Transcranial Doppler Ultrasound Battery Reliably Identifies Severe Internal Carotid Artery Stenosis
Background and Purpose There is a clinical imperative for noninvasive tests for carotid disease that have high sensitivity. Previous studies have shown that transcranial Doppler ultrasound (TCD) can identify intracranial collateral flow patterns and other hemodynamic consequences of carotid occlusion. We hypothesized that a battery of such TCD findings would have a greater sensitivity than any one TCD finding alone and would have clinical utility in identifying carotid disease.
Methods We determined the prevalence of seven TCD findings in patients with various degrees of carotid stenosis as measured by a blinded observer on 138 cerebral angiograms. We further determined the sensitivity and specificity of any one finding or any single abnormality in the TCD battery (the combination of all seven findings) for identifying severe (≥70%) carotid stenosis by angiography.
Results The following four individual TCD findings were associated (P<.001) with ≥70% carotid stenosis on cerebral angiography: ophthalmic and anterior cerebral artery flow reversal and low middle cerebral artery flow acceleration and pulsatility. The presence of any single abnormality in the TCD battery had a similar association (P<.001) with ≥70% carotid stenosis. The individual TCD findings had sensitivities of 3% to 83% and specificities of 60% to 100% for identifying ≥70% carotid stenosis. The TCD battery had a sensitivity of 95% and specificity of 42% for identifying ≥70% carotid stenosis.
Conclusions A battery of TCD findings that can be routinely measured reliably identified patients with ≥70% angiographic internal carotid artery stenosis with high sensitivity.
With the demonstration of efficacy of carotid endarterectomy in preventing stroke in patients with high-grade carotid stenosis, there is an increased need for reliable noninvasive tests to detect this disease in high-risk patients.
Several TCD findings have a high correlation with severe ipsilateral extracranial carotid stenosis. For example, reversed flow in the ipsilateral ophthalmic artery suggests collateral flow from the external carotid artery to the ICA downstream from severe carotid disease.1 Also, reversed flow in the ipsilateral ACA or elevated flow velocity in the contralateral ACA suggests collateral flow from the contralateral ICA through the anterior communicating artery.1 2 3 Other investigators have associated certain hemodynamic changes in the ipsilateral MCA with severe proximal ICA stenosis. These include diminished blood flow velocity, diminished pulsatility index, and diminished flow acceleration.1 3 4 5 6 We previously reported an association between absent ophthalmic artery and carotid siphon TCD signals and severe ICA disease.7
The association of these TCD findings in patients with high-grade carotid disease is generally accepted. However, their sensitivity and specificity in predicting both high-grade carotid stenosis and occlusion are not well established, either individually or in the aggregate; therefore, they do not have a clearly defined clinical utility in this setting.
In this study, we sought to identify a battery of TCD findings that can be routinely measured and that, individually or in combination, can reliably identify patients with severe ICA disease.
Materials and Methods
We reviewed a computerized database (Helix Express) of carotid duplex and TCD examinations performed in the Neurology Cerebrovascular Laboratory at Rhode Island Hospital; we found that during a 38-month period, 4595 carotid bifurcations had been examined with carotid duplex and had undergone complete TCD examinations. Complete TCD examination is defined as successful insonation of the ipsilateral transorbital and transtemporal windows. Of these carotid bifurcations, 138 were also examined with cerebral angiography.
The angiograms of 138 carotid bifurcations in 84 patients were interpreted by a single investigator (J.L.W.), blinded to ultrasound results, using the method of the North American Symptomatic Carotid Endarterectomy Trial.8 The percentage of stenosis of the ICA was measured as 100%×1−(narrowest residual lumen diameter/lumen diameter distal to stenosis). The angiograms were performed in the Diagnostic Imaging Department of Rhode Island Hospital. Biplane digital subtraction images of selective carotid arteriography were reviewed.
Carotid duplex is routinely performed and interpreted in our laboratory with criteria adapted from Langlois et al.9 In our laboratory, a peak systolic frequency >6 kHz defines a ≥50% diameter stenosis, and a simultaneous end-diastolic frequency ≥4.5 kHz defines a ≥80% stenosis. The diagnosis of arterial occlusion is made when no Doppler signal is detected. These criteria are internally validated by biannual correlation with angiography, and they have shown accuracy between 90% and 95% for hemodynamically significant stenosis.
Standard TCD examination in our laboratory includes examination of the carotid siphon and the MCA, ACA, and posterior cerebral, ophthalmic, vertebral, and basilar arteries. Mean blood flow velocity and direction of blood flow are routinely recorded for each artery. Elevated flow velocity in the ACA is noted if it is >80 cm/s.
Additional TCD parameters, pulsatility index and flow acceleration in the ipsilateral MCA, were measured by a single investigator (K.L.F.), blinded to the carotid duplex and angiographic results, in the subset of ICAs that were also examined by cerebral angiography. Flow acceleration was calculated as the difference in velocity between the minimum at the systolic upstroke of the Doppler waveform and the maximum at the systolic peak of Doppler waveform, divided by the time differential4 (Figure⇓). This is the average slope of the upstroke of the waveform. Pulsatility index was calculated as the difference in the peak systolic and end-diastolic velocities divided by the mean velocity, after the method of Gosling.10 The mean values and confidence intervals of these parameters were compared with the angiographic determination of carotid stenosis to determine a “cutoff point” below which flow acceleration and pulsatility index reliably identified patients with ≥70% angiographic stenosis. The cutoff points were determined as MCA flow acceleration of <290 cm/s2 and pulsatility index of <0.88.
These seven TCD parameters, reversed flow in the ipsilateral ophthalmic artery (OA rev), reversed flow in the ipsilateral ACA (ACA rev), elevated flow velocity (>80 cm/s) in the contralateral ACA (cACA el), absence of Doppler signal in the ipsilateral ophthalmic artery (OA abs) or carotid siphon (CS abs), and diminished pulsatility (low PI) or flow acceleration (low FA) in the ipsilateral MCA, have been individually reported to have a high association with severe ICA disease previously.1 2 3 4 5 7 The combination of these TCD parameters defined our “TCD battery.” If any one TCD parameter was abnormal, the “battery” was considered positive. We determined the prevalence of abnormalities of any individual TCD parameter and of the TCD battery for different degrees of carotid stenosis, identified either by duplex ultrasound or angiography. Statistical comparisons were made using the paired two-tailed t test.
The association between duplex ultrasound stenosis severity and the prevalence of routinely measured TCD parameters in 4595 carotid duplex examinations is presented in Table 1⇓. The prevalences of any single TCD parameter and of the combination of these parameters increase with the degree of ICA stenosis, becoming statistically significant when the stenosis is >80% as defined by our duplex criteria. The prevalences of individual TCD parameters ipsilateral to occluded carotid arteries are between 11% and 50%, whereas the combined prevalence of any one TCD parameter is nearly 80%. The prevalences are lower in carotid arteries with 80% to 99% stenosis (4% to 28% individually and 45% in combination) but are still statistically significantly higher than in carotid arteries with lower degrees of stenosis. In the detection of severe (>80%) carotid stenosis, the individual sensitivities vary between 8% and 39%. In combination, the sensitivity of all five TCD parameters in this “mini-TCD battery” is 63%. These five parameters are very specific for severe carotid artery disease, with specificities of 99% individually and 98% in combination.
In the subset of TCD examinations with corresponding angiographic information, the correlation of TCD abnormalities with angiographic stenosis is similar to the correlation observed for TCD abnormalities with carotid duplex stenosis (Table 2⇓). The number of examinations is smaller in this data set, leading to relatively wide 95% confidence intervals; these intervals explain apparent disparities in the angiographic versus the carotid duplex results, while showing that these results are still consistent with those reported for carotid duplex.
Additionally, in the 138 examinations for which corroborative angiographic information was available, the flow acceleration and pulsatility index in the ipsilateral MCA were measured. Low MCA flow acceleration (<290 cm/s2) and pulsatility index (<0.88) were significantly more prevalent in severe ICA disease (≥70% stenosis) than in normal or less severe ICA disease (Table 2⇑). As a marker of severe ICA disease (70% to 100% stenosis), both low MCA flow acceleration and pulsatility index have higher sensitivities (83% and 78%, respectively) and lower specificities (60% and 64%, respectively) than the other TCD parameters. When these parameters are combined with the others, the resulting TCD battery has a sensitivity of 95% and a specificity of 42% for identifying angiographic carotid stenosis ≥70%.
This study demonstrates a significant association between a battery of routinely measurable TCD parameters and severe ICA disease. The prevalence of TCD markers of collateral flow patterns distal to ICA occlusion in this study was similar to those previously reported.1 3 5 We also found these markers to be significantly associated with severely stenotic but still patent ICAs, although with a lower prevalence compared with occluded ICAs. While other investigators have used extracranial carotid compression to detect collateral flow patterns with a higher degree of sensitivity,3 11 12 these techniques require special experience and may be risky or contraindicated in some patients.13
Previous investigators have found that a diminished mean blood flow velocity in the ipsilateral MCA or a difference in mean blood flow velocities in the ipsilateral and contralateral MCAs correlated with severe extracranial ICA disease.1 2 3 4 14 However, in our study we were unable to demonstrate this association, as were others.2 5
The high specificity and low sensitivity of certain TCD parameters (OA rev, OA abs, CS abs, ACA rev, cACA el) were expected, since the presence of any one of these parameters may obviate the presence of another. For example, the development of one collateral pathway may remove the stimulus required for the development of another. Also, well-developed collateral flow patterns may also lead to normalization of hemodynamic parameters in distal arteries such as the MCA. It is therefore expected that the combination of these parameters would have a much higher sensitivity than any one alone.
The sensitivity and specificity of hemodynamic parameters such as MCA flow acceleration and pulsatility index for severe carotid disease in our study were similar to those reported previously.6 In comparison with other TCD parameters, flow acceleration and pulsatility index have relatively poor specificity compared with sensitivity. This was also expected. These parameters are affected by an enormous number of variables, including cardiovascular status, hematologic factors, and age,5 15 16 17 which vary widely and are difficult to control, especially in a retrospective study.
In this analysis, we did not control for severe occlusive disease in the contralateral ICA or in the vertebral or basilar arteries. The presence of such disease may be expected to decrease differences in TCD parameters among categories of stenosis. However, in a separate analysis that excluded those examinations in which there was a ≥70% stenosis of the contralateral ICA, the overall results were similar. These findings differ from the results reported by Kelley et al6 and Lindegaard et al,5 in which the presence of contralateral carotid stenosis did affect the MCA flow acceleration and pulsatility index, but are similar to those of Schneider et al,3 who found that MCA pulsatility index was not affected by the degree of contralateral ICA disease.
The design of a TCD battery depends on the desired function of such a battery. TCD is a noninvasive test that can identify patients with a high-risk disease, severe carotid stenosis, before confirmatory testing that may be invasive (angiography) or expensive (MR angiography). Because the risk of failing to identify severe symptomatic carotid disease is higher than the risk of performing unnecessary angiography or MR angiography, a high sensitivity is more important than a high specificity.18
Determining the actual clinical utility of a TCD battery requires prospective testing in patients who have the disease of interest, carotid territory ischemic symptoms. Because cutoff values for certain criteria (flow acceleration and pulsatility index) were defined retrospectively in the same database, sensitivity and specificity would be expected to be high, further emphasizing the need for prospective validation. Not all of the carotid arteries examined in this series were associated with ischemic symptoms. The presence or absence of cerebral ischemic symptoms may influence the prevalence of TCD abnormalities either because they represent the presence of protective collateral flow patterns or limits of cerebrovascular reserve.3 Therefore, it is possible that different intracranial hemodynamic patterns in symptomatic and asymptomatic patients may be reflected in the pattern of abnormalities found on TCD.
A limitation of the clinical utility of the TCD battery is the failure to insonate the MCA and ACA because of temporal bone thickening, a problem in 5% to 19% of patients.19 The presence of atherosclerotic disease in the major intracranial blood vessel may limit interpretation of the TCD battery results, but this condition is relatively rare. In fact, none of the cerebral angiograms in our series revealed carotid siphon or MCA stenosis.
The TCD battery described in our study may be a useful adjunct to carotid duplex examination. The battery provides confirmation of severe ipsilateral ICA disease in patients for whom duplex examination may have been difficult or inconclusive. For example, occlusion of the ICA may be misinterpreted as normal, particularly when there is “internalization” of external carotid artery blood flow. An abnormal TCD battery in such a patient prompts the technologist to reexamine that carotid. A TCD battery may also improve the clinical utility of carotid duplex when the tests are used in combination by improving the detection of patients with surgically treatable disease with a minimum number of invasive or expensive confirmatory tests.20 Whether the addition of the TCD battery to carotid duplex results increases the sensitivity and specificity of carotid duplex requires further study.
In conclusion, we found that a battery of routinely measurable TCD parameters had excellent sensitivity (98%) for identifying severe ICA disease. Further study is needed to define its role in the routine ultrasound evaluation of stroke patients.
Selected Abbreviations and Acronyms
|ACA||=||anterior cerebral artery|
|ICA||=||internal carotid artery|
|MCA||=||middle cerebral artery|
|TCD||=||transcranial Doppler ultrasound|
- Received August 30, 1996.
- Revision received October 9, 1996.
- Accepted October 9, 1996.
- Copyright © 1997 by American Heart Association
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