European Journal of Radiology 155 (2022) 110501

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Association of contrast enhancement of proximal internal carotid artery

wall and champagne bottle neck sign with ipsilateral stroke in moyamoya
disease patients
Fei Zhou a, 1, Maoxue Wang a, 1, Lei Cao a, 1, Xueping Li a, Jiaming Lu a, Yongbo Yang b,
Jian Wang b, Xin Zhang a, *, Bing Zhang a, *
a
Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
b
Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

A R T I C L E I N F O A B S T R A C T

Keywords: Objective: To investigate the characteristics of the proximal internal carotid artery (ICA) and their relationships
Moyamoya disease with ipsilateral intracranial stroke in sufferers of moyamoya disease (MMD) with champagne bottle neck sign
Champagne bottle neck sign (CBNS).
Intracranial stroke
Patients and methods: Forty-four patients with MMD（mean age 43.98 ± 10.54 years, 21 males）confirmed by
Magnetic resonance vessel wall imaging
digital subtraction angiography were enrolled and carotid magnetic resonance vessel wall imaging was intro­
Internal carotid artery
duced in this study. CBNS was defined as the ratio of the diameters of proximal ICA to the common carotid artery
(CCA) (DpICA/CCA) < 0.5. The wall thickness and enhancement of the proximal ICA was measured on post­
contrast T1-VISTA images. The correlations between these characteristics of the proximal ICA and ipsilateral
intracranial stroke were analysed.
Results: Among the 44 patients with MMD, twelve patients (27.3 %) had bilateral CBNS and fourteen patients
(31.8 %) without CBNS. Compared with normal extracranial arteries, in arteries with CBNS, the proximal ICA
had a smaller diameter (3.03 ± 1.05 mm vs 3.95 ± 1.10 mm, p < 0.001), the maximum wall thickness of the
proximal ICA was thicker (1.34 ± 0.31 mm vs 1.06 ± 0.26 mm, p < 0.001), and arterial wall contrast
enhancement was more frequently observed (66.7 % vs 2 %, p = 0.001). Logistic regression analysis revealed
that the wall enhancement of the proximal ICA with CBNS (OR = 15.16, 95 % CI, 2.32–99.02; P = 0.005) was
independently associated with intracranial multiple lesions. The AUC of the wall enhancement of the proximal
ICA with CBNS was 0.79(P = 0.003).
Conclusions: Vessel wall enhancement of the proximal ICA with CBNS is independently associated with intra­
cranial stroke in the ipsilateral hemispheres of patients with MMD, particularly those with multiple lesions.

1. Introduction ischaemia of brain tissues and saccular aneurysms [4–6]. A previous

Moyamoya disease (MMD) is an uncommon but important cerebro­
vascular disorder. It is characterized by progressive bilateral occlusion
or stenosis of the distal portion of the ICA and the proximal portion of
the middle cerebral arteries (MCAs) and anterior cerebral arteries [1].
This occlusion may lead to ischaemic or haemorrhagic stroke and has
poor outcomes [2,3]. Clinically, the study of MMD patients having the
risk of intracranial stroke has mainly focused on intracranial charac­
teristics, such as the stenosis of blood vessels, which can lead to
study reported that MMD could affect arterial wall structure at multiple
foci, including the extracranial and intracranial arteries [7,8]. In 2006,
Yasakaet al [9] described the “champagne bottle neck sign” (CBNS), an
abrupt reduction of the diameter of the proximal ICA rapidly to less than
half of the diameter of the common carotid, which is considered an
important feature of the extracranial ICA in patients with MMD [9,10].
Although CBNS is prevalent in sufferers of MMD [11], the characteristics
of CBNS and its relationship with intracranial stroke are unknown.
Therefore, identifying the potential changes that could occur in the

* Corresponding authors at: Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
E-mail addresses: neuro_zx@163.com (X. Zhang), zhangbing_nanjing@nju.edu.cn (B. Zhang).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.ejrad.2022.110501
Received 23 April 2022; Received in revised form 10 August 2022; Accepted 22 August 2022
Available online 27 August 2022
0720-048X/© 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
F. Zhou et al.
vessel wall of the proximal ICA in MMD patients with CBNS is important
to both develop a treatment strategy prior to surgery and estimate the
prognosis of these patients.
Clinically, the gold standard of diagnosing MMD relies on digital
subtraction angiography (DSA) [1]. Although this technique shows the
morphology of blood vessels, it does not demonstrate the characteristics
of the vessel wall or the cause of luminal stenosis [12]. Vessel wall
magnetic resonance imaging (VW-MRI) has become a useful tool to
evaluate vascular disease in both intracranial and extracranial carotid
arteries, such as atherosclerosis, vasculitis, dissection and MMD
[13–16]. This technique can effectively describe arterial morphology
and compositional features. Recently, investigators have found that the
enhancement of the intracranial vessel wall is associated with acute
ischaemic infarction in patients with MMD [17].
The aim of our study is to explore the characteristics of the proximal
ICA and their relationships with ipsilateral intracranial stroke in suf­
ferers of MMD with CBNS. We hypothesized that stenosis and
enhancement of the ICA wall are more likely to lead to stroke.
2. Materials and methods
2.1. Patients
Patients with MMD confirmed by DSA and recent cerebrovascular
symptoms were recruited for this study. Inclusion criteria: (1) age from
18 to 80 years old, (2) neurovascular symptoms, including but not
limited to physical weakness, dizziness, headache and aphasia, etc., and
(3) no revascularization. The exclusion criteria were as follows: 1)
atherosclerotic plaque from the distal CCA to the proximal ICA as this
would influence CBNS measurement, 2) intracranial aneurysm, 3) po­
tential sources of cardioaortic embolism, and 4) contraindications to MR
imaging，and 5) patients with failure of renal function (glomerular
filtration rate < 60 mL/min). All patients underwent brain imaging and
extracranial 3D VW-MRI. Clinical information, including age, gender,
smoking (current or former), history of hypertension (defined as dia­
stolic blood pressure ≥ 90 mm Hg or systolic blood pressure ≥ 140 mm
Hg), hyperlipidaemia (defined as elevated concentrations of any or all of
the lipids in the plasma, such as low density lipoprotein (LDL) > 140
mg/dL, total cholesterol (TC) > 200 mg/dL, or triglycerides (TG) > 150
mg/dL), diabetes mellitus (fasting blood sugar level ≥ 126 mg/dL, 2-
hour oral glucose tolerance test result ≥ 200 mg/dL, or haemoglobin
A1c ≥ 6.5 %), was collected from clinical records. The study protocol
was approved by the local institutional review board prior to the initi­
ation of the study, and the written consent was obtained from all
subjects.
2.2. MRI protocol
MRI data were collected from a 3.0 Tesla MR scanner (Achieva TX,
Philips Medical Systems, The Netherlands) platform with a 16-channel
phased array head-neck coil. The following sequences and parameters:
diffusion-weighted imaging (DWI): time to repetition (TR)/time to echo
(TE) 2322/88 ms, flip angle (FA) 90◦ , field of view (FOV) 230 × 230
mm2, matrix size 152 × 121, and slice thickness 6 mm; T1W imaging:
TR/TE 250/2.3 ms, FA 75◦ , FOV 230 × 183 mm2, matrix size 256 × 163,
and slice thickness 6 mm; susceptibility-weighted imaging (SWI): TR/TE
24.2/15 ms, FA 15◦ , FOV 230 × 190 mm2, voxel size 0.6 × 0.6 × 1.2
mm3, and slice thickness 1.2 mm; and T2-weighted imaging: TR/TE
2223/80 ms, FA 90◦ , FOV 230 × 183 mm2, matrix size 328 × 267, and
slice thickness 6 mm. The intracranial and extracranial vessel walls were
imaged by using pre- and post-contrast T1W imaging with a sequence of
3D-improved motion-sensitized driven-equilibrium (iMSDE)-prepared
volumetric isotropic turbo spin-echo acquisition (VISTA) using the
following parameters: TR/TE 800/19 ms, FOV 200 × 180 × 40 mm3, FA
90◦ , and voxel size 0.6 × 0.6 × 0.6 mm3. Low refocusing flip-angles (50)
were used to increase flow-void effects and decrease image blurring.
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European Journal of Radiology 155 (2022) 110501
Postcontrast T1-VISTA images were acquired after gadolinium (Gd-
DTPA-BMA, Nycomed) contrast agent was administered intravenously
at a dose of 0.1 mmol/kg and the flow rate of 2 mL/s.
2.3. Image analysis
Two independent neuroradiologists (each with five years of experi­
ence) interpreted the vessel wall images with consensus blinded to
clinical information and conventional brain MR images. All manually
measured values in this article are the average of the values measured by
two observers. The segment of the ICA (most proximal to the carotid
bulb) was defined as proximal ICA. The diameter of the CCA (proximal
to bulbus) and the ICA (immediately distal to the bulbus) were measured
on both sides. A previous study demonstrated that luminal stenosis was
comparable after being measured by DSA and VW-MRI imaging [12].
The maximum wall thickness of the proximal ICA was measured by
using 3D T1-VISTA images on the Philips MR workstation (Philips
Extended MR WorkSpace 2.6.3.4, Best, The Netherlands). The most
stenotic position was observed in the sagittal view and the wall thickness
was measured at this position in the resliced axial images. The com­
parison of T1 pre-contrast and post-contrast images was performed to
evaluate the presence or absence of contrast-enhanced lesions in the
proximal ICA. The champagne bottle neck sign was defined as a luminal
diameter ICA/CCA ratio of < 0.5 [11](Figure S1). According to the
severity of intracranial diseases, they were classified into no lesions,
single infarction or single haemorrhage and multiple lesions. Acute
infarction was defined by DWI hyperintensity with low ADC values and
DWI hypointensity with high or equal ADC values was considered as
chronic infarction. Haemorrhage was recorded when lesions were
observed with hyperintensity on T1 WI images with hypointense rims
around the lesion on T2 WI images or hypointensity on SWI images.
According to patients’ clinical history and MR images, we defined the
multiple lesions as one of the following conditions: haemorrhage with
infarction, repeated haemorrhage, or recurrent infarction in ipsilateral
cerebral hemisphere.
2.4. Reproducibility study
All subjects were selected for inter-observer and intra-observer
reproducibility studies. One observer revaluated all the images again
after 1 month time interval, blinded to the results of the first round of
review to minimize memory bias. These indicators were measured by
another radiologist for inter-reader reproducibility analysis blinded to
the previous results reviewed by the first radiologist.
2.5. Statistical analysis
All variables are summarized as the mean ± SD or frequencies
(percentage). The independent-samples T test and the χ2 test were used
as appropriate to compare baseline characteristics. Logistic regression
analysis was introduced to calculate the odds ratio (OR) and corre­
sponding 95 % confidence interval (CI) The P value<0.05 was consid­
ered statistically significant. All statistical analyses were performed by
using SPSS 16.0 software (SPSS, Chicago, IL, USA).
3. Results
3.1. Clinical characteristics
From January 2016 to December 2016, 44 patients with MMD were
consecutively recruited into this study. The flow chart of patient
recruitment is shown in Figure S2. Among these patients, twelve (mean
age: 43.50 ± 12.05 years; six males) had bilateral CBNS, eighteen (mean
age: 45.95 ± 9.34 years; twelve males) had unilateral CBNS, and four­
teen (mean age: 41.18 ± 10.69 years; three males) didn’t have CBNS.
Sixteen patients went to hospital due to the extremity adynamia, ten
F. Zhou et al. European Journal of Radiology 155 (2022) 110501

with dizziness, twelve with headache, four with aphasia and two with Table 2
numbness. There were no significant differences in vascular risk factors Characteristics of extracranial vessel wall and cerebral diseases in the internal
between patients with and without CBNS (all p > 0.05). The clinical carotid artery with and without CBNS.
characteristics of these patients were detailed in Table 1. Mean ± SDorN (%) P Value

Arteries with Arteries without

3.2. Characteristics of extracranial arteries and cerebral diseases CBNS N = 48 CBNS N = 40

Diameter of pICA, mm 3.03 ± 1.05 3.95 ± 1.10 ＜0.001

Table 2 presented the results of extracranial VW-MRI findings and Diameter of CCA, mm 7.34 ± 2.39 6.54 ± 1.73 0.083
the characteristics of cerebral diseases on sides with normal arteries and Ratio of DpICA/CCA 0.41 ± 0.06 0.61 ± 0.09 ＜0.001
Contrast enhancement of 32(66.7) 8(2) ＜0.001
those with CBNS. Compared with extracranial arteries without CBNS, in pICA
arteries with CBNS, the proximal ICA was smaller (3.03 ± 1.05 vs 3.95 Wall thickness of pICA, mm 1.34 ± 0.31 1.06 ± 0.26 ＜0.001
± 1.10, p＜0.001), the maximum wall thickness of the proximal ICA was Cerebral diseases
thicker (1.34 ± 0.31 vs 1.06 ± 0.26, p＜0.001), and the presence of No lesions 12(25) 22(55) 0.004
Single infarction or Single 27(56.2) 17(42.5)
contrast-enhanced walls in the proximal ICA was more frequent (66.7 %
haemorrhage
vs 2 %, p = 0.001). Multiple lesions were more frequently found in the Multiple lesions 9(18.8) 1(2.5)
hemispheres with CBNS than those on normal sides (18.8 % vs 2.5 %, p
CBNS: champagne bottle neck sign; pICA: proximal internal carotid arteries;
= 0.004). There was no significant results be found in comparison the
ICA: internal carotid arteries; CCA: external carotid arteries; Multiple lesions
clinical characteristics between patients with and without intracranial
were defined as either haemorrhage with infarctions, repeated haemorrhage or
multiple lesions (Table S1). recurrent infarction.

3.3. Associations between characteristics of CBNS and different types of proximal ICA with CBNS was 0.79 (95 % CI 0.687–0.867, P < 0.001) to
cerebrovascular events discriminate the presence of multiple lesions in the ipsilateral petrous
ICA in sufferers of MMD (Fig. 2). Fig. 3 shows an example of a patient
The ratio of the DpICA/CCA diameters decreased as the severity of with significant stenosis, the wall enhancement in the proximal ICA as
intracranial diseases increased (p = 0.005). The prevalence of CBNS and well as multiple lesions in his ipsilateral hemisphere. Figure S3 shows
the enhancement observed in the proximal ICA in different intracranial another example of a patient with significant stenosis, the wall
disease groups were 35.3 % (12/34), 61.4 % (27/44), and 90 % (9/10), enhancement in the proximal ICA as well as repeat cerebral haemor­
respectively, and 23.5 % (8/34), 52.3 % (23/44), and 90 % (9/10), rhage in his ipsilateral hemisphere.
respectively, in the ipsilateral hemispheres (Fig. 1). As the prevalence of
CBNS (p = 0.004) and the enhancement in the proximal ICA (p < 0.001) 4. Reproducibility
increased, the severity of intracranial diseases in the ipsilateral hemi­
sphere also went up. Excellent inter-observer (ICC: 0.84–0.96) and intra-observer (ICC:
Univariate logistic regression analysis revealed that the ratio of the 0.78–0.94) agreements were found in measuring the characteristics of
DpICA/CCA diameters, enhancement of pICA, the presence of CBNS and extracranial arteries and cerebral diseases (Table S2).
enhancement of pICA with CBNS in discriminating presence of multiple
lesions in ipsilateral hemisphere were 4.88(95 % CI, 1.39–17.21; P = 5. Discussion
0.014), 13.65(95 % CI, 1.64–113.13; P = 0.015), 900(95 % CI,
1.09–74.47; P = 0.042), and 9.00(95 % CI, 1.77–45.59; P = 0.008). This study reveals the characteristics of the walls of extracranial
Logistic regression analysis revealed that after adjusting for the tradi­ arteries with CBNS in patients with MMD and its role in predicting the
tional risk factors, including age, gender, history of hypertension, stroke risk. We found that the proximal ICA vessel wall often showed
smoking, diabetes, and hyperlipemia the association between wall enhancement, its thickness increased, and luminal stenosis was common
enhancement in the proximal ICA with CBNS and the presence of mul­ in arteries with CBNS. Besides, they were significantly related to intra­
tiple lesions remained statistically significant (OR = 15.16, 95 % CI, cranial strokes, especially multiple lesions in ipsilateral hemispheres.
2.32–99.02; P = 0.005) (Table 3). The AUC of the enhancement in the Our findings suggest that compared with arteries without CBNS, the
ipsilateral carotid arteries with CBNS showing enhancement in the
Table 1 vessel wall may have a significantly higher risk of developing intracra­
Clinical characteristics of 44 patients included in this study. nial multiple lesions. The enhancement of the pICA with CBNS was
MMD patients, Mean ± SD or n (%) P independently associated with intracranial multiple lesions.
Total Without With With
Value In this study, CBNS was found to be frequent (54.5 %) in the carotid
(n = CBNS (n bilateral unilateral arteries of MMD patients, consistent with a previous study. Yasuda et al
44) = 14) CBNS (n = CBNS (n = reported that CBNS was found in 56 % of the carotid arteries of MMD
12) 18) patients [10]. In our study, we also found the similar results that CBNS
Gender, male 21 3(21.4) 6(50) 12(66.7) 0.150 indicated a sharp reduction in the internal diameter of the proximal ICA
(47.7) by HR-VWI [9,10]. It has been shown that at the carotid bifurcation,
Age, years 43.98 41.18 ± 43.50 ± 45.95 ± 0.491
there is a transitional zone between the muscular portion (>5 mm distal
± 10.69 12.05 9.34
10.54 to the bifurcation) and elastic portion (>5 mm proximal to the bifur­
Vascular risk cation) of the carotid artery [18,19]. Investigators have speculated that
factors the muscular portion is more susceptible than the elastic portion because
Current smoker 9 1(9.0) 4(28.6) 4(21.1) 0.486 of its thinner intimal membrane [18]. Therefore, narrowness of the
(20.5)
Diabetes mellitus 4(9.1) 0(0) 2(14.3) 2(10.5) 0.448
proximal ICA above the bulb results in CBNS. We also found that the
Hypertension 14 3(27.3) 5(35.7) 6(31.6) 0.903 enhancement and thickening of the proximal ICA vessel wall appeared
(31.8) more frequently in arteries with CBNS than those without CBNS. In
Hyperlipidaemia 10 4(36.4) 2(14.3) 4(21.1) 0.414 recent studies, authors have speculated that CBNS may be a represen­
(22.7)
tative feature of this disease and may be caused by vasculitis in the
CBNS: champagne bottle neck sign; pICA: proximal internal carotid arteries. proximal ICA [20–22]. Hiroto Ito et al [22] found that the difference

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F. Zhou et al. European Journal of Radiology 155 (2022) 110501

Fig. 1. Characteristics of pICA among different intracranial strokes in ipsilateral hemispheres. Grade 0: No lesions; Grade 1: Single infarction or Single haemorrhage;
Grade 2: Multiple lesions.CBNS: champagne bottle neck sign; pICA: proximal internal carotid artery; CCA: common carotid artery; Multiple lesions were defined as
either haemorrhage with infarctions, repeated haemorrhage or recurrent infarction. **: p＜0.01.

Table 3
Association of multiple lesions with vascular characteristics.
Logistic analysis

OR (95 % CI) P

Before adjustmenta
Diameter of pICA 0.54(0.29–1.02) 0.057
Diameter of CCA 0.95(0.69–1.30) 0.736
1 / Ratio of DpICA/CCA 4.88(1.39–17.21) 0.014
Enhancement of pICA 13.65(1.64–113.13) 0.015
Wall thickness of pICA, 4.43(0.62–31.87) 0.139
The presence of CBNS 9.00(1.09–74.47) 0.042
Enhancement of pICA with CBNS 9.00(1.77–45.59) 0.008
After adjustmenta
Diameter of pICA 0.51(0.25–1.05) 0.067
Diameter of CCA 1.01(0.73–1.42) 0.94
1 / Ratio of DpICA/CCA 7.92(1.74–36.05) 0.007
Fig. 2. Areas under the ROC curves for the three prediction models in the
Enhancement of pICA 14.1(1.57–125.82) 0.018
validation data for lesions. The AUC of the enhancement of the proximal ICA
Wall thickness of pICA, 5.77(0.55–61.09) 0.145
The presence of CBNS 24.39(1.86–319.99) 0.015 with CBNS was most advantageous for discriminating the presence of multiple
Enhancement of pICA with CBNS 15.16(2.32–99.02) 0.005 lesions in the ipsilateral petrous ICA in MMD patients.

CBNS: champagne bottle neck sign; pICA: proximal internal carotid artery; CCA:
external carotid artery; Multiple lesions were defined as either haemorrhage
with infarctions, repeated haemorrhage or recurrent infarction. aThe logistic
analysis was conducted before and after adjusting for the traditional risk factors,
including age, gender, history of hypertension, smoking, diabetes, and
hyperlipemia.
between the thickness and enhancement of the walls between vessels
showing CBNS and normal vessels seemed to become gradually clearer
in a progressive case of moyamoya vasculopathy (MMV) associated with
Grave’s disease (GD). Investigators have also shown that there is a
correlation between vessel wall thickness and inflammation [20,21].
These findings seem to lead to the formation of stenosis in the extra­
cranial ICA and CBNS in MMD and reflect the pathological state of the
extracranial ICA. Hence, future studies should investigate the histology
of CBNS in patients with MMD.
We found that CBNS was significantly associated with intracranial
stroke in the ipsilateral hemisphere and that the ratio of DpICA/CCA
decreased as the severity degree and grade of intracranial diseases
increased. The relationship between CBNS and the presence of clinical
symptoms has been seldom comprehensively reported. Yasaka et al [11]
reported that haemorrhagic events were observed in 13.3 % of hemi­
spheres with CBNS. Wang J et al [23] found that CBNS was significantly
associated with intracranial haemorrhage in the ipsilateral hemisphere
in patients with MMD. Our study clearly demonstrates that intracranial
stroke is more frequent in hemispheres with CBNS than those without
CBNS (75 % vs 45 %). In previous reports, authors speculated that CBNS
was related to impaired cerebral vasoreactivity, which was itself
responsible for the occurrence and recurrence of stroke [10]. We also
found that multiple lesions became more prevalent as the DpICA/CCA

4
F. Zhou et al.
ratio decreased.
Furthermore, we found that the enhancement of the proximal ICA
wall with CBNS was independently associated with multiple lesions in
the ipsilateral hemisphere. The main enhancement of the arterial wall
mechanisms includes a series of inflammatory activities and prolifera­
tion of the vasa vasorum that lead to an increase in the permeability of
vessel walls [24]. Some studies have shown that the characteristics of
intracranial vessel walls showing enhancement may give important
insight into ischaemic stroke risk factors [17]. In our study, arterial wall
thickening with enhancement was observed in the proximal ICA.
Mounting evidence indicates that the progression of MMD is accompa­
nied by systemic inflammation. Some studies have shown that in the
retina, angiogenetic factors, such as monocyte chemoattractant protein-
1, vascular endothelial growth factor (VEGF) and other inflammatory
cytokines, are more highly expressed in the endothelia of moyamoya-
affected arteries than in those of normal arteries [25,26]. These results
reflect the presence of active angiogenetic processes and inflammation
in the enhanced vessel wall in patients with MMD. X. Chen et al also
found the proximal internal carotid artery luminal narrowing is inde­
pendently associated with diffuse wall thickening in the ipsilateral
petrous internal carotid artery in patients with MMD which also
confirmed that MMD is a multi-vessel involvement disease, not only the
intracranial segment. These factors caused inflammatory and hemody­
namic changes of the internal carotid artery, which further may led to
the occurrence of cerebrovascular events [20–22]. Based on the results
of this study, we suggest that the thickness and enhancement of the
proximal ICA and the presence of CBNS among MMD patients could be
explained by systemic inflammation and that the characteristics of CBNS
might be an effective indicator of intracranial stroke progression in the
future.
There are several limitations in this study. Firstly, this is a cross-
sectional, single-centre, retrospective study with a small sample size
and some age bias. Future studies with larger sample sizes and follow-up
data will be warranted. Secondly, this study investigated the
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European Journal of Radiology 155 (2022) 110501
Fig. 3. Example of a patient with moyamoya
disease with multiple events and carotid ar­
tery champagne bottle neck sign. A 50-year-
old female patient with MMD. (A) VW-MRI
image showing significant stenosis in the
right proximal ICA, and the ratio of the
luminal diameter of the internal carotid ar­
tery/common carotid artery was 0.32.
Concentric wall thickening (wall thickness =
1.37 mm) and enhancement was seen in the
right proximal ICA on axial views of the T1W
and CE-T1W images (B, C). Ischaemic
infarction of the right frontal lobe on FLAIR
images and remote cerebral haemorrhage of
the right basal ganglia region on T2WI im­
ages (D, E).
relationship between intracranial symptoms and CBNS, however, it
didn’t penetrate the stage of the intracranial moyamoya vessels. Thirdly,
this study lacked histological validation of vessel wall enhancement
with thickening in the proximal ICA, thus it couldn’t t be validated.
Fourthly, in this study, the 16 channel Head-neck coil had a slightly
poorer image quality than the 8-channel coil for extracranial carotid
artery vessel wall imaging. In subsequent experiments, we will obtain
better images and more accurate data by the 8-channel coil.
6. Conclusion
Vessel wall enhancement of the proximal ICA accompanied with
CBNS is independently associated with intracranial stroke in the ipsi­
lateral hemisphere in patients with MMD, particularly those with mul­
tiple lesions.
Compliance with ethical standards
Funding
This study was funded by grants from the National Natural Science
Foundation of China (81720108022 B.Z., 81971596, X.Z., 82001793,
JM.L.), Supported by the Fundamental Research Funds for the Central
Universities, Nanjing University, 2020-021414380462; The social
development project of science and technology project in Jiangsu
Province (BE2017707); Key medical talents of the Jiangsu province, the
“13th Five-Year” health promotion project of the Jiangsu province
(ZDRCA2016064); Jiangsu Provincial Key Medical Discipline (Labora­
tory) (ZDXKA2016020); the project of the sixth peak of talented people
(WSN -138).The funders had no role in the study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
Code availability
All software application and custom code support our published
claims and comply with field standards.
Author Contributions
F. Zhou et al.
FZ contributed to the study design and statistical analyses and wrote
the manuscript. MW and LC contributed to the imaging processing and
reviewed the manuscript. XL and JL contributed to the revision of the
manuscript. YY and JW participated in discussions of the results and
reviewed the manuscript. XZ and BZ supervised the entire study and
reviewed the manuscript. BZ is the guarantor of this work and, as such,
had full access to all the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Ethical approval
We declare that all procedures performed in studies involving human
participants were in accordance with the ethical standards of the insti­
tutional and/or national research committee and with the 1964 Helsinki
declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants
included in the study.
Consent for publication
All authors agree to publish the paper.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Data Availability Statement.
All data and materials support our published claims and comply with
field standards.
Acknowledgements
This work was supported by the National Natural Science Foundation
of China (81720108022, 81971596, 82001793); Supported by the
Fundamental Research Funds for the Central Universities, Nanjing
University, 2020-021414380462; The social development project of
science and technology project in Jiangsu Province (BE2017707); Key
medical talents of the Jiangsu province, the “13th Five-Year” health
promotion project of the Jiangsu province (ZDRCA2016064); Jiangsu
Provincial Key Medical Discipline (Laboratory) (ZDXKA2016020); the
project of the sixth peak of talented people (WSN -138).The funders had
no role in the study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ejrad.2022.110501.
References
[1] J. Suzuki, A. Takaku, Cerebrovascular “moyamoya” disease. Disease showing
abnormal net-like vessels in base of brain, Arch. Neurol. 20 (3) (1969) 288–299.
[2] R.M. Scott, E.R. Smith, Moyamoya disease and moyamoya syndrome, New England
J. Med. 360 (12) (2009) 1226–1237.
[3] K. Wakai, A. Tamakoshi, K. Ikezaki, M. Fukui, T. Kawamura, R. Aoki, M. Kojima,
Y. Lin, Y. Ohno, Epidemiological features of moyamoya disease in Japan: findings
from a nationwide survey, Clin. Neurol. Neurosurg. 99 (Suppl 2) (1997) S1–S5.
[4] K. Kazumata, M. Ito, K. Tokairin, Y. Ito, K. Houkin, N. Nakayama, S. Kuroda,
T. Ishikawa, H. Kamiyama, The frequency of postoperative stroke in moyamoya
disease following combined revascularization: a single-university series and
systematic review, J. Neurosurg. 121 (2) (2014) 432–440.
[5] W. Ni, H. Jiang, B. Xu, Y. Lei, H. Yang, J. Su, Y. Gu, Y. Mao, Treatment of
aneurysms in patients with moyamoya disease: a 10-year single-center experience,
J. Neurosurg. 128 (6) (2018) 1813–1822.
European Journal of Radiology 155 (2022) 110501
[6] L.-B. Yu, Q. Zhang, Z.-Y. Shi, M.-Q. Wang, D. Zhang, High-resolution Magnetic
Resonance Imaging of Moyamoya Disease, Chinese Med. J. 128 (23) (2015)
3231–3237.
[7] M. Kaczorowska, S. Jóźwiak, M. Litwin, T. Kmieć, D. Kuczyński, E. Jurkiewicz,
I. Kościerza, Moyamoya disease associated with stenosis of extracranial arteries: a
case report and review of the literature, Neurologia i neurochirurgia polska 39 (3)
(2005) 242–246.
[8] O. Togao, F. Mihara, T. Yoshiura, A. Tanaka, Y. Kuwabara, T. Morioka,
T. Matsushima, T. Sasaki, H. Honda, Prevalence of stenoocclusive lesions in the
renal and abdominal arteries in moyamoya disease, AJR Am. J. Roentgenol. 183
(1) (2004) 119–122.
[9] T. Shimogawa, T. Morioka, T. Sayama, T. Hamamura, C. Yasuda, S. Arakawa,
Champagne bottle neck sign in a patient with Moyamoya syndrome, World J. Clin.
Cases 2 (9) (2014) 474–477.
[10] C. Yasuda, S. Arakawa, T. Shimogawa, Y. Kanazawa, T. Sayama, S. Haga,
T. Morioka, Clinical Significance of the Champagne Bottle Neck Sign in the
Extracranial Carotid Arteries of Patients with Moyamoya Disease AJNR, Am. J.
Neuroradiol. 37 (10) (2016) 1898–1902.
[11] M. Yasaka, T. Ogata, K. Yasumori, T. Inoue, Y. Okada, Bottle neck sign of the
proximal portion of the internal carotid artery in moyamoya disease, J. Ultrasound.
Med. 25 (12) (2006) 1547–1554.
[12] H. Zhao, J. Wang, X. Liu, X. Zhao, D.S. Hippe, Y. Cao, J. Wan, C. Yuan, J. Xu,
Assessment of carotid artery atherosclerotic disease by using three-dimensional fast
black-blood MR imaging: comparison with DSA, Radiology 274 (2) (2015)
508–516.
[13] G.H. Chung, H.S. Kwak, S.B. Hwang, G.Y. Jin, High resolution MR imaging in
patients with symptomatic middle cerebral artery stenosis, Eur. J. Radiol. 81 (12)
(2012) 4069–4074.
[14] B.A. Wasserman, A.R. Sharrett, S. Lai, A.S. Gomes, M. Cushman, A.R. Folsom, D.
E. Bild, R.A. Kronmal, S. Sinha, D.A. Bluemke, Risk factor associations with the
presence of a lipid core in carotid plaque of asymptomatic individuals using high-
resolution MRI: the multi-ethnic study of atherosclerosis (MESA), Stroke 39 (2)
(2008) 329–335.
[15] Y. Xu, C. Yuan, Z. Zhou, L. He, D. Mi, R. Li, Y. Cui, Y. Wang, Y. Wang, G. Liu,
Z. Zheng, X. Zhao, Co-existing intracranial and extracranial carotid artery
atherosclerotic plaques and recurrent stroke risk: a three-dimensional
multicontrast cardiovascular magnetic resonance study, J. Cardiovasc. Magn.
Reson. 18 (1) (2016) 90.
[16] Y.J. Kim, D.H. Lee, J.Y. Kwon, D.W. Kang, D.C. Suh, J.S. Kim, S.U. Kwon, High
resolution MRI difference between moyamoya disease and intracranial
atherosclerosis, Eur. J. Neurol. 20 (9) (2013) 1311–1318.
[17] M. Wang, Y. Yang, F. Zhou, M. Li, R. Liu, M. Guan, R. Li, L. He, Y. Xu, B. Zhang,
B. Zhu, X. Zhao, The Contrast Enhancement of Intracranial Arterial Wall on High-
resolution MRI and Its Clinical Relevance in Patients with Moyamoya
Vasculopathy, Sci. Rep. 7 (2017) 44264.
[18] E. Hori, N. Hayashi, H. Hamada, T. Masuoka, N. Kuwayama, Y. Hirashima,
H. Origasa, O. Ohtani, S. Endo, A development of atheromatous plaque is restricted
by characteristic arterial wall structure at the carotid bifurcation, Surg Neurol 69
(6) (2008) 586–591.
[19] J. Janzen, P. Lanzer, K. Rothenberger-Janzen, P.N. Vuong, Variable extension of
the transitional zone in the medial structure of carotid artery tripod, Vasa 30 (2)
(2001) 101–106.
[20] X. Chen, J. Wang, Y. Liu, Y. Yang, F. Zhou, X. Li, B. Zhang, X. Zhao, Proximal
internal carotid artery stenosis associates with diffuse wall thickening in petrous
arterial segment of moyamoya disease patients: a three-dimensional magnetic
resonance vessel wall imaging study, Neuroradiology 61 (1) (2019) 29–36.
[21] X. Chen, H. Zhao, Z. Chen, H. Qiao, Y. Cui, D. Li, Z. Zhou, L. He, R. Li, C. Yuan,
X. Zhao, Association between proximal internal carotid artery steno-occlusive
disease and diffuse wall thickening in its petrous segment: a magnetic resonance
vessel wall imaging study, Neuroradiology 59 (5) (2017) 485–490.
[22] H. Ito, S. Yokoi, K. Yokoyama, T. Asai, K. Uda, Y. Araki, S. Takasu, R. Kobayashi,
H. Okada, S. Okuda, Progressive stenosis and radiological findings of vasculitis
over the entire internal carotid artery in moyamoya vasculopathy associated with
graves’ disease: a case report and review of the literature, BMC Neurol. 19 (1)
(2019) 34.
[23] J. Wang, G. Chen, Y. Yang, B. Zhang, Z. Jia, P. Gu, D. Wei, J. Ji, W. Hu, X. Zhao,
Association Between Champagne Bottle Neck Sign of Internal Carotid Artery and
Ipsilateral Hemorrhagic Stroke in Patients with Moyamoya Disease, World
Neurosurg. 118 (2018) e18–e24.
[24] S. Aoki, I. Shirouzu, Y. Sasaki, T. Okubo, N. Hayashi, T. Machida, E. Hoshi,
K. Suzuki, N. Funada, T. Araki, et al., Enhancement of the intracranial arterial wall
at MR imaging: relationship to cerebral atherosclerosis, Radiology 194 (2) (1995)
477–481.
[25] O.Y. Bang, M. Fujimura, S.-K. Kim, The Pathophysiology of Moyamoya Disease: An
Update, J. Stroke 18 (1) (2016) 12–20.
[26] J. Chmelova, Z. Kolar, V. Prochazka, R. Curik, J. Dvorackova, P. Sirucek, O. Kraft,
T. Hrbac, Moyamoya disease is associated with endothelial activity detected by
anti-nestin antibody, Biomed. Pap Med. Fac. Univ. Palacky Olomouc Czech Repub
154 (2) (2010) 159–162.