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Variability of Doppler US Measurements along the Common Carotid Artery: Effects on Estimates of Internal Carotid Arterial Stenosis in Patients with Angiographically Proved Disease¹

¹ From the Department of Radiology, Duke University Medical Center, Durham, NC. From the 1998 RSNA scientific assembly. Received November 23, 1998; revision requested January 5, 1999; final revision received May 14; accepted June 2. Address reprint requests to V.S.L., Department of Radiology, New York University Medical Center, 530 First Ave, HCC Basement-MRI, New York, NY 10016 (e-mail: lee@mri.med.nyu.edu).

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To determine the effect of variability of common carotid arterial (CCA) velocities on velocity ratios used to assess internal carotid arterial (ICA) stenosis.

MATERIALS AND METHODS: Doppler ultrasonographic (US) velocity measurements were obtained at three levels in the CCA and in the carotid bulb and ICA in all patients referred for carotid US between September 1996 and October 1997. Only ICAs (n = 98, in 57 patients) without ipsilateral CCA disease at angiography were analyzed. The range of CCA peak systolic velocities (PSVs) and end diastolic velocities (EDVs) and velocity ratios were calculated for each CCA measurement. For each ICA/CCA velocity ratio, receiver operating characteristic analysis was performed.

RESULTS: CCA PSV and EDV ranges averaged 23.1 cm/sec ± 15.7 (SD) and 5.1 cm/sec ± 3.6, respectively. For a given side, the difference averaged 1.0 ± 1.3 for PSV ratios and 2.7 ± 6.9 for EDV ratios, depending on where CCA measurements were taken. By using a threshold of 60% stenosis as indication for endarterectomy, variability in CCA velocities could have altered recommendations in 16 (28%) of 57 patients. Receiver operating characteristic analysis showed that ratios made by using the three CCA velocities or their mean were not significantly different.

CONCLUSION: Variability in velocity measurements along the course of the CCA in patients with ICA disease can be substantial and can result in inaccuracies in assessment of carotid stenosis.

Index terms: Carotid arteries, flow dynamics, 172.91 • Carotid arteries, stenosis or obstruction, 172.721 • Carotid arteries, US, 172.12984 • Ultrasound (US), Doppler studies, 172.12984

	Introduction

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Duplex ultrasonography (US) is widely used to estimate the degree of luminal narrowing in the carotid arteries. To arrive at these estimates, investigators rely on gray-scale and color Doppler flow imaging, as well as on quantitative Doppler measurements such as internal carotid artery (ICA) peak systolic velocity (PSV) and end diastolic velocity (EDV) (1–17). These absolute velocities in the ICA can be normalized to the corresponding velocities in the ipsilateral common carotid artery (CCA) by generating ICA/CCA ratios. Such ratios are theoretically more robust measures because they may compensate for differences in scanning devices (18,19) and for physiologic factors such as blood pressure and cardiac function, which can affect absolute velocity measurements throughout the carotid system (2).

Two groups recently have shown that velocities along the course of the CCA can vary considerably in patients with normal carotid arteries (20,21). In one of the studies (21), variability in CCA values resulted in misleadingly abnormal velocity ratios in up to 31% of ICAs that had no visible plaque at US. We postulate that such variability might substantially influence estimates of ICA stenosis in patients with visible disease and that this would have important implications for the validity of velocity ratio criteria that are used to interpret the degree of ICA stenosis at US.

The purpose of this study was to examine prospectively the variability of velocity measurements in the CCA in patients with proved atherosclerotic disease with the specific goal of ascertaining the effect of such variability on the validity of ICA/CCA velocity ratios in assessing ICA stenosis.

	MATERIALS AND METHODS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Patient Selection
Velocity measurements were obtained at three predetermined levels along the course of the CCA in all patients referred for carotid US at our institution between September 1996 and October 1997. Patients who also underwent conventional carotid angiography performed within 4 months after US (n = 59) were included in the initial study group. To minimize the possibility that variability in velocities along the course of the CCA might be attributable to the hemodynamic aberrations resulting from CCA atherosclerotic disease, the two patients with bilateral CCA narrowing and the 12 individual ICAs with angiographically proved ipsilateral CCA stenosis were excluded from analysis, leaving 57 patients and 102 arteries. For the four patients who underwent only unilateral selective angiography, only the ipsilateral ICA was analyzed. The final study cohort thus consisted of 98 carotid arteries in 57 patients (20 women, 37 men; mean age, 69.6 years; age range, 49–85 years).

US Examination
Patients were examined while they were in a supine position. Heart rate and blood pressure were recorded prior to US examination. Bilateral carotid US was performed by using standard equipment (HDI 3000, Advanced Technology Laboratories, Bothell, Wash; Acuson 128, Acuson, Mountain View, Calif) and broadband (7–4-MHz) linear transducers. In all patients, routine carotid US studies were performed, which included gray-scale, pulsed Doppler, and color Doppler flow US examinations of the CCA, ICA, external carotid artery, and vertebral arteries. Doppler spectral waveforms were obtained at prescribed intervals in the CCA, carotid bulb, and ICA. All measurements were made by using angle correction.

Sampling sites in the CCA were defined as proximal (as close to the aortic arch as possible), middle, or distal (immediately before the widening of the bulb). The ICA was sampled proximally just beyond the bulb widening and distally in the most distal segment of ICA visible, as well as in areas of maximal stenosis. The measured angle of insonation was less than 60° for all measurements.

With the use of electronic calipers, absolute PSV and EDV values were recorded prospectively for all waveforms. ICA/CCA PSV and EDV ratios were then computed by dividing the maximal ICA velocity by each of the three corresponding CCA velocity measurements. The range in ICA/CCA ratios along the course of the CCA (maximum minus minimum values) was calculated. The following published thresholds (3) were used to predict ICA stenosis of 60% of more: ICA/CCA PSV ratio greater than 1.8 and ICA/CCA EDV ratio greater than 2.4. For purposes of comparison, two alternative thresholds for ICA/CCA PSV, 2.1 for ICA stenosis of 50% or more (11) and 3.5 for ICA stenosis of 60% or more (10), were also considered.

Excluding the 12 patients with unilateral CCA disease, the ratios of right-to-left CCA PSV were computed for each possible combination of CCA velocities for the 45 patients without angiographic evidence of CCA disease on either side. Published thresholds of less than 0.7 or greater than 1.3 were used to predict ICA stenosis greater than 50% (22). The maximum and minimum right-to-left CCA PSV ratios were determined for all patients. In addition, ratios of PSV values taken from matching locations in the CCA were also calculated.

Each study was interpreted by an experienced US radiologist who provided an estimate of the degree of stenosis on the basis of gray-scale and color Doppler flow images and Doppler velocity parameters (3). All US examiners were blinded to angiographic results.

Angiography
Carotid angiography was performed by using an intraarterial digital technique (Integris BV 3000, Philips Medical Systems, Shelton, Conn; CAS-30B, Toshiba Medical Systems, Carson, Calif) with biplane imaging capabilities and a 1,024 x 1,024 digital matrix. Oblique aortic aortography was followed by at least two views of the carotid bifurcation in all patients. Biplane cerebral views were also obtained in all patients. Initial angiographic interpretation was made by one interventional radiologist.

Percentage of ICA stenosis was calculated by using electronic digital calipers according to the method used in the North American Symptomatic Carotid Endarterectomy Trial, or NASCET (23). With this technique, the single view with the highest degree of stenosis is used, and the minimal diameter of the residual lumen at the site of greatest stenosis is compared with the normal ICA well beyond the arterial bulb where the arterial walls become parallel.

For all angiographic studies, CCA disease was also assessed. Percentage of CCA stenosis was estimated by means of dividing the lumen diameter at the point of maximum stenosis by the CCA lumen diameter at the closest normal-looking arterial segment proximal to the lesion. All ICA and CCA measurements were made once and retrospectively by two investigators in consensus (M.J.W., T.P.S.) who were blinded to US results.

Statistical Analysis
Analysis of variance was used to evaluate the statistical significance of differences in velocity measurements along the course of the CCA. Pearson product moment correlation coefficients were used to calculate correlation between the range of CCA velocities in the left and right sides and between ipsilateral CCA velocity variability and percentage of ICA stenosis measured at angiography.

To assess the effects of patient age, blood pressure, and heart rate on Doppler parameters, correlation coefficients between variability of CCA velocities and these variables were computed. Furthermore, patients were placed into the following pairs of groups: 60 years of age or younger or more than 60 years of age, hypertensive (systolic blood pressure of 160 mm Hg or more or diastolic blood pressure of 95 mm Hg or more) or normotensive, and a heart rate of 75 beats per minute or more or a heart rate of less than 75 beats per minute. A two-tailed Student t test was used to compare variability of PSV and EDV measurements for each pair.

Receiver operating characteristic analysis was performed for classification of ICA stenosis greater than 60% for all ICA/CCA velocity ratios (24). Areas under the curve were estimated by using the Mann-Whitney U test with values from the right and left sides combined. Patients were considered independent replicates for estimates of variances and covariances, which were then used to test for differences in areas under the curve.

The sensitivity and specificity of ICA/CCA velocity ratios for predicting ICA stenosis greater than 60% were computed for a range of ratio thresholds. Sensitivity and specificity values were computed by means of combining data from left and right sides. The corresponding standard errors were computed by means of a jackknife estimator for all patients. For all statistical tests, a P value less than .05 was used to assign statistical significance.

	RESULTS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
The distribution of severity of ICA occlusive disease at angiography for the study cohort is given in Table 1. Seven patients (12%) had unilateral ICA occlusion (100% stenosis); 35 (36%) of 98 ICAs (32 [56%] of 57 patients) had stenosis of 60% or more. Of the patients with ICA occlusion at angiography, four also showed occlusion at US (ICA velocity = 0), and three had severe stenosis (80%–99%). For each of the three patients with discrepant results, angiography was performed within 1–5 days of US.

Mean systolic blood pressure, diastolic blood pressure, and heart rate in our population were 152 mm Hg ± 27, 76 mm Hg ± 14, and 70 beats per minute ± 11, respectively. We found no significant correlation between variability of PSV or EDV and patient age, systolic or diastolic blood pressure, or heart rate (r < 0.2 for all).

Variability of PSV measurements along the CCA did not differ significantly in patients older than 60 years (n = 45 [79%]) compared with those 60 years or younger (n = 12; P > .86). The range of EDV measurements along the CCA was slightly higher in the younger group (6.6 cm/sec ± 4.6 vs 5.0 cm/sec ± 3.3, respectively), although the difference did not achieve statistical significance (P = .06). Of note, the absolute PSV and EDV values in the CCA were consistently lower in the older patient group at all locations (P = .06 for PSV in the proximal CCA, P < .01 for middle and distal CCA velocities).

When placed into categories according to blood pressure, 18 (32%) patients were considered hypertensive (systolic blood pressure 160 mm Hg or diastolic blood pressure 95 mm Hg). No statistically significant difference in variability of CCA velocities was observed between patients who were normotensive and those who were hypertensive (P > .15). Similarly, no significant difference was found in CCA variability between patients with a heart rate of 75 beats per minute or more compared with those with a heart rate less than 75 beats per minute (P > .5). Patients who were tachycardic tended to have higher EDV values in the CCA than those with normal heart rates (P = .04–.16 for different locations in the CCA); no such difference was observed for PSV measurements.

We also looked for a potential relationship between degree of ICA stenosis at angiography and variability in ipsilateral CCA velocities and found no significant correlation (r < 0.3).

For the 45 patients without angiographic evidence of CCA disease, calculations of the ratios of right-to-left CCA PSV revealed widely discordant ratios for most patients. By using published criteria of less than 0.7 or greater than 1.3 to indicate stenosis greater than 50% (22), 28 (62%) of 45 patients would have had a difference in US estimation of disease (50% or >50% stenosis), depending on the location in which CCA measurements were made (Table 3).

View larger version (52K): [in this window] [in a new window]   Figure 1. Graph shows distribution of ranges of ICA/CCA PSV ratio for all carotid arteries (n = 98). Black bars represent the span of ICA/CCA PSV values depending on locations CCA velocities were measured. The arrows indicate the line that demarcates the published threshold of ICA/CCA PSV ratio greater than 1.8 (3) used to indicate ICA stenosis 60% or greater. In this study, nine patients had ICA/CCA PSV values on both sides of this threshold (Table 4) and are considered to have equivocal results indicating either normal or diseased carotid arteries. These are depicted in this figure as those black bars that intersect the threshold line. The effects of shifting the threshold (vertical line, arrows) on the accuracy of ratios in predicting ICA stenosis were further examined by using receiver operating characteristic analysis.

For EDV ratios, on the basis of a threshold of ICA/CCA EDV ratio greater than 2.4 (3) to indicate ICA stenosis of 60% or more, variability in CCA measurements would have resulted in a different recommendation in eight (14%) of 57 patients. By using either criterion (ICA/CCA PSV ratio greater than 1.8 or ICA/CCA EDV ratio greater than 2.4), 16 (28%) of 57 patients had velocity ratios that would have produced discrepant recommendations for surgery, depending on CCA location. Details of these 16 patients are given in Table 4.

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
In healthy populations, systolic and diastolic velocity measurements can vary markedly along the course of an individual CCA (20,21). Meyer et al (20) showed that in a population of healthy volunteers systolic velocities decrease an average of 9 cm/sec for each centimeter of distance toward the carotid bifurcation from the aorta. Likewise, in a different disease-free population of patients referred for carotid US, the range of PSV measurements along the course of the CCA averaged 20 cm/sec ± 13 (21). In the current study, we observed a similar pattern and degree of variability in a cohort of patients who had angiographically proved ICA occlusive disease and no visible CCA disease. Although our study is inherently limited by selection bias because decisions to proceed to angiography were based on US findings, these effects may not be substantial given the similar patterns of variability identified in healthy persons.

Causes of variability in CCA velocities may be related to several factors that affect the pattern of blood flow, including vascular geometry, vessel wall compliance, and hemodynamic parameters such as cardiac output, heart rate, and blood pressure (25–27). Contrary to findings of a study by Ferrara et al (26), patients with hypertension in our population demonstrated less variability in CCA velocities than did patients who were normotensive. Although we observed higher absolute EDV values in the CCA in patients who were tachycardic (heart rate 75 beats per minute) than in those with lower heart rates, we found no difference in the variability of velocities along the CCA. However, these observations should be interpreted with caution, since they are based on a single measurement of blood pressure and heart rate.

Whereas several authors (27,28) observed decreased vascular compliance with age and hypertension, we found no statistically significant correlation between variability in velocities and those factors. It is possible that our sample size is insufficient to detect effects of age and hypertension on velocity variability. However, we did find that older patients had lower absolute systolic and diastolic velocity values in the CCA compared with those in younger patients. Whether this trend is related to vascular compliance remains to be established.

Our results show that variability of velocities along the course of the CCA can have a substantial effect on Doppler velocity ratios such as the ICA/CCA velocity ratio or the ratio of right-to-left CCA PSV. To be sure, these parameters are routinely calculated and interpreted in the context of other imaging and Doppler evidence. Doppler velocity parameters usually corroborate gray-scale and color Doppler flow findings in vessels with either very little or very severe disease but are more often discordant with regard to the 60% diameter stenosis threshold frequently used to establish a patient's candidacy for endarterectomy. It is in just this setting that parameters such as ICA/CCA velocity ratios are invoked to estimate more precisely the degree of ICA stenosis. When we compared the degree of stenosis based on ICA/CCA ratios with the surgical threshold of 60% stenosis, we found that variability in CCA velocities could have resulted in a different therapeutic recommendation in 16 (28%) of 57 patients in our study.

In an attempt to arrive at a recommendation for a preferred location for CCA velocity measurements, we compared the accuracy of ICA/CCA PSV and EDV ratios to predict ICA stenosis greater than 60% by using CCA values taken from the proximal, middle, and distal CCA. However, on the basis of receiver operating characteristic analysis, we found no significant difference.

The published thresholds (3) that we used represent one of many criteria that have been published in the literature (1–17). Nevertheless, variability of CCA velocities can affect interpretation of ICA/CCA ratios, regardless of the criteria used (Figure). For our study, we used a published ICA/CCA PSV threshold of 1.8 to indicate stenosis of 60% or more (3) and found nine (16%) of 57 patients had values on both sides of the threshold. If we instead perform the same analysis by using an ICA/CCA PSV threshold of 2.1 to indicate stenosis of 50% or more, as was suggested by Faught et al (11), a similar number of patients, 11 (19%) of 57, would have had equivocal values. Likewise, with use of a different published threshold of 3.5 to indicate stenosis of 60% or more (10), 11 (19%) of 57 patients again would have had discrepant ICA/CCA velocity ratios.

Although velocity ratios have the theoretic advantage of being less affected by factors such as intrinsic differences in circulation and different scanning technique (2), several groups have found maximum PSV velocities in the ICA more accurate than ratio measurements for predicting degree of angiographically demonstrable ICA stenosis (7,11,12,17). However, the majority of previous US reports in which Doppler parameters were evaluated have not specified the sampling site within the CCA (1,2,4,5,9–11,14,17). Some authors took measurements just below the bifurcation (3,8,12,13,15), whereas others sampled in the middle of the CCA (7). It is therefore conceivable that unrecognized variability in CCA measurements may have substantially compromised the accuracy of ICA/CCA velocity ratios in such studies and also undermined the generalizability of results across different laboratories. Hence, before abandoning ratios altogether, we believe that ICA/CCA velocity ratios need to be reexamined following more rigorous definition predicated on careful CCA velocity measurements at clearly prescribed locations.

In conclusion, we have demonstrated that the substantial variability of CCA velocities in patients with angiographically proved ICA disease can cause important inaccuracies in estimates of ICA stenosis that are based on ICA/CCA velocity ratios. Larger studies are needed to examine the accuracy and utility of Doppler velocity ratios by using CCA velocities obtained at carefully defined sampling sites. Until then, the recognition of potential sources of ambiguity in Doppler values underscores the importance of using a composite assessment including gray-scale US, color Doppler flow US, and both absolute velocity and velocity ratio parameters to estimate carotid arterial stenosis.

	Footnotes

 
Abbreviations: CCA = common carotid artery EDV = end diastolic velocity ICA = internal carotid artery PSV = peak systolic velocity

Author contributions: Guarantor of integrity of entire study, V.S.L.; study concepts and design, B.A.C., B.S.H., V.S.L., M.A.K.; definition of intellectual content, B.A.C., B.S.H., V.S.L., M.A.K.; literature research, V.S.L., B.A.C.; clinical studies, B.A.C., B.S.H., V.S.L., M.A.K., T.P.S., M.J.W.; data acquisition, B.A.C., B.S.H., V.S.L., M.A.K., T.P.S., M.J.W.; data analysis, V.S.L.; statistical analysis, V.S.L., M.A.K., D.M.D.; manuscript preparation, V.S.L.; manuscript editing, V.S.L., B.A.C., B.S.H., M.A.K., T.P.S., M.J.W.; manuscript review, B.A.C., B.S.H., M.A.K., T.P.S., M.J.W.

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, V. S. Articles by Carroll, B. A. Search for Related Content PubMed PubMed Citation Articles by Lee, V. S. Articles by Carroll, B. A.