Diagnostic Accuracy of Magnetic Resonance Angiography

for Internal Carotid Artery Disease

A Systematic Review and Meta-Analysis
Sarah M. Debrey, BA; Hua Yu, MD; John K. Lynch, DO, MPH; Karl-Olof Lövblad, MD;
Violet L. Wright, RN; Sok-Ja D. Janket, MD, MPH; Alison E. Baird, FRACP, PhD

Background and Purpose—Accurate diagnosis of the degree of internal carotid artery (ICA) stenosis is needed for
decisions regarding optimal stroke prevention. Noninvasive magnetic resonance angiography (MRA) is being proposed
and used as a replacement for the gold standard, intra-arterial angiography. Our purpose was to perform a systematic
review and diagnostic meta-analysis to determine the sensitivity and specificity of time-of-flight (TOF) MRA and
contrast-enhanced (CE) MRA for the detection of (1) high-grade (ⱖ70% to 99%) ICA stenoses; (2) ICA occlusions; (3)
moderately severe (50% to 69%) ICA stenoses; and (4) compare the overall accuracy of the 2 MRA techniques.
Methods—The medical literature on MRA and the diagnosis of ICA steno-occlusive disease was reviewed through the
PubMed, EMBASE, and SCOPUS databases. All publication years were included through to November 2006. Studies
were eligible for inclusion if they compared the accuracy of TOF or CE MRA for the detection of ICA disease against
intra-arterial angiography and reported sufficient data.
Results—The overall sensitivity of TOF MRA for the detection of ⱖ70% to 99% ICA stenoses was 91.2% (95% CI: 88.9%
to 93.1%) with a specificity of 88.3% (86.7% to 89.7%), whereas the sensitivity of CE MRA was 94.6% (92.4% to
96.4%) with a specificity of 91.9% (90.3% to 93.4%). For the detection of ICA occlusions, the sensitivity of TOF MRA
was 94.5% (91.2% to 96.8%) and the specificity was 99.3% (98.9% to 99.6%), whereas the sensitivity and specificity
values for CE MRA were 99.4% (96.8% to 100%) and 99.6% (99.2% to 99.9%), respectively. For moderately severe
(50% to 69%) stenoses, TOF MRA had a sensitivity of only 37.9% (29.3% to 47.1%) and a specificity of 92.1% (89.6%
to 94.1%); for CE MRA, the pooled sensitivity value was somewhat better at 65.9% (57.0% to 74.0%), whereas the
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specificity was 93.5% (91.3% to 95.3%).

Conclusions—TOF MRA and CE MRA showed high accuracy for the detection of high-grade ICA stenoses and occlusions
with CE MRA having the edge over TOF MRA, but had only poor (TOF MRA) to fair (CE MRA) sensitivity for the
detection of moderately severe stenoses. (Stroke. 2008;39:2237-2248.)
Key Words: carotid arteries 䡲 carotid artery stenosis 䡲 magnetic resonance angiography
䡲 angiography 䡲 contrast-enhanced magnetic resonance angiography

B ecause stroke is the third leading cause of death and the

principal cause of disability in America, the public
health implications for its prevention are monumental. In
particular, with the aging of the United States population
rising rapidly, stroke rates are expected to increase substan-
tially over the next decade. Atherosclerotic internal carotid
artery disease (ICAD) is responsible for many ischemic
strokes (estimates range from 20% to 40%)1 and a significant
proportion of transient ischemic attacks.
The accurate diagnosis of stenotic and occlusive ICAD is
essential for determining which surgical or medical inter-
ventions should be used for primary and secondary stroke
prevention. Carotid endarterectomy (CEA) is the most com-
monly performed surgery for the treatment of atherosclerotic
ICAD with over 660 000 surgeries performed between 2000
and 2005 in nonfederal US hospitals.2 In patients with
symptomatic high-grade (70% to 99%) internal carotid artery
(ICA) stenoses, the North American Symptomatic Carotid
Endarterectomy Trial (NASCET) reported an absolute reduc-
tion in the risk of stroke at 2 years of 17% after CEA relative
to medical therapy; the European Carotid Surgery Trial
(ECST) reported an 11.6% absolute risk reduction at 5 years
in patients with moderate and high-grade stenoses.3–5 In the
NASCET trial, there was also some benefit of CEA in

Received November 12, 2007; final revision received December 27, 2007; accepted January 14, 2008.
From the Stroke Neuroscience Unit (S.M.D., V.L.W., H.Y., J.K.L., A.E.B.), National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, MD; and Boston University School of Dental Medicine (S.J.J.), Boston, Mass, USA and HUG Hôpital Cantonal, Geneva,
Switzerland.
Correspondence to Alison E. Baird, FRACP, PhD, Professor of Neurology, Physiology and Pharmacology, and, Director of the Division of
Cerebrovascular Disease and Stroke, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 1213, Brooklyn, NY 11203. E-mail alison.baird@
downstate.edu
© 2008 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.107.509877

2237
 2238 Stroke August 2008
patients with moderate (50% to 69%) stenoses: symptomatic
patients with 50% to 69% ICA stenoses had an absolute risk
reduction of stroke of 4.6% at 5 years.3 Furthermore, in the
Asymptomatic Carotid Atherosclerosis Study, asymptomatic
patients with 60% to 99% stenoses showed a modest benefit
from CEA.6 Similar results were obtained in patients with
asymptomatic 60% to 99% stenoses randomized to either
immediate or deferred CEA.7 Based on these figures, CEA is
recommended for the secondary prevention of stroke in
patients with high-grade stenoses and after consideration of
other clinical factors for many with moderate-grade stenoses
and also some with asymptomatic disease.8,9 Carotid artery
stenting may be an alternative to CEA in patients who are at
very high surgical risk.10 –13
Intra-arterial angiography (IAA), most commonly performed
using digital subtraction angiography (DSA), is considered the
gold standard technique for evaluating the presence and
extent of ICAD. The stenosis grades used in the NASCET
and ECST trials were determined by IAA. However, IAA is
invasive, costly, and has risks that include an approximate 4%
risk of transient ischemic attack and a 1% risk of disabling
stroke or death.14 Because of these risks, there have been
increasing calls for noninvasive screening methods for ICAD.
In many hospitals, noninvasive imaging methods such as
ultrasound, magnetic resonance angiography (MRA) and com-
puted tomography angiography, either alone or in combina-
tion, are already being used to screen and select patients for
CEA.15 Ultrasound is affordable and readily available, but the
images produced by ultrasound are often lower in quality than
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that of computed tomography angiography or MRA and the
accuracy is highly operator-dependent.
MRA has become widely used as a noninvasive diagnostic
imaging modality for ICAD. It avoids the radiation and
iodinated contrast exposure associated with computed tomog-
raphy angiography. The first MRA method, phase-contrast
MRA, was developed in the 1980s and was quickly followed
by 2-dimensional (2D) and 3-dimensional (3D) time-of-flight
(TOF) MRA. TOF MRA has been widely adopted for an
array of clinical indications but is relatively insensitive to
slow flow and is associated with long scan times and signal
voids, all of which can lead to poor-quality imaging and
overestimation of stenoses. More recently, contrast-enhanced
(CE) MRA has been introduced. CE MRA produces high-
quality images in a very short period of time and may alleviate
some of the drawbacks associated with TOF MRA.16 Yet, to
be a useful method for studying ICAD, the accuracy of MRA
is imperative, because decisions regarding optimum stroke
prevention depend on the results obtained. Of particular
importance are the potential overcall of stenosis grade and the
differentiation of high-grade stenosis from occlusion (occlu-
sions not usually being amenable to surgery) and the accurate
diagnosis of moderate-grade (50% to 69%) stenosis for the
patient to receive optimal management.
Despite the rapid technological advances in MRA and a
large radiological literature, there has been little systematic
evaluation of its diagnostic accuracy.17–21 The one prior
meta-analysis included a select population of symptomatic
patients studied up to April 2004, and data for moderate-
grade stenoses were available in a very small number of
patients only.22 Our purpose was to provide an update and
determine the sensitivity and specificity of TOF MRA and
CE MRA for the detection of (1) high-grade (70% to 99%)
ICA stenoses; (2) ICA occlusions; (3) moderately severe
(50% to 69%) ICA stenoses; and (4) to compare the overall
accuracies of the 2 MRA techniques using IAA as the gold
standard.
Materials and Methods
Data Sources
The medical literature on MRA and diagnosis of ICA stenosis was
reviewed through a variety of databases. Searches were run by 2 of
the reviewers (SMD and AEB) using PubMed, EMBASE, SCOPUS,
and the Cochrane Controlled Trials Register. All publication years
were included with the search being performed for all papers published
through to November 2006. PubMed was searched using medical
subject headings terms and from the papers identified using these
terms, reference lists were searched to identify any additional articles.
No initial limits were set in this search, although only papers
published in English were accepted. The Cochrane Controlled Trials
Register database, SCOPUS, and EMBASE were all searched using
particular keywords, described subsequently. Hand searches of
selected papers’ references as well as recent publications of several
key journals, including Stroke, Neurology, Circulation, and Radiol-
ogy, were performed. Two independent searches were performed,
one for TOF MRA and one for CE MRA. However, the key words
and medical subject headings terms searched were the same, because
both TOF and CE MRA can be searched with identical terms. By
performing separate searches for forms of MRA, the researchers
were able to accurately exclude papers according to specific criteria.
The medical subject headings terms were carotid arteries, carotid
stenosis, magnetic resonance angiography, and angiography. The
key words were carotid artery, carotid artery stenosis, magnetic
resonance angiography, contrast-enhanced magnetic resonance an-
giography, and angiography. Although other search terms exist in
Embase and Scopus, it was found that the terms used were thorough
and sufficient, due to the large quantity of results, in addition to the
high overlap of papers found using different search terms. Hand
searches of relevant journals resulted in complete concordance with
the online databases, thereby validating these database searches as
comprehensive and complete. During the initial search strategy, over
11 000 papers (duplicates included) were identified using 3 online
databases (8231 with PubMed, 1209 with EMBASE, and 2119 with
SCOPUS). The titles of all articles obtained were screened, and all
abstracts of possible articles were further screened. Papers with
abstracts that clearly fitted into a category for exclusion or diagnostic
tests for medical conditions unrelated to cerebrovascular disease
were eliminated at this level of the search before a full text was
printed. After search completion, independent readers checked for
agreement. On identification of a possible abstract for inclusion, the
full text of the article was read and assessed for inclusion. In our
search, there were no possible abstracts lacking full text versions.
Any disagreements over article inclusion were solved by discussion.
The search protocol is provided in Figure 1.
Study Selection
Inclusion Criteria
Studies were eligible for inclusion if they (1) evaluated the accuracy
of 2D and/or 3D TOF MRA and/or CE MRA for the diagnosis of
ICA stenosis (with or without data on occlusion) against the gold
standard of IAA; (2) reported sufficient data to construct a 2⫻2 table
of test performance; (3) conformed to the Standards for Reporting
of Diagnostic Accuracy criteria23; and (4) had image evaluations
performed by blinded observers. Due to the limited number of
studies published on this topic, all study designs were included
(Tables 1 and 2). Papers that included only symptomatic patients
were included and evaluated separately in the subgroup analyses.
The QUADAS tool for evaluating the quality of included studies was
 Debrey et al
PubMed Embase Scopus
Search 1: 764 Search 1: 817 Search 1: 1536
Search 2: 551 Search 2: 392 Search 2: 583
Search 3: 6916
74 TOF MRA
24 CE MRA
37 TOF MRA Final Included
21 CE MRA Studies
Head to head
comparison of
TOF MRA and CE 5 TOF MRA
and CE MRA
MRA
For PubMed, the three searches were entered as follows:
1) carotid arteries [MeSH terms} AND magnetic resonance angiography [MeSH
terms]
2) carotid stenosis [MeSH terms] AND magnetic resonance angiography [MeSH
terms]
3) carotid arteries [MeSH terms] AND angiography [MeSH terms]
For Embase and Scopus, the two searches used were:
1) ‘carotid artery’ AND ‘magnetic resonance angiography’
2) ‘carotid artery stenosis’ AND ‘magnetic resonance angiography’
Figure 1. Literature search strategy.
used as a reference as well; however, 3 of the 14 items of the
QUADAS tool were not entirely applicable to this particular diag-
nostic meta analysis.24 For instance, the spectrum of subjects being
screened for ICAD was not necessarily the same as those patients
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receiving the test in practice, which would potentially include only
symptomatic or “high-risk” patients. However, it was necessary in
this analysis to include studies that examined a range of healthy and
ill subjects to determine the accuracy of these imaging techniques
across a large spectrum. Additionally, the clinical data available to
radiologists during image interpretation for these studies was not the
same as would be available when the test is used in practice, and
uninterpretable test results in many studies were often not discussed
in great detail.
Exclusion Criteria
Exclusion criteria were lack of comparison with angiography as the
gold standard or lack of data for a 2⫻2 table. Where data were
insufficient, efforts were made to contact the study authors, but if
there was no response, the papers were excluded. Studies that used
duplicate data were excluded.
Data Extraction
Measurement of Stenosis
In the majority of the studies after 1995, the degree of ICA stenosis
was measured using either NASCET guidelines (in which the grade
of the stenotic lesion is determined relative to a segment of distal
disease-free ICA) or ECST guidelines (where the grade of the stenotic
lesion is compared relative to what the original ICA arterial outline
would have been at the point of maximum stenosis); a 70% ECST
stenosis is approximately equivalent to a 50% NASCET stenosis.
The ECST measurements in this meta-analysis were not corrected to
NASCET measurements; therefore, because this contributes to het-
erogeneity in the study, a subgroup analysis was performed in which
the ECST papers were excluded. After final selection of included
papers, data were extracted to form 2⫻2 tables of diseased and
nondiseased vessels as seen on MRA using conventional angiogra-
phy as the gold standard. The following comparisons of stenosis
grades were performed: (1) to evaluate high-grade stenoses, patients
with ⱖ70% to 99% ICA stenosis (ie, operative candidates) were
Diagnostic Accuracy of MRA for ICA Disease 2239
compared with those with 0% to 69% stenosis and 100% stenosis (ie,
occlusions); (2) to evaluate ICA occlusion (nonoperative), patients
with occlusion were compared with those with 0% to 99% stenosis;
and (3) to evaluate moderate-grade ICA stenosis (potential operative
candidates), patients with 50% to 69% stenosis were compared with
those with 0% to 49% and 70% to 100% stenosis.
Study Quality
Study quality was evaluated by examining the following criteria:
duration of time between imaging procedures, prospective/retrospec-
tive design, number of subjects involved, the number of symptomatic
versus asymptomatic patients, setting of study, blinding of readers,
and whether subjects were consecutive (ie, as opposed to sporadic).
Data Synthesis
The diagnostic accuracy of MRA in comparison to IAA was assessed
by sensitivity and specificity values, receiver operator characteristic
(ROC) curves, and positive and negative likelihood ratios. Meta-DiSC
software25 was used to generate pooled sensitivities and specificities and
summary ROC plots. In this fixed effects modeling approach, each
study was assigned a weight dependent on the number of arteries
analyzed in that study. The degree of heterogeneity between studies
was reported using the Cochran ␹2 (Cochrane Q) statistic. When this
value was divided by the degrees of freedom (number of studies
minus 1), a value of greater than 1 is indicative of heterogeneity.
When this value was found to be statistically significant, causes of
heterogeneity were examined; sources of heterogeneity were also
explored when Q/degrees of freedom was found to be greater than 1
but not statistically significant. In interpreting the ROC plots, an
ROC curve for an inconclusive test will have a flatter slope and will
lie close to the diagonal line as it rises, whereas the ROC line of a
perfect diagnostic test will have a very steep ascent, because both
sensitivity and specificity are equal to 100%. In clinical practice, it
is suggested that a positive likelihood ratio of greater than 10 or a
negative likelihood ratio less than 0.1 support high diagnostic
accuracy for the respective test. Because likelihood ratios, diagnostic
ORs, and summary ROC curves take into account both the sensitivity
and specificity data, and therefore illustrate any tradeoffs that may
occur, these values are considered to be more valuable in terms of
diagnostic accuracy than a pooled, weighted value for sensitivity and
specificity.
Results
Included Studies
After the initial screening period, 72 papers investigating TOF
MRA and 24 papers investigating CE MRA, some overlapping,
were selected for further screening. Of these papers, 37 TOF
MRA17,18,26 – 60 and 21 CE MRA papers16,26,27,33,35,37,61–75 ful-
filled the inclusion criteria (Tables 1 and 2). Of the TOF
papers, 11 used 2D TOF MRA, 14 used 3D TOF MRA, and
12 included both 2D and 3D TOF data (Table 1). For TOF
MRA, there were 1651 subjects, whereas for CE MRA, there
were 1047 subjects. Reasons for exclusion between primary
and secondary screening included: duplicate data (5 TOF),
poor quality (4 TOF), failure to use conventional angiography
as the gold standard (4 TOF), data not provided/failed
attempts to locate data (11 TOF MRA, 3 CE MRA), and other
reasons, including papers only investigating intracranial ste-
noses or unrelated subject matter (12 TOF). The NASCET
criteria for the grading of stenoses were used in the majority
of studies; ECST criteria were used in 2 of 37 TOF MRA
studies and one of 21 CE MRA study; in 11 early TOF MRA
studies (before 1995), the method of stenosis measurement
was not described. In one CE MRA study, the method of
 2240 Stroke August 2008

Table 1. Included TOF MRA Papers

No. of Type of Consecutive Time Between Definition of
Author Year Patients TOF Population Prospective? Patients? MRA and DSA High-Grade Stenosis*
Anzalone 2005 49 3D Symptomatic Yes Yes 48 hours ⬎70%
Fellner 2005 21 3D Prescreened with ultrasound No Yes 14 days ⬎80%†
DeMarco 2004 51 2D Prescreened with ultrasound No Not stated Not stated ⬎70%
or symptomatic
Scarabino 2003 23 3D Clinical signs of CVI Not stated Yes 24 hours ⬎80%
Nederkoorn 2002 203 3D 186 of 203 symptomatic Not stated Yes 1 month ⬎70%
Patel 2002 47 2D and 3D Symptomatic Yes Yes 24 hours ⬎80%†
Binaghi 2001 19 2D and 3D Prescreened with DSA Not stated Yes 24 hours ⬎70%
Johnson 2000 40 3D Symptomatic Yes Not stated Not stated ⬎70%
Back 2000 40 2D Referred for CEA No No Not stated ⬎75%
Elgersma 2000 38 3D Prescreened with ultrasound No Not stated 2 days ⬎70%
and symptomatic
Serfaty 2000 33 3D Half symptomatic Yes Yes Not stated ⬎70%
Modaresi 1999 50 3D Referred for CEA Not stated No Not stated ⬎70%
Sardanelli 1999 32 2D and 3D Symptomatic Not stated Yes 7 days ⬎70%
Ozaki 1999 29 3D Some symptomatic No No Not stated ⬎70%
Scarabino 1998 64 2D and 3D Clinical signs of CVI Not stated Yes 24 hours ⬎70%
Magarelli 1998 20 3D Symptomatic, referred for DSA Not stated Not stated 3 days ⬎70%
Jackson 1998 50 2D Prescreened with ultrasound, Yes Yes 21 days ⬎60%
referred for DSA
Strotzer 1998 40 3D Suspected ICAD Not stated Yes Not stated ⬎70%
Huston 1998 50 2D and 3D Referred for DSA Yes Yes 2 weeks ⬎70%
Fellner 1997 31 2D and 3D Prescreened with ultrasound Yes Not stated Not stated ⬎70%
Patel 1995 88 2D and 3D 74 of 88 symptomatic Yes Not stated Not stated ⬎70%
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Nicholas 1995 40 2D Prescreened with ultrasound No Not stated Not stated ⬎70%
and DSA
Dadachanji 1995 20 2D Clinical signs of CVI Not stated Yes Not stated ⬎70%‡
Vanninen 1995 65 3D 55 of 65 referred for DSA Not stated Yes 1 day to 2 months ⬎70%
Young 1994 70 2D and 3D Prescreened with ultrasound Yes Yes 2 to 3 weeks ⬎70%‡
and symptomatic
DeMarco 1994 20 2D and 3D Referred for DSA Yes Yes 3 days ⬎70%‡
White 1994 60 2D Symptomatic Yes Yes Within days ⬎60%‡
Mittl 1994 38 2D Clinical signs of CVI No Not stated Not stated ⬎70%
Sitzer 1993 50 2D Prescreened with ultrasound Yes Yes 2 to 43 days ⬎70%‡
and symptomatic
Turnipseed 1993 30 2D Symptomatic Yes Yes Not stated ⬎70%
Chiesa 1993 63 3D Prescreened with ultrasound Not stated Not stated Not stated ⬎60%‡
and symptomatic
Huston 1993 50 2D Symptomatic, referred for DSA Yes Yes Same day ⬎80%
Anson 1993 20 2D Symptomatic No Not stated Less than 2 weeks ⬎75%‡
Pan 1992 34 2D and 3D Symptomatic Not stated Not stated Not stated ⬎60%‡
Furuya 1992 22 3D Suspected ICAD No Not stated Not stated ⬎60%‡
Mattle 1991 20 2D or 3D 13 of 20 symptomatic No Not stated Not stated ⬎70%‡
Kido 1991 31 2D Suspected ICAD Not stated Not stated 24 hours ⬎80%‡
*NASCET measurement method used to determine stenosis grade except where stated.
†ECST method.
‡Method used to determine stenosis grade measurement not stated.
CVI indicates cerebrovascular insufficiency.

measurement was not reported. Less than half of these studies TOF papers, 26 defined high-grade stenosis as 70% to 99%,
were prospectively carried out or were conducted in un- 5 as 60% to 99%, 2 as 75% to 99%, and 4 as 80% to 99%
selected populations. Only 12 of 37 TOF MRA and 5 of 21 (Table 1). Of the 21 CE MRA papers included in this
CE MRA papers had sample sizes ⱖ50 subjects. Of the 37 analysis, 18 defined high-grade stenosis as 70% to 99% (Table
 Debrey et al Diagnostic Accuracy of MRA for ICA Disease 2241

Table 2. Included CE MRA Papers

No. of Consecutive Time Between Definition of
Author Year Patients Population Prospective? Patients? MRA and DSA High-Grade Stenosis*
Wright 2005 81 Prevalent population Yes Yes 72 hours ⬎70%
Fellner 2005 21 Prescreened with ultrasound No Yes 14 days ⬎80%†
Anzalone 2005 49 Symptomatic Yes Yes 48 hours§ ⬎70%
Yang 2005 40 Suspected ICAD No Not stated 1 month ⬎70%‡
Butz 2004 50 30 of 50 symptomatic No Yes 1 week ⬎70%
U-King-Im 2004 167 Symptomatic Yes Yes 3 weeks ⬎70%
Willinek 2004 50 Suspected ICAD Yes Yes 5 days ⬎70%
Borisch 2003 39 Symptomatic Yes Yes 10 days ⬎70%
Randoux 2003 33 Prescreened with ultrasound Yes Yes 2 weeks ⬎50%
Alvarez-Linera 2003 40 Symptomatic, referred for DSA No Yes 2 days ⬎70%
Cosottini 2003 92 87 of 92 symptomatic No Not stated 1 month ⬎70%
Remonda 2002 120 Prescreened with ultrasound No Yes ⬍2 weeks ⬎70%
Sundgren 2002 24 Prescreened with ultrasound and symptomatic Yes Yes 48 hours ⬎66%
Lenhart 2002 43 Suspected ICAD Yes Yes 24 hours ⬎70%
Wutke 2002 30 Prescreened with ultrasound No Not stated ⬍4 days ⬎70%
Randoux 2001 22 Symptomatic No Yes 2 weeks ⬎70%
Serfaty 2000 33 Prescreened with ultrasound or symptomatic Yes Yes Not stated ⬎70%
Johnson 2000 39 Prescreened with ultrasound and symptomatic Yes Not stated Not stated ⬎70%
Scarabino 1999 23 Symptomatic No Yes 24 hours ⬎70%‡
Sardanelli 1998 30 Symptomatic No Yes 7 days ⬎70%
Remonda 1998 21 17 of 21 symptomatic Yes Yes 12 hours ⬎70%
*NASCET measurement method used to determine stenosis grade except where stated.
†ECST method.
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‡Method used to determine stenosis grade measurement not stated.

§Rotational angiography used as the gold standard.

2), whereas one measured stenosis of 80% to 99%, one of
66% to 99%, and the last 50% to 99%.
Detection of >70% to 99% Internal Carotid
Artery Stenoses
The results for 70% to 99% stenosis include the 32 of 37 TOF
MRA and 19 of 21 CE MRA papers that reported results for
ⱖ70% to 99% stenoses, because these patients are operative
candidates (Table 3). The results for pooled sensitivities and
specificities for ⱖ70% to 99% ICA stenosis are depicted in
Figure 2A–D. The pooled sensitivities for TOF MRA and CE
MRA for the detection of ⱖ70% to 99% stenosis were 91.2%
(95% CI: 88.9% to 93.1%) and 94.6% (92.4% to 96.5%), respec-
tively. The results for specificity were 88.3% (86.7% to 89.7%)
for TOF MRA and 91.9% (90.3% to 93.4%) for CE MRA
(Table 3). Summary ROC results are presented in Figure 3A–B.
In addition to pooled sensitivity and specificity plots, positive
and negative likelihood ratios and diagnostic ORs were also
calculated. For TOF MRA, the positive and negative likeli-
hood ratios were 7.53 (5.75 to 9.87) and 0.13 (0.10 to 0.16),
respectively, whereas for CE MRA, the values were 12.26
(8.00 to 18.8) and 0.07 (0.05 to 0.11). Although the diagnos-
tic accuracy for both MRA types was high, a difference
between TOF MRA and CE MRA does exist, CE MRA being
the more accurate and proven to be more robust in the likelihood
ratio data than in the pooled sensitivity and specificity data.
Detection of Internal Carotid Artery Occlusions
Occlusion data were available in 29 of 37 TOF MRA studies
and 18 of 21 CE MRA studies (Table 3). The sensitivity of
TOF MRA for the detection of ICA occlusions was 94.5%

Table 3. Diagnostic Accuracy for >70% to 99% ICA Stenosis, ICA Occlusion, and 50% to 69% ICA Stenosis
TOF MRA CE MRA

Studies, N Patients, N Sensitivity, % Specificity, % Studies, N Patients, N Sensitivity, % Specificity, %

ⱖ70% to 99% 32 1422 91.2 (88.9–93.1) 88.3 (86.7–89.7) 19 990 94.6 (92.4–96.4) 91.9 (90.3–93.4)
Occlusion 29 1341 94.5 (91.2–96.8) 99.3 (98.9–99.6) 18 923 99.4 (96.8–100) 99.6 (99.2–99.9)
50% to 69% 7 415 37.9 (29.3–47.1) 92.1 (89.7–94.1) 8 454 65.9 (57.0–74.0) 93.5 (91.3–95.3)
TOF MRA versus CE 5 172 89.6 (82.2–94.7) 92.7 (88.5–95.7) 5 172 96.2 (90.5–99.0) 92.7 (88.6–95.7)
MRA 70% to 99%*
*Head-to-head comparison of TOF MRA and CE MRA in the same group of 172 subjects for the detection of 70% to 99% ICA stenosis.
 2242 Stroke August 2008

Pooled Sensitivity- 70-99% stenosis Pooled Specificity- 70-99% stenosis

A TOF MRA C TOF MRA

Sensitivity (95% CI) Specificity (95% CI)
Anzalone 2005 0.90 (0.73 - 0.98) Anzalone 2005 0.94 (0.85 - 0.98)
Fellner 2005 1.00 (0.72 - 1.00) Fellner 2005 0.97 (0.83 - 1.00)
DeMarco 2004 0.94 (0.80 - 0.99) DeMarco 2004 0.97 (0.89 - 1.00)
Scarabino 2003 0.89 (0.52 - 1.00) Scarabino 2003 0.94 (0.81 - 0.99)
Nederkoorn 2002 0.93 (0.85 - 0.97) Nederkoorn 2002 0.83 (0.78 - 0.87)
Patel 2002 1.00 (0.83 - 1.00) Patel 2002 0.57 (0.29 - 0.82)
Binaghi 2001 0.93 (0.66 - 1.00) Binaghi 2001 1.00 (0.84 - 1.00)
Johnson 2000 0.82 (0.65 - 0.93) Johnson 2000 1.00 (0.92 - 1.00)
Back 2000 1.00 (0.87 - 1.00) Back 2000 0.79 (0.64 - 0.89)
Elgersma 2000 0.93 (0.66 - 1.00) Elgersma 2000 0.60 (0.39 - 0.79)
Serfaty 2000 0.88 (0.64 - 0.99) Serfaty 2000 0.93 (0.82 - 0.99)
Modaresi 1999 0.98 (0.89 - 1.00) Modaresi 1999 0.73 (0.54 - 0.87)
Sardanelli 1999 1.00 (0.77 - 1.00) Sardanelli 1999 0.80 (0.66 - 0.91)
Ozaki 1999 0.83 (0.36 - 1.00) Ozaki 1999 0.68 (0.53 - 0.81)
Scarabino 1998 1.00 (0.78 - 1.00) Scarabino 1998 0.99 (0.95 - 1.00)
Magarelli 1998 1.00 (0.74 - 1.00) Magarelli 1998 1.00 (0.88 - 1.00)
Strotzer 1998 0.92 (0.74 - 0.99) Strotzer 1998 0.94 (0.84 - 0.99)
Huston 1998 0.78 (0.56 - 0.93) Huston 1998 0.90 (0.80 - 0.96)
Fellner 1997 0.95 (0.74 - 1.00) Fellner 1997 0.92 (0.83 - 0.97)
Patel 1995 0.94 (0.85 - 0.99) Patel 1995 0.85 (0.78 - 0.91)
Nicholas 1995 0.88 (0.64 - 0.99) Nicholas 1995 0.98 (0.91 - 1.00)
Dadachanji 1995 1.00 (0.48 - 1.00) Dadachanji 1995 1.00 (0.90 - 1.00)
Vanninen 1995 0.93 (0.68 - 1.00) Vanninen 1995 0.89 (0.80 - 0.95)
Young 1994 0.86 (0.74 - 0.94) Young 1994 0.93 (0.85 - 0.97)
DeMarco 1994 1.00 (0.63 - 1.00) DeMarco 1994 0.90 (0.74 - 0.98)
Mittl 1994 0.91 (0.71 - 0.99) Mittl 1994 0.75 (0.60 - 0.86)
Sitzer 1993 0.74 (0.58 - 0.86) Sitzer 1993 0.86 (0.75 - 0.94)
Turnipseed 1993 0.93 (0.77 - 0.99) Turnipseed 1993 0.92 (0.74 - 0.99)
Huston 1993 0.90 (0.55 - 1.00) Huston 1993 0.83 (0.73 - 0.90)
Anson 1993 1.00 (0.74 - 1.00) Anson 1993 0.78 (0.40 - 0.97)
Mattle 1991 0.90 (0.55 - 1.00) Mattle 1991 0.93 (0.77 - 0.99)
Kido 1991 0.77 (0.46 - 0.95) Kido 1991 0.91 (0.80 - 0.98)

Pooled Sensitivity = 0.91 (0.89 to 0.93) Pooled Specificity = 0.88 (0.87 to 0.90)
Chi-square = 51.00; df = 31 (p = 0.0133) Chi-square = 146.80; df = 31 (p = 0.0000)
0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 39.2 % 0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 78.9 %
Sensitivity Specificity

B CE MRA D CE MRA
Specificity (95% CI)
Sensitivity (95% CI)
Wright 2005 0.86 (0.80 - 0.92)
Wright 2005 0.64 (0.35 - 0.87)
Fellner 2005 0.84 (0.66 - 0.95)
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Fellner 2005 1.00 (0.72 - 1.00)

Anzalone 2005 0.96 (0.88 - 0.99)
Anzalone 2005 0.97 (0.82 - 1.00)
Yang 2005 0.99 (0.92 - 1.00)
Yang 2005 0.92 (0.62 - 1.00)
Butz 2005 0.91 (0.81 - 0.96)
Butz 2005 0.94 (0.81 - 0.99)
U-King-Im 2004 0.81 (0.73 - 0.87)
U-King-Im 2004 0.93 (0.84 - 0.98) Willinek 2004 1.00 (0.94 - 1.00)
Willinek 2004 0.93 (0.76 - 0.99)
Borisch 2003 0.79 (0.64 - 0.91)
Borisch 2003 0.97 (0.84 - 1.00)
Alvarez-Linera 2003 0.96 (0.85 - 0.99)
Alvarez-Linera 2003 0.97 (0.85 - 1.00)
Cosottini 2003 0.96 (0.91 - 0.99)
Cosottini 2003 0.98 (0.92 - 1.00)
Remonda 2002 0.96 (0.92 - 0.99)
Remonda 2002 0.93 (0.85 - 0.98) Lenhart 2002 0.86 (0.75 - 0.94)
Lenhart 2002 0.96 (0.80 - 1.00)
Wutke 2002 0.92 (0.78 - 0.98)
Wutke 2002 1.00 (0.85 - 1.00)
Randoux 2001 1.00 (0.89 - 1.00)
Randoux 2001 0.92 (0.64 - 1.00)
Serfaty 2000 0.85 (0.71 - 0.94)
Serfaty 2000 0.94 (0.71 - 1.00)
Johnson 2000 0.95 (0.84 - 0.99)
Johnson 2000 0.94 (0.80 - 0.99) Scarabino 1999 1.00 (0.91 - 1.00)
Scarabino 1999 1.00 (0.66 - 1.00)
Sardanelli 1999 1.00 (0.92 - 1.00)
Sardanelli 1999 1.00 (0.77 - 1.00)
Remonda 1998 0.96 (0.80 - 1.00)
Remonda 1998 0.94 (0.73 - 1.00)

Pooled Specificity = 0.92 (0.90 to 0.93)

Pooled Sensitivity = 0.95 (0.92 to 0.96)
Chi-square = 81.41; df = 18 (p = 0.0000)
Chi-square = 23.38; df = 18 (p = 0.1764)
0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 77.9 %
0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 23.0 %
Specificity
Sensitivity

Figure 2. A–D, Pooled sensitivity and specificity values for the detection of ⱖ70% to 99% stenosis by TOF MRA and CE MRA.

(91.2% to 96.8%) with a specificity of 99.3% (98.9% to
99.6%), whereas the sensitivity of CE MRA was 99.4% (95%
CI: 96.8% to 100%) with a specificity of 99.6% (99.2% to
99.9%). The positive and negative likelihood ratios of TOF
MRA were 56.24 (38.87 to 81.36) and 0.12 (0.07 to 0.19). For
CE MRA, these values were 80.5 (48.16 to 134.70) and 0.07
(0.04 to 0.13), respectively, again supporting a superior accu-
racy of CE MRA over TOF MRA for the detection of ICA
occlusion. The corresponding summary ROC curves are shown
in Figure 3C–D.
Detection of Moderate-Grade Internal Carotid
Artery Stenoses 50% to 69%
Although it has been shown that CEA can be effective in
symptomatic patients with 50% to 69% stenosis, very few
papers published data on this level of stenosis. Only 7 of 37
TOF MRA and 8 of 21 CE MRA papers presented these data
(Table 3; Figure 4). The 7 TOF papers resulted in a pooled
sensitivity of only 37.9% (29.3% to 47.1%) and a pooled
specificity of 92.1% (89.7% to 94.1%). The 8 CE MRA
papers had a pooled sensitivity of 65.9% (57.0% to 74.0%)
and a pooled specificity of 93.5% (91.3% to 95.3%).
Studies Comparing Time-of-Flight Magnetic
Resonance Angiography and Contrast-Enhanced
Magnetic Resonance Angiography in the Same
Patients for the Detection of High-Grade Internal
Carotid Artery Stenoses
Only 5 studies assessed both TOF MRA and CE MRA in the
same subjects (n⫽172) for the detection of high-grade steno-
 Debrey et al Diagnostic Accuracy of MRA for ICA Disease 2243

sROC Curves- 70-99% stenosis sROC Curves- ICA Occlusion

A TOF MRA C TOF MRA

Sensitiv ity SROC Curv e
1 Sensitiv ity SROC Curv e
1

Symmetric SROC
0.9 AUC = 0.9597 Symmetric SROC
SE(AUC) = 0.0063 0.9 AUC = 0.9880
SE(AUC) = 0.0047
Q* = 0.9040
SE(Q*) = 0.0091 Q* = 0.9537
0.8 SE(Q*) = 0.0107
0.8

0.7
0.7

0.6 0.6

0.5 0.5

0.4 0.4

0.3 0.3

0.2 0.2

0.1 0.1

0 0
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1-specificity 1-specificity

D CE MRA
B CE MRA
Sensitivity SROC Curve
Sensitiv ity SROC Curv e 1
1
Symmetric SR
Symmetric SROC 0.9 AUC = 0.9922
0.9 AUC = 0.9812 SE(AUC) = 0.0
SE(AUC) = 0.0055 Q* = 0.9640
Q* = 0.9395 SE(Q*) = 0.010
SE(Q*) = 0.0106 0.8
0.8

0.7
0.7
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0.6
0.6

0.5 0.5

0.4 0.4

0.3 0.3

0.2 0.2

0.1 0.1

0 0
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1-specificity 1-specificity

Figure 3. A–D, Summary ROC curves for detection of 70% to 99% stenosis and occlusion by TOF MRA and CE MRA.

ses.26,27,33,35,37 CE MRA was more accurate than TOF MRA
with a higher sensitivity and a similar specificity to TOF
MRA (Table 3). TOF MRA produced a pooled sensitivity of
89.6% (82.2% to 94.7%) and a pooled specificity of 92.7%
(88.5% to 95.7%), whereas CE MRA produced a pooled
sensitivity of 96.2% (90.5% to 99.0%) and a pooled speci-
ficity of 92.7% (88.6% to 95.7%).
Subgroup Analyses
To study the robustness of the results, a number of subgroups
were analyzed in a sensitivity analysis. When the analyses
were broadened to include the data from all of the included
studies, according to each paper’s definition of “high-grade”
stenosis, the results were very similar (Table 4) to those for
ⱖ70% to 99% stenosis. In case overcall of occlusion by MRA
was not being detected in these analyses, a separate analysis
was performed in patients with angiographic stenoses of 70%
to 100%, but this gave essentially the same results (Table 4).
The other sections of the sensitivity analyses include papers
that studied high-grade stenosis detection in only symptomatic
subjects as opposed to a population of symptomatic and asymp-
tomatic patients and papers published after 2003 (Table 4). Both
methods showed high accuracy for the detection of high-grade
stenosis in symptomatic patients. Results for both MRA methods
for high-grade stenosis were highly accurate for papers pub-
lished after 2003.
As shown in Tables 1 and 2, some papers did not report the
method of stenosis measurement. To decipher whether these
studies, as well as the few studies that used ECST instead of
NASCET methods, contributed to heterogeneous results, a
sensitivity analysis was completed, including only those
papers that explicitly stated the NASCET protocol was
 2244 Stroke August 2008

Pooled Sensitivity- 50-69% Stenosis Pooled Specificity- 50-69% Stenosis

A TOF MRA C TOF MRA

Specificity (95% CI)
Sensitivity (95% CI)
Anzalone 2005 0.90 (0.82 - 0.96)
Anzalone 2005 0.62 (0.32 - 0.86)
Fellner 2005 0.92 (0.79 - 0.98)
Fellner 2005 0.50 (0.01 - 0.99) Nederkoorn 2002 0.92 (0.89 - 0.95)
Nederkoorn 2002 0.35 (0.24 - 0.48) Back 2000 0.98 (0.90 - 1.00)
Back 2000 0.44 (0.22 - 0.69) Serfaty 2000 0.84 (0.72 - 0.92)
Serfaty 2000 0.43 (0.10 - 0.82)
Ozaki 1999 0.90 (0.77 - 0.97)
Ozaki 1999 0.18 (0.02 - 0.52) Nicholas 1995 0.95 (0.87 - 0.99)
Nicholas 1995 0.25 (0.03 - 0.65)

Pooled Specificity = 0.92 (0.90 to 0.94)

Pooled Sensitivity = 0.38 (0.29 to 0.47) Chi-square = 9.80; df = 6 (p = 0.1333)
Chi-square = 6.28; df = 6 (p = 0.3925) 0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 38.8 %
0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 4.5 %
Specificity
Sensitivity

B CE MRA D CE MRA
Sensitivity (95% CI) Specificity (95% CI)
Fellner 2005 0.00 (0.00 - 0.84) Fellner 2005 0.95 (0.83 - 0.99)
Anzalone 2005 0.92 (0.64 - 1.00) Anzalone 2005 0.92 (0.84 - 0.97)
U-King-Im 2004 0.57 (0.42 - 0.70) U-King-Im 2004 0.86 (0.80 - 0.91)
Alvarez-Linera 2003 0.80 (0.44 - 0.97) Alvarez-Linera 2003 0.99 (0.92 - 1.00)
Cosottini 2003 0.79 (0.61 - 0.91) Cosottini 2003 0.98 (0.94 - 1.00)
Wutke 2002 0.67 (0.22 - 0.96) Wutke 2002 1.00 (0.93 - 1.00)
Randoux 2001 0.80 (0.28 - 0.99) Randoux 2001 0.97 (0.87 - 1.00)
Serfaty 2000 0.14 (0.00 - 0.58) Serfaty 2000 0.86 (0.74 - 0.94)

Pooled Sensitivity = 0.66 (0.57 to 0.74) Pooled Specificity = 0.93 (0.91 to 0.95)
Chi-square = 23.48; df = 7 (p = 0.0014) Chi-square = 34.29; df = 7 (p = 0.0000)
0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 70.2 % 0 0.2 0.4 0.6 0.8 1 Inconsistency (I-square) = 79.6 %
Sensitivity Specificity

Figure 4. A–D, Pooled sensitivity and specificity values for detection of 50% to 69% stenosis by TOF MRA and CE MRA.

followed. Results for this subgroup were nearly identical to TOF MRA is that for every 30 MRA studies, one ⱖ70% to
the overall analysis results for high-grade stenosis. 99% stenosis would be detected on CE MRA that was missed
on TOF MRA. Similarly, for every 20 MRA studies, an ICA
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Discussion occlusion would be detected on CE MRA that was missed on

The major findings of this systematic review and meta-anal-
ysis are (1) that MRA is highly accurate for the diagnosis of
high-grade ICA stenoses and occlusion with both TOF and
CE techniques, with CE MRA having the edge over TOF
MRA; (2) that MRA is of high accuracy for distinguishing
occlusions from high-grade stenoses, particularly CE MRA;
and (3) that both CE MRA and especially TOF MRA appear
to be poor diagnostic tools for moderate ICA stenoses. It was
also noted that despite the large literature on MRA, the
number of high-quality studies was very small. From these
data, the quantitative estimate of benefit of CE MRA over
TOF MRA.
Variations in study design and reporting are significant
sources of heterogeneity in a meta-analysis of this kind. Five
major potential sources of heterogeneity were identified: (1)
The lack of data in unselected populations is felt to be a major
limitation of the studies in this meta-analysis. Many studies
were restricted to patients with symptomatic ICA disease or
those found to have a stenosis on screening with ultrasound.
Optimal technology assessment, however, requires inclusion
of individuals without the disease (ie, patients who are not
symptomatic and those who do not have ICAD). (2) Two

Table 4. Subgroup Analyses

TOF MRA CE MRA

Studies, N Patients, N Sensitivity, % Specificity, % Studies, N Patients, N Sensitivity, % Specificity, %

All studies: high-grade 37 1651 90.6 (88.5–92.4) 88.2 (86.7–89.5) 21 1047 94.3 (92.1–96.0) 92.1 (90.6–93.5)
stenosis*
Occlusion versus high-grade 26 1168 96.2 (93.1–98.2) 98.4 (97.1–99.2) 18 923 99.4 (96.8–100) 98.9 (97.7–99.6)
stenosis†
ⱖ70% to 99% NASCET‡ 23 1123 92.5 (90.0–94.5) 87.8 (86.0–89.4) 16 906 94.5 (92.2–96.3) 91.5 (89.7–93.0)
50% to 69% NASCET‡ 6 394 37.7 (29.1–46.9) 92.1 (89.6–94.1) 8 454 66.9 (58.0–75.0) 93.4 (91.1–95.2)
Symptomatic§ 27 1347 91.1 (88.9–93.0) 87.2 (85.5–88.8) 10 633 95.4 (92.8–97.3) 91.7 (89.7–93.5)
Publication ⬎2003 4 144 92.9 (85.1–97.3) 95.5 (91.6–97.9) 11 662 94.3 (91.3–96.5) 91.5 (89.5–93.3)
*Variably defined as 70% to 99%, 60% to 99%, 75% to 99%, 80% to 99%, or 50% to 99% stenosis.
†Analysis limited to patients with stenoses 70% to 100% to evaluate if overcall of high-grade stenosis was a limitation in the differentiation of high-grade ICA
stenosis (ie, 70% to 99%) from ICA occlusion; data on stenoses ⬍70% were dropped from this analysis.
‡Analysis limited to studies that used the NASCET method for stenosis measurement.
§Patients with symptomatic ICA disease.
 Debrey et al
further major sources of heterogeneity were the variation in
(a) the methods used to measure stenosis grade, and (b) the
number and types of stenosis grades that were reported as
evidenced by the lack of data on moderate-grade stenoses.
Evaluation of varying degrees of stenosis can result in
suboptimal positive predictive values as evidenced in a recent
study.76 The use of varying stenosis grade may explain why
Wright et al16 was an outlier; this study also used a head and
neck coil and hence evaluated ICA stenoses in a much wider
field of view. (3) Although it was necessary to compare data
from both CE MRA and TOF studies, the majority of the
included TOF papers were published earlier than those
investigating the accuracy of CE MRA. Approximately 76%
of the CE MRA papers were published in the last 4 years
compared with only 16% of the TOF papers. MRA is a
relatively new technology with first reports of its clinical use
being less than 25 years old and the rate of improvement in
technological advancements and user reliability has been
marked. Although it was believed that the dates of the studies
would be a serious source of heterogeneity, the data proved
otherwise with surprisingly high rates of sensitivity and speci-
ficity for TOF MRA over 10 years ago. (4) This apparent high
degree of accuracy raises the question as to whether some of
the earlier TOF MRA images were dropped from analysis due
to poor imaging quality, thus giving the potential for selection
bias in the TOF MRA studies, resulting in the overprojection
of its accuracy. This issue was frequently discussed in the
early MRA literature, because poor imaging quality, due to a
variety of factors including patient movement, artifact, and
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slow flow, were common concerns with TOF MRA. In later
years, technology and imaging technique improvements led
to a decrease in these difficulties. The raw data in the 2⫻2
tables do not show this dilemma, because images graded as
“nondiagnostic” quality are simply removed from the analysis
before being compared with the corresponding IAA images.
This was not as common an occurrence in the CE MRA studies;
in the cases of blurred images due to patient motion or artifact,
these images were more often included in the analyses. Other
papers stated that the precise definition of stenosis was not
always feasible with the TOF images due to flow voids or
signal dropout. In these cases, a signal dropout was usually
identified in these papers as a severe stenosis, which would
alter the data dramatically on the topic of differentiating
high-grade stenosis from occlusion. Signal dropout can be the
result of many factors, including turbulent flow, patient
movement, and other technical difficulties and may actually
not be due to a high-grade stenosis. Regardless, imaging
failure and the reporting of signal voids as a high-grade
stenosis are limitations in early TOF studies and must be
taken into account in the comparison of TOF MRA and CE
MRA data in this meta-analysis. (5) The majority of TOF
MRA studies used 3D TOF MRA; however, there are several
studies that incorporated both 2D and 3D techniques. Al-
though 3D is often considered a stronger diagnostic technique
due to improved signal-to-noise ratio, in areas of slow flow it
may be advantageous to use 2D instead of 3D TOF. Studies
using both forms may be more complete, because transverse
2D images are more sensitive to slow flow and can therefore
discriminate between critical stenosis (ie, ⬎95%) and occlu-
Diagnostic Accuracy of MRA for ICA Disease 2245
sion. As can be seen from both the forest plots of sensitivity
and specificity, as well as the ROC curves, more heteroge-
neity exists in the TOF MRA data than in the CE MRA data
for high-grade stenosis. In particular, the CE MRA sensitivity
plot shows very little heterogeneity. This could be due to a
variety of factors and is most likely the result of similar study
designs across these papers.
It should also be noted that publication bias may be a
source of heterogeneity. It is possible that studies demonstrat-
ing poor accuracy of MRA as compared with IAA may not
have been published. The accuracy of imaging results de-
pends on the instruments and technology used as well as the
experience of the operator and radiologist. Studies showing
excellent concordance between MRA and IAA are most often
performed in academic radiology departments. Therefore,
results from centers with decreased quality control may be
less optimistic and perhaps less likely to be published.
Differences in diagnostic threshold could potentially have
contributed to heterogeneity in this analysis. It has been stated
previously that differences in study design, including NASCET/
ECST measurements and varying definitions of “high-grade”
stenosis contribute to heterogeneity. However, it is possible
for differences in diagnostic threshold to exist despite the use
of the same diagnostic threshold such as defining 70% to 99%
stenosis as severe. If a threshold effect is present, it can be
visually interpreted through the ROC plots. Sensitivity will
increase with decreasing specificity or vice versa. This is
illustrated on the corresponding ROC plots, which, in this
case, show weak evidence of diagnostic threshold, because
both sensitivity and specificity increase simultaneously.
Only limited data were available for 50% to 69% stenoses;
sometimes 30% to 69% stenosis data were reported, although
such a large range of data is not useful for CEA decision-
making.8 At present, many, but not all, patients with moderate-
grade stenosis are referred for surgery after consideration of a
number of clinical factors; patients with the best operative
outcomes are male, those with hemispheric stroke or transient
ischemic attack (as opposed to retinal ischemia), and those
who do not have contralateral ICA occlusion. In cases of
endovascular angioplasty or stenting, the results of noninva-
sive imaging will be de facto confirmed or rejected by IAA.
Even with the limited data available, both CE MRA and
especially TOF MRA appear to be poor diagnostic tools for
moderate ICA stenosis. Their higher specificities only show
that MRA is somewhat more accurate in ruling out the presence
of a moderate stenosis. The cause of the reduced sensitivity
may relate to image resolution. It is quite possible that some
patients assessed as having high-grade stenosis on MRA, in
fact, only have moderate-grade disease and vice versa,
patients with moderate-grade disease may have high-grade
disease. The potential clinical impact of these findings is most
important for good clinical practice and will need to be
considered and investigated as a matter of urgency.
This new information updates results obtained in the prior
systematic reviews. MRA techniques have shown a continued
evolution and improvement in their accuracy for the assess-
ment of ICA stenoses. It is clear that many research centers
and hospitals have already made the transition to noninvasive
MRA as a sole imaging modality and determinant for CEA
 2246 Stroke August 2008
despite some reports that may demonstrate that MRA does
not meet the threshold of diagnostic quality that would allow
its independent use in all clinical settings.77 MRA has the
advantages of being less expensive, less time-consuming, and
noninvasive as compared with DSA. It is also capable of
imaging vessels with unusual pathologies and produces stron-
ger images of vessels not normally imaged with traditional
noninvasive imaging, including the vertebral and subclavian
arteries. Although the data for TOF MRA and CE MRA are
fairly similar in this meta-analysis, especially for high-grade
ICA stenoses and occlusions, there are other factors that must
be taken into account. For instance, CE MRA unquestionably
provides clearer, more defined images than TOF MRA. Also,
because CE MRA is flow-independent, there is not a risk of
signal void due to turbulent flow. Because TOF MRA appears
to be in the process of being phased out in some centers, some
studies have only looked at issues such as patient preference
with CE MRA versus DSA. It has been found in a recent study
that patients appear to prefer CE MRA over DSA. According to
U-King-Im et al, 67% of subjects were willing to have a repeat
MRA versus 41% for DSA.78
In conclusion, from this meta-analysis, the current change
to the use of MRA to detect high-grade ICA stenoses and
occlusions appears justified with CE MRA having the edge
over TOF MRA. However, the accuracy of MRA has yet to
be proven for the detection of moderate-grade stenoses, and it
is recommended that a second noninvasive study be obtained
to confirm the grade of ICA disease at this time before
treatment decisions are made. A complimentary diagnostic
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tool such as ultrasound or computed tomography angiography
or DSA is necessary in these cases for decision-making
regarding potential carotid endarterectomy or stenting. With
over 660 000 CEAs performed in the United States over the
past 5 years, there is a need for larger studies including both
symptomatic and asymptomatic subjects with tighter study
guidelines to address the serious problem of heterogeneity
and reporting of age data. Future studies should include patients
with varying degrees of ICA stenosis severity, including mild
stenoses. This work is also needed to confirm that the more
expensive CE MRA, which the literature has shown to be
largely replacing TOF MRA in recent studies, is truly a better
diagnostic tool. It is essential that these studies be completed
in a prospective and blinded fashion to fully answer the
questions arising from this meta-analysis and systematic
review and to ensure that each patient receives optimal care.
Sources of Funding
This research was supported in part by the Intramural Research
Program of the NIH, NINDS. S.D.J. is supported by the National
Scientist Development Grant from the American Heart Association.
Disclosures
None.
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