ORIGINAL PAPER

Digital Subtraction Angiography Imaging Characteristicsof Patients with Extra–Intracranial Atherosclerosis and ItsRelationship to Stroke

Juan Liu • Xiao-Jun Jia • Yan-Jiang Wang •

Meng Zhang • Tao Zhang • Hua-Dong Zhou

� Springer Science+Business Media New York 2014

Abstract To investigate the angiographic characteristics

and clinical features in patients with suspected extra–

intracranial atherosclerosis in a large cohort of Chinese

population. On the basis of digital subtraction angiography

characteristics, pathological morphology of extra–intra-

cranial atherosclerosis was divided into tortuosity, kink-

ing, coiling, and stenosis in 2,218 individuals aged

45–89 years. The degree of stenosis was further divided

into low-grade (\30 %), intermediate-grade (30–69 %),

and high-grade stenosis (C70 %). Clinical manifestations

were divided into transient ischemic attack, cerebral

infarction and cerebral hemorrhage. The prevalence of

tortuosity and stenosis were significantly higher in the

extracranial arterial system than that of intracranial arterial

system. The prevalence of tortuosity and kinking were

significantly higher on the left side than the right side. The

prevalence of mild and moderate stenosis in the internal

carotid artery was significantly higher in the left side than

the right side. The incidence of cerebral infarction was

significantly higher in the internal carotid arterial (ICA)

system than the vertebrobasilar arterial (VBA) system.

Tortuosity is a common carotid abnormality in the Chi-

nese population. The prevalence of ICA tortuosity is

higher than that of VBA. The incidence of cerebral

infarction in each atherosclerosis group was significantly

higher in ICA than that of VBA. The prevalence of stroke

is higher in the ICA system than the VBA system.

Kinkings and coilings may not have a clinical significance

if these lesions are not associated with atheromatous

plaques or carotid stenosis.

Keywords Extra–intracranial atherosclerosis � Digital

subtraction angiography � Stroke

Introduction

Cerebrovascular disease is the leading cause of disability

in the adult population worldwide. Extra–intracranial

atherosclerosis is an important underlying pathological

basis for cerebrovascular accidents [1, 2]. Arterial tortu-

osity, kinking, coiling, and stenosis are the most common

lesions of the extra and intracranial vessels. Previous

studies suggested that variations of the internal carotid

artery occur in approximately 10–40 % of the population.

In early angiography and postmortem reports, arterial

variations have been classified as coiling, kinking, and

tortuosity. Although the exact cause and natural history of

kinking, coiling, and tortuosities of cerebral vessels are

not clear, atherosclerosis is believed to be the underlying

cause of tortuosity and kinking. Currently, digital sub-

traction angiography (DSA) is the gold standard for the

evaluation of cerebral vasculatures. DSA provides essen-

tial information regarding hemodynamic status and col-

lateral circulation in patients with stroke. It is an ideal

imaging method of choice for diagnosis of cerebrovascular

disorders. Imaging study of extra- and intracranial ath-

erosclerosis with DSA is important for understanding of

the pathophysiology of cerebrovascular diseases. It also

helps with therapeutic decision making in triage patients

for medical treatment and surgical/interventional therapy.

Investigation of extra- and intracranial arterial coiling,

Juan Liu and Xiao-Jun Jia have contributed equally.

J. Liu � X.-J. Jia � Y.-J. Wang � M. Zhang � T. Zhang �H.-D. Zhou (&)

Department of Neurology, Daping Hospital, Third Military

Medical University, Chongqing, China

e-mail: zhouhuad@163.com

123

Cell Biochem Biophys

DOI 10.1007/s12013-014-9839-1

kinking, tortuosity, and stenosis may contribute to the

diagnosis and treatment of extra–intracranial atheroscle-

rosis [3, 4].

The purpose of our study was to determine the preva-

lence of extra–intracranial atherosclerosis by using DSA.

The clinical profiles of the patients were correlated with

angiographic findings in our case cohort.

Materials and Methods

Subjects

The present study was approved by the Ethics Committee

of the Third Military Medical University. We retrospec-

tively examined the DSA images of patients with suspected

stroke, who underwent cerebral angiography in the

department of neurology at Da Ping Hospital between

January 2006 and December 2008. Patients underwent

DSA if they had signs or symptoms suggestive of stroke.

All patients had CT or MRI scan before DSA examination.

DSA was performed in those with the diagnosis of stroke

based on CT or MRI findings. Patients were excluded from

the study if they were diagnosed of stroke mimics.

DSA Analysis and Interpretation

Three- or four-vessel DSA was performed via a transfe-

moral approach under local anesthesia. DSA was per-

formed by selective injection of 8–10-mL contrast

material in the internal carotid and vertebral arteries. A

standard projection format, including anteroposterior,

lateral and oblique views, was routinely obtained. DSA

images were sent through picture archiving and com-

munication systems (PACS) and viewed on the neurology

workstation. The extra- and intracranial atherosclerosis

lesions were classified into four categories: tortuosity,

kinking, coiling, and stenosis. Tortuosity was character-

ized by a C-shaped elongation and generalized tortuosity

of the cerebral vessels. Kinking was defined as elonga-

tion and angulation of blood vessels. Coiling was defined

as elongation of blood vessels in a S-shaped circular

configuration [5]. Arterial stenosis was documented

according to the North American Symptomatic Carotid

Endarterectomy (NASCET) trial measurements [6]. The

narrowest diameter (N) of the stenosis lumen is compared

with the patent luminal diameter (D) of the internal

carotid artery. The percentage of stenosis was calculated

by using the formula: Stenosis = (1 – N/D) 100. Ste-

noses were classified as mild (0–29 %), moderate

(30–69 %), or severe (70–99 %) according to the NAS-

CET criteria. Two experienced neurologists (Juan Liu

and Xiao-Jun Jia, with 10 and 15 years experience in

vascular imaging) who were blinded to the clinical

information independently assessed all the DSA images.

If the interpreters had disagreement, they discussed until

a consensus was reached. The reviewers had to assess

DSA images for the presence of intra- and extracranial

elongation (tortuosity, kinking, coiling) and the degree of

stenosis. The degree of stenosis was measured by the

internal digital caliber and documented. In evaluation of

the vascular lesions, the internal carotid artery system

and vertebrobasilar artery (VBA) system were indepen-

dently assessed and recorded.

Statistical Analysis

Statistical data were analyzed using the SPSS package

(Version 10.0; SPSS Inc., 2010). Group comparisons were

made by using Student’s t test. For differences in cate-

gorical variables, Chi square tests were performed. A

P value of \0.05 was considered statistically significant.

Results

Baseline Clinical Profiles

A total of 2,218 patients (1,475 male; 743 female) were

included in our study. The average patient age was

66.9 ± 7.4 years. Of the 2,218 patients; 1,816 (81.9 %)

patients (1,213 male; 603 female) had arterial atheroscle-

rosis on DSA exam.

DSA Characteristics of Patients with Atherosclerosis

Of the 1,816 patients with intra- and extracranial athero-

sclerosis, tortuosity is the most common type of vascular

abnormalities, which accounted for 59.3 % of cases. The

highest prevalence of atherosclerosis was observed in the

60–4 years age group. In the internal carotid arterial (ICA)

system, the prevalence of extracranial arterial tortuosity

was significantly higher than intracranial tortuosity

(P \ 0.01). All kinking and coiling were located at the

extracranial arterial segments. The prevalence of tortuosity

and kinking were significantly higher in the left side than

the right side (P \ 0.01). There is no significant difference

in the prevalence of coiling on both sides. In the vertebra-

basilar arterial system, the prevalence of extracranial

arterial tortuosity was significantly higher than intracranial

tortuosity (P \ 0.01). The prevalence of tortuosity and

kinking were significantly higher in the left side than the

right side (P \ 0.01). Similarly, all kinking and coiling

were located at the extracranial arterial segments. The

imaging characteristics of the extra- and intracranial

lesions are illustrated in Figure 1. The distribution of the

Cell Biochem Biophys

123

lesions is listed in Table 1. In the ICA system, the preva-

lence of extracranial arterial stenosis was significantly

higher than intracranial stenosis (P \ 0.01). The preva-

lence of mild and moderate were significantly higher in the

left side than the right side (P \ 0.01). The prevalence of

severe stenosis was similar on both sides.

In the VBA system, the prevalence of extracranial

arterial stenosis was significantly higher than intracranial

Fig. 1 Diagram of different cerebral vascular elongation. a tortuosity, b coiling, c kinking

Table 1 Distribution of extra- and intracranial arterial system Tortuosity, kinking and coiling in 1,382 patients

Tortuosity Kinking Coiling

ICA VBA ICA VBA ICA VBA

n 687 513 135 139 48 24

% 63.8 47.6 57.7 59.4 67.6 33.8

Extracranial 343 (49.9)a 296 (57.7)a 135 (100.0) 139 (100.0) 48 (100.0) 24 (100.0)

Intracranial 203 (29.5) 125 (24.4) 0 0 0 0

Extra–intra 141 (20.6) 92 (17.9) 0 0 0 0

Left 287 (41.8)b 233 (45.4)b 69 (51.1)b 96 (69.1)b 23 (47.9) 17 (70.8)b

Right 241 (35.1) 183 (35.7) 57 (42.2) 36 (25.9) 21 (43.8) 5 (20.8)

Left–right 159 (23.1) 97 (18.9) 9 (6.7) 7 (5.0) 4 (8.3) 2 (8.4)

a Extracranial versus intracranial, P \ 0.01b Left versus right, P \ 0.01

Table 2 Distribution of extra- and intracranial stenosis in 434 patients

Low-grade stenosis Intermediate-grade stenosis High-grade stenosis

ICA VBA ICA VBA ICA VBA

n 104 138 64 72 53 62

% 50.2 66.7 53.8 60.5 49.1 57.7

Extracranial 81 (77.9)a 101 (73.2)a 48 (75.0)a 62 (86.1)a 41 (77.4)a 51 (82.2)a

Intracranial 14 (13.5) 26 (18.8) 11 (17.2) 8 (11.1) 9 (16.9) 10 (16.1)

Extra–intra 9 (8.6) 11 (8.0) 5 (7.8) 2 (2.8) 3 (5.7) 1 (1.7)

Left 49 (47.1)b 75 (54.3)b 32 (50.0)b 37 (51.4) 25 (47.2) 33 (53.2)b

Right 39 (37.5) 45 (32.6) 26 (40.6) 31 (43.1) 23 (43.4) 27 (43.5)

Left–right 16 (15.4) 18 (13.1) 6 (9.4) 4 (5.5) 5 (9.4) 2 (2.3)

a Extracranial versus intracranial, P \ 0.01b Left versus right, P \ 0.01

Cell Biochem Biophys

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stenosis (P \ 0.01). The prevalence of mild and severe

stenosis was significantly higher in the left side than the

right side (P \ 0.01). The prevalence of moderate stenosis

was similar on both sides. The distribution of extra- and

intracranial stenosis is listed in Table 2.

Clinical Characteristics of Extra- and Intracranial

Artery Atherosclerosis

The clinical characteristics of extra- and intracranial tor-

tuosity, kinking, and coiling were listed in Table 3. In

Table 3 Clinical characteristics in 1,382 patients with extra- and intracranial artery atherosclerosis

Clinical manifestations Tortuosity Kinking Coiling

ICA VBA P ICA VBA P ICA VBA P

Asymptomatic 282 (41.0) 181 (35.3) [0.05 30 (22.2) 40 (28.7) [0.05 13 (27.1) 14 (58.3) \0.05

TIA 232 (33.8) 287 (55.9) \0.05 46 (34.1) 80 (57.6) \0.05 11 (22.9) 6 (25.0) [0.05

Cerebral infarction 166 (24.2) 37 (7.2) \0.01 54 (40.0) 14 (10.1) \0.01 23 (47.9) 4 (16.7) \0.01

Cerebral hemorrhage 7 (1.0) 8 (1.6) [0.05 5 (3.7) 5 (3.6) [0.05 1 (2.1) 0 [0.05

TIA transient ischemic attack

Fig. 2 Diagram of stenosis of ICA and VBA. a, b refers to stenosis of

ICA. a high-grade stenosis of left carotid sinus. b high-grade stenosis

of left MCA. c, d stenosis of VBA. c high-grade stenosis of V1

segments of right vertebral artery. d high-grade stenosis of V4

segments of right vertebral artery

Cell Biochem Biophys

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patients with transient ischemic attack (TIA), the preva-

lence of tortuosity and kinking were significantly lower in

the ICA system than the VBA system (P \ 0.05). In the

coiling group, there was no significant difference between

the ICA system and the VBA system (Figure 2). In patients

with ischemic stroke, the prevalence of tortuosity, kinking,

and coiling were significantly higher in the ICA system

than the VBA system (P \ 0.01). The clinical character-

istics of extra- and intracranial stenosis are listed in

Table 4. In asymptomatic patients, the prevalence of

moderate stenosis was significantly lower in the ICA sys-

tem than the VBA system (P \ 0.05) (Fig. 2). In the severe

stenosis group, there was no significant difference between

the ICA system and the VBA system (P [ 0.05). In

patients with ischemic stroke, the prevalence of tortuosity,

kinking, and coiling were significantly higher in the ICA

system than the VBA system (P \ 0.01).

Discussion

Technical innovations in modern imaging have greatly

advanced the role of DSA in the diagnosis and treatment of

extra- and intracranial atherosclerosis. DSA is the current

golden standard in cerebrovascular imaging. It not only

allows accurate depiction of vascular structures with high

spatial resolution, but also provides additional hemody-

namic information [6–8]. Angiographic classification of

extra- and intracranial atherosclerosis is of great impor-

tance for further cerebrovascular intervention.

In previous reports [9, 10], a variety of terms were used

to define a carotid artery abnormality. Coiling, elongation,

and kinking are some of the terms most commonly used to

define these variants. In our present study, we have clas-

sified extra- and intracranial vascular lesions into four

categories. According to our criteria, extra- and intracranial

vascular lesions were further categorized as tortuosity,

kinking, coiling, and stenosis. In 1965, Weibel [11, 12] and

colleagues described the angiographic characteristics of

internal carotid artery in 1,438 patients. They classified the

lesions as tortuosity, kinking, and coiling. According to

their classification, tortuosity was defined as an S-or

C-shaped elongation in the course of the ICA. Coiling was

defined as an exaggerated S-shaped elongation or redun-

dancy of the ICA. Kinking was described as an acute

angulation of the ICA. They found that kinking was the

most frequently reported type of carotid abnormalities. In

the present study, the classification was partly based on

Weibel’s definitions. In our study, we have extended

Weibel’s classification to the posterior circulation. In

addition, we also investigated the prevalence and charac-

teristics of stenosis in patients with extra- and intracranial

atherosclerosis. In our present study, we have classified

stenosis as mild (0–29 %), moderate (30–69 %), or severe

(70–99 %) according to the NASCET trial criteria (Fig. 2).

The NASCET trial classification was well-established for

identifying the degree of stenosis worldwide and it is also

useful in clinical practice for treatment decision-making. In

our study, we have examined 1,816 patients with athero-

sclerosis by using DSA. Consistent with previous reports,

we found the most common lesion was tortuosity, which

accounted for 59.6 % of cases. According to our study, the

prevalence of tortuosity was 63.8 % in the internal arterial

system, 47.6 % in the vertebrobasilar system. We found the

prevalence of tortuosity was significantly higher in the ICA

system than the vertebrobasilar system. In previous autopsy

studies, Paulsen [13] and colleagues investigated 282

patients and they found the prevalence of tortuosity was

26–28 % in the internal carotid artery. In another study of

100 healthy subjects by echocolor Doppler, Macchi et al.

[14] reported that carotid kinkings were present in 38 % of

the individuals. The reported prevalence of tortuosity in our

study was significantly higher than the previous reports.

Extra- and intracranial atherosclerosis is the underlying

pathological basis for a variety of cerebrovascular disease

including TIA, ischemic, and hemorrhagic stroke [15, 16].

Kinking and coiling were common lesions in patients with

TIA and ischemic stroke. The possible explanations were

kinking and coiling may lead to a series of hemodynamic

changes, which are responsible for TIA and ischemic stroke.

In our present study, the incidence of stroke was significantly

higher in the ICA system than the VBA system. In previous

Table 4 Clinical characteristics of 434 patients with extra- and intracranial stenosis

Clinical manifestations Low-grade stenosis Intermediate-grade stenosis High-grade stenosis

ICA VBA P ICA VBA P ICA VBA P

Asymptomatic 50 (48.0) 59 (42.8) [0.05 18 (29.8) 27 (37.5) \0.05 10 (18.9) 23 (37.1) \0.01

TIA 34 (32.7) 68 (49.3) \0.01 24 (37.5) 35 (48.6) \0.01 24 (45.3) 30 (48.4) [0.05

Cerebral infarction 19 (18.3) 9 (6.5) \0.01 19 (29.7) 8 (11.1) \0.01 19 (35.8) 9 (14.5) \0.01

Cerebral hemorrhage 1 (1.0) 2 (1.4) [0.05 3 (4.7) 2 (2.8) [0.05 0 0 0

TIA transient ischemic attack

Cell Biochem Biophys

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reports [11, 12], cerebrovascular insufficiency was reported

in 4-16 % of patients with internal carotid artery turtuosity.

In patients with kinking, 51 % had cerebrovascular insuffi-

ciency. Of those with kinking, 93 % patients with cerebro-

vascular insufficiency were older than 50 years old. In

patients with coiling, 59 % had cerebrovascular insuffi-

ciency. Of those with coiling, 80 % patients with cerebro-

vascular insufficiency were older than 50 years old. In our

study, we have investigated the prevalence of extra- and

intracranial atherosclerosis in patients with suspected stroke

and correlated the atherosclerosis with clinical features of

TIA and stroke in the internal carotid and VBA system. We

found that the prevalence of stroke is significantly higher in

the ICA system than the VBA system. However, the preva-

lence of TIA was lower in the ICA system than the VBA

system. We proposed that kinkings and coilings may not

have a clinical significance if these lesions were not associ-

ated with atheromatous plaques or carotid stenosis. In clin-

ical practice, we also noticed that the degree of stenosis was

not in proportion with the severity of clinical symptoms. One

possible explanation for a patient with severe MCA stenosis

remains asymptomatic could be the good collateral com-

pensation. The exact etiology of carotid abnormality remains

unclear. In previous reports, Paulsen, and colleagues con-

sider these variations as congenital anomalies [17], while

most authors consider artery elongation a consequence of

atherosclerotic vessel remodeling [18]. Recently, Beigelman

et al. [19] proposed that carotid dolichoarteriopathies are a

result of developmental abnormalities rather than vascular

remodeling secondary to aging and/or atherosclerosis. This

controversy remains an unsolved issue. Future studies are

needed to establish a more detailed classification of intra-

and extracranial atherosclerosis.

Conclusions

Our studies suggest that the incidence of cerebral infarction

and stroke in each atherosclerosis group was significantly

higher in patients with ICA tortuosity, which has a higher

prevalence rate, than in patients with VBA tortuosity. We

also suggest that the lesions of kinkings and coilings

become clinically significant when they are associated with

atheromatous plaques or carotid stenosis.

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