CLINICAL ARTICLE

Detection rates and sites of unruptured intracranial
aneurysms according to sex and age: an analysis of MR
angiography–based brain examinations of 4070 healthy
Japanese adults
Yohichi Imaizumi, MD,1 Tohru Mizutani, MD,1 Katsuyoshi Shimizu, MD,1 Yosuke Sato, MD,1 andJunichi Taguchi, MD2
1

Department of Neurosurgery, Showa University School of Medicine; and 2Tokyo Midtown Medical Center, Tokyo, JapanOBJECTIVE The purpose of this study was to evaluate the detection rate and occurrence site according to patient sex
and age of unruptured intracranial aneurysms detected through MRI and MR angiography (MRA).
METHODS A total of 4070 healthy adults 22 years or older (mean age [± SD] 50.6 ± 11.0 years; 41.9% women) who
underwent a brain examination known as “Brain Dock” in the central Tokyo area between April 2014 and March 2015
were checked for unruptured saccular aneurysm using 3-T MRI/MRA. The following types of cases were excluded:
1) protrusions with a maximum diameter < 2 mm at locations other than arterial bifurcations, 2) conical protrusions atarterial bifurcations with a diameter < 3 mm, and 3) cases of suspected aneurysms with unclear imaging of the involved
artery. When an aneurysm was definitively diagnosed, the case was included in the aneurysm group. The authors also
investigated the relationship between aneurysm occurrence and risk factors (age, sex, smoking history, hypertension,
diabetes, and hyperlipidemia).
RESULTS One hundred eighty-eight aneurysms were identified in 176 individuals (detection rate 4.32%), with the detection rate for women being significantly higher (6.2% vs 3.0%, p < 0.001). The average age in the aneurysm group was
significantly higher than in the patients in whom aneurysms were not detected (53.0 ± 11.1 vs 50.5 ± 11.0 years). The
detection rate tended to increase with age. The detection rates were 3.6% for people in their 30s, 3.5% for those in their
40s, 4.1% for those in their 50s, 6.9% for those in their 60s, and 6.8% for those in their 70s. Excluding persons in their
20s and 80s—age groups in which no aneurysms were discovered—the detection rate in women was higher in all age
ranges. Of the individuals with aneurysms, 12 (6.81%) had multiple cerebral aneurysms; no sex difference was observedwith respect to the prevalence of multiple aneurysms. Regarding aneurysm size, 2.0–2.9 mm was the most common
size range, with 87 occurrences (46.3%), followed by 3.0–3.9 mm (67 [35.6%]) and 4.0–4.9 mm (20 [10.6%]). The largest
aneurysm was 13 mm. Regarding location, the internal carotid artery (ICA) was the most common aneurysm site, with148 (78.7%) occurrences. Within the ICA, C1 was the site of 46 aneurysms (24.5%); C2, 57 (30.3%); and C3, 29 (15.4%).
The aneurysm detection rates for C2, C3, and C4 were 2.23%, 1.23%, and 0.64%, respectively, for women and 0.68%,
0.34%, and 0.21%, respectively, for men; ICA aneurysms were significantly more common in women than in men (5.27%
vs 2.20%, p < 0.001). Multivariate logistic regression analysis revealed that age (p < 0.001, OR 1.03, 95% CI 1.01–1.04),
female sex (p < 0.001, OR 2.28, 95% CI 1.64–3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10–2.11) weresignificant risk factors for aneurysm occurrence
CONCLUSIONS In this study, both female sex and older age were independently associated with an increased aneurysm detection rate. Aneurysms were most common in the ICA, and the frequency of aneurysms in ICA sites was markedly higher in women.
https://thejns.org/doi/abs/10.3171/2017.9.JNS171191

KEYWORDS cerebral aneurysm; MRA; brain check; vascular disorders

ABBREVIATIONS ACA = anterior cerebral artery; ACoA = anterior communicating artery; ICA = internal carotid artery; MCA = middle cerebral artery; MIP = maximum
intensity projection; MRA = MR angiography; PCoA = posterior communicating artery; PICA = posterior inferior cerebellar artery; VA = vertebral artery.
SUBMITTED May 15, 2017. ACCEPTED September 1, 2017.
INCLUDE WHEN CITING Published online April 6, 2018; DOI: 10.3171/2017.9.JNS171191.
©AANS 2018, except where prohibited by US copyright law

J Neurosurg April 6, 20181

Y. Imaizumi et al.

In Japan, which has the highest prevalence of MRI
equipment in the world, the number of facilities incorporating brain examinations into medical care is increasing. Brain assessments were established in Japan for
the first time in 1988. MRI and MR angiography (MRA)
are the core examinations conducted during a checkup andplay an important role in screening for unruptured intracranial aneurysms. The 2012 report of UCAS Japan9 (theUnruptured Cerebral Aneurysm Study of Japan) shows
the yearly rupture rate by size and location for aneurysms≥ 3 mm. With this report as a reference, treatment strategies for detected unruptured aneurysms are currently being studied, but standard data based only on MRA that
could provide an index for the detection frequency of unruptured intracranial aneurysms are almost nonexistent.
We performed a large-scale study of individuals who
underwent brain imaging examinations in central Tokyo,
evaluating their 3-T MRI and MRA findings in detail andcalculating aneurysm detection rates. In line with the roleof brain examinations, the examinees are informed of thepossibility of an aneurysm even when the findings are
not definitive and such a lesion is only suspected. For thisstudy, confirmed aneurysm cases were extracted and analyzed, while suspected cases were excluded.

Methods

Study GroupA total of 4084 healthy adults, essentially without
symptoms, underwent a standardized brain evaluation
known as “Brain Dock” between April 2014 and March
2015 at the Tokyo Midtown Clinic. Fourteen individuals
with a history of brain surgery were excluded, and findings in the remaining 4070 individuals (age range 22–89
years) were considered for inclusion in this analysis (Fig.
1). MRA examination for unruptured intracranial aneurysm was performed using Magnetom Spectra 3-T MRI(Siemens Inc.). At that time, T1-weighted, T2-weighted,
FLAIR, and diffusion-weighted imaging sequences were
simultaneously recorded and used to assist in the diagnosis. Additionally, when a brain aneurysm was suspectedbased on the MRA maximum intensity projection (MIP)
images, the images were carefully evaluated via primaryinterpretation by a radiologist and secondary interpretation by a neurosurgeon with more than 17 years’ experience. The secondary interpretation results were reported
to the examinees, and the detection rate was calculated,
including suspicious cases based on these results. All images from these aneurysm cases were assessed a second
time. We excluded cases in which a protrusion area < 2
mm outside of an arterial bifurcation was found, or thearea corresponding to arterial bifurcation protruded ina conical shape < 3 mm in diameter, or the image of the
branched artery was unclear. Individuals with confirmed
aneurysms were included in the aneurysm group. This
group was evaluated for sex, age range, aneurysm occurrence site frequency and detection rate, and aneurysm
size. Suspicious cases in which an aneurysm could not
be completely excluded and cases in which an aneurysm
was excluded were combined into a nonverified aneurysm
group. We also investigated the relationship between an2

J Neurosurg April 6, 2018

FIG. 1. Flowchart for this study. The values are numbers of examinees
and percentages.

eurysm occurrence and risk factors (age, sex, smoking
history, hypertension [blood pressure > 140/90 mm Hg],diabetes [HbA1c > 6.5%], and hyperlipidemia [LDL >180 mg/dl]). The study protocol was consistent with theJapanese Government’s Ethical Guidelines Regarding
Epidemiological Studies in accordance with the Declaration of Helsinki. Informed consent was waived becauseof minimal patient risk and because only de-identified
data were included.
Statistical Analysis
The aneurysm detection rate was calculated for eachage range and for each sex. Thereafter, the aneurysm
detection rates according to sex for each age range werecompared using the chi-square test. In addition, the detection rate was calculated based on the site of the detected
aneurysms. A p value < 0.05 was considered statisticallysignificant. Furthermore, the multivariate analysis of risk
factors for aneurysm occurrence, such as age, sex, smoking history, hypertension, diabetes, and hyperlipidemia,
was performed using the logistic regression technique.
All statistical analyses were performed with Excel 2013
(Microsoft Corp.) and R 3.0.2 (available at http://www.rproject.org).

Results

Of the 4070 participants, 1707 (41.9%) were female(mean age [± SD] 51.4 ± 11.7 years) and 2363 (58.1%) weremale (mean age 50.0 ± 10.4 years). The female/male ratio was 0.72:1. The mean age was significantly higher for
women (p < 0.05). The verified aneurysm group, in whichaneurysms were diagnosed with certainty, consisted of
176 individuals (detection rate 4.32%) and 188 aneurysms(Fig. 1). Suspicious cases, in which aneurysms could
not be completely excluded, comprised 122 individuals(3.00%) and 130 aneurysms.
Of the 176 members of the verified aneurysm group,Y. Imaizumi et al.

TABLE 1. Baseline characteristics of 4070 screened individuals
stratified by the presence of verified aneurysms

Characteristic

Total(n = 4070)

Verified
No Verified
Aneurysms Aneurysms(n = 176)(n = 3894)

p
Value

Female sex
1707 (41.9) 106 (60.2) 1601 (41.1) <0.005
Mean age in yrs
50.6 ± 11.0 53.0 ± 11.1 50.5 ± 11.0 <0.001
Medical history
Hypertension
586 (14.4)
24 (13.6)
562 (14.4) 0.769
Diabetes mellitus 172 (4.2)
7 (4.0)165 (4.2)
0.981
Hyperlipidemia
501 (12.3)
23 (13.1)
478 (12.3) 0.754
Former or current
1750 (43.0)
80 (45.5) 1670 (42.9) 0.518
smokerValues are number of individuals (%) unless otherwise indicated. The p value
for sex was analyzed as a single variable with the chi-square test. The p value
for the mean age of the patients was calculated with the Student t-test.

106 (60.2%) were women (female/male ratio 1.51:1). In theverified aneurysm group, there were significantly more
women (p < 0.005, Table 1). Multiple cerebral aneurysms
were confirmed in 12 individuals (6.81%), and a sex difference was not found. All examinees were between theages of 22 and 89 years (mean age 50.6 ± 11.0 years); however, the mean age of individuals in the verified aneurysm
group was significantly greater than the mean age of thosein the nonverified aneurysm group (53.0 ± 11.1 vs 50.5 ±11.0 years, p < 0.001). No significant difference was foundbetween the verified aneurysm and nonverified aneurysm
groups regarding the presence of hypertension, diabetes,
hyperlipidemia, or smoking. Table 2 shows the numberof verified aneurysm and nonverified aneurysm cases according to sex and age range and the ratios.
The aneurysm detection rate increased with age andwas 3.63% for the 30s, 3.53% for the 40s, 4.12% for the
50s, 6.95% for the 60s, and 6.76% for the 70s. The overall
aneurysm detection rate for women was 6.2%, and it wassignificantly higher than the rate for men (p < 0.001). Even
after excluding the 20s and 80s age groups, in which there
were no aneurysm cases, the aneurysm detection rate wasstill higher for women in every age group. In particular,

the rate was significantly higher for women than for men
in the 40s (p < 0.05), 50s (p < 0.05), and 70s (p < 0.01) age
groups.
The occurrence sites of the 188 aneurysms detected in
the 176 individuals in the aneurysm group were the internal carotid artery (ICA), which was the most common
site, with 148 (78.7%) of the detected aneurysms (right/
left ratio 66:82), followed by the anterior communicatingartery (ACoA) with 22 (11.7%) and the middle cerebral
artery (MCA) with 17 (9.0%; right/left ratio 12:5). Whenthe ICA was divided into the 5 segments proposed in 1938
by Fischer,1 C2—from the initial segment of the ophthalmic artery to the proximal side of the posterior communicating artery (PCoA)—had 57 aneurysms (30.3%; right/
left ratio 22:35), the most of any section. The distal areaof the ICA from the PCoA to the anterior cerebral artery(ACA)—C1—had 46 aneurysms (24.5%; right/left ratio
23:23), and C3—from the proximal curve of the carotid
siphon to the ophthalmic artery—had 29 (15.4%; right/
left ratio 9:20) (Fig. 2, Table 3). Specifically, in C1, there
were 32 aneurysms in the PCoA section, 13 in the anterior choroidal artery section, and 1 in the apex of the ICA.
There were 16 (8.5%; right/left ratio 12:4) in the cavernous
segment (C4). No aneurysms were found from the inlet ofthe carotid artery to the proximal cavernous sinus (C5).
Moreover, only 1 aneurysm was observed in the posterior
circulation, a 4.3-mm lesion in the left vertebral artery(VA) and posterior inferior cerebellar artery (PICA). Moreaneurysms tended to occur on the right in the MCA and C4
and on the left in C3.
Smaller aneurysms tended to be more common. Of the188, 87 (46.3%) were 2–2.9 mm; 67 (35.6%), 3–3.9 mm;
20 (10.6%), 4–4.9 mm; 9 (4.8%), 5–5.9 mm; and 5 (2.7%),≥ 6 mm. A total of 101 (53.7%) of the aneurysms were ≥ 3mm; aneurysms ≥ 3 mm were identified in 97 individuals(detection rate 2.38%) (Table 3).
Comparison of detection rates according to sex for eachoccurrence site showed a statistically significant difference
between the rates for men and women with respect to the
ICA as the occurrence site (5.27% for women and 2.20%
for men [female/male ratio 2.40:1], p < 0.001), but no significant difference with respect to either ACoA or MCA(ACoA, 0.64% for women and 0.47% for men [female/

TABLE 2. Age distribution of the patients with verified aneurysms
Total (%)

Women (%)

Men (%)

Age
Group
(yrs)

Verified
Aneurysms

No Verified
Aneurysms

Verified
Aneurysms

No Verified
Aneurysms

Verified
Aneurysms

No Verified
Aneurysms

20–29
30–39
40–49
50–59
60–69
70–79
80–89
All

0 (0)
21 (3.6)
49 (3.5)
50 (4.1)
41 (6.9)
15 (6.8)0 (0)176 (4.3)

52 (100)558 (96.4)
1338 (96.5)
1164 (95.9)
549 (93.1)
207 (93.2)
26 (100)
3894 (95.7)

0 (0)12 (5.8)
28 (5.0)27 (5.6)
25 (8.9)
14 (11.1)0 (0)106 (6.2)

32 (100)
194 (94.2)
535 (95.0)457 (94.4)
256 (91.1)
112 (88.9)
15 (100)
1601 (93.8)0 (0)9 (2.4)21 (2.5)
23 (3.2)
16 (5.2)
1 (1.0)0 (0)70 (3.0)

20 (100)
364 (97.6)
803 (97.5)
707 (96.8)
293 (94.8)
95 (99.0)
11 (100)
2293 (97.0)

p Value
0.06
<0.05
<0.05
0.08
<0.01
<0.001The p value for sex was analyzed as a single variable with the chi-square test.
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Y. Imaizumi et al.

FIG. 2. Sites of 188 verified aneurysms.

male ratio 1.36:1]; MCA, 0.47% for women and 0.34% formen [female/male ratio 1.38:1]). Regarding ICA segments,
no significant difference was found between the rates formen and women in C1. However, in C2 the rate was 2.23%
for women and 0.68% for men (female/male ratio 3.28:1, p< 0.001); in C3 the rate was 1.23% for women and 0.34%
for men (female/male ratio 3.62:1, p < 0.005); and in C4 it
was 0.64% for women and 0.21% for men (female/maleratio 3.05:1, p = 0.05). In C2 and C3, the detection rate forwomen was significantly higher (Table 4).
The multivariate logistic regression analysis revealed
that age (p < 0.001, OR 1.03, 95% CI 1.01–1.04), femalesex (p < 0.001, OR 2.28, 95% CI 1.64–3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10–2.11) weresignificant risk factors for aneurysm occurrence (Table 5).

Discussion

Intracranial Aneurysm Detection Rate
To date, there have been a handful of studies on thedetection rate of unruptured intracranial aneurysms;
however, there are few reports on healthy adults who underwent brain examinations. Regarding the diagnosis of
intracranial aneurysm using 1.5-T MRA, Jeon et al.5 reported that intracranial aneurysms were detected in 137(4.5%) of 3049 outpatient examinees. In that report, aneurysms ≥ 2 mm were investigated and 15% of aneurysms
were < 3 mm. Additionally, in a 1994 study by Nakagawa
and Hashi,8 in which MRI was conducted on 400 healthy
adult volunteers and digital subtraction angiography was
conducted on 370 of these volunteers, intracranial aneurysms were detected in 6.5% of the participants; 59.3% of
the detected aneurysms were ≤ 5 mm, but the minimum
diameter was not clearly stated. In our present study, 87(46.3%) of the 188 aneurysms detected were < 3 mm. Although a clear diagnosis was difficult with sizes < 2 mm,
it is thought that 3-T MRI/MRA increases the ability todiagnose aneurysms of 2–3 mm.
In 1990, Inagawa and Hirano3 reported their analysisof the results of 10,259 autopsies performed at a single
facility between 1951 and 1987; intracranial aneurysms
were identified in 84 individuals (102 aneurysms, detection rate of 0.82%). In their study, small aneurysms (< 4mm) were common (54%), but the minimum diameter was
not clarified. Additionally, in a study by Iwamoto et al.,4
73 intracranial aneurysms were found in 57 individuals(detection rate of 4.6%) through 1230 autopsies conductedin the town of Hisayama between 1962 and 1991. In thatstudy, however, the cavernous carotid artery and carotid
cave were not assessed. In the autopsy reports of Inagawa

TABLE 3. Size and site of 188 verified aneurysms

4

Site

2.0–2.9 mm

3.0–3.9 mm

4.0–4.9 mm

5.0–5.9 mm≥6.0 mm

Total (%)

ACoA
ICA
C1
C2
C3
C4
MCA
VA/PICA
Total (%)

13
69
16
29
13
11
5
0
87 (46.3)

5
55
21
17
14
3
7
0
67 (35.6)

2
16
5
8
2
1
1
1
20 (10.6)

1
5
2
2
0
1
3
0
9 (4.8)

1
3
2
1
0
0
1
0
5 (2.7)22 (11.7)
148 (78.7)
46 (24.5)
57 (30.3)
29 (15.4)
16 (8.5)
17 (9.0)
1 (0.5)188

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Y. Imaizumi et al.

TABLE 4. Detection of verified aneurysms stratified by site and
sex
Site

Women (n = 1707)

Men (n = 2363)

Total (n = 4070)

ACoA
ICA
C1
C2
C3
C4
MCA
VA/PICA

11 (0.64)
90 (5.27)
20 (1.17)
38 (2.23)
21 (1.23)
11 (0.64)
8 (0.47)0 (0)11 (0.47)
52 (2.20)
23 (0.97)
16 (0.68)
8 (0.34)
5 (0.21)8 (0.34)
1 (0.04)

22 (0.54)
142 (3.49)
43 (1.06)
54 (1.33)
29 (0.71)
16 (0.39)
16 (0.39)
1 (0.03)

Data represent the number of individuals (%) in whom 1 or more aneurysms
were detected on the specified artery or segment. The percentage value is thedetection rate.

et al., the extent of evaluation of the central area of the ICA
was not specified.
Sex Differences
In the present study, there were fewer female than maleexaminees, but the aneurysm detection rate tended to behigher in women for every age group (Table 2). A report
by UCAS Japan9 stated that the aneurysm detection rate
in women is approximately twice that in men. In our present results, the findings were similar, with men having a
3.0% detection rate compared with 6.2% in women. To
the best of our knowledge, no reports investigating the sex
difference at each occurrence site exist. In this study, thedetection rates were calculated by occurrence site and also
by sex, and in all areas of the anterior circulation, the ratetended to be higher in women. Regarding the central areaof the ICA (C2 and C3), there was a marked sex difference,with the rate in women being significantly higher than thatin men. Considering the ICA as a whole, women had significantly higher rates than men (Table 4).
Jeon et al.5 reported that there was no sex difference indetection rate and that the rate increased with age for both
sexes, with an overall value of about 5%. In the present
study, excluding the 20s and 80s age groups, the female
detection rate was higher across all age ranges.
Site and Diagnosis
To date, there have been multiple reports on ruptured
intracranial aneurysm occurrence sites, the most common
TABLE 5. Multivariate logistic regression analysis of risk factors
for aneurysm occurrence
Risk Factor

OR (95% CI)

p Value

Age
Female sex
Smoking history
Hypertension
Diabetes
Hyperlipidemia

1.03 (1.02–1.01)
2.28 (1.64–3.17)
1.52 (1.10–2.11)
0.78 (0.48–1.26)
0.62 (0.31–1.27)
0.89 (0.61–1.29)<0.001
0.001
0.011
0.31
0.19
0.52

site being the ACoA at 26%–34%.2,6,7 However, there area few reports regarding occurrence site for unruptured intracranial aneurysms. In one study regarding unruptured
intracranial aneurysms detected during autopsy, the mostcommon occurrence site was the MCA, which was the siteof 39 (38%) of 102 intracranial aneurysms.3 The MCA wasthe most common site in another report also, in which 23(32%) of 72 intracranial aneurysms were located.4 In thesereports, since the search site was limited to the dura mater
during autopsy, it can be presumed that the assessment of
the ICA, and in particular, the assessment of the central
area from the anterior clinoid process, was insufficient, andthat the frequency of ICA aneurysms was not only 29 (28%)
and 8 (11%), respectively. A study similar to the present one
revealed the ICA as the most common occurrence site (86[52%] of 164 aneurysms detected by MRA).4 However, in
our current research, by examining a more central area, ourICA aneurysm occurrence of 148 (78.7% of detected aneurysms) showed a higher rate than previous studies. Whenthe findings are limited to the distal ICA (C1 and C2), ourdetection rate of 103 (54.8%) of 188 aneurysms is similar
to the rates reported in these other studies.
Limitations
Unfortunately, there are limitations of the generalizability of the results in this study due to the ethnic homogeneity of the Japanese study population and the lack of
information about family history. Although the large number of examinees (4070) and the use of 3-T MRI/MRA
revealed a higher incidence of unruptured aneurysms thanpreviously reported, further studies with a considerationof other factors will be needed to address this issue more
completely.

Conclusions

In 4070 healthy adults who underwent brain evaluation,
there were 176 individuals with confirmed intracranial aneurysm (188 aneurysms, detection rate 4.32%). The detection rate increased with age, and aneurysms were identified more frequently in women. Regarding aneurysm site
frequency, the ICA had the most aneurysms, and the rate
for women in the central area of the ICA was particularly
high.

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Disclosures

The authors report no conflict of interest concerning the materi-

6

J Neurosurg April 6, 2018als or methods used in this study or the findings specified in thispaper.

Author Contributions

Conception and design: Imaizumi, Mizutani. Acquisition of data:
Imaizumi, Mizutani, Shimizu, Taguchi. Analysis and interpretation of data: Imaizumi, Mizutani, Sato. Drafting the article: Imaizumi, Shimizu. Critically revising the article: Imaizumi, Mizutani, Shimizu. Reviewed submitted version of manuscript: allauthors. Approved the final version of the manuscript on behalfof all authors: Imaizumi. Statistical analysis: Imaizumi, Shimizu,
Sato. Administrative/technical/material support: Imaizumi, Taguchi. Study supervision: Mizutani.

Correspondence

Yohichi Imaizumi: Showa University School of Medicine, Tokyo,
Japan. imaizumi@med.showa-u.ac.jp.