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INTRODUCTION
Unruptured intracranial aneurysms (UIAs) are found in approximately 3.2% of the adult population without comorbidity [1] and there has been an increasing tendency to detect UIAs due to widespread use of high-resolution magnetic resonance imaging (MRI). After the international subarachnoid aneurysm trial (ISAT) trial, the relative safety and efficacy of coiling and surgical clipping were demonstrated in preventing hemorrhage from the treated aneurysm [2-4]. Moreover, advances in devices and increased experience in aneurysm treatment continue to result in improvements in clinical outcomes and safety. However, the major concern when a UIA is detected is still whether to treat it or to manage it conservatively. In the real world, there is a lack of evidence on the treatment of UIAs, except for two prospective studies [5,6].
Regarding the treatment strategy for UIAs, it is important to understand their natural history. Especially, the prevalence of UIAs shows a big discrepancy among several studies according to the populations studied, method of case confirmation, imaging modalities, and study design, such as prospective or retrospective. In a previous meta-analysis, the incidence of UIAs ranged from 0% to 41.8% [1]. In Korea, some authors suggested a UIA prevalence from 1.5% to 5% in adults where 1.5 T MRI was used [7,8].
The purpose of this study was to evaluate the prevalence and associated risk factors of UIAs, which can help to establish guidelines of treatment in healthy Korean adults when 3T MRI is used.
MATERIALS AND METHODS
Patient selection
Our Institutional Review Board approved this retrospective study, and informed consent was waived. All patients consisted of healthy individuals who underwent brain MR angiography (MRA) between January 2011 and December 2012 as part of a routine health in Gangnam Severance Checkup Center. They paid at their own expense for their brain imaging. Patient data including age, sex, comorbidities (hypertension, diabetes, hyperlipidemia, previous stroke history, and smoking), family history of cerebrovascular disease (intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction), and follow-up results were obtained from medical records. Patients were excluded if they had fusiform, traumatic, or mycotic aneurysms, which have different etiologies, or aneurysms in an extradural location.
Image acquisition and interpretation
All 3-dimensional time-of-flight MRA was performed by using 1 of 2 3.0T MRI systems at our institution (Discovery MR750; GE Medical Systems, Milwaukee, WI, USA/Achieva; Philips Medical Systems, Best, The Netherlands). MRA was performed with the following parameters for the Discovery MR750 instrument: repetition time/echo time, 23/2.5 ms; flip angle, 20 degrees; field of view, 210×185 mm; 4 slabs (176 slices); slice thickness, 1.4 mm; matrix, 416×224; and acquisition time, 5 minutes and 9 seconds. MRA was performed with the following parameters for the Achieva instrument: repetition time/echo time, 25/3.5 ms; flip angle, 20 degrees; field of view, 250×198 mm; 1 slab (170 slices); slice thickness, 1.4 mm; matrix, 832×414; and acquisition time, 6 minutes and 52 seconds.
UIA was defined as abnormal focal outpouchings of the cerebral artery [6]. All radiologic reports from both instruments were reviewed, and 2 experienced neurologists (KY Lee and SH Suh) independently reviewed the MRA images of patients with UIA and possible UIA according to those reports. In cases of discrepancy, a consensus interpretation was made. Patients with known UIAs before the MRA were also included regardless of treatment.
Aneurysm size was measured by the largest diagonal measurement. Aneurysm locations were classified as internal carotid artery (ICA), anterior cerebral artery, anterior communicating artery, middle cerebral artery (MCA), posterior communicating artery, and vertebrobasilar artery (including vertebral artery, basilar artery, posterior cerebral artery, and anterior and posterior cerebellar arteries). In addition, multiple aneurysms and the presence of daughter sacs were analyzed.
The enrolled patients were divided into 2 groups, a UIA group and a non-UIA group, which were compared according to the above criteria.
Statistical analysis
Continuous variables were described as mean±standard deviation, and categorical variables as frequencies in percentages. Differences between the 2 groups were evaluated using an Independent 2-sample t-test for continuous variables and the chi-square test (or Fisher’s exact test) for categorical variables. The Mantel–Haenszel chi-square test was used to compare trends between groups according to age. All P-values were considered statistically significant if they were 0.05 or less. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).
RESULTS
Patient characteristics
A total of 2,118 individuals (mean age=53.87±9.59 years, male:female=1,188:930) who had undergone brain MRAs for personal health check-ups were enrolled in the study. In Table 1, the mean age of the UIA group was significantly higher than that of the non-UIA group (57.05±8.77 years vs. 53.75±9.61 years, P=0.0025, respectively). Female predominance (55% in UIA vs. 43.47% in non-UIA, P=0.0416) and hypertension were more common in the UIA group (43.75% vs. 28.8%, P=0.004, respectively).
Prevalence and characteristics of UIA
In total, 80 patients had 105 UIAs (3.77%). The mean size of the aneurysms was 3.10±1.62 mm, and they were all saccular in shape and asymptomatic (Table 2). The locations of UIAs were as follows: ICA (62/105, 59.1%), internal carotid-posterior communicating artery (16/105, 15.2%), MCA (10/105, 9.5%), anterior communicating artery (Acom, 9/105, 8.6%), anterior cerebral artery (5/105, 4.8%) and vertebral artery (3/105, 2.9%). Multiple aneurysms were seen in 28 of 80 patients (35%); 2 UIAs in 14, 3 UIAs in 1, and 4 UIAs in 3. Although more than 60% of UIAs were less than 3 mm in size, 6 were more than 7 mm in size (5.71%). Diagnostic angiography was performed for confirmation in 73 patients, and 4 patients were treated previously with unruptured aneurysms.
Incidence of UIAs according to aging
The incidence of UIAs increased significantly with aging (P=0.0144), which was 1.33% in less than 40 years, 2.98% in the 40s, 3.95% in the 50s, 4.39% in the 60s, and 6.67% in the 70s (Table 3). Especially compared to the overall prevalence of UIAs in this study, the incidence of UIAs was higher in patients aged more than 50 years, and patients aged more than 70 years showed approximately double the overall incidence.
DISCUSSION
This study demonstrated that the prevalence of UIAs was 3.77% in asymptomatic adults, which was similar to a recent meta-analysis of UIAs. In autopsy cases [9], an incidence of 4.6% was suggested in UIAs, and Ujiie et al. [10] showed 2.7% using conventional angiography. Jeon et al. [7] described a higher incidence of 5% in 3,049 healthy individuals using 1.5T MRI. In the era of 3T MRI, Li et al. [11] found a prevalence of 7.0% in 4,813 Chinese adults aged 35 to 75 years, and Imaizumi et al. [12] showed a prevalence of 4.32% in 4,032 Japanese healthy adults. Moreover, 60.95% (64/105) of UIAs were less than 3 mm in this study, which may be possible to detect by using 3T MRI. Although Vlak et al. [1] presented an incidence of 3.2% (95% confidence interval 1.9–5.2), differences among the prevalence of UIAs according to ethnic group, imaging method/device, or gender ratio should be taken into consideration.
The distribution of UIAs in this study was not much different from previous publications. The most common location of UIAs was ICA with an incidence of 74.3% in our study, which was comparable to other studies [1,7,10,13]. In total, 8.6% of UIAs were found in the Acom, which had the highest tendency of rupture compared to others in the Unruptured Cerebral Aneurysm Study of Japan (UCAS Japan) [6]. The incidence of MCA aneurysms was 9.5% in this study, which was lower than in previous studies, and MCA aneurysms had a lower rupture risk than other aneurysm locations [6]. UIAs in posterior circulation showed a low incidence in general, and our study revealed only 2.9% in the vertebral artery. Although some retrospective studies [14,15] showed posterior circulation aneurysms have a high risk of rupture, other prospective studies [6,16] did not demonstrate a high rupture risk due to the small sample size of posterior circulation aneurysms.
Our study showed an incidence of multiple aneurysms to be quite higher than in previous publications [7,11-13]. Iwamoto et al. [9] reported an incidence of 21.3% for multiple UIAs, and 2 prospective Japanese studies for UIAs showed an incidence of multiple aneurysms to be 26.4% in the UCAS Japan [6] and 33.2% in the Small Unruptured Intracranial Aneurysm Verification (SUAVe) study [16], which showed a similar result with ours. Although this result may have some bias due to its retrospective nature, it is important to contemplate multiple UIAs as a major factor for aneurysm growth and rupture [14,17].
In this study, there were some limitations to interpret the results for UIAs due to the ethnic bias of the Korean adult population, and UIAs were determined using MRA, which has some disadvantages for the detection of small UIAs. Although our study has the strength of a large number of asymptomatic participants and the application of 3T MRA, further longitudinal studies will need to evaluate the life of UIAs.
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