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INTRODUCTION — Computed tomographic (CT) scanning and magnetic resonance imaging (MRI)
are useful for evaluating the question of cerebral infarction which may result from carotid artery
stenosis. Infarctions related to internal carotid artery stenosis may be deep, subcortical, or cortical.
However, carotid stenosis may exist in the absence of infarction on MRI and CT.
The definition of asymptomatic or symptomatic carotid artery stenosis is based upon the history and
physical examination, depending upon whether or not there are symptoms or signs of carotid
territory ischemia. In the large clinical trials addressing the management of carotid artery stenosis,
the detection of "silent" infarcts on CT or MRI did not qualify the stenosis as symptomatic. In clinical
practice, however, radiographic evidence of ischemia in the territory of a stenotic internal carotid
artery may affect management.
Four diagnostic modalities are used to directly image the internal carotid artery:
• Cerebral angiography
ULTRASOUND
Carotid duplex ultrasound — Carotid duplex ultrasound (CDUS) uses B-mode ultrasound imaging
and Doppler ultrasound to detect focal increases in blood flow velocity indicative of high grade
carotid stenosis [15-17]. The peak systolic velocity is the most frequently used measurement to
gauge the severity of the stenosis (show radiograph 1), but the end-diastolic velocity, spectral
configuration, and the carotid index or peak internal carotid artery velocity-to-common carotid artery
velocity ratio provide additional information [18,19]. Color Doppler flow imaging may improve the
efficiency of the test, but it has not been shown to improve accuracy [15,17,20,21].
We examined the correlation between Doppler velocities and the residual lumen diameters of
internal carotid arteries from surgical pathological specimens to establish Doppler criteria for residual
lumen diameter, independent of the percent stenosis [22]. Peak systolic velocity (PSV), end-diastolic
velocity (EDV), and carotid index (peak internal carotid artery [ICA] velocity ÷ common carotid artery
[CCA] velocity) correlated with the residual lumen diameter.
By adjustment of velocity criteria, we found that CDUS can be either highly specific or highly
sensitive for detecting a residual lumen diameter of <1.5 mm [22]:
• A specificity of 100 percent was found for PSV >440 cm/sec, EDV >155 cm/sec, or carotid
index >10. The sensitivity for these measures was 58 percent, 63 percent, and 30 percent,
respectively. By combining these criteria, the sensitivity increased to 72 percent.
• A sensitivity of 96 percent was found for PSV >200 cm/sec combined with either an EDV
>140 cm/sec or a carotid index >4.5. The specificity for these combined measures was 61
percent.
A meta-analysis published in 2006 concluded that CDUS compared with intraarterial cerebral
angiography for the diagnosis of 70 to 99 percent carotid stenosis had a sensitivity and specificity of
0.89 (95% CI 0.85-0.92) and 0.84 (95% CI 0.77-0.89), respectively [23]. An earlier systematic review
concluded that the sensitivity and specificity of CDUS compared with digital subtraction angiography
for diagnosing complete carotid occlusion were 96 and 100 percent [24].
Although limited, CDUS has utility in obtaining information about plaque composition and intraplaque
hemorrhage, which may increase the risk of embolism and impact on prognosis [11,15-17,25,26]. In
one study, patients with echolucent atherosclerotic plaques had a significantly increased risk of
ischemic cerebrovascular events compared with patients with echogenic plaques [27].
Advantages — CDUS is a noninvasive, safe, and relatively inexpensive technique for evaluation the
carotid arteries. It is 81 to 98 percent sensitive and 82 to 89 percent specific in detecting a significant
stenosis of the internal carotid artery [15-17,28]. Data from the NASCET trial showed that a carotid
index (peak ICA velocity ÷ CCA velocity) above 4.0 provided the highest accuracy (sensitivity 91
percent, specificity 87 percent, overall accuracy 88 percent) for predicting a high grade (70 to 99
percent) stenosis amenable to surgery [29].
Using published outcome data and receiver operator characteristic analysis, test criteria can be
developed that maximize patient outcome for a specific clinical scenario [30,31]. However, as
discussed below, the positive predictive value of CDUS for identifying appropriate asymptomatic
candidates for carotid intervention may be lower in community centers.
Disadvantages — The absence of flow in the internal carotid artery may be due to occlusion, but
hairline residual lumens can be missed on CDUS [32]. In addition, several studies have found that
CDUS tends to overestimate the degree of stenosis [28,33].
CDUS is less precise in determining stenoses of less than 50 percent compared with stenoses of
higher degrees [15,16], but this rarely impacts on its clinical utility. CDUS may also be less accurate
in determining stenoses in the range of 50 to 69 percent compared with 70 percent or greater [28].
However, this too rarely impacts on its clinical utility because most patients are not considered for
endarterectomy unless the degree of stenosis is 70 percent or higher. (See "Carotid endarterectomy
in symptomatic patients", section on Summary and Recommendations).
CDUS imaging may be limited by features such as calcific carotid lesions, tortuous or kinked carotid
arteries, and patient body habitus. Another limitation of CDUS is that only the cervical portion of the
internal carotid artery can be evaluated, although transcranial Doppler may provide some information
about downstream vessels. (See "Transcranial Doppler" below).
The limitations of CDUS are illustrated in studies performed in community-based centers which
showed that performing carotid endarterectomy on the basis of CDUS alone would result in a
significant number of unnecessary surgeries [34,35]. (See "Carotid endarterectomy: Preoperative
evaluation; surgical technique; and complications", section on Role of other imaging studies, for a
more complete discussion of this issue.)
Finally, the accuracy of CDUS relies heavily upon the experience and expertise of the
ultrasonographer [17,36]. Measurement threshold properties may vary widely between laboratories,
and the magnitude of the variation is clinically important [37]. There may be substantial variability in
interpretation even when the same scanner and same criteria for carotid stenosis are used [36].
Although important, it may be difficult for the clinician to know the accuracy of his/her local
ultrasound laboratory. Accreditation by the Intersocietal Commission for the Accreditation of Vascular
Laboratories (ICAVL), a multidisciplinary group assures that the ultrasound data meet certain criteria,
including correlation against the gold standard of conventional angiography.
Transcranial Doppler — As an adjunct to CDUS, transcranial Doppler (TCD) examines the major
intracerebral arteries through the orbit and at the base of the brain. TCD is often used in conjunction
with CDUS to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis, and it
can be used to improve the accuracy of CDUS in identifying surgical carotid disease [38].
TCD can evaluate the intracranial hemodynamic consequences of high grade carotid lesions, such
as the development of collateral flow patterns in the circle of Willis, reversal of flow in the ophthalmic
and anterior cerebral arteries, absence of ophthalmic or carotid siphon flow, and reduced MCA flow
velocity and pulsatility [39,40].
An assessment of TCD by the American Academy of Neurology (AAN) concluded that TCD is
possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion, but in general
carotid duplex and MRA are the tests of choice [41]. The AAN report noted that the clinical utility of
TCD to detect impaired cerebral hemodynamics distal to high grade extracranial ICA stenosis or
occlusion and assist with stroke risk assessment requires evaluation and confirmation in randomized
clinical trials.
We examined the sensitivity and specificity of TCD criteria in detecting a hemodynamically significant
stenosis (residual lumen diameter <1.5 mm) at the origin of the ICA [42].
• For the transorbital approach, the strongest indicators of a residual lumen diameter <1.5
mm were reversed flow in the ipsilateral ophthalmic artery (OA) and a >50 percent peak
systolic velocity difference between the carotid siphons (distal ICAs) in patients with
unilateral ICA origin stenosis. These findings were 100 percent specific and 31 percent
and 26 percent sensitive respectively.
• For the transtemporal approach in patients with a unilateral stenosis, a >35 percent
difference in ipsilateral middle cerebral artery (MCA) peak systolic velocity relative to the
contralateral MCA, or a >50 percent difference in contralateral anterior cerebral artery
(ACA) peak systolic velocity relative to the ipsilateral ACA were 100 percent specific for
identifying a residual lumen diameter of <1.5 mm. Sensitivities were 32 percent and 43
percent respectively. Irrespective of contralateral stenosis, a >35 percent difference in
ipsilateral MCA peak systolic velocity relative to the ipsilateral posterior cerebral artery
(PCA) had a 100 percent specificity and a 23 percent sensitivity for detecting a <1.5 mm
minimal residual lumen diameter.
TCD can also be used for detection of middle cerebral artery microemboli that arise from the heart or
carotid artery [43]. These are visualized as high intensity signal transients (HITS) within the Doppler
spectrum. Although preliminary evidence in some studies suggests that detection of asymptomatic
emboli associated with carotid stenosis may predict stroke risk [44], other studies have not confirmed
a significant relationship [45]. Thus, the clinical utility of microembolic signal detection by TCD is not
yet established [46]. A larger multicenter prospective cohort study is underway to determine whether
TCD embolus detection in the MCA is useful as a predictor of stroke risk [47,48].
Additional modalities — Newer modalities such as 3-dimensional ultrasound and compound B-
mode ultrasound may offer improved carotid plaque imaging compared with CDUS. If so, they may
provide a means of assaying carotid plaque features that are markers for different stages and
phenotypes of atherosclerosis.
3D ultrasound — Three dimensional (3D) ultrasound improves 3D visualization [49]. Advantages
compared with B-mode ultrasound include the potential for quantitative monitoring of plaque volume
changes in all three directions (circumferentially as well as length and thickness) rather than one or
two directions [50]. This in turn could allow measurement of plaque volume change, which may be a
more sensitive marker of plaque progression than measurements of plaque area, intima-media
thickness, and carotid stenosis.
Disadvantages of 3D ultrasound include a tendency for underestimation of vessel stenosis and
difficulty imaging areas of calcification [51].
Compound ultrasound — Compound ultrasound utilizes a technique called compounding to
average several images taken from different perspectives [52]. Advantages compared with B-mode
ultrasound include improved visualization of plaque texture and surface, as well as reduction of
artifacts [53]. In addition, reproducibility in the evaluation of plaque morphology appears to be good,
and interobserver agreement of plaque echogenicity is higher than with B mode [53]. Advances in
computational power have made real time compound imaging available for clinical practice.
CHOICE OF IMAGING TEST — Conventional cerebral angiography has been considered the gold
standard for the evaluation of internal carotid artery stenosis [67]. However, angiography is
associated with a small but real risk of stroke, which makes it ill suited to be used as a screening
test. In addition, most patients with ischemic symptoms referable to the carotid vascular territory do
not have severe carotid stenosis [68,69]. In one series of 261 patients with carotid ischemic strokes
and 813 patients with carotid TIA, carotid disease was absent in 55 and 64 percent, respectively
(and in 69 and 77 percent of those without a carotid bruit) [69].
As a result, patients are generally selected for angiography using one of the noninvasive tests
(CDUS, TOF MRA, CEMRA, and CTA). These noninvasive tests have essentially replaced
conventional cerebral angiography in the presurgical evaluation of carotid stenosis.
In a meta-analysis of 41 studies and 2541 patients published in 2006 that assessed different
noninvasive imaging methods, the following observations were made [23]:
• CDUS, MRA, CEMRA and CTA all have high sensitivities and specificities for diagnosing
70 to 99 percent carotid stenosis in patients with ipsilateral carotid territory ischemic
symptoms
• CEMRA may be marginally more accurate than the other noninvasive methods, but this
technique is relatively new and the published studies included in the meta-analysis came
from research environments as opposed to routine clinical practice environments
• The accuracy of the noninvasive tests for 50 to 69 percent carotid stenosis appears to be
substantially reduced compared with 79 to 99 percent stenosis. However, the data are
sparse.
The combination of carotid ultrasound and MRA may obviate the need for conventional angiography
in the presurgical assessment of patients with carotid artery disease, particularly when the tests
agree [33,70,71]. Some have reported that the combination of ultrasound and MRA is cost-effective
[72,73] and results in an overall error rate that is comparable to the interobserver reliability when two
radiologists are presented with the same conventional angiogram revealing carotid artery disease
[74]. (See "Carotid endarterectomy: Preoperative evaluation; surgical technique; and
complications").
Bypassing angiography before surgery requires that noninvasive tests be highly specific as well as
sensitive. TCD may be beneficial in this setting, increasing the specificity of carotid duplex ultrasound
in detecting a <1.5 mm residual lumen diameter [42].
Conclusions — Our general approach to patients with suspected carotid stenosis is to first perform
carotid duplex ultrasound. Those with stenoses less than 50 percent are followed with serial
examinations, usually on an annual basis to determine if there is progression. If there is greater than
50 percent stenosis suspected, the patient is evaluated with transcranial Doppler examination and
MRA. CTA is performed in lieu of MRA if there is a contraindication to magnetic resonance imaging
and in cases where the duplex ultrasound and MRA do not agree.
Conventional angiography is rarely performed; indications include patients who cannot tolerate an
MRA and in whom the risk of dye is sufficient to warrant bypassing CTA in favor of the gold standard
examination. Angiography is also done if nonatherosclerotic disease is suspected (eg, dissection,
vasculitis).