(Stroke. 1999;30:2302-2306.)
© 1999 American Heart Association, Inc.
Original Contributions |
Echocontrast-Enhanced Ultrasound of Extracranial Internal Carotid Artery High-Grade Stenosis and Occlusion
From the Departments of Neurology (D.W.D, R.J., D.G.N., E.B.R.) and Radiology (G.S.), University of Münster; and Schering AG (S.W.), Berlin, Germany.
Correspondence and reprint requests to Dr Dirk W. Droste, Klinik und Poliklinik für Neurologie der WWU Münster, Albert-Schweitzer-Straße 33, D-48129 Münster, Germany.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—Proper assessment of extracranial internal carotid artery high-grade stenosis and occlusion by extracranial color-coded duplex sonography (ECCD) is occasionally made difficult by shadowing, an unfavorable insonation angle, low flow velocity or volume, or a deep insonation depth. In these cases, echocontrast could be helpful to quantify the degree of stenosis and to diagnose occlusion.
Methods—We investigated 17 arteries with poor precontrast investigation conditions and suspected high-grade stenosis or occlusion by contrast-enhanced ECCD.
Results—Compared with the precontrast scans, echocontrast allowed for significantly more segments to be evaluated by pulsed Doppler sonography (P<0.001) and for longer lumen segments to be displayed on color mode (P<0.001). Because it was now possible to place the sample volume right into the jet of the stenosis, the maximal flow velocity registered increased in all patients with stenosis.
Conclusions—Echocontrast-enhanced ECCD of the carotid arteries is helpful for stenosis classification in a small group of preselected patients with poor original examination conditions.
Key Words: carotid arteries • contrast media • occlusion • stenosis • ultrasonography
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Extracranial color-coded duplex sonography (ECCD) is a noninvasive, highly accurate procedure to detect stenoses and occlusions of the carotid arteries.1 2 3 The refined spatial resolution and the appearance of color-coded flow signals help to adequately place the Doppler sample volume in the different vessel segments of interest. Peak systolic flow velocity is an important and highly reproducible parameter for stenosis quantification.4 5 Patients with symptomatic extracranial high-grade carotid artery stenosis generally undergo surgery. In occlusions, surgery is only possible in exceptional cases. ECCD serves as a screening procedure, eventually followed by intra-arterial angiography, when carotid artery endarterectomy is scheduled. In many specialized centers, carotid endarterectomy is already performed on the basis of ECCD findings without angiography.6 7 8 9 10 In conjunction with continuous-wave Doppler of the periorbital arteries and transcranial Doppler sonography, ECCD plays a key role in the accurate quantification of the degree of stenosis, assessment of the exact location of the stenosis in relation to the flow divider, and discrimination of subtotal stenosis from occlusion.11 12
ECCD is occasionally made difficult by ultrasonic shadowing of calcified plaques, the thickness of the tissue between the probe and the artery, an unfavorable insonation angle, and the low flow volume or low flow velocity in very tight stenosis. Echocontrast agents that are able to survive pulmonary and capillary transit and to improve the echogenicity of the flowing blood were developed to overcome these limitations. Levovist (Schering AG) currently is the most widely used echocontrast agent in neurosonology. After preparation, Levovist is a suspension of air-filled microbubbles adherent to galactose granules with a palmitic acid coating and a median diameter of 3 µm. Presently, attempts are made to extend the diagnostic window of this echocontrast agent by continuously infusing it intravenously.
In neurology, echocontrast agents are mainly used for transcranial color-coded ultrasound enhancement. There are only a few reports on the use of echocontrast agents in the extracranial cerebral vasculature.13 14 15 16 In the present study, we describe the benefits and pitfalls of echocontrast enhancement in patients with extracranial carotid artery high-grade stenosis or suspected subtotal stenosis or occlusion.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We prospectively investigated 17 carotid arteries of 15 patients. In the patients selected for extracranial echo enhancement, either peak systolic flow velocity measured in the extracranial internal carotid artery (ICA) did not correspond to the severity of narrowing expected from indirect signs upstream or downstream, or the location (intracranial or extracranial) of a suspected ICA stenosis was not clear, or a definite discrimination between occlusion and subtotal stenosis could not be made. In the study time period of 4 months, a total of 637 patients were investigated in our neurosonological laboratory. Of these, 133 patients had extracranial carotid artery occlusion or high-grade stenosis. All patients received a continuous-wave Doppler investigation of their neck arteries and of the supratrochlear arteries, including compression tests of the facial and the superficial temporal arteries. Furthermore, they underwent transcranial Doppler sonography or transcranial color-coded duplex sonography of the large basal arteries. The carotid arteries and the intervertebral part of the vertebral arteries (V2 segment) were also investigated by ECCD. For extracranial continuous-wave Doppler and intracranial pulsed-wave Doppler, we used the MultiDop X (DWL) with 4-, 8-, and 2-MHz probes, respectively. Extracranial and intracranial color-coded duplex sonography was performed with the Sonos 2500 system by Hewlett Packard with a 7.5-MHz linear probe and a 2.0-MHz sector probe, respectively.
We classified the stenoses taking into account the peak
systolic velocity in the jet of the stenosis,
broadening of the poststenotic spectrum, peak systolic
velocity in the poststenotic ICA, direction of ophthalmic flow,
presence of collateral flow via communicating arteries, asymmetry in
pulsatility, and absolute velocity in the common carotid artery and in
the middle cerebral artery (MCA). A peak systolic velocity of
120 cm/s was the threshold for a stenosis of 50%,
excluding subtotal stenosis with a variable signal. In the
case of indirect hemodynamic criteria, the
stenosis was classified as 80%. Occlusion was diagnosed in
the complete absence of detectable flow in and above the
stenosis in the ICA and in the presence of corresponding
indirect hemodynamic criteria. Plaques with
stenosis <50% were classified according to their lumen
reduction on B-mode ultrasonography.17 18 19
There were 6 women and 9 men aged 36 to 76 years (mean 65 years). There were 4 smokers and 1 diabetic patient. Nine individuals were hypertensive, and 7 had hyperlipidemia. Ten patients had suffered a stroke and 1 patient had a transient ischemic attack (TIA) on the side of the carotid artery under investigation up to 884 days before the investigation. Three patients had recurrent ipsilateral events, 3 had a contralateral event, and 1 had an event in the vertebrobasilar circulation. From the corresponding clinical presentation and their ultrasound appearance, all the lesions were presumed to be atherosclerotic in nature.
The original and echocontrast-enhanced investigations were continuously recorded on videotape for offline analysis. Important images were also printed out.
One 4-g vial of the echo-enhancer Levovist was applied in a concentration of 400 mg/mL by a pump injector (P400 anesthesia syringe pump, Ivac Medical Systems) at a rate of 2.5 mL/min.
The possible diagnostic benefit of the investigation was
assessed immediately after the examination. The tapes were then
subjected to an offline analysis that included assessment of
the following parameters for both precontrast and
postcontrast conditions: peak systolic blood flow velocity in
the maximum stenosis; length of the color-coded blood
flow column in 4 segments, each 1 cm in length starting from the flow
divider; and the possibility of recording a Doppler
spectrum in 1 location within these segments.
Six patients with 8 investigated arteries underwent intra-arterial digital subtraction angiography of their carotid arteries in close temporal relationship to the ultrasound investigation. In 1 patient, CT angiography was performed, and in another patient with 2 arteries under investigation, MR angiography was performed.
The nonparametric Friedman ANOVA was performed to test the effect of echocontrast enhancement on the length of the color column in each of the 4 segments and the possibility of recording a pulsed-wave Doppler spectrum in each of the 4 segments.
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Results |
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The investigations did not cause any side effects. There were 8 ICA occlusions and 9 high-grade stenoses on ultrasound. Figure 1
demonstrates the ECCD findings of the
left carotid artery of patient 10. Before contrast was applied, only a
normal peak systolic flow velocity (91 cm/s) was obtained. The
maximum stenosis was presumed to be close to the sample volume;
however, due to shadowing, it could not be visualized. Even after
contrast application, there was no continuous visualization of the
color-coded blood stream, but a high velocity (298 cm/s), indicative of
an 80% stenosis, was seen.
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The Table summarizes patients'
precontrast and postcontrast ECCD findings and also gives the results
of angiography, if performed. In the first ICA segment of 1 cm in
length distal to the flow divider, the mean length of the color-coded
flow column was 9.4 mm with contrast versus 8.2 mm without
contrast. The corresponding values for the second segment were 6.2
versus 3.3 mm, 4.3 versus 0.6 mm for the third segment , and
2.3 versus 0.6 mm for the fourth segment. The mean ranks from the
Friedman 2-way ANOVA for the length of the color-coded flow column in
each segment were (same order) 7.1 versus 6.4, 5.6 versus 4.1, 4.5
versus 2.5, and 3.2 versus 2.6, respectively (P<0.001). The
corresponding values for the possibility of obtaining a pulsed-wave
Doppler spectrum were (same order) 6.2 versus 5.9, 5.7 versus 4.7,
4.5 versus 3.3, and 3.3 versus 2.4, respectively (P<0.001).
In the corresponding segments, all the ranks were higher for the
contrast-enhanced investigation, indicating color visualization of
longer parts of each segment and of more Doppler spectra with
contrast than with the precontrast investigation. Figure 2 shows the benefit of contrast
application for obtaining a Doppler spectrum of the different
segments of the ICA.
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In all but 2 of the 7 arteries (patients 4 and 15) also investigated by
angiography, the ultrasound diagnosis was confirmed. In patient 15,
ultrasound diagnosed an occlusion with the absence of color-coded flow
and the absence of a Doppler spectrum in the course of the ICA.
After the ultrasound investigation, a CT angiography was performed that
demonstrated no contrast enhancement in the proximal ICA but filling of
the submandibular distal ICA. The patient was again taken to the
ultrasound laboratory. Filling of the very distal ICA could be
confirmed by echocontrast with the knowledge of the CT angiogram, but
we still could not demonstrate any color-coded Doppler signal or a
Doppler spectrum in the proximal ICA. Intra-arterial
angiography diagnosed a subtotal stenosis, which was confirmed
during subsequent endarterectomy. Figure 3 (top) shows the impossibility of
detecting any flow in the proximal ICA on a longitudinal section even
in the echocontrast investigation. In the bottom panel of Figure 3, the residual flow on a transverse submandibular section by
echocontrast is demonstrated.
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In patient 4, the degree of stenosis was underestimated by ultrasound (75%) compared with intra-arterial angiography (filiform). In patient 5, the diagnosis of recanalization of an occluded ICA by a vas vasorum was made based mainly on knowledge of the previous occlusion. An additional feature suggesting the recanalization by a vas vasorum was the uniformly narrow lumen over a segment of 1.5 cm. CT angiography confirmed a long, narrow vas vasorum that did not meet the distal ICA lumen.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In this study, we present our experiences with echocontrast-enhanced ECCD of the carotid artery in a highly selected group of patients with difficult precontrast insonation conditions and suspected high-grade stenosis or occlusion. In most patients investigated in our neurosonological laboratory during the time period of the study, a conclusive extracranial diagnosis could be made without the use of echocontrast.
Echo enhancement enabled both the visualization of color-coded blood flow in more vessel segments and the recording of Doppler spectra in more vessel segments of the diseased artery, especially in the distal parts. Identification of the area of maximal narrowing was facilitated both for spectral and color Doppler recording. The absence of both color-coded blood flow and Doppler spectrum increased the investigator's diagnostic confidence that ICA occlusion existed. Otis et al16 described a different condition that was not observed in our study: using contrast, they detected a still permeable tight stenosis in 4 patients with suspected occlusion. Sitzer et al13 also described the benefit of better plaque surface characterization, an aspect that was not considered in this investigation. Furthermore, unlike in their investigation, we applied contrast only in those difficult cases in which a reliable diagnosis was not possible with the original scan.
An increase of blood flow velocity was found with the enhanced
investigation used in the present study (see the Table
) and
has also been reported previously.20 Several reasons may
account for this finding. The contrast agent enhanced faint parts of
the spectrum, which correspond to high velocities. Because the gain was
downregulated if necessary during the blooming phase, this effect could
only be of minor importance. In addition, the use of contrast allowed
color flow and spectrum visualization in areas of the stenosis
not assessable in the original scans. We applied contrast in a group of
preselected patients in whom a discrepancy was found between the low
maximal Doppler shift and indirect signs of an occlusive disease
upstream and downstream. Visualization of the maximum stenosis
thus allowed the determination of the correct maximal flow velocity and
helped to quantify the stenosis.4 5 17 True flow
velocity is not altered by the application of contrast
agents.11
In filiform stenosis, peak systolic blood flow velocity can be low, similar to values obtained in 70% to 85% stenosis or without stenosis at all (see patient 6).21 This was the reason for underestimation of the degree of stenosis in patient 4. In this case, additional criteria, such as the thin color-coded flow column, B-mode ultrasonography, decreased prestenotic and poststenotic flow velocity, low pulsatility upstream and high pulsatility downstream, and pathological collateral flow, were subsidiary. Gahn et al15 also described a similar case with a 95% to 99% stenosis underestimated as 70% to 80% on enhanced ultrasound.
In patient 5, the correct diagnosis of a recanalization of a previously occluded ICA was made with knowledge of the previous occlusion and on the basis of the long, uniformly narrow lumen.22
In patient 15, our ultrasound diagnosis was obviously wrong. The medial origin of the artery and deep insonation depth may have contributed to this error. Careful submandibular investigation of the ICA by echocontrast is necessary to preclude a subtotal stenosis, which may still be accessible to surgery. The lack of contrast filling in the proximal ICA on CT angiography raises the question of whether CT angiography and possibly MR angiography can serve as a reference for contrast-enhanced ultrasound studies. Intra-arterial angiography remains the "gold standard." The risk of misdiagnosing a subtotal stenosis by ultrasound is low but nevertheless exists.
Echocontrast-related side effects reported in the literature were all minor and transient.23 Investigations like MRI, MR angiography, CT angiography, and intra-arterial angiography are potentially harmful. Of 415 patients who underwent angiography after randomization in the ACAS trial (Asymptomatic Carotid Artery Study), 3 (1.0%) suffered a disabling stroke during the investigation or between the investigation and surgery, and 1 patient died.24 A review of 8 prospective studies25 revealed rates of arteriography-related disabling strokes or death of 1% and 0.06% in a total of 2227 cerebral arteriographies. Moreover, MRI, MR angiography, CT angiography, and intra-arterial angiography are expensive and not yet generally available. These are additional arguments for the use of echocontrast in the ultrasound diagnosis of extracranial internal carotid artery pathology.
In summary, echocontrast agents are not only useful in intracranial color-coded duplex sonography, which still is their predominant domain, but in a small group of preselected patients, these agents were also helpful in the assessment of extracranial ICA stenoses and occlusions.
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Acknowledgments |
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This work was supported by the Foundation Verein zur Bekämpfung der Gefäßkrankheiten e.V., Engelskirchen, Germany. We are very grateful to Ruth Lerch and Britta Nientiedt for their help in performing the investigations.
Received May 4, 1999; revision received July 8, 1999; accepted July 8, 1999.
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