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Meta-analysis of computed tomography
angiography versus magnetic resonance
angiography for intracranial aneurysm
Xiaodan Chen, MD
a
, Yun Liu, MD
b
, Huazhang Tong, MD
c
, Yonghai Dong, MD
d,∗
, Dongyang Ma, MD
e
,
Lei Xu, MD
d
, Cheng Yang, MD
d
Abstract
Background: Whether the diagnosis value of computed tomography angiography (CTA) for intracranial aneurysm is in accordance
with magnetic resonance angiography (MRA) remains inconclusive. This meta-analysis aims to synthesize relevant studies to
compare the diagnostic efficacies of the 2 methods.
Methods: Potentially relevant studies were selected through PubMed, Embase, Wanfang, Chongqing VIP, and China National
Knowledge Infrastructure databases by using the core terms “computer tomography angiography”(CTA) and “magnetic resonance
angiography”(MRA) and “intracranial aneurysm∗”in the titles, abstracts, and keywords of the articles. Quality Assessment for
Diagnostic Accuracy Studies (QUADAS-2) was utilized to evaluate the quality. Pooled sensitivity, specificity, positive likelihood ratio
(PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were count. Summary receiver operating characteristic curves
(SROC) and area under the curve (AUC) were used to summarize the overall diagnostic performance. Statistical analyses were
performed by Stata version 12.0 and MetaDisc 1.4 software.
Results: Ten articles were identified in this current paper. For CTA, the pooled estimates of diagnostic parameters for intracranial
aneurysm were as follows: sensitivity, 0.84 (95%CI =0.81–0.86); specificity, 0.85 (95%CI =0.79–0.89); PLR, 4.09 (95%CI =2.45–
6.81); NLR, 0.18 (95%CI =0.11–0.28); DOR, 23.74 (95%CI =10.49–53.74); AUC, 0.90, respectively. For MRA, the pooled estimates
of diagnostic parameters for intracranial aneurysm were as follows: sensitivity, 0.80 (95%CI =0.77–0.83); specificity, 0.87 (95%CI =
0.82–0.91); PLR, 3.61 (95%CI =1.72–7.55); NLR; 0.27 (95%CI =0.21–0.35); DOR, 16.77 (95%CI =7.38–38.11); AUC, 0.87,
respectively. No significant difference was found the AUC value between CTA and MRA for intracranial aneurysm (Z=0.828, P>.05).
Conclusion: This comprehensive meta-analysis demonstrated that the diagnosis value of CTA was in accordance with MRA for
intracranial aneurysm. However, considering the limitation of sample size, the results should be treated with caution.
Abbreviations: AUC =area under the curve, CTA =computed tomography angiography, DSA =digital subtraction angiography,
DOR =diagnostic odds ratio, FN =false negative, FP =false positive, MRA =magnetic resonance angiography, NLR =negative
likelihood ratio, PLR =positive likelihood ratio, QUADAS =Quality Assessment for Diagnostic Accuracy Studies, SROC =summary
receiver operating characteristic curves, TN =true negative, TP =true positive.
Keywords: CTA, intracranial aneurysm, meta-analysis, MRA
1. Introduction
The prevalence of intracranial aneurysm in the general popula-
tion is approximately 1% to 5%.
[1–4]
Ruptured intracranial
aneurysm is reportedly the dominant cause leading to non-
traumatic subarachnoid hemorrhage, and it can give raise to
severe disability and even death.
[5–7]
Thus, a precise diagnosis is
especially important to the patients with intracranial aneurysm.
In clinical practice, the conventionally accepted gold standard
for the detection of intracranial aneurysm is digital subtraction
angiography (DSA).
[8–10]
Despite the high sensitivity and specifici-
ty of DSA, several flaws have restricted its wide application. First
and foremost, the high cost of DSA puts the technology beyond
some families. Secondly, DSA requires a high level of skill. Thirdly,
DSA can lead to a minimal invasive procedure, such as cerebral
thromboembolism and contrast nephrotoxicity.
[11,12]
Thus, an
imaging tool that is fast, efficient, convenient, affordable, and
noninvasive is required in clinical practice.
Computed tomography angiography (CTA) and magnetic
resonance angiography (MRA) have been widely used to screen
Editor: Kou Yi.
XC, YL, HT, and YD contributed equally to this manuscript.
Formatting of funding sources: This research did not receive any specific grant
from funding agencies in the public, commercial, or not-for-profit sectors.
The authors have no conflicts of interest to disclose.
a
Department of Science and Education, Jiangxi Provincial Cancer Hospital,
b
Cadre
Wards of Neurology Medicine,
c
Department of Cancer Radiotherapy, Jiangxi
Provincial People’s Hospital,
d
Jiangxi Provincial Center for Disease Control and
Prevention, Nanchang,
e
Nanhui Mental Health Center, Pudong New Area,
Shanghai, China.
∗
Correspondence: Yonghai Dong, Jiangxi Provincial Center for Disease Control
and Prevention, Nanchang, 330029, China (e-mail: dyhai123@126.com).
Copyright ©2018 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial
and non-commercial, as long as it is passed along unchanged and in whole, with
credit to the author.
Medicine (2018) 97:20(e10771)
Received: 4 January 2018 / Accepted: 23 April 2018
http://dx.doi.org/10.1097/MD.0000000000010771
Systematic Review and Meta-Analysis Medicine®
OPEN
1
intracranial aneurysms. Prior clinical evaluations that compared
CTA or MRA with DSA revealed that the diagnostic value of
CTA or MRA approaches that of DSA. A recent investigation
[13]
pooled 8 studies to explore the accuracy of subtraction CTA
compared with DSA for diagnosing intracranial aneurysm; the
pooled sensitivity and specificity were 96% and 91%, respec-
tively. In addition, the author also suggested that CTA is a highly
sensitive, specific and noninvasive imaging method to diagnose
intracranial aneurysms. Another investigation
[14]
pooled 26
studies that addressed the diagnostic value of MRA based on
DSA; for time of flight-MRA, the sensitivity and specificity were
86% and 84%, respectively, with rates of 86% and 89%,
respectively, for contrast-enhanced MRA. Our review of previous
articles indicates that comparative weakness of studies compar-
ing the diagnostic value between CTA and MRA performed on
the same objects with intracranial aneurysms, with varied results.
For example, Xu et al
[15]
studied 98 patients with suspected
aneurysms to compare the diagnosis accuracy of CTA and MRA;
the sensitivity and specificity was 95% and 67% for CTA, and
71% and 50% for MRA. However, Hiratsuka et al
[16]
found the
diagnosis value of the 2 methods was similar.
This meta-analysis systematically compares the diagnosis value
between CTA and MRA for intracranial aneurysms.
2. Materials and methods
2.1. Literature search
This meta-analysis was designed according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis
(PRISMA) recommendations. Two investigators independently
conducted a comprehensive literature search using several large
databases using the terms “computer tomography angiography”
(CTA) and “magnetic resonance angiography”(MRA) and
“intracranial aneurysm∗”in the article titles, abstracts, and
keywords. The databases included PubMed-Medline (1966–
October 2017), Embase (1950–October 2017), China National
Knowledge Infrastructure (CNKI, 1994–October 2017), Wan-
fang Data (1980–October 2017), and Chongqing VIP (1989–
October 2017). Also, the reference lists of the identified articles
were evaluated to identify relevant studies.
2.2. Study selection
Two reviewers (YY and LM) independently reviewed the
potential articles on the basis of predetermined inclusion
and exclusion criteria. At the end of the review, in case of
divergences of opinion for the articles, a third reviewer
evaluated whether the article in question was eligible. All the
selected studies needed to meet the following inclusion criteria:
studies adopted a clinical study design based on a human
population; intracranial aneurysms were identified by CTA or
MRA; studies provided sufficient information to calculate effect
size; articles were in English or Chinese; and in case of duplicated
cohorts, the study with the largest number of patients were
included. Any study that failed to meet these criteria was
excluded.
2.3. Data extraction
The same 2 investigators independently extracted the study
information using a standardized form for each study. The
basic information included the name of the first author, year of
publication, country, mean age of participants, and sample size.
In addition, they extracted the information with true positive
(TP), false positive (FP), false negative (FN), and true negative
(TN) from each study to pool the effect size of diagnosis
accuracy. If required, information that had previously been
omitted was retrieved by communication with the authors of
the studies.
2.4. Quality assessment
In this review, Chen X and Xiong M independently assessed the
quality of the included studies according to the Quality
Assessment of Diagnostic Accuracy Studies—version 2 (QUA-
DAS-2) scale.
[17]
This scale has 14 items and covers 4 domains
(patient selection, index test, reference standard, flow, and
timing). For each case, the answer should be provided as yes/no/
unclear in order to evaluate it. “Yes”indicated a low risk of bias
for this domain. “No”or “unclear”presented lacking the details
or not certain, and indicated a potential bias.
2.5. Ethical approval
No ethical approval was required because all the data were
extracted from the previous published articles.
2.6. Statistical analyses
Statistical analyses were carried out by Stata version 12.0 (Stata
Corporation, College Station, TX) and MetaDisc 1.4 (XI.
Cochrane Colloquium, Barcelona, Spain). In this review, we
pooled sensitivity, specificity, positive likelihood ratio (PLR),
negative likelihood ratio (NLR), and diagnostic odds ratio
(DOR) with 95% confidence intervals (CI) to evaluate CTA and
MRA diagnosis accuracy for intracranial aneurysms. In addition,
summary receiver-operating curves (SROC) and area under the
SROC curve (AUC) were performed to explain the interaction
between sensitivity and specificity and the diagnostic ability
respectively. Q-statistics was used to evaluate the heterogeneity.
I
2
was determined to assess the degree of heterogeneity between
studies. If P>.10 by Qtest and I
2
<50%, no obvious
heterogeneity existed.
[18]
If so, a fixed effects model (Mantel–
Haenszel method) was adopted. Conversely, a random effects
model (DerSimonian and Laird method) was performed.
[19,20]
To
further determine the difference in AUC between CTA and MRA
for intracranial aneurysm, Ztest was performed.
In diagnostic accuracy studies, the predominant cause of
heterogeneity was threshold effect. In order to identify the
threshold effect, Spearman’s correlation coefficient between logit
of sensitivity and logit of (1-speciticity) was calculated. P<.05
indicated that the threshold effect existed.
2.7. Publication bias
Publication bias was accessed by Deeks’funnel plot asymmetry
test. If P<.05, the potential publication bias was absent.
[21]
3. Results
3.1. Literature search
In this meta-analysis, the initial search strategy yielded 376
relevant citations. Of these, 74 articles were retrieved for detailed
evaluation and 62 were excluded. Finally, 10 articles met the rigid
inclusion criteria.
[15,16,22–29]
The flowchart of study selection is
shown in Figure 1.
Chen et al. Medicine (2018) 97:20 Medicine
2
3.2. Study characteristics
The main characteristics of the included studies are shown in
Table 1. The publication year ranged from 2001 to 2017. Among
the 10 studies, 868 subjects were evaluated by CTA and 872 were
by MRA. Six studies were conducted in China,
[15,22–26]
3 in the
United Kingdom,
[27–29]
, and one in the United States.
[16]
Three
studies had a prospective design,
[16,27,29]
, 6 had a retrospective
design,
[15,22–26]
and 1 did not report detailed information.
[28]
Of
the 10 studies, 2 used DSA and operation as the reference
standard for the final result of intracranial aneurysms
[24,26]
and 6
used DSA as the reference standard.
[15,16,22,23,25,29]
Details were
not provided for the remaining 2 studies.
[27,28]
3.3. Quality assessment
We used the QUADAS-2 checklist to assess the quality of the
included studies. The details were provided in Table 2. The
overall quality of the included studies was favorable, with all
studies fulfilling 11 or more of the 14 items.
3.4. Diagnostic accuracy
3.4.1. CTA. To assess the threshold effect heterogeneity, the
Spearman correlation coefficient was used to analyze the
diagnostic threshold. The Spearman correlation coefficient for
CTA was 0.299 (P=.402), which suggested that not enough
evidence supported a threshold effect heterogeneity. The pooled
results showed that the combined sensitivity, specificity, PLR, and
NLR were 0.84 (95% CI, 0.81–0.86; Fig. 2A), 0.85 (95% CI,
0.79–0.89; Fig. 2B), 4.09 (95% CI, 2.45–6.81; Fig. 2C), and 0.18
(95% CI, 0.11–0.28; Fig. 2D), respectively. The pooled DOR was
Figure 1. Flowchart of study selection procedure.
Table 1
Characteristics of included studies.
ID
CTA MRA
Author Year Country Age Design Gold standard Total TP FP FN TN TP FP FN TN
1 Tang 2013 China CTA: 31–76;MRA: 29–77 Retrospective DSA and operation 36 17 0 1 1 12 2 2 1
2 White 2001 UK 41(19–71) Prospective NA 114 36 6 9 63 32 2 13 67
3 Chen 2016 China 31–68 Retrospective DSA 120 90 3 14 8 82 7 22 8
4 Hiratsuka 2008 USA 60.2 ±10.8 (32–78) Prospective DSA 46 36 0 2 8 37 1 2 7
5 Cui 2016 China NA Retrospective DSA and operation 48 19 1 0 1 16 3 2 1
6 White 2003 UK 45(21–70) NA NA 60 24 4 6 26 21 3 9 27
7 White 2001 UK 19–75 Prospective DSA 142 52 10 11 69 47 5 16 74
8 Li 2009 China 38–78 Retrospective DSA 58 54 0 3 1 52 0 5 1
9 Xu 2017 China 52.4 ±1.2(25–76) Retrospective DSA 98 87 1 5 2 66 1 27 1
10 Zhao 2015 China NA Retrospective DSA 198 119 10 53 16 145 6 27 20
CTA =computed tomography angiography, DSA =digital subtraction angiography, FN =false-negative, FP =false-positive, MRA =magnetic resonance angiography, NA =not available, TN =true negative, TP =
true positive.
Table 2
Quality assessment of included studies.
ID Study 1 2 3 4 5 6 7891011121314
1 Tang et al
[24]
YYY?YYYYY Y ? Y Y Y
2 White et al
[27]
YYNYYYYYY Y Y Y Y Y
3 Chen et al
[25]
YYY?YYYYY Y Y Y Y ?
4 Hiratsuka et al
[16]
YYYYYYYYY Y Y Y ? Y
5 Cui et al
[26]
YYY?YYYYY Y Y N Y N
6 White et al
[28]
YYNYYYYYY Y ? Y Y Y
7 White et al
[27]
YYYYYYYYY Y Y Y ? Y
8Lietal
[23]
YYY?YYYYY Y Y Y Y ?
9Xuetal
[15]
YYY?YYYYY Y Y N Y N
10 Zhao et al
[22]
YYY?YYYYY Y Y Y Y Y
Chen et al. Medicine (2018) 97:20 www.md-journal.com
3
Figure 2. The pooled diagnostic indices for the diagnosis of intracranial aneurysm through CTA (A) sensitivity (B) specificity (C) positive LR (D) Negative LR. CTA =
computed tomography angiography, LR =likelihood ratio.
Figure 3. Diagnostic odds ratio (DOR) (A) CTA (B) MRA. CTA =computed tomography angiography, DOR =diagnostic odds ratio, MRA =magnetic resonance
angiography.
Figure 4. Summary receiver characteristics (SROC) (A) CTA (B) MRA. CTA=computed tomography angiography, MRA =magnetic resonance angiography,
SROC =summary receiver operating characteristic curves.
Chen et al. Medicine (2018) 97:20 Medicine
4
23.74 (95% CI, 10.49–53.74; Fig. 3A). The SROC curve revealed
a Q value of 0.83, and the AUC was 0.90 (Fig. 4A). The result of
Deeks’funnel plot asymmetry test suggested no evidence for the
presence of publication bias (P=.56; Fig. 5A).
3.4.2. MRA. The Spearman correlation coefficient for the
diagnostic threshold of MRA was 0.358 (P=.310). This
indicated insufficient evidence of heterogeneity resulting from
threshold effect. The overall pooled sensitivity, specificity, PLR,
and NLR were 0.80 (95% CI, 0.77–0.83; Fig. 6A), 0.87 (95% CI,
0.82–0.91; Fig. 6B), 3.61 (95% CI, 1.72–7.55; Fig. 6C), and 0.27
(95% CI, 0.21–0.35; Fig. 6D), respectively. The pooled DOR was
16.77 (95% CI, 7.38–38.11; Fig. 3B). The SROC curve showed
the Q value was 0.80, and the AUC was 0.87 (Fig. 4B). The result
of Deeks’funnel plot asymmetry test indicated there was no
publication bias (P=.15; Fig. 5B).
3.4.3. AUC value between CTA and MRA. In this study, the
AUC index was used to compare the difference of diagnosis value
between CTA and MRA for intracranial aneurysm. We found
there was no significant difference between the 2 methods (Z=
0.828, P>.05).
4. Discussion
For the detection of intracranial aneurysm, CTA, MRA, and DSA
are frequently used medical imaging methods. DSA is widely
acknowledged as the gold standard. CTA has essentially replaced
Figure 5. Deeks’funnel plot (A) CTA (B) MRA. CTA =computed tomography angiography, MRA =magnetic resonance angiography.
Figure 6. The pooled diagnostic indices for the diagnosis of intracranial aneurysm through MRA (A) sensitivity (B) specificity (C) positive LR (D) negative LR. LR =
likelihood ratio, MRA =magnetic resonance angiography.
Chen et al. Medicine (2018) 97:20 www.md-journal.com
5
DSA to detect intracranial aneurysms in many medical
institutions because of the lower cost. Furthermore, MRA is
widely used to detect the vascular disease because of its high
definition and noninvasive nature.
Although some studies have demonstrated the high sensitivity
and specificity of CTA and MRA for intracranial aneurysms, no
systematic review has evaluated which is better. This meta-
analysis is the first comparative evaluation of the diagnostic
performance of CTA and MRA for the detection of intracranial
aneurysms. Ten studies met the inclusion criteria. The studies
collectively comprised 868 patients evaluated by CTA and 872
patients evaluated by MRA. The inclusion of studies from China,
UK, and USA resulted in inevitable language bias. According to
the QUADAS-2 checklist, the qualities of the included studies
were favorable. Overall, based on several indexes in this meta-
analysis, such as sensitivity, specificity, PLR, NLR, DOR, and
AUC, CTA and MRA both had a high diagnostic value for
intracranial aneurysm.
For diagnosing intracranial aneurysm, CTA had a higher
sensitivity (0.84, 95% CI, 0.81–0.86 vs 0.80, 95% CI, 0.77–0.83)
and a slight lower specificity (0.85, 95% CI, 0.79–0.89 vs 0.87,
95% CI, 0.82–0.91) than MRA, which suggested that CTA is
better able to recognize the true patients with intracranial
aneurysm, despite the slightly higher false negative rate. In this
study, the AUC of CTA and MRA for diagnosing intracranial
aneurysm was 0.90 and 0.87, respectively. This indicates that
CTA has a slight higher accuracy than MRA in diagnosis of
intracranial aneurysms on the surface, which is consistent with
several prior studies.
[15,23]
A recent systematic review
[30]
involving 5 retrospective studies and thirteen prospective studies
evaluated the diagnostic value of three-dimensional time-of-flight
MRA to detect intracranial aneurysm; the sensitivity, specificity,
and AUC (0.89, 0.94, and 0.96, respectively) indicated that the
technique was an excellent diagnostic method. However,
compared the AUC value of CTA with MRA for intracranial
aneurysm through Ztest, we did not find a statistic difference
between the 2 methods (Z=0.828, P>.05).
The use of CTA or MRA to diagnose intracranial aneurysm
has advantages and disadvantages. For instance, El Khalidi
[31]
carried out 130 patients with nontraumatic acute subarachnoid
haemorrhage to assess the usefulness of multislice CTA in
identifying cerebral aneurysms compared with intra-arterial
DSA; the sensitivity of CTA was similar to DSA, even for
intracranial aneurysms <3 mm in size. For intracranial aneur-
ysms ≥5 mm in size, contrast-enhanced MRA reportedly has a
lower diagnostic value than CTA, with CTA recommended as the
preferred method for the ≥5 mm intracranial aneurysms.
[24]
An
examination
[32]
of the turbulent flow within aneurysms revealed
different visualizations of the aneurysms with CTA and MRA
and the findings indicated that the sensitivity of the 2 methods in
diagnosing intracranial aneurysms relies mainly on sub-mm slice
thickness for MRA and narrow collimation for CTA, respective-
ly. However, in the present meta-analysis, we could not
distinguish the relative performance advantage of CTA and
MRA for different size of tumors because of insufficient
information in the included studies.
Several limitations should be considered. First and foremost,
despite the comprehensive search strategy, with screening of
the literature, study selection, extraction of data, and
independent assessment of study quality, only 10 articles were
included. The limited number of studies might influence the
results. Further high-quality studies on a larger scale are
needed. Secondly, the exclusion of other than English studies
might have led to an inevitable publication bias. Thirdly,
because of the limitation of extracted data, we were not able to
analyze the value of CTA or MRA for detecting different
periods of intracranial aneurysm.
In conclusion, this comprehensive meta-analysis results that
CTA and MRA both have the same and high diagnostic value for
intracranial aneurysm. However, considering the limitation of
sample size, the results should be viewed with caution.
Acknowledgments
XC, YD, and YL designed the study and wrote the manuscript.
DM and LX performed the statistical analysis. HT, YL and CY
discussed the results.
Author contributions
Conceptualization: Yonghai Dong.
Data curation: Dongyang Ma.
Formal analysis: Dongyang Ma, Lei Xu.
Investigation: Xiaodan Chen.
Methodology: Yonghai Dong.
Project administration: Yonghai Dong.
Supervision: Cheng Yang.
Writing –original draft: Yun Liu, Yonghai Dong.
Writing –review & editing: Xiaodan Chen, Huazhang Tong.
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