 segments: AA1 group, oneside A1 aplasia; AA2, A1 DRD ≥ 50%; AA3, A1 DRD between 10 and 50%. Similarly, 3 posterior communicating artery (PcomA) asymmetry (PA) groups were defined: PA1 group, one fetalorigin posterior cerebral artery and absent contralateral PcomA; PA2, PcomA DRD ≥ 50%; PA3, PcomA DRD between 10 and 50%.
Results
With A1 asymmetry, the ICA diameter of the dominant A1 is significantly greater than the contralateral side. Significant differences of bilateral ICA flow were present in the AA1 and AA2 groups (mean flow difference 42.9 and 30.7%, respectively). Significant bilateral ICA diameter and flow differences were only found in the PA1 group. Linear regression analysis of ICA diameter and flow found a moderately positive correlation between ICA diameter and flow in all AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. The product of bilateral ICA diameter and flow volume difference (ICAPDF) could be a potential discriminator with a cutoff of 4.31 to predict A1 asymmetry ≥50% with a sensitivity of 0.81 and specificity of 0.76.
Conclusions
The study verifies that A1 asymmetry causes unequal bilateral carotid inflow, and consequently different bilateral ICA diameters. Adjustment of the inflow boundary conditions according to the COW variants would be necessary to improve the accuracy of numerical simulation.

sec

Background
The purpose of this study was to clarify the effect of asymmetric COW variants on carotid flow changes, and proposed an easy estimate of the representative carotid flow volume for accurate numerical simulation.

title

Background

p

The purpose of this study was to clarify the effect of asymmetric COW variants on carotid flow changes, and proposed an easy estimate of the representative carotid flow volume for accurate numerical simulation.

sec

Methods
A total of 210 healthy adults receiving magnetic resonance angiography and carotid duplex sonography were included. Three anterior cerebral artery asymmetry (AA) groups were defined based on the diameter ratio difference (DRD) of bilateral A1 segments: AA1 group, oneside A1 aplasia; AA2, A1 DRD ≥ 50%; AA3, A1 DRD between 10 and 50%. Similarly, 3 posterior communicating artery (PcomA) asymmetry (PA) groups were defined: PA1 group, one fetalorigin posterior cerebral artery and absent contralateral PcomA; PA2, PcomA DRD ≥ 50%; PA3, PcomA DRD between 10 and 50%.

title

Methods

p

A total of 210 healthy adults receiving magnetic resonance angiography and carotid duplex sonography were included. Three anterior cerebral artery asymmetry (AA) groups were defined based on the diameter ratio difference (DRD) of bilateral A1 segments: AA1 group, oneside A1 aplasia; AA2, A1 DRD ≥ 50%; AA3, A1 DRD between 10 and 50%. Similarly, 3 posterior communicating artery (PcomA) asymmetry (PA) groups were defined: PA1 group, one fetalorigin posterior cerebral artery and absent contralateral PcomA; PA2, PcomA DRD ≥ 50%; PA3, PcomA DRD between 10 and 50%.

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Results
With A1 asymmetry, the ICA diameter of the dominant A1 is significantly greater than the contralateral side. Significant differences of bilateral ICA flow were present in the AA1 and AA2 groups (mean flow difference 42.9 and 30.7%, respectively). Significant bilateral ICA diameter and flow differences were only found in the PA1 group. Linear regression analysis of ICA diameter and flow found a moderately positive correlation between ICA diameter and flow in all AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. The product of bilateral ICA diameter and flow volume difference (ICAPDF) could be a potential discriminator with a cutoff of 4.31 to predict A1 asymmetry ≥50% with a sensitivity of 0.81 and specificity of 0.76.

title

Results

p

With A1 asymmetry, the ICA diameter of the dominant A1 is significantly greater than the contralateral side. Significant differences of bilateral ICA flow were present in the AA1 and AA2 groups (mean flow difference 42.9 and 30.7%, respectively). Significant bilateral ICA diameter and flow differences were only found in the PA1 group. Linear regression analysis of ICA diameter and flow found a moderately positive correlation between ICA diameter and flow in all AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. The product of bilateral ICA diameter and flow volume difference (ICAPDF) could be a potential discriminator with a cutoff of 4.31 to predict A1 asymmetry ≥50% with a sensitivity of 0.81 and specificity of 0.76.

sec

Conclusions
The study verifies that A1 asymmetry causes unequal bilateral carotid inflow, and consequently different bilateral ICA diameters. Adjustment of the inflow boundary conditions according to the COW variants would be necessary to improve the accuracy of numerical simulation.

title

Conclusions

p

The study verifies that A1 asymmetry causes unequal bilateral carotid inflow, and consequently different bilateral ICA diameters. Adjustment of the inflow boundary conditions according to the COW variants would be necessary to improve the accuracy of numerical simulation.

body

Background
In patients with cerebral aneurysms, numerical simulation could provide important hemodynamic information about the aneurysm formation, enlargement, and rupture [1, 2]. Accurate computation fluid dynamic calculations are based on 2 basic conditions: 1) detailed 3dimensional (3D) angioarchitecture and 2) accurate/reasonable physiologic setting of the target vascular tree [2–4]. However, essential patientspecific physiologic data, such as flow volume and flow rate of the proximal parent artery, are usually lacking for numerical analysis. Consequently, average blood flow data from the general population, rather than patientspecific values, are used [5–8].
It is reported that approximately half of the population has Circle of Willis (COW) variants [9–12]. On the other hand, cerebral aneurysms are not uncommon in patients with asymmetric COW variants, such as anterior communicating artery (AcomA) aneurysms in A1 aplasia, and posterior communicating artery (PcomA) aneurysms in fetal posterior cerebral artery (FPCA) [13, 14]. Moreover, carotid flow contralateral to A1 aplasia, and ipsilateral to FPCA, has been shown to be greater than those with a normal COW [15–18]. Total brain blood flow and distribution in different COWtypes also had been proposed [16]. It had been shown that inflow boundary condition [3, 19], especially parent artery flow volume and the conjoint inflow ratio, affect the hemodynamic parameters of cerebral aneurysms. Therefore, adjustment of inflow boundary conditions for cerebral aneurysm analysis according to different COW types is important for obtaining reliable simulation results.
Thus, the purpose of this study was to investigate the association of bilateral ICA flow in healthy adults with asymmetric COW variants, and develop a method for predicting COW asymmetry and the representative carotid flow volume.
Methods
Patients
This retrospective study was approved by the Institutional Review Board of our hospital. The requirement to obtain informed consent was waived due to its retrospective nature.
We retrospectively reviewed the PACS of our institution for subjects who received simultaneous head and neck MRA and carotid duplex sonography from January 2017 to June 2018 as part of a routine health examination. A total of 223 healthy subjects without any history or symptoms of cerebrovascular disease were identified.
Based on the imaging studies, 3 subjects were excluded due to segmental narrowing (> 50%) of the common/internal carotid arteries, 4 due to proximal anterior cerebral artery (ACA)/ middle cerebral artery stenosis, 1 due to a persistent trigeminal artery, 2 due to vascular anomalies such as cerebral aneurysm, 2 due to arteriovenous malformation/fistula, and 1 due to a moyamoya syndrome. These 13 excluded subjects were used for the interobserver reliability test. Thus, 210 subjects (133 males, 77 females; mean age 54 ± 9 years; range, 31 to 76 years) were included in the analysis.
Imaging studies
Threedimensional timeofflight magnetic resonance angiography (TOFMRA) of the head was obtained with the parameters: TR/TE, 21/2 ms; flip angle, 20°; FOV, 200 mm; matrix, 320 × 192; NEX, 1. The major extracranial arteries in the neck were visualized by contrastenhanced MRA on a 3 T MR scanner (Discovery MR 750, GE Medical Systems, Milwaukee, WI, USA) using a single dose (0.1 mmol/ kg; 5–7 ml) of gadobutrol (GdBTDO3A, Gadovist™, Bayer Healthcare, Leverkusen, Germany) with an injection rate of 1.5 ml/s and MR parameters of TR/TE, 4/1 ms; flip angle, 25°; FOV, 300 mm; matrix, 320 × 224; and NEX, 1. Carotid Doppler sonography was performed by the same technician with more than 10 years of experience using a Philips HD15 ultrasound system to evaluate bilateral ICA flow volume. For ICA flow volume measurement, a straight ICA segment at least 2 cm above the carotid bulb was selected with the doppler angle of incidence adjusted at or below 60 degrees. At the same site, the sample volume box was put to cover the entire vessel diameter (d). The anglecorrected timeaverage flow velocity (TAV) was determined over 3 to 5 complete cardiac cycles. The ICA flow volume was calculated as the product of TAV and the crosssectional area (A) of the vessel according to the formula FV = TAV x A = TAV x [(d/2)2xπ].
MR imaging interpretations
At first, vessel diameter and COW calcification of the 13 excluded subjects were recorded by two experienced neuroradiologists (TCW and TYC with 12 and 17 years of experience, respectively) for the interobserver reliability tests. Due to substantial to almost perfect reproducibility (ICC values of 0.82–0.97), the vessel diameter measurements of all 210 included subjects were completed by only one reader (TCW). For COW classification, the diameter ratios between the bilateral A1 segments and between the ipsilateral PcomA and P2 segments were recorded (Fig. 1a, b). The diameters of the bilateral distal cervical ICAs were measured at 1 cm below the petrous segment of the ICA (Fig. 1c). In each case, the diameter of the dominant A1 segment was set as 100%, and the diameter of the nondominant A1 segment was set as the percentage compared to the dominant A1 segment. Bilateral PcomA diameters were transformed into the percentage of the ipsilateral P2 segment diameters. FPCA was defined as a PcomA diameter equal to the ipsilateral P2 segment diameter with an absence of the ipsilateral P1 segment.
Fig. 1 Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment
The classification of COW variants is summarized in Fig. 2. Three ACA asymmetry (AA) groups were defined based on the diameter ratio difference of bilateral A1 segments: AA1 group, 1 side A1 aplasia; AA2, bilateral A1 diameter ratio difference ≥ 50%; AA3, bilateral A1 ratio difference between 10 and 50%. Similarly, 3 PcomA asymmetry (PA) groups were defined: PA1 group, 1 FPCA, and absent PcomA on the contralateral side; PA2, bilateral PcomA diameter ratio difference ≥ 50%; PA3, bilateral PcomA diameter ratio difference between 10 and 50%. According to the vessel diameter, bilateral A1 segments and PcomAs in each patient were denoted as a dominant or nondominant side. Symmetry was defined as both bilateral A1 segment and PcomA diameter ratio differences < 10%, with the exclusion of cases with bilateral FPCAs.
Fig. 2 Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]
Several parameters were used to determine the ability of ICA diameter and flow volume for prediction of COW variants: (1) Bilateral ICA diameter difference; (2) Bilateral ICA flow volume difference; (3) Bilateral ICA flow volume difference percentage (2× bilateral ICA flow difference/ bilateral ICA sum); (4) Product of bilateral ICA diameter and flow volume difference (ICAPDF), expressed as ICA diameter difference (right ICA diameter – left ICA diameter) × ICA flow volume difference percentage [2 × (right ICA flow  left ICA flow)/(right ICA flow + left ICA flow)].
Statistical analysis
Vessel diameter and flow volume measurements were expressed as mean and standard deviation. Vessel diameter and flow volume were compared in the following ways with different statistical tests: 1) Oneway ANOVA and Bonferroni method for multiintergroup analysis; 2) Student ttest for comparisons between each AA/PA subgroup and symmetric group; 3) Paired ttest for intragroup analysis of each subgroup to compare dominant vs. nondominant side and right vs. left side. Linear regression analysis was used to examine the relations between ICA diameter and flow volume in each COW type. To examine the ability of ICA diameter and flow parameters for prediction of each COW variant, receiver operating characteristic (ROC) curve analysis was performed. Interobserver reliability for COW calcification of 13 excluded cases was determined by using the Cohen κ coefficient. For continuous data, the intraclass correlation coefficient (ICC) was calculated with the twoway random model and absolute agreement on average measures. The Cohen κ and ICC were interpreted according to methods described by Landis et al. [20]. Cohen K coefficient values of 0.85 ~ 0.96 were obtained for categorical COW classification and ICC values of 0.82–0.97 were obtained for the continuous data, both indicating almost perfect reproducibility. All data analyses were performed using the statistical software package SPSS for Windows version 24.0 (IBM, Chicago, IL, USA). Values of Pvalue < 0.05 were considered to indicate statistical significance.
Results
Vascular anatomy
The demographic data of the subjects are summarized in Table 1. All 210 subjects were asymptomatic HanChinese adults, and only 81 (38.6%) had complete symmetric of the COW. Seven subjects with bilateral FPCAs and symmetric A1s were not included in the symmetric group due to a lack of bilateral P1 segments. Sixtyseven subjects had asymmetric A1 segments (31.9% of all cases), including 19 (9%; AA1 group) with unilateral A1 aplasia, 33 (15.7%; AA2 group) with ≥50% A1 asymmetry, and 15 (7.1%; AA3 group) with < 50% A1 asymmetry.
Table 1 Subjects demographic data by Circle of Willis variants
All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820
aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs
Seventyeight subjects (37.1% of all cases) were included in the PA group, including 15 in the PA1 group (7.1%) with a unilateral FPCA and absent contralateral PcomAA, 45 in the PA2 group (21.4%) with ≥50% PcomA asymmetry, and 18 in the PA3 group (8.6%) with < 50% PcomA asymmetry. Twentythree subjects had both A1 and PcomA asymmetry. In these subjects, the dominant A1 was most likely to be on the same side as the nondominant PcomA (19 patients, P < 0.001, McNemar’s test). Only 4 subjects had the dominant A1 and dominant PcomA on the same side.
Comparison of vessel diameters and flow in different subgroups
AA group
When ACA asymmetry was present, there were significant differences in ICA diameter between dominant and nondominant sides in the AA1, AA2, and AA3 groups (Fig. 3a). Compared with the symmetric group, the AA1 and AA2 groups had a significantly larger ICA diameter on the dominant side and a significantly smaller ICA diameter on the nondominant side. Similarly, significant differences in bilateral ICA flow were also found in the AA1 and AA2 groups (Fig. 3b). The average bilateral ICA flow volume difference percentages of the AA1, AA2, and AA3 groups were 42.9, 30.7, and 29%, respectively (Table 2). A greater asymmetry between the bilateral A1 segments tended to be associated with a larger difference between the bilateral ICA flow volume.
Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)
Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852
PA group & FPCA
A significant difference in bilateral ICA diameter and flow was only found in the PA1 group with unilateral FPCA and no contralateral PcomA. If an FPCA was present, there was a trend for the ipsilateral ICA to have a larger diameter and higher flow volume as compared with the symmetric group (Fig. 3c, d). However, there was no significant difference between these 2 groups concerning diameter (P = 0.059) and flow volume (P = 0.085). On the other hand, the difference between ICA flow ipsilateral to the FPCA and in the symmetric group reached statistical significance (P = 0.049) after the exclusion of 15 patients with an FPCA with concomitant A1 asymmetry (Fig. 3e, f).
Association of ICA diameter with ICA flow
A moderately positive linear correlation between ICA diameter and ICA flow in the AA group (R2 = 0.238) was noted (Fig. 4a) According to the linear equation, there was a 62.6 ml increase in the ICA flow volume per 1 mm increase in the ICA diameter. Based on the average ICA flow volume of 265.9 ml/min in the AA group, it implied a change of 23.5% of the ICA flow volume per 1 mm change in the ICA diameter. On the other hand, no significant association was noted between ICA diameter and flow volume in either the PA (Fig. 4b) and symmetric groups (Fig. 4c). Carotid diameter and flow differences for each group of COW variants are shown in Table 2. All parameters, including ICA diameter difference, ICA flow difference, ICA flow difference percentage, and product of bilateral ICA diameter and flow difference (ICAPDF) of each AA group exhibited significant differences. Among them, ICAPDF had the highest area under the ROC curve (AUC = 0.807) for discriminating the AA1 and AA2 groups from the others, followed by ICA diameter difference (AUC = 0.771), ICA flow difference percentage (AUC = 0.703), and ICA flow difference (AUC = 0.695) (Fig. 5a). For the prediction of A1 absence, ICAPDF and ICAdiameter difference exhibited even higher accuracy for discriminating the AA1 group from the other groups (Fig. 5b). The optimal cutoff value for bilateral A1 asymmetry ≥50% was a PDF = 4.31 with a sensitivity of 0.81 and specificity of 0.76.
Fig. 4 Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group
Fig. 5 ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others
Discussion
This study attempted to clarify the effect of asymmetric COW variants on carotid flow changes and proposed an easy estimate of the representative carotid flow volume. In the present study, 52 of the 210 cases (34.7%) had bilateral A1 asymmetry ≥50%, in whom there was significantly greater dominant ICA flow with larger dominant ICA diameter, and lower nondominant ICA flow with smaller nondominant ICA diameter, as compared with the symmetric group. There was a moderately positive association between ICA vessel diameter and ICA flow volume in the AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Moreover, an ICAPDF cutoff value of 4.31 was found to be a useful predictor of bilateral A1 asymmetry ≥50%.
While the COW serves as an important intracranial collateral pathway, there are multiple incomplete or asymmetric variants with variable prevalence according to different classification criteria, including A1 absence (2.6–15.4%; 9% in our study), A1 hypoplasia (2.6–28.9%; 15.7% in our study), true FPCA without a P1 segment (0.9–29.5%; 10.7% in our study), and FPCA with P1 hypoplasia (4.5–37.2%; 4.5% in our study) [9–12, 14, 15, 17, 18, 21–23]. In our study, we used a bilateral A1 and PcomA diameter ratio difference of 50% to define asymmetry rather than the usual criteria using an absolute vessel diameter of 1.0 mm as a cutoff value. Based on reports indicating the mean diameters of the A1 segment and the P2 segment are 2 mm [9, 11], a bilateral vessel diameter ratio difference of 50% equals a 1 mm cutoff value for the hypoplastic vessels. This vessel diameter ratio had been used in several studies focused on the effect of inflow inequality on cerebral aneurysms [23–26].
Our study showed a mean individual carotid flow difference percentage of 42.9% in the AA1 group. The result was consistent with several previous studies showing that the carotid flow ipsilateral to A1 aplasia is significantly lower than that of the contralateral side, with the flow difference percentage ranging from 34 to 50% [15–18]. Moreover, we also demonstrated that there was a significantly higher individual carotid flow difference percentage (30%) when A1 asymmetry was present. Since each A1 segment carries about 10% of the total brain flow to the ipsilateral hemisphere [17, 24], A1 segment asymmetry indicates redistribution of bilateral A1 flow and is crucial for computational hemodynamic studies for 2 reasons. First, A1 hypoplasia is associated with AcomA aneurysms [1, 13, 23, 27]. This relation can be explained by hemodynamic studies using either an experimental design with an A1 diameter ratio of ≥50% [25], or patientspecific 3D geometry with an unequal A1 inflow [28]. Both types of studies [25, 28] showed elevated intraaneurysmal wall shear stress in the setting of A1 hypoplasia or unequal flow that would trigger AcomA aneurysm formation. Our results further emphasized that A1 asymmetry, even with a diameter difference of < 50%, could also cause unequal inflow and might be associated with Acom aneurysm formation. Second, several studies have indicated the importance of using patientspecific inflow boundary conditions to obtain reliable computational fluid dynamic results, especially for aneurysms with more than 2 inflow avenues, such as AcomA aneurysms [3, 19, 25, 28, 29]. Venugopal et al. [19] showed that the wall shear stress distribution on an aneurysm surface is sensitive to the bilateral A1 flow ratio and flow rate by using different inflow boundary conditions for a patientspecific AcomA aneurysm geometry with an original flow ratio of 1.87. Similarly, Karmonik et al. [29] reported that changes in the flow distribution of bilateral A1 segments could cause variations of the average wall shear stress as high as 43%, again using a patientspecific AcomA aneurysm model with an original flow ratio of 1.72. On the other hand, blood flow changes of the parent artery would not change the characterization of the intraaneurysmal flow pattern substantially in the setting of a sidewall aneurysm/terminal aneurysm or AcomA aneurysm with relatively symmetric A1 segments [30]. In our study, we proposed a linear equation between the ipsilateral ICA diameter and ICA flow volume to provide a representative inflow boundary condition for the numerical simulation while A1 asymmetry is present.
As for PcomA asymmetry, only the PA1 group exhibited a significant carotid flow and diameter difference, but to a lesser extent of 25%. A significantly higher carotid flow with an FPCA compared with the symmetric group was only found after the exclusion of coincident A1 asymmetry. When A1 asymmetry occurred simultaneously with PcomA asymmetry (23 cases), a nondominant A1 (19 cases) was more frequently on the same side of the dominant PcomA. A PcomA usually serves as a conduit connecting the anterior and posterior circulation to provide a collateral pathway when there is proximal vessel comprise or there is an incomplete COW. The average net flow of a PcomA is usually low, and in an anterior to posterior direction, and accounts for about 5% of the ipsilateral carotid flow [31]. Considering all the aforementioned findings, it is reasonable that PcomA asymmetry has little influence on carotid flow changes.
In all AA groups and the PA1 group, there was a consistent relation between dominant and nondominant carotid diameter and flow, i.e., there was larger vessel diameter and higher carotid flow on the dominant side. This finding is consistent with a “formfunction” relation, wherein the form (anatomy: vessel radius) proportionately informs its function (physiology: blood flow). This concept has been extensively applied in the study of coronary artery disease [32, 33]. Similar findings have also been reported in studies of carotid flow, such as a small carotid diameter ipsilateral to A1 absence [21], and a linear relationship between whole brain volume and cerebral blood flow [16]. Cebral et al. [34] studied the flowarea relation in the carotid arteries of 11 healthy adults using the leastsquares method for curve fitting and reported an average relative error between the predicted and the measured ratio to be 20%. This relation is also reflected in our finding of a moderately positive linear correlation (Fig. 4a) between carotid diameter and carotid flow in the AA groups (r2 = 0.238). Despite a significant difference in carotid diameter and flow between each of the AA groups, there was also a large standard deviation in each parameter owing to large individual variances. To cancel out the individual variances (Table S1 in the supplement) and amplify the flowdiameter difference in the subjects with A1 asymmetry (Figure S1 in the supplement), we proposed the product of bilateral ICA diameter and flow difference (ICAPDF) as a potential discriminator. Recognition of an incomplete COW could offer stroke risk stratification in patients vulnerable to proximal artery compromise, such as those receiving cardiovascular surgery or carotid artery trapping [35].
Several limitations of our study should be addressed. First, the majority of subjects were middleaged (40–60 years old, 64%) healthy HanChinese adults. The progressive decline of cerebral blood flow at a rate of 3 ml per year has been also reported [36]. The estimate of carotid flow in younger or aged populations might need adjustment. Second, it’s hard to assure the bright vessel lumen on TOFMRA reflecting the “true” vessel size, especially when scanning a hypoplastic vessel. Moreover, the vessel diameter was calculated by only 1 reader. Thus, to minimize the measurement error of smallsized A1 segments and PcomA (< 3 mm), the vessel diameter ratio compared to the contralateral A1 or ipsilateral P2 segment, rather than the exact vessel diameter, was used for COW classification. It was reflected by the almost perfect reproducibility of categorical COW calcification in the 13 excluded subjects (Cohen K coefficient values of 0.85 ~ 0.96). Third, there was no validation performed for the estimate of carotid flow by the ipsilateral carotid diameter in A1 asymmetry and patients with specific neurovascular diseases such as cerebral aneurysms. Validation with another dataset, or with prospective study might be helpful.
Conclusion
A1 asymmetry plays an important role in ICA flow distribution, contributing to bilateral unequal carotid inflow and significant carotid diameter difference. When A1 asymmetry is present, there is a moderately positive linear correlation between carotid diameter and carotid flow, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Our study improved the understanding of the association of bilateral ICA flow in healthy adults with asymmetric COW variants. Our results can potentially be applied to improve the accuracy of numerical simulation by the adjustment of the inflow boundary conditions according to the COW variants.
Supplementary information
Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.
Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

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Background
In patients with cerebral aneurysms, numerical simulation could provide important hemodynamic information about the aneurysm formation, enlargement, and rupture [1, 2]. Accurate computation fluid dynamic calculations are based on 2 basic conditions: 1) detailed 3dimensional (3D) angioarchitecture and 2) accurate/reasonable physiologic setting of the target vascular tree [2–4]. However, essential patientspecific physiologic data, such as flow volume and flow rate of the proximal parent artery, are usually lacking for numerical analysis. Consequently, average blood flow data from the general population, rather than patientspecific values, are used [5–8].
It is reported that approximately half of the population has Circle of Willis (COW) variants [9–12]. On the other hand, cerebral aneurysms are not uncommon in patients with asymmetric COW variants, such as anterior communicating artery (AcomA) aneurysms in A1 aplasia, and posterior communicating artery (PcomA) aneurysms in fetal posterior cerebral artery (FPCA) [13, 14]. Moreover, carotid flow contralateral to A1 aplasia, and ipsilateral to FPCA, has been shown to be greater than those with a normal COW [15–18]. Total brain blood flow and distribution in different COWtypes also had been proposed [16]. It had been shown that inflow boundary condition [3, 19], especially parent artery flow volume and the conjoint inflow ratio, affect the hemodynamic parameters of cerebral aneurysms. Therefore, adjustment of inflow boundary conditions for cerebral aneurysm analysis according to different COW types is important for obtaining reliable simulation results.
Thus, the purpose of this study was to investigate the association of bilateral ICA flow in healthy adults with asymmetric COW variants, and develop a method for predicting COW asymmetry and the representative carotid flow volume.

title

Background

p

In patients with cerebral aneurysms, numerical simulation could provide important hemodynamic information about the aneurysm formation, enlargement, and rupture [1, 2]. Accurate computation fluid dynamic calculations are based on 2 basic conditions: 1) detailed 3dimensional (3D) angioarchitecture and 2) accurate/reasonable physiologic setting of the target vascular tree [2–4]. However, essential patientspecific physiologic data, such as flow volume and flow rate of the proximal parent artery, are usually lacking for numerical analysis. Consequently, average blood flow data from the general population, rather than patientspecific values, are used [5–8].

p

It is reported that approximately half of the population has Circle of Willis (COW) variants [9–12]. On the other hand, cerebral aneurysms are not uncommon in patients with asymmetric COW variants, such as anterior communicating artery (AcomA) aneurysms in A1 aplasia, and posterior communicating artery (PcomA) aneurysms in fetal posterior cerebral artery (FPCA) [13, 14]. Moreover, carotid flow contralateral to A1 aplasia, and ipsilateral to FPCA, has been shown to be greater than those with a normal COW [15–18]. Total brain blood flow and distribution in different COWtypes also had been proposed [16]. It had been shown that inflow boundary condition [3, 19], especially parent artery flow volume and the conjoint inflow ratio, affect the hemodynamic parameters of cerebral aneurysms. Therefore, adjustment of inflow boundary conditions for cerebral aneurysm analysis according to different COW types is important for obtaining reliable simulation results.

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Thus, the purpose of this study was to investigate the association of bilateral ICA flow in healthy adults with asymmetric COW variants, and develop a method for predicting COW asymmetry and the representative carotid flow volume.

sec

Methods
Patients
This retrospective study was approved by the Institutional Review Board of our hospital. The requirement to obtain informed consent was waived due to its retrospective nature.
We retrospectively reviewed the PACS of our institution for subjects who received simultaneous head and neck MRA and carotid duplex sonography from January 2017 to June 2018 as part of a routine health examination. A total of 223 healthy subjects without any history or symptoms of cerebrovascular disease were identified.
Based on the imaging studies, 3 subjects were excluded due to segmental narrowing (> 50%) of the common/internal carotid arteries, 4 due to proximal anterior cerebral artery (ACA)/ middle cerebral artery stenosis, 1 due to a persistent trigeminal artery, 2 due to vascular anomalies such as cerebral aneurysm, 2 due to arteriovenous malformation/fistula, and 1 due to a moyamoya syndrome. These 13 excluded subjects were used for the interobserver reliability test. Thus, 210 subjects (133 males, 77 females; mean age 54 ± 9 years; range, 31 to 76 years) were included in the analysis.
Imaging studies
Threedimensional timeofflight magnetic resonance angiography (TOFMRA) of the head was obtained with the parameters: TR/TE, 21/2 ms; flip angle, 20°; FOV, 200 mm; matrix, 320 × 192; NEX, 1. The major extracranial arteries in the neck were visualized by contrastenhanced MRA on a 3 T MR scanner (Discovery MR 750, GE Medical Systems, Milwaukee, WI, USA) using a single dose (0.1 mmol/ kg; 5–7 ml) of gadobutrol (GdBTDO3A, Gadovist™, Bayer Healthcare, Leverkusen, Germany) with an injection rate of 1.5 ml/s and MR parameters of TR/TE, 4/1 ms; flip angle, 25°; FOV, 300 mm; matrix, 320 × 224; and NEX, 1. Carotid Doppler sonography was performed by the same technician with more than 10 years of experience using a Philips HD15 ultrasound system to evaluate bilateral ICA flow volume. For ICA flow volume measurement, a straight ICA segment at least 2 cm above the carotid bulb was selected with the doppler angle of incidence adjusted at or below 60 degrees. At the same site, the sample volume box was put to cover the entire vessel diameter (d). The anglecorrected timeaverage flow velocity (TAV) was determined over 3 to 5 complete cardiac cycles. The ICA flow volume was calculated as the product of TAV and the crosssectional area (A) of the vessel according to the formula FV = TAV x A = TAV x [(d/2)2xπ].
MR imaging interpretations
At first, vessel diameter and COW calcification of the 13 excluded subjects were recorded by two experienced neuroradiologists (TCW and TYC with 12 and 17 years of experience, respectively) for the interobserver reliability tests. Due to substantial to almost perfect reproducibility (ICC values of 0.82–0.97), the vessel diameter measurements of all 210 included subjects were completed by only one reader (TCW). For COW classification, the diameter ratios between the bilateral A1 segments and between the ipsilateral PcomA and P2 segments were recorded (Fig. 1a, b). The diameters of the bilateral distal cervical ICAs were measured at 1 cm below the petrous segment of the ICA (Fig. 1c). In each case, the diameter of the dominant A1 segment was set as 100%, and the diameter of the nondominant A1 segment was set as the percentage compared to the dominant A1 segment. Bilateral PcomA diameters were transformed into the percentage of the ipsilateral P2 segment diameters. FPCA was defined as a PcomA diameter equal to the ipsilateral P2 segment diameter with an absence of the ipsilateral P1 segment.
Fig. 1 Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment
The classification of COW variants is summarized in Fig. 2. Three ACA asymmetry (AA) groups were defined based on the diameter ratio difference of bilateral A1 segments: AA1 group, 1 side A1 aplasia; AA2, bilateral A1 diameter ratio difference ≥ 50%; AA3, bilateral A1 ratio difference between 10 and 50%. Similarly, 3 PcomA asymmetry (PA) groups were defined: PA1 group, 1 FPCA, and absent PcomA on the contralateral side; PA2, bilateral PcomA diameter ratio difference ≥ 50%; PA3, bilateral PcomA diameter ratio difference between 10 and 50%. According to the vessel diameter, bilateral A1 segments and PcomAs in each patient were denoted as a dominant or nondominant side. Symmetry was defined as both bilateral A1 segment and PcomA diameter ratio differences < 10%, with the exclusion of cases with bilateral FPCAs.
Fig. 2 Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]
Several parameters were used to determine the ability of ICA diameter and flow volume for prediction of COW variants: (1) Bilateral ICA diameter difference; (2) Bilateral ICA flow volume difference; (3) Bilateral ICA flow volume difference percentage (2× bilateral ICA flow difference/ bilateral ICA sum); (4) Product of bilateral ICA diameter and flow volume difference (ICAPDF), expressed as ICA diameter difference (right ICA diameter – left ICA diameter) × ICA flow volume difference percentage [2 × (right ICA flow  left ICA flow)/(right ICA flow + left ICA flow)].
Statistical analysis
Vessel diameter and flow volume measurements were expressed as mean and standard deviation. Vessel diameter and flow volume were compared in the following ways with different statistical tests: 1) Oneway ANOVA and Bonferroni method for multiintergroup analysis; 2) Student ttest for comparisons between each AA/PA subgroup and symmetric group; 3) Paired ttest for intragroup analysis of each subgroup to compare dominant vs. nondominant side and right vs. left side. Linear regression analysis was used to examine the relations between ICA diameter and flow volume in each COW type. To examine the ability of ICA diameter and flow parameters for prediction of each COW variant, receiver operating characteristic (ROC) curve analysis was performed. Interobserver reliability for COW calcification of 13 excluded cases was determined by using the Cohen κ coefficient. For continuous data, the intraclass correlation coefficient (ICC) was calculated with the twoway random model and absolute agreement on average measures. The Cohen κ and ICC were interpreted according to methods described by Landis et al. [20]. Cohen K coefficient values of 0.85 ~ 0.96 were obtained for categorical COW classification and ICC values of 0.82–0.97 were obtained for the continuous data, both indicating almost perfect reproducibility. All data analyses were performed using the statistical software package SPSS for Windows version 24.0 (IBM, Chicago, IL, USA). Values of Pvalue < 0.05 were considered to indicate statistical significance.

title

Methods

sec

Patients
This retrospective study was approved by the Institutional Review Board of our hospital. The requirement to obtain informed consent was waived due to its retrospective nature.
We retrospectively reviewed the PACS of our institution for subjects who received simultaneous head and neck MRA and carotid duplex sonography from January 2017 to June 2018 as part of a routine health examination. A total of 223 healthy subjects without any history or symptoms of cerebrovascular disease were identified.
Based on the imaging studies, 3 subjects were excluded due to segmental narrowing (> 50%) of the common/internal carotid arteries, 4 due to proximal anterior cerebral artery (ACA)/ middle cerebral artery stenosis, 1 due to a persistent trigeminal artery, 2 due to vascular anomalies such as cerebral aneurysm, 2 due to arteriovenous malformation/fistula, and 1 due to a moyamoya syndrome. These 13 excluded subjects were used for the interobserver reliability test. Thus, 210 subjects (133 males, 77 females; mean age 54 ± 9 years; range, 31 to 76 years) were included in the analysis.

title

Patients

p

This retrospective study was approved by the Institutional Review Board of our hospital. The requirement to obtain informed consent was waived due to its retrospective nature.

p

We retrospectively reviewed the PACS of our institution for subjects who received simultaneous head and neck MRA and carotid duplex sonography from January 2017 to June 2018 as part of a routine health examination. A total of 223 healthy subjects without any history or symptoms of cerebrovascular disease were identified.

p

Based on the imaging studies, 3 subjects were excluded due to segmental narrowing (> 50%) of the common/internal carotid arteries, 4 due to proximal anterior cerebral artery (ACA)/ middle cerebral artery stenosis, 1 due to a persistent trigeminal artery, 2 due to vascular anomalies such as cerebral aneurysm, 2 due to arteriovenous malformation/fistula, and 1 due to a moyamoya syndrome. These 13 excluded subjects were used for the interobserver reliability test. Thus, 210 subjects (133 males, 77 females; mean age 54 ± 9 years; range, 31 to 76 years) were included in the analysis.

sec

Imaging studies
Threedimensional timeofflight magnetic resonance angiography (TOFMRA) of the head was obtained with the parameters: TR/TE, 21/2 ms; flip angle, 20°; FOV, 200 mm; matrix, 320 × 192; NEX, 1. The major extracranial arteries in the neck were visualized by contrastenhanced MRA on a 3 T MR scanner (Discovery MR 750, GE Medical Systems, Milwaukee, WI, USA) using a single dose (0.1 mmol/ kg; 5–7 ml) of gadobutrol (GdBTDO3A, Gadovist™, Bayer Healthcare, Leverkusen, Germany) with an injection rate of 1.5 ml/s and MR parameters of TR/TE, 4/1 ms; flip angle, 25°; FOV, 300 mm; matrix, 320 × 224; and NEX, 1. Carotid Doppler sonography was performed by the same technician with more than 10 years of experience using a Philips HD15 ultrasound system to evaluate bilateral ICA flow volume. For ICA flow volume measurement, a straight ICA segment at least 2 cm above the carotid bulb was selected with the doppler angle of incidence adjusted at or below 60 degrees. At the same site, the sample volume box was put to cover the entire vessel diameter (d). The anglecorrected timeaverage flow velocity (TAV) was determined over 3 to 5 complete cardiac cycles. The ICA flow volume was calculated as the product of TAV and the crosssectional area (A) of the vessel according to the formula FV = TAV x A = TAV x [(d/2)2xπ].

title

Imaging studies

p

Threedimensional timeofflight magnetic resonance angiography (TOFMRA) of the head was obtained with the parameters: TR/TE, 21/2 ms; flip angle, 20°; FOV, 200 mm; matrix, 320 × 192; NEX, 1. The major extracranial arteries in the neck were visualized by contrastenhanced MRA on a 3 T MR scanner (Discovery MR 750, GE Medical Systems, Milwaukee, WI, USA) using a single dose (0.1 mmol/ kg; 5–7 ml) of gadobutrol (GdBTDO3A, Gadovist™, Bayer Healthcare, Leverkusen, Germany) with an injection rate of 1.5 ml/s and MR parameters of TR/TE, 4/1 ms; flip angle, 25°; FOV, 300 mm; matrix, 320 × 224; and NEX, 1. Carotid Doppler sonography was performed by the same technician with more than 10 years of experience using a Philips HD15 ultrasound system to evaluate bilateral ICA flow volume. For ICA flow volume measurement, a straight ICA segment at least 2 cm above the carotid bulb was selected with the doppler angle of incidence adjusted at or below 60 degrees. At the same site, the sample volume box was put to cover the entire vessel diameter (d). The anglecorrected timeaverage flow velocity (TAV) was determined over 3 to 5 complete cardiac cycles. The ICA flow volume was calculated as the product of TAV and the crosssectional area (A) of the vessel according to the formula FV = TAV x A = TAV x [(d/2)2xπ].

sec

MR imaging interpretations
At first, vessel diameter and COW calcification of the 13 excluded subjects were recorded by two experienced neuroradiologists (TCW and TYC with 12 and 17 years of experience, respectively) for the interobserver reliability tests. Due to substantial to almost perfect reproducibility (ICC values of 0.82–0.97), the vessel diameter measurements of all 210 included subjects were completed by only one reader (TCW). For COW classification, the diameter ratios between the bilateral A1 segments and between the ipsilateral PcomA and P2 segments were recorded (Fig. 1a, b). The diameters of the bilateral distal cervical ICAs were measured at 1 cm below the petrous segment of the ICA (Fig. 1c). In each case, the diameter of the dominant A1 segment was set as 100%, and the diameter of the nondominant A1 segment was set as the percentage compared to the dominant A1 segment. Bilateral PcomA diameters were transformed into the percentage of the ipsilateral P2 segment diameters. FPCA was defined as a PcomA diameter equal to the ipsilateral P2 segment diameter with an absence of the ipsilateral P1 segment.
Fig. 1 Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment
The classification of COW variants is summarized in Fig. 2. Three ACA asymmetry (AA) groups were defined based on the diameter ratio difference of bilateral A1 segments: AA1 group, 1 side A1 aplasia; AA2, bilateral A1 diameter ratio difference ≥ 50%; AA3, bilateral A1 ratio difference between 10 and 50%. Similarly, 3 PcomA asymmetry (PA) groups were defined: PA1 group, 1 FPCA, and absent PcomA on the contralateral side; PA2, bilateral PcomA diameter ratio difference ≥ 50%; PA3, bilateral PcomA diameter ratio difference between 10 and 50%. According to the vessel diameter, bilateral A1 segments and PcomAs in each patient were denoted as a dominant or nondominant side. Symmetry was defined as both bilateral A1 segment and PcomA diameter ratio differences < 10%, with the exclusion of cases with bilateral FPCAs.
Fig. 2 Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]
Several parameters were used to determine the ability of ICA diameter and flow volume for prediction of COW variants: (1) Bilateral ICA diameter difference; (2) Bilateral ICA flow volume difference; (3) Bilateral ICA flow volume difference percentage (2× bilateral ICA flow difference/ bilateral ICA sum); (4) Product of bilateral ICA diameter and flow volume difference (ICAPDF), expressed as ICA diameter difference (right ICA diameter – left ICA diameter) × ICA flow volume difference percentage [2 × (right ICA flow  left ICA flow)/(right ICA flow + left ICA flow)].

title

MR imaging interpretations

p

At first, vessel diameter and COW calcification of the 13 excluded subjects were recorded by two experienced neuroradiologists (TCW and TYC with 12 and 17 years of experience, respectively) for the interobserver reliability tests. Due to substantial to almost perfect reproducibility (ICC values of 0.82–0.97), the vessel diameter measurements of all 210 included subjects were completed by only one reader (TCW). For COW classification, the diameter ratios between the bilateral A1 segments and between the ipsilateral PcomA and P2 segments were recorded (Fig. 1a, b). The diameters of the bilateral distal cervical ICAs were measured at 1 cm below the petrous segment of the ICA (Fig. 1c). In each case, the diameter of the dominant A1 segment was set as 100%, and the diameter of the nondominant A1 segment was set as the percentage compared to the dominant A1 segment. Bilateral PcomA diameters were transformed into the percentage of the ipsilateral P2 segment diameters. FPCA was defined as a PcomA diameter equal to the ipsilateral P2 segment diameter with an absence of the ipsilateral P1 segment.
Fig. 1 Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment

figure

Fig. 1 Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment

label

Fig. 1

p

Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment

caption

Examples of vascular diameter measurement. a) Typical location of bilateral A1 diameter measurement at in the middle of the A1 segment. b) Typical location of PcomA and P2 diameter measurement at in the middle of the PcomA and proximal P2 segment, respectively. Note there was no PcomA on the contralateral side. c) Typical location of bilateral distal cervical ICA diameter measurement at 1 cm below the petrous ICA segment

p

The classification of COW variants is summarized in Fig. 2. Three ACA asymmetry (AA) groups were defined based on the diameter ratio difference of bilateral A1 segments: AA1 group, 1 side A1 aplasia; AA2, bilateral A1 diameter ratio difference ≥ 50%; AA3, bilateral A1 ratio difference between 10 and 50%. Similarly, 3 PcomA asymmetry (PA) groups were defined: PA1 group, 1 FPCA, and absent PcomA on the contralateral side; PA2, bilateral PcomA diameter ratio difference ≥ 50%; PA3, bilateral PcomA diameter ratio difference between 10 and 50%. According to the vessel diameter, bilateral A1 segments and PcomAs in each patient were denoted as a dominant or nondominant side. Symmetry was defined as both bilateral A1 segment and PcomA diameter ratio differences < 10%, with the exclusion of cases with bilateral FPCAs.
Fig. 2 Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]

figure

Fig. 2 Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]

label

Fig. 2

p

Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]

caption

Classification of Circle of Willis variants (modified from KrabbeHartkamp, Radiology 1998) [9]

p

Several parameters were used to determine the ability of ICA diameter and flow volume for prediction of COW variants: (1) Bilateral ICA diameter difference; (2) Bilateral ICA flow volume difference; (3) Bilateral ICA flow volume difference percentage (2× bilateral ICA flow difference/ bilateral ICA sum); (4) Product of bilateral ICA diameter and flow volume difference (ICAPDF), expressed as ICA diameter difference (right ICA diameter – left ICA diameter) × ICA flow volume difference percentage [2 × (right ICA flow  left ICA flow)/(right ICA flow + left ICA flow)].

sec

Statistical analysis
Vessel diameter and flow volume measurements were expressed as mean and standard deviation. Vessel diameter and flow volume were compared in the following ways with different statistical tests: 1) Oneway ANOVA and Bonferroni method for multiintergroup analysis; 2) Student ttest for comparisons between each AA/PA subgroup and symmetric group; 3) Paired ttest for intragroup analysis of each subgroup to compare dominant vs. nondominant side and right vs. left side. Linear regression analysis was used to examine the relations between ICA diameter and flow volume in each COW type. To examine the ability of ICA diameter and flow parameters for prediction of each COW variant, receiver operating characteristic (ROC) curve analysis was performed. Interobserver reliability for COW calcification of 13 excluded cases was determined by using the Cohen κ coefficient. For continuous data, the intraclass correlation coefficient (ICC) was calculated with the twoway random model and absolute agreement on average measures. The Cohen κ and ICC were interpreted according to methods described by Landis et al. [20]. Cohen K coefficient values of 0.85 ~ 0.96 were obtained for categorical COW classification and ICC values of 0.82–0.97 were obtained for the continuous data, both indicating almost perfect reproducibility. All data analyses were performed using the statistical software package SPSS for Windows version 24.0 (IBM, Chicago, IL, USA). Values of Pvalue < 0.05 were considered to indicate statistical significance.

title

Statistical analysis

p

Vessel diameter and flow volume measurements were expressed as mean and standard deviation. Vessel diameter and flow volume were compared in the following ways with different statistical tests: 1) Oneway ANOVA and Bonferroni method for multiintergroup analysis; 2) Student ttest for comparisons between each AA/PA subgroup and symmetric group; 3) Paired ttest for intragroup analysis of each subgroup to compare dominant vs. nondominant side and right vs. left side. Linear regression analysis was used to examine the relations between ICA diameter and flow volume in each COW type. To examine the ability of ICA diameter and flow parameters for prediction of each COW variant, receiver operating characteristic (ROC) curve analysis was performed. Interobserver reliability for COW calcification of 13 excluded cases was determined by using the Cohen κ coefficient. For continuous data, the intraclass correlation coefficient (ICC) was calculated with the twoway random model and absolute agreement on average measures. The Cohen κ and ICC were interpreted according to methods described by Landis et al. [20]. Cohen K coefficient values of 0.85 ~ 0.96 were obtained for categorical COW classification and ICC values of 0.82–0.97 were obtained for the continuous data, both indicating almost perfect reproducibility. All data analyses were performed using the statistical software package SPSS for Windows version 24.0 (IBM, Chicago, IL, USA). Values of Pvalue < 0.05 were considered to indicate statistical significance.

sec

Results
Vascular anatomy
The demographic data of the subjects are summarized in Table 1. All 210 subjects were asymptomatic HanChinese adults, and only 81 (38.6%) had complete symmetric of the COW. Seven subjects with bilateral FPCAs and symmetric A1s were not included in the symmetric group due to a lack of bilateral P1 segments. Sixtyseven subjects had asymmetric A1 segments (31.9% of all cases), including 19 (9%; AA1 group) with unilateral A1 aplasia, 33 (15.7%; AA2 group) with ≥50% A1 asymmetry, and 15 (7.1%; AA3 group) with < 50% A1 asymmetry.
Table 1 Subjects demographic data by Circle of Willis variants
All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820
aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs
Seventyeight subjects (37.1% of all cases) were included in the PA group, including 15 in the PA1 group (7.1%) with a unilateral FPCA and absent contralateral PcomAA, 45 in the PA2 group (21.4%) with ≥50% PcomA asymmetry, and 18 in the PA3 group (8.6%) with < 50% PcomA asymmetry. Twentythree subjects had both A1 and PcomA asymmetry. In these subjects, the dominant A1 was most likely to be on the same side as the nondominant PcomA (19 patients, P < 0.001, McNemar’s test). Only 4 subjects had the dominant A1 and dominant PcomA on the same side.
Comparison of vessel diameters and flow in different subgroups
AA group
When ACA asymmetry was present, there were significant differences in ICA diameter between dominant and nondominant sides in the AA1, AA2, and AA3 groups (Fig. 3a). Compared with the symmetric group, the AA1 and AA2 groups had a significantly larger ICA diameter on the dominant side and a significantly smaller ICA diameter on the nondominant side. Similarly, significant differences in bilateral ICA flow were also found in the AA1 and AA2 groups (Fig. 3b). The average bilateral ICA flow volume difference percentages of the AA1, AA2, and AA3 groups were 42.9, 30.7, and 29%, respectively (Table 2). A greater asymmetry between the bilateral A1 segments tended to be associated with a larger difference between the bilateral ICA flow volume.
Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)
Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852
PA group & FPCA
A significant difference in bilateral ICA diameter and flow was only found in the PA1 group with unilateral FPCA and no contralateral PcomA. If an FPCA was present, there was a trend for the ipsilateral ICA to have a larger diameter and higher flow volume as compared with the symmetric group (Fig. 3c, d). However, there was no significant difference between these 2 groups concerning diameter (P = 0.059) and flow volume (P = 0.085). On the other hand, the difference between ICA flow ipsilateral to the FPCA and in the symmetric group reached statistical significance (P = 0.049) after the exclusion of 15 patients with an FPCA with concomitant A1 asymmetry (Fig. 3e, f).
Association of ICA diameter with ICA flow
A moderately positive linear correlation between ICA diameter and ICA flow in the AA group (R2 = 0.238) was noted (Fig. 4a) According to the linear equation, there was a 62.6 ml increase in the ICA flow volume per 1 mm increase in the ICA diameter. Based on the average ICA flow volume of 265.9 ml/min in the AA group, it implied a change of 23.5% of the ICA flow volume per 1 mm change in the ICA diameter. On the other hand, no significant association was noted between ICA diameter and flow volume in either the PA (Fig. 4b) and symmetric groups (Fig. 4c). Carotid diameter and flow differences for each group of COW variants are shown in Table 2. All parameters, including ICA diameter difference, ICA flow difference, ICA flow difference percentage, and product of bilateral ICA diameter and flow difference (ICAPDF) of each AA group exhibited significant differences. Among them, ICAPDF had the highest area under the ROC curve (AUC = 0.807) for discriminating the AA1 and AA2 groups from the others, followed by ICA diameter difference (AUC = 0.771), ICA flow difference percentage (AUC = 0.703), and ICA flow difference (AUC = 0.695) (Fig. 5a). For the prediction of A1 absence, ICAPDF and ICAdiameter difference exhibited even higher accuracy for discriminating the AA1 group from the other groups (Fig. 5b). The optimal cutoff value for bilateral A1 asymmetry ≥50% was a PDF = 4.31 with a sensitivity of 0.81 and specificity of 0.76.
Fig. 4 Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group
Fig. 5 ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

title

Results

sec

Vascular anatomy
The demographic data of the subjects are summarized in Table 1. All 210 subjects were asymptomatic HanChinese adults, and only 81 (38.6%) had complete symmetric of the COW. Seven subjects with bilateral FPCAs and symmetric A1s were not included in the symmetric group due to a lack of bilateral P1 segments. Sixtyseven subjects had asymmetric A1 segments (31.9% of all cases), including 19 (9%; AA1 group) with unilateral A1 aplasia, 33 (15.7%; AA2 group) with ≥50% A1 asymmetry, and 15 (7.1%; AA3 group) with < 50% A1 asymmetry.
Table 1 Subjects demographic data by Circle of Willis variants
All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820
aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs
Seventyeight subjects (37.1% of all cases) were included in the PA group, including 15 in the PA1 group (7.1%) with a unilateral FPCA and absent contralateral PcomAA, 45 in the PA2 group (21.4%) with ≥50% PcomA asymmetry, and 18 in the PA3 group (8.6%) with < 50% PcomA asymmetry. Twentythree subjects had both A1 and PcomA asymmetry. In these subjects, the dominant A1 was most likely to be on the same side as the nondominant PcomA (19 patients, P < 0.001, McNemar’s test). Only 4 subjects had the dominant A1 and dominant PcomA on the same side.

title

Vascular anatomy

p

The demographic data of the subjects are summarized in Table 1. All 210 subjects were asymptomatic HanChinese adults, and only 81 (38.6%) had complete symmetric of the COW. Seven subjects with bilateral FPCAs and symmetric A1s were not included in the symmetric group due to a lack of bilateral P1 segments. Sixtyseven subjects had asymmetric A1 segments (31.9% of all cases), including 19 (9%; AA1 group) with unilateral A1 aplasia, 33 (15.7%; AA2 group) with ≥50% A1 asymmetry, and 15 (7.1%; AA3 group) with < 50% A1 asymmetry.
Table 1 Subjects demographic data by Circle of Willis variants
All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820
aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs

tablewrap

Table 1 Subjects demographic data by Circle of Willis variants
All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820
aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs

label

Table 1

p

Subjects demographic data by Circle of Willis variants

caption

Subjects demographic data by Circle of Willis variants

table

All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c
AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue
Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)
Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507
Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588
Sex
Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262
Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)
Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494
Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543
Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820

tr

All Symmetrica A1 Asymmetry (AA group)b PcomA Asymmetry (PA group)c

th

All

th

Symmetrica

th

A1 Asymmetry (AA group)b

th

PcomA Asymmetry (PA group)c

tr

AA1 AA2 AA3 Pvalue PA1d PA2 PA3 Pvalue

th

AA1

th

AA2

th

AA3

th

Pvalue

th

PA1d

th

PA2

th

PA3

th

Pvalue

tr

Number of cases 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%)

td

Number of cases

td

210

td

81 (38.6%)

td

19 (9%)

td

33 (15.7%)

td

15 (7.1%)

td

15 (7.1%)

td

45 (21.4%)

td

18 (8.6%)

tr

Age (years) 53.9 ± 9.4 50.4 ± 9.3 52.6 ± 11.5 54.6 ± 10.1 49.9 ± 8.3 0.344 55.4 ± 7.9 53.3 ± 9.5 51.8 ± 7.0 0.507

td

Age (years)

td

53.9 ± 9.4

td

50.4 ± 9.3

td

52.6 ± 11.5

td

54.6 ± 10.1

td

49.9 ± 8.3

td

0.344

td

55.4 ± 7.9

td

53.3 ± 9.5

td

51.8 ± 7.0

td

0.507

tr

Rightside 6 (31.6%) 8 (24.2%) 7 (46.7%) 0.311 10 (66.7%) 29 (64.4%) 14 (77.8%) 0.588

td

Rightside

td

6 (31.6%)

td

8 (24.2%)

td

7 (46.7%)

td

0.311

td

10 (66.7%)

td

29 (64.4%)

td

14 (77.8%)

td

0.588

td

Sex

tr

Sex

tr

Female 77 (36.7%) 32 (39.5%) 7 (36.8%) 8 (24.2%) 4 (26.7%) 0.601 7 (46.7%) 15 (33.3%) 10 (55.6%) 0.262

td

Female

td

77 (36.7%)

td

32 (39.5%)

td

7 (36.8%)

td

8 (24.2%)

td

4 (26.7%)

td

0.601

td

7 (46.7%)

td

15 (33.3%)

td

10 (55.6%)

td

0.262

tr

Male 133 (63.3%) 49 (60.5%) 12 (63.2%) 25 (75.8%) 11 (73.3%) 8 (53.3%) 30 (66.7%) 8 (44.4%)

td

Male

td

133 (63.3%)

td

49 (60.5%)

td

12 (63.2%)

td

25 (75.8%)

td

11 (73.3%)

td

8 (53.3%)

td

30 (66.7%)

td

8 (44.4%)

tr

Height (cm) 165.2 ± 8.1 165.2 ± 8.7 166.7 ± 8.2 165.5 ± 6.6 166.1 ± 6.1 0.841 163.3 ± 7.8 165.6 ± 8.7 163.4 ± 7.6 0.494

td

Height (cm)

td

165.2 ± 8.1

td

165.2 ± 8.7

td

166.7 ± 8.2

td

165.5 ± 6.6

td

166.1 ± 6.1

td

0.841

td

163.3 ± 7.8

td

165.6 ± 8.7

td

163.4 ± 7.6

td

0.494

tr

Weight (Kg) 68.0 ± 13.2 69.6 ± 14.6 69.4 ± 13.7 65.8 ± 9.9 69.7 ± 13.7 0.428 64.9 ± 11.4 67.9 ± 13.5 64.5 ± 11.0 0.543

td

Weight (Kg)

td

68.0 ± 13.2

td

69.6 ± 14.6

td

69.4 ± 13.7

td

65.8 ± 9.9

td

69.7 ± 13.7

td

0.428

td

64.9 ± 11.4

td

67.9 ± 13.5

td

64.5 ± 11.0

td

0.543

tr

Heart rate (/min) 67.3 ± 10.0 66.8 ± 11.1 65.8 ± 10.4 68.3 ± 8.0 65.5 ±12.6 0.551 67.8 ± 8.2 68.4 ± 7.9 69.7 ± 12/0 0.820

td

Heart rate (/min)

td

67.3 ± 10.0

td

66.8 ± 11.1

td

65.8 ± 10.4

td

68.3 ± 8.0

td

65.5 ±12.6

td

0.551

td

67.8 ± 8.2

td

68.4 ± 7.9

td

69.7 ± 12/0

td

0.820

tablewrapfoot

aSeven subjects with bilateral FPCAs were excluded
bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3
cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3
dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs

p

aSeven subjects with bilateral FPCAs were excluded

p

bTwentythree patients in the AA group had PcomA asymmetry, including 2 PA1, 14 PA2, and 7 PA3

p

cTwentythree patients in the PA group had A1 asymmetry, including 5 AA1, 13 AA2, and 5 AA3

p

dThirtyseven subjects with 45 FPCA, with 20 rightside FPCA, 9 leftside FPCA, and 8 bilateral FPCAs

p

Seventyeight subjects (37.1% of all cases) were included in the PA group, including 15 in the PA1 group (7.1%) with a unilateral FPCA and absent contralateral PcomAA, 45 in the PA2 group (21.4%) with ≥50% PcomA asymmetry, and 18 in the PA3 group (8.6%) with < 50% PcomA asymmetry. Twentythree subjects had both A1 and PcomA asymmetry. In these subjects, the dominant A1 was most likely to be on the same side as the nondominant PcomA (19 patients, P < 0.001, McNemar’s test). Only 4 subjects had the dominant A1 and dominant PcomA on the same side.

sec

Comparison of vessel diameters and flow in different subgroups
AA group
When ACA asymmetry was present, there were significant differences in ICA diameter between dominant and nondominant sides in the AA1, AA2, and AA3 groups (Fig. 3a). Compared with the symmetric group, the AA1 and AA2 groups had a significantly larger ICA diameter on the dominant side and a significantly smaller ICA diameter on the nondominant side. Similarly, significant differences in bilateral ICA flow were also found in the AA1 and AA2 groups (Fig. 3b). The average bilateral ICA flow volume difference percentages of the AA1, AA2, and AA3 groups were 42.9, 30.7, and 29%, respectively (Table 2). A greater asymmetry between the bilateral A1 segments tended to be associated with a larger difference between the bilateral ICA flow volume.
Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)
Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852
PA group & FPCA
A significant difference in bilateral ICA diameter and flow was only found in the PA1 group with unilateral FPCA and no contralateral PcomA. If an FPCA was present, there was a trend for the ipsilateral ICA to have a larger diameter and higher flow volume as compared with the symmetric group (Fig. 3c, d). However, there was no significant difference between these 2 groups concerning diameter (P = 0.059) and flow volume (P = 0.085). On the other hand, the difference between ICA flow ipsilateral to the FPCA and in the symmetric group reached statistical significance (P = 0.049) after the exclusion of 15 patients with an FPCA with concomitant A1 asymmetry (Fig. 3e, f).

title

Comparison of vessel diameters and flow in different subgroups

sec

AA group
When ACA asymmetry was present, there were significant differences in ICA diameter between dominant and nondominant sides in the AA1, AA2, and AA3 groups (Fig. 3a). Compared with the symmetric group, the AA1 and AA2 groups had a significantly larger ICA diameter on the dominant side and a significantly smaller ICA diameter on the nondominant side. Similarly, significant differences in bilateral ICA flow were also found in the AA1 and AA2 groups (Fig. 3b). The average bilateral ICA flow volume difference percentages of the AA1, AA2, and AA3 groups were 42.9, 30.7, and 29%, respectively (Table 2). A greater asymmetry between the bilateral A1 segments tended to be associated with a larger difference between the bilateral ICA flow volume.
Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)
Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852

title

AA group

p

When ACA asymmetry was present, there were significant differences in ICA diameter between dominant and nondominant sides in the AA1, AA2, and AA3 groups (Fig. 3a). Compared with the symmetric group, the AA1 and AA2 groups had a significantly larger ICA diameter on the dominant side and a significantly smaller ICA diameter on the nondominant side. Similarly, significant differences in bilateral ICA flow were also found in the AA1 and AA2 groups (Fig. 3b). The average bilateral ICA flow volume difference percentages of the AA1, AA2, and AA3 groups were 42.9, 30.7, and 29%, respectively (Table 2). A greater asymmetry between the bilateral A1 segments tended to be associated with a larger difference between the bilateral ICA flow volume.
Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)
Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852

figure

Fig. 3 Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)

label

Fig. 3

p

Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)

caption

Vessel diameter and flow in each group of COW variants. (a) Diameter and (b) Flow volume of the nondominant and dominant ICAs in the different AA groups; (c) Diameter and (d) Flow volume of the nondominant and dominant ICAs in the different PA groups; (e) Diameter and (f) Flow volume of the nondominant and dominant ICAs in different PA groups without A1 asymmetry.* Significant difference between nondominant and dominant ICA in a certain subgroup (P < 0.05). # Significant difference between nondominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). & Significant difference between dominant ICA of a certain subgroup and ICA of the symmetric subgroup (P < 0.05). The cover bar indicates a significant difference between different COW subgroups. (P < 0.05)

tablewrap

Table 2 ICA flow and diameter parameters for each group of COW variants
All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852

label

Table 2

p

ICA flow and diameter parameters for each group of COW variants

caption

ICA flow and diameter parameters for each group of COW variants

table

All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)
AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue
Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)
ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993
ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655
ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943
ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852

tr

All Symmetric A1 Asymmetry (AA group) PcomA Asymmetry (PA group)

th

All

th

Symmetric

th

A1 Asymmetry (AA group)

th

PcomA Asymmetry (PA group)

tr

AA1 AA2 AA3 NonAA Pvalue PA1 PA2 PA3 NonPA Pvalue

th

AA1

th

AA2

th

AA3

th

NonAA

th

Pvalue

th

PA1

th

PA2

th

PA3

th

NonPA

th

Pvalue

tr

Number of subjects 210 81 (38.6%) 19 (9%) 33 (15.7%) 15 (7.1%) 143 (68.1%) 15 (7.1%) 45 (21.4%) 18 (8.6%) 132 (62.9%)

td

Number of subjects

td

210

td

81 (38.6%)

td

19 (9%)

td

33 (15.7%)

td

15 (7.1%)

td

143 (68.1%)

td

15 (7.1%)

td

45 (21.4%)

td

18 (8.6%)

td

132 (62.9%)

tr

ICAPDF 6.9 ± 16.6 −0.1 ± 7.9 30.8 ± 22.4 17.4 ± 20.3 9.5 ± 16.4 1.0 ± 9.1 < 0.0001 7.3 ± 14.8 6.2 ± 13.3 7.3 ± 22.5 7.0 ± 17.0 0.993

td

ICAPDF

td

6.9 ± 16.6

td

−0.1 ± 7.9

td

30.8 ± 22.4

td

17.4 ± 20.3

td

9.5 ± 16.4

td

1.0 ± 9.1

td

< 0.0001

td

7.3 ± 14.8

td

6.2 ± 13.3

td

7.3 ± 22.5

td

7.0 ± 17.0

td

0.993

tr

ICA diameter difference (mm) 0.37 ± 0.32 0.22 ± 0.22 0.76 ± 0.33 0.55 ± 0.38 0.48 ± 0.38 0.26 ± 0.22 < 0.0001 0.40 ± 0.29 0.41 ± 0.34 0.40 ± 0.37 0.34 ± 0.31 0.655

td

ICA diameter difference (mm)

td

0.37 ± 0.32

td

0.22 ± 0.22

td

0.76 ± 0.33

td

0.55 ± 0.38

td

0.48 ± 0.38

td

0.26 ± 0.22

td

< 0.0001

td

0.40 ± 0.29

td

0.41 ± 0.34

td

0.40 ± 0.37

td

0.34 ± 0.31

td

0.655

tr

ICA flow difference (ml/min) 65.9 ± 51.6 51.0 ± 38.8 124.6 ± 73.2 76.9 ± 45.8 76.2 ± 62.2 54.6 ± 42.0 < 0.0001 65.1 ± 47.3 64.0 ± 54.2 72.9 ± 53.4 65.6 ± 51.5 0.943

td

ICA flow difference (ml/min)

td

65.9 ± 51.6

td

51.0 ± 38.8

td

124.6 ± 73.2

td

76.9 ± 45.8

td

76.2 ± 62.2

td

54.6 ± 42.0

td

< 0.0001

td

65.1 ± 47.3

td

64.0 ± 54.2

td

72.9 ± 53.4

td

65.6 ± 51.5

td

0.943

tr

ICA flow difference percentage (%) 24.5 ± 17.8 19.6 ± 14.3 42.9 ± 24.1 30.7 ± 18.6 29.0 ± 19.0 20.2 ± 14.2 < 0.0001 25.0 ± 14.9 22.5 ± 16.0 25.5 ± 18.0 25.1 ± 18.7 0.852

td

ICA flow difference percentage (%)

td

24.5 ± 17.8

td

19.6 ± 14.3

td

42.9 ± 24.1

td

30.7 ± 18.6

td

29.0 ± 19.0

td

20.2 ± 14.2

td

< 0.0001

td

25.0 ± 14.9

td

22.5 ± 16.0

td

25.5 ± 18.0

td

25.1 ± 18.7

td

0.852

sec

PA group & FPCA
A significant difference in bilateral ICA diameter and flow was only found in the PA1 group with unilateral FPCA and no contralateral PcomA. If an FPCA was present, there was a trend for the ipsilateral ICA to have a larger diameter and higher flow volume as compared with the symmetric group (Fig. 3c, d). However, there was no significant difference between these 2 groups concerning diameter (P = 0.059) and flow volume (P = 0.085). On the other hand, the difference between ICA flow ipsilateral to the FPCA and in the symmetric group reached statistical significance (P = 0.049) after the exclusion of 15 patients with an FPCA with concomitant A1 asymmetry (Fig. 3e, f).

title

PA group & FPCA

p

A significant difference in bilateral ICA diameter and flow was only found in the PA1 group with unilateral FPCA and no contralateral PcomA. If an FPCA was present, there was a trend for the ipsilateral ICA to have a larger diameter and higher flow volume as compared with the symmetric group (Fig. 3c, d). However, there was no significant difference between these 2 groups concerning diameter (P = 0.059) and flow volume (P = 0.085). On the other hand, the difference between ICA flow ipsilateral to the FPCA and in the symmetric group reached statistical significance (P = 0.049) after the exclusion of 15 patients with an FPCA with concomitant A1 asymmetry (Fig. 3e, f).

sec

Association of ICA diameter with ICA flow
A moderately positive linear correlation between ICA diameter and ICA flow in the AA group (R2 = 0.238) was noted (Fig. 4a) According to the linear equation, there was a 62.6 ml increase in the ICA flow volume per 1 mm increase in the ICA diameter. Based on the average ICA flow volume of 265.9 ml/min in the AA group, it implied a change of 23.5% of the ICA flow volume per 1 mm change in the ICA diameter. On the other hand, no significant association was noted between ICA diameter and flow volume in either the PA (Fig. 4b) and symmetric groups (Fig. 4c). Carotid diameter and flow differences for each group of COW variants are shown in Table 2. All parameters, including ICA diameter difference, ICA flow difference, ICA flow difference percentage, and product of bilateral ICA diameter and flow difference (ICAPDF) of each AA group exhibited significant differences. Among them, ICAPDF had the highest area under the ROC curve (AUC = 0.807) for discriminating the AA1 and AA2 groups from the others, followed by ICA diameter difference (AUC = 0.771), ICA flow difference percentage (AUC = 0.703), and ICA flow difference (AUC = 0.695) (Fig. 5a). For the prediction of A1 absence, ICAPDF and ICAdiameter difference exhibited even higher accuracy for discriminating the AA1 group from the other groups (Fig. 5b). The optimal cutoff value for bilateral A1 asymmetry ≥50% was a PDF = 4.31 with a sensitivity of 0.81 and specificity of 0.76.
Fig. 4 Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group
Fig. 5 ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

title

Association of ICA diameter with ICA flow

p

A moderately positive linear correlation between ICA diameter and ICA flow in the AA group (R2 = 0.238) was noted (Fig. 4a) According to the linear equation, there was a 62.6 ml increase in the ICA flow volume per 1 mm increase in the ICA diameter. Based on the average ICA flow volume of 265.9 ml/min in the AA group, it implied a change of 23.5% of the ICA flow volume per 1 mm change in the ICA diameter. On the other hand, no significant association was noted between ICA diameter and flow volume in either the PA (Fig. 4b) and symmetric groups (Fig. 4c). Carotid diameter and flow differences for each group of COW variants are shown in Table 2. All parameters, including ICA diameter difference, ICA flow difference, ICA flow difference percentage, and product of bilateral ICA diameter and flow difference (ICAPDF) of each AA group exhibited significant differences. Among them, ICAPDF had the highest area under the ROC curve (AUC = 0.807) for discriminating the AA1 and AA2 groups from the others, followed by ICA diameter difference (AUC = 0.771), ICA flow difference percentage (AUC = 0.703), and ICA flow difference (AUC = 0.695) (Fig. 5a). For the prediction of A1 absence, ICAPDF and ICAdiameter difference exhibited even higher accuracy for discriminating the AA1 group from the other groups (Fig. 5b). The optimal cutoff value for bilateral A1 asymmetry ≥50% was a PDF = 4.31 with a sensitivity of 0.81 and specificity of 0.76.
Fig. 4 Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group
Fig. 5 ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

figure

Fig. 4 Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group

label

Fig. 4

p

Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group

caption

Linear regression analysis of ICA diameter and ICA flow in each group of COW variants. (a) AA group, (b) PA group, and (c) symmetric group

figure

Fig. 5 ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

label

Fig. 5

p

ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

caption

ROC curve of all parameters of ICA diameter and flow difference of different AA groups. (a) AA1 & AA2 vs others and (b) AA1 vs others

sec

Discussion
This study attempted to clarify the effect of asymmetric COW variants on carotid flow changes and proposed an easy estimate of the representative carotid flow volume. In the present study, 52 of the 210 cases (34.7%) had bilateral A1 asymmetry ≥50%, in whom there was significantly greater dominant ICA flow with larger dominant ICA diameter, and lower nondominant ICA flow with smaller nondominant ICA diameter, as compared with the symmetric group. There was a moderately positive association between ICA vessel diameter and ICA flow volume in the AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Moreover, an ICAPDF cutoff value of 4.31 was found to be a useful predictor of bilateral A1 asymmetry ≥50%.
While the COW serves as an important intracranial collateral pathway, there are multiple incomplete or asymmetric variants with variable prevalence according to different classification criteria, including A1 absence (2.6–15.4%; 9% in our study), A1 hypoplasia (2.6–28.9%; 15.7% in our study), true FPCA without a P1 segment (0.9–29.5%; 10.7% in our study), and FPCA with P1 hypoplasia (4.5–37.2%; 4.5% in our study) [9–12, 14, 15, 17, 18, 21–23]. In our study, we used a bilateral A1 and PcomA diameter ratio difference of 50% to define asymmetry rather than the usual criteria using an absolute vessel diameter of 1.0 mm as a cutoff value. Based on reports indicating the mean diameters of the A1 segment and the P2 segment are 2 mm [9, 11], a bilateral vessel diameter ratio difference of 50% equals a 1 mm cutoff value for the hypoplastic vessels. This vessel diameter ratio had been used in several studies focused on the effect of inflow inequality on cerebral aneurysms [23–26].
Our study showed a mean individual carotid flow difference percentage of 42.9% in the AA1 group. The result was consistent with several previous studies showing that the carotid flow ipsilateral to A1 aplasia is significantly lower than that of the contralateral side, with the flow difference percentage ranging from 34 to 50% [15–18]. Moreover, we also demonstrated that there was a significantly higher individual carotid flow difference percentage (30%) when A1 asymmetry was present. Since each A1 segment carries about 10% of the total brain flow to the ipsilateral hemisphere [17, 24], A1 segment asymmetry indicates redistribution of bilateral A1 flow and is crucial for computational hemodynamic studies for 2 reasons. First, A1 hypoplasia is associated with AcomA aneurysms [1, 13, 23, 27]. This relation can be explained by hemodynamic studies using either an experimental design with an A1 diameter ratio of ≥50% [25], or patientspecific 3D geometry with an unequal A1 inflow [28]. Both types of studies [25, 28] showed elevated intraaneurysmal wall shear stress in the setting of A1 hypoplasia or unequal flow that would trigger AcomA aneurysm formation. Our results further emphasized that A1 asymmetry, even with a diameter difference of < 50%, could also cause unequal inflow and might be associated with Acom aneurysm formation. Second, several studies have indicated the importance of using patientspecific inflow boundary conditions to obtain reliable computational fluid dynamic results, especially for aneurysms with more than 2 inflow avenues, such as AcomA aneurysms [3, 19, 25, 28, 29]. Venugopal et al. [19] showed that the wall shear stress distribution on an aneurysm surface is sensitive to the bilateral A1 flow ratio and flow rate by using different inflow boundary conditions for a patientspecific AcomA aneurysm geometry with an original flow ratio of 1.87. Similarly, Karmonik et al. [29] reported that changes in the flow distribution of bilateral A1 segments could cause variations of the average wall shear stress as high as 43%, again using a patientspecific AcomA aneurysm model with an original flow ratio of 1.72. On the other hand, blood flow changes of the parent artery would not change the characterization of the intraaneurysmal flow pattern substantially in the setting of a sidewall aneurysm/terminal aneurysm or AcomA aneurysm with relatively symmetric A1 segments [30]. In our study, we proposed a linear equation between the ipsilateral ICA diameter and ICA flow volume to provide a representative inflow boundary condition for the numerical simulation while A1 asymmetry is present.
As for PcomA asymmetry, only the PA1 group exhibited a significant carotid flow and diameter difference, but to a lesser extent of 25%. A significantly higher carotid flow with an FPCA compared with the symmetric group was only found after the exclusion of coincident A1 asymmetry. When A1 asymmetry occurred simultaneously with PcomA asymmetry (23 cases), a nondominant A1 (19 cases) was more frequently on the same side of the dominant PcomA. A PcomA usually serves as a conduit connecting the anterior and posterior circulation to provide a collateral pathway when there is proximal vessel comprise or there is an incomplete COW. The average net flow of a PcomA is usually low, and in an anterior to posterior direction, and accounts for about 5% of the ipsilateral carotid flow [31]. Considering all the aforementioned findings, it is reasonable that PcomA asymmetry has little influence on carotid flow changes.
In all AA groups and the PA1 group, there was a consistent relation between dominant and nondominant carotid diameter and flow, i.e., there was larger vessel diameter and higher carotid flow on the dominant side. This finding is consistent with a “formfunction” relation, wherein the form (anatomy: vessel radius) proportionately informs its function (physiology: blood flow). This concept has been extensively applied in the study of coronary artery disease [32, 33]. Similar findings have also been reported in studies of carotid flow, such as a small carotid diameter ipsilateral to A1 absence [21], and a linear relationship between whole brain volume and cerebral blood flow [16]. Cebral et al. [34] studied the flowarea relation in the carotid arteries of 11 healthy adults using the leastsquares method for curve fitting and reported an average relative error between the predicted and the measured ratio to be 20%. This relation is also reflected in our finding of a moderately positive linear correlation (Fig. 4a) between carotid diameter and carotid flow in the AA groups (r2 = 0.238). Despite a significant difference in carotid diameter and flow between each of the AA groups, there was also a large standard deviation in each parameter owing to large individual variances. To cancel out the individual variances (Table S1 in the supplement) and amplify the flowdiameter difference in the subjects with A1 asymmetry (Figure S1 in the supplement), we proposed the product of bilateral ICA diameter and flow difference (ICAPDF) as a potential discriminator. Recognition of an incomplete COW could offer stroke risk stratification in patients vulnerable to proximal artery compromise, such as those receiving cardiovascular surgery or carotid artery trapping [35].
Several limitations of our study should be addressed. First, the majority of subjects were middleaged (40–60 years old, 64%) healthy HanChinese adults. The progressive decline of cerebral blood flow at a rate of 3 ml per year has been also reported [36]. The estimate of carotid flow in younger or aged populations might need adjustment. Second, it’s hard to assure the bright vessel lumen on TOFMRA reflecting the “true” vessel size, especially when scanning a hypoplastic vessel. Moreover, the vessel diameter was calculated by only 1 reader. Thus, to minimize the measurement error of smallsized A1 segments and PcomA (< 3 mm), the vessel diameter ratio compared to the contralateral A1 or ipsilateral P2 segment, rather than the exact vessel diameter, was used for COW classification. It was reflected by the almost perfect reproducibility of categorical COW calcification in the 13 excluded subjects (Cohen K coefficient values of 0.85 ~ 0.96). Third, there was no validation performed for the estimate of carotid flow by the ipsilateral carotid diameter in A1 asymmetry and patients with specific neurovascular diseases such as cerebral aneurysms. Validation with another dataset, or with prospective study might be helpful.

title

Discussion

p

This study attempted to clarify the effect of asymmetric COW variants on carotid flow changes and proposed an easy estimate of the representative carotid flow volume. In the present study, 52 of the 210 cases (34.7%) had bilateral A1 asymmetry ≥50%, in whom there was significantly greater dominant ICA flow with larger dominant ICA diameter, and lower nondominant ICA flow with smaller nondominant ICA diameter, as compared with the symmetric group. There was a moderately positive association between ICA vessel diameter and ICA flow volume in the AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Moreover, an ICAPDF cutoff value of 4.31 was found to be a useful predictor of bilateral A1 asymmetry ≥50%.

p

While the COW serves as an important intracranial collateral pathway, there are multiple incomplete or asymmetric variants with variable prevalence according to different classification criteria, including A1 absence (2.6–15.4%; 9% in our study), A1 hypoplasia (2.6–28.9%; 15.7% in our study), true FPCA without a P1 segment (0.9–29.5%; 10.7% in our study), and FPCA with P1 hypoplasia (4.5–37.2%; 4.5% in our study) [9–12, 14, 15, 17, 18, 21–23]. In our study, we used a bilateral A1 and PcomA diameter ratio difference of 50% to define asymmetry rather than the usual criteria using an absolute vessel diameter of 1.0 mm as a cutoff value. Based on reports indicating the mean diameters of the A1 segment and the P2 segment are 2 mm [9, 11], a bilateral vessel diameter ratio difference of 50% equals a 1 mm cutoff value for the hypoplastic vessels. This vessel diameter ratio had been used in several studies focused on the effect of inflow inequality on cerebral aneurysms [23–26].

p

Our study showed a mean individual carotid flow difference percentage of 42.9% in the AA1 group. The result was consistent with several previous studies showing that the carotid flow ipsilateral to A1 aplasia is significantly lower than that of the contralateral side, with the flow difference percentage ranging from 34 to 50% [15–18]. Moreover, we also demonstrated that there was a significantly higher individual carotid flow difference percentage (30%) when A1 asymmetry was present. Since each A1 segment carries about 10% of the total brain flow to the ipsilateral hemisphere [17, 24], A1 segment asymmetry indicates redistribution of bilateral A1 flow and is crucial for computational hemodynamic studies for 2 reasons. First, A1 hypoplasia is associated with AcomA aneurysms [1, 13, 23, 27]. This relation can be explained by hemodynamic studies using either an experimental design with an A1 diameter ratio of ≥50% [25], or patientspecific 3D geometry with an unequal A1 inflow [28]. Both types of studies [25, 28] showed elevated intraaneurysmal wall shear stress in the setting of A1 hypoplasia or unequal flow that would trigger AcomA aneurysm formation. Our results further emphasized that A1 asymmetry, even with a diameter difference of < 50%, could also cause unequal inflow and might be associated with Acom aneurysm formation. Second, several studies have indicated the importance of using patientspecific inflow boundary conditions to obtain reliable computational fluid dynamic results, especially for aneurysms with more than 2 inflow avenues, such as AcomA aneurysms [3, 19, 25, 28, 29]. Venugopal et al. [19] showed that the wall shear stress distribution on an aneurysm surface is sensitive to the bilateral A1 flow ratio and flow rate by using different inflow boundary conditions for a patientspecific AcomA aneurysm geometry with an original flow ratio of 1.87. Similarly, Karmonik et al. [29] reported that changes in the flow distribution of bilateral A1 segments could cause variations of the average wall shear stress as high as 43%, again using a patientspecific AcomA aneurysm model with an original flow ratio of 1.72. On the other hand, blood flow changes of the parent artery would not change the characterization of the intraaneurysmal flow pattern substantially in the setting of a sidewall aneurysm/terminal aneurysm or AcomA aneurysm with relatively symmetric A1 segments [30]. In our study, we proposed a linear equation between the ipsilateral ICA diameter and ICA flow volume to provide a representative inflow boundary condition for the numerical simulation while A1 asymmetry is present.

p

As for PcomA asymmetry, only the PA1 group exhibited a significant carotid flow and diameter difference, but to a lesser extent of 25%. A significantly higher carotid flow with an FPCA compared with the symmetric group was only found after the exclusion of coincident A1 asymmetry. When A1 asymmetry occurred simultaneously with PcomA asymmetry (23 cases), a nondominant A1 (19 cases) was more frequently on the same side of the dominant PcomA. A PcomA usually serves as a conduit connecting the anterior and posterior circulation to provide a collateral pathway when there is proximal vessel comprise or there is an incomplete COW. The average net flow of a PcomA is usually low, and in an anterior to posterior direction, and accounts for about 5% of the ipsilateral carotid flow [31]. Considering all the aforementioned findings, it is reasonable that PcomA asymmetry has little influence on carotid flow changes.

p

In all AA groups and the PA1 group, there was a consistent relation between dominant and nondominant carotid diameter and flow, i.e., there was larger vessel diameter and higher carotid flow on the dominant side. This finding is consistent with a “formfunction” relation, wherein the form (anatomy: vessel radius) proportionately informs its function (physiology: blood flow). This concept has been extensively applied in the study of coronary artery disease [32, 33]. Similar findings have also been reported in studies of carotid flow, such as a small carotid diameter ipsilateral to A1 absence [21], and a linear relationship between whole brain volume and cerebral blood flow [16]. Cebral et al. [34] studied the flowarea relation in the carotid arteries of 11 healthy adults using the leastsquares method for curve fitting and reported an average relative error between the predicted and the measured ratio to be 20%. This relation is also reflected in our finding of a moderately positive linear correlation (Fig. 4a) between carotid diameter and carotid flow in the AA groups (r2 = 0.238). Despite a significant difference in carotid diameter and flow between each of the AA groups, there was also a large standard deviation in each parameter owing to large individual variances. To cancel out the individual variances (Table S1 in the supplement) and amplify the flowdiameter difference in the subjects with A1 asymmetry (Figure S1 in the supplement), we proposed the product of bilateral ICA diameter and flow difference (ICAPDF) as a potential discriminator. Recognition of an incomplete COW could offer stroke risk stratification in patients vulnerable to proximal artery compromise, such as those receiving cardiovascular surgery or carotid artery trapping [35].

p

Several limitations of our study should be addressed. First, the majority of subjects were middleaged (40–60 years old, 64%) healthy HanChinese adults. The progressive decline of cerebral blood flow at a rate of 3 ml per year has been also reported [36]. The estimate of carotid flow in younger or aged populations might need adjustment. Second, it’s hard to assure the bright vessel lumen on TOFMRA reflecting the “true” vessel size, especially when scanning a hypoplastic vessel. Moreover, the vessel diameter was calculated by only 1 reader. Thus, to minimize the measurement error of smallsized A1 segments and PcomA (< 3 mm), the vessel diameter ratio compared to the contralateral A1 or ipsilateral P2 segment, rather than the exact vessel diameter, was used for COW classification. It was reflected by the almost perfect reproducibility of categorical COW calcification in the 13 excluded subjects (Cohen K coefficient values of 0.85 ~ 0.96). Third, there was no validation performed for the estimate of carotid flow by the ipsilateral carotid diameter in A1 asymmetry and patients with specific neurovascular diseases such as cerebral aneurysms. Validation with another dataset, or with prospective study might be helpful.

sec

Conclusion
A1 asymmetry plays an important role in ICA flow distribution, contributing to bilateral unequal carotid inflow and significant carotid diameter difference. When A1 asymmetry is present, there is a moderately positive linear correlation between carotid diameter and carotid flow, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Our study improved the understanding of the association of bilateral ICA flow in healthy adults with asymmetric COW variants. Our results can potentially be applied to improve the accuracy of numerical simulation by the adjustment of the inflow boundary conditions according to the COW variants.

title

Conclusion

p

A1 asymmetry plays an important role in ICA flow distribution, contributing to bilateral unequal carotid inflow and significant carotid diameter difference. When A1 asymmetry is present, there is a moderately positive linear correlation between carotid diameter and carotid flow, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. Our study improved the understanding of the association of bilateral ICA flow in healthy adults with asymmetric COW variants. Our results can potentially be applied to improve the accuracy of numerical simulation by the adjustment of the inflow boundary conditions according to the COW variants.

sec

Supplementary information
Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.
Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

title

Supplementary information

p

Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.
Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

sec

Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.
Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

p

Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.

caption

Additional file 1: Figure S1.ICA diameter difference and ICA flow difference percentage for each AA subgroup and nonAA subgroup.

p

Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

caption

Additional file 2: Table S1. ICA flow & diameter parameters for each AA subgroup and nonAA subgroup.

back

Abbreviations
COW Circle of Willis
ICA Internal carotid artery
ACA Anterior cerebral artery
AcomA Anterior communicating artery
A1 The 1st segment of anterior cerebral artery
AA A1 asymmetry
PcomA Posterior communicating artery
P1 The 1st segment of posterior cerebral artery
PA P1 asymmetry
FPCA Fetal posterior cerebral artery
TOF Timeofflight
MRA Magnetic resonance angiography
TAV Timeaverage flow velocity
DRD Diameter ratio difference
ICAPDF Product of bilateral ICA diameter and flow volume difference
Publisher’s Note
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Supplementary information
Supplementary information accompanies this paper at 10.1186/s1288302001831z.
Acknowledgements
Not applicable.
Authors’ contributions
TW participated in the study design, image data acquisition and interpretation, and drafted the manuscript. TC participated in the image data acquisition and interpretation, and manuscript writing. CK participated in the image data acquisition, statistical analysis and manuscript writing. JC and CL participated in the study conception and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.
Funding
No funding was received.
Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
This retrospective study was approved by the institutional review board of the ChiMei Medical Center (IRB Serial No.:10707–007), and the need for informed consent was waived.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no conflict of interest.

title

Abbreviations

p

Circle of Willis

p

Internal carotid artery

p

Anterior cerebral artery

p

Anterior communicating artery

p

The 1st segment of anterior cerebral artery

p

A1 asymmetry

p

Posterior communicating artery

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The 1st segment of posterior cerebral artery

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P1 asymmetry

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Fetal posterior cerebral artery

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Timeofflight

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Magnetic resonance angiography

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Timeaverage flow velocity

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Diameter ratio difference

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Product of bilateral ICA diameter and flow volume difference

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Publisher’s Note

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Supplementary information
Supplementary information accompanies this paper at 10.1186/s1288302001831z.

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Supplementary information

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Supplementary information accompanies this paper at 10.1186/s1288302001831z.

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Acknowledgements
Not applicable.

title

Acknowledgements

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Not applicable.

notes

Authors’ contributions
TW participated in the study design, image data acquisition and interpretation, and drafted the manuscript. TC participated in the image data acquisition and interpretation, and manuscript writing. CK participated in the image data acquisition, statistical analysis and manuscript writing. JC and CL participated in the study conception and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.

title

Authors’ contributions

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TW participated in the study design, image data acquisition and interpretation, and drafted the manuscript. TC participated in the image data acquisition and interpretation, and manuscript writing. CK participated in the image data acquisition, statistical analysis and manuscript writing. JC and CL participated in the study conception and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.

notes

Funding
No funding was received.

title

Funding

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No funding was received.

notes

Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

title

Availability of data and materials

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The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

notes

Ethics approval and consent to participate
This retrospective study was approved by the institutional review board of the ChiMei Medical Center (IRB Serial No.:10707–007), and the need for informed consent was waived.

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Ethics approval and consent to participate

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This retrospective study was approved by the institutional review board of the ChiMei Medical Center (IRB Serial No.:10707–007), and the need for informed consent was waived.

notes

Consent for publication
Not applicable.

title

Consent for publication

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Not applicable.

notes

Competing interests
The authors declare that they have no conflict of interest.

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Competing interests

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The authors declare that they have no conflict of interest.
