Color Doppler Imaging Evaluation of Proximal Vertebral Artery Stenosis

Vascular and Interventional Radiology Original Research Hua et al. Color Doppler Imaging of Proximal Vertebral Artery Stenosis Vascular and Interventional Radiology Original Research Yang Hua 1 Xiu-Feng Meng 1 Ling-Yun Jia 1 Chen Ling 1 Zhong-Rong Miao 2 Feng Ling 2 Ji-Bin Liu 3 Hua Y, Meng XF, Jia LY, et al. Keywords: cerebrovascular disease, color Doppler imaging, diagnostic criteria, proximal vertebral artery stenosis DOI:10.2214/AJR.09.2624 Received February 22, 2009; accepted after revision April 30, 2009. 1 Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, 45 Changchun Rd., Beijing 100053, China. Address correspondence to Y. Hua (dryanghua@sohu.com). 2 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. 3 Department of Radiology, Thomas Jefferson University, Philadelphia, PA. AJR 2009; 193:1434 1438 0361 803X/09/1935 1434 American Roentgen Ray Society Color Doppler Imaging Evaluation of Proximal Vertebral Artery Stenosis OBJECTIVE. The sonographic diagnostic criteria for vertebral artery stenosis have not been fully investigated. The purpose of this study was to assess hemodynamic parameters at color Doppler imaging and to determine, with digital subtraction angiography as the reference standard, the optimal thresholds for evaluation of proximal vertebral artery stenosis. MATERIALS AND METHODS. Among 653 patients with symptoms of ischemia of the posterior circulation, 247 subjects with normal arteries or stenosis of the proximal vertebral artery confirmed with digital subtraction angiography were included in the study. Peak systolic velocity at the origin of the vertebral artery ( ) and in intervertebral segments of the vertebral artery (PSV IV ), end-diastolic velocity at the origin and in the intervertebral segments of the vertebral artery, and the diameter of the vascular lumen were measured. The cutoff values for the diagnosis of < 50%, 50 69%, and 70 99% stenosis were determined with receiver operating characteristics analysis. RESULTS. The optimal cutoff values of hemodynamic parameters in evaluation of stenosis of the proximal vertebral artery for < 50% stenosis were 85 cm/s, / PSV IV 1.3, and end-diastolic velocity at the origin 27 cm/s; for 50 69% stenosis were PSVorigin 140 cm/s, 2.1, and end-diastolic velocity at the origin 35 cm/s; and for 70 99% stenosis were 210 cm/s, 4.0, and end-diastolic velocity at the origin 50 cm/s. was the most useful hemodynamic parameter, having accuracy of 94.5%, 96.2%, and 88.7% for the diagnosis of < 50%, 50 69%, and 70 99% stenosis. CONCLUSION. Color Doppler imaging is a reliable method for evaluation of vertebral artery stenosis. The results derived from this study can be used as a reference for establishing sonographic criteria for proximal vertebral artery stenosis. S troke is one of the leading causes of death and disability. The risk of subsequent stroke due to vertebral artery ischemia is much higher than that due to internal carotid artery ischemia, especially in the acute phase of the disease [1, 2]. Anatomically, the vertebral artery is divided into segments V1 V4. Segments V1 V3 constitute the extracranial portion of the vertebral artery, and segment V4, the intracranial portion [3]. Because it is vulnerable to hemodynamically significant lesions, such as atherosclerosis and arterial dissection, the proximal vertebral artery (segment V1, defined as the portion from the origin of the vertebral artery to its entrance into the foramen of the transverse process of the vertebra) is the most common site of stenosis, especially in its origin [4]. Thus, it is important to diagnose proximal vertebral artery steno- sis early to make sure that patients are treated in time to reduce the risk of stroke. As a noninvasive, accurate, and cost-effective method, duplex sonography has been widely used for evaluation of arterial stenosis in various locations, including the carotid, renal, extremity, and vertebral arteries [3]. Although the sonographic diagnostic criteria for internal carotid artery stenosis [5] have been accepted and applied worldwide, few studies have focused on the hemodynamic parameters and diagnostic thresholds for vertebral arterial stenosis, especially stenosis of the proximal portion of the vertebral artery. The purpose of this study was to assess, with digital subtraction angiography (DSA) as the reference standard, the hemodynamic parameters used at color Doppler imaging (CDI) for determining the optimal thresholds for evaluation of proximal vertebral arterial stenosis. We categorized the degrees of 1434 AJR:193, November 2009

Color Doppler Imaging of Proximal Vertebral Artery Stenosis proximal vertebral arterial stenosis as mild (< 50%), moderate (50 69%), and severe (70 99%) because these categories often are used as clinical references for determining whether medical or surgical intervention should be undertaken. Materials and Methods Subjects The study protocol was approved by our institutional review board. All patients were fully informed of the procedure and signed a consent form. The study was conducted in compliance with HIPAA regulations. From January 2006 to June 2008, a total of 653 patients with symptoms of cerebral ischemia of the posterior circulation were referred to our hospital for CDI examinations. We retrospectively selected 247 of the 653 patients who qualified according to the following criteria: the patient had undergone a DSA examination within 2 weeks after sonography, and the patient had a normal vertebral artery (n = 30) or unilateral (< 50% [n = 25], 50 69% [n = 76], or 70 99% [n = 116]) stenosis of the vertebral artery origin diagnosed with DSA. The exclusion criteria were as follows: severe stenosis or dissection of the intracranial vertebral artery or basilar artery (n = 60), > 70% stenosis of a carotid artery or subclavian artery (n = 139), > 50% stenosis of the contralateral vertebral artery (velocity of ipsilateral vertebral artery can be overestimated) (n = 31), occlusion of the vertebral A C artery (n = 58), vertebral arterial hypoplasia (n = 72), interventional or surgical management of cerebrovascular disease between the imaging studies (n = 32), and other conditions, such as cerebral hemorrhage detected with CT and severe heart disease with low cerebral blood flow (n = 14). The study group consisted of 194 men and 53 women with a mean age of 63.9 ± 10.3 years (range, 39 89 years). Sonographic Examination According to the vascular ultrasound protocol previously described by Zwiebel and Pellerito [3], CDI examinations were performed by physicians who had at least 5 years of vascular ultrasound experience. Those performing the CDI evaluations were blinded to the DSA results. An ultrasound system (IU-22 or HDI 5000, Philips Healthcare) with a 4.0- to 8.0-MHz linear array probe and a 2.0- to 5.0- MHz curvilinear array probe was used to examine segment V1 of the extracranial portion of the vertebral artery. To image the origin of the vertebral artery under the clavicle, we used a low-frequency (2.0 5.0 MHz) curvilinear array probe to increase the imaging penetration and improve display of the vessels. With the use of adequate compression technique and an appropriate scanning angle, all proximal vertebral arteries were visualized. The ultrasound parameters measured included the narrowest diameter of the lumen (D S ), the diameter of distal normal lumen (D O ), peak systolic B D Fig. 1 62-year-old man with severe stenosis at origin of left vertebral artery. A, Digital subtraction angiogram shows severe stenosis (arrow) at origin of left vertebral artery. B, Color Doppler image shows severe stenosis (arrow) at origin of left vertebral artery. LVA = left vertebral artery; LSA = left subclavian artery. C, Spectral Doppler waveform shows high-velocity flow in origin of left vertebral artery (peak systolic velocity at origin, 350 cm/s; end-diastolic velocity at origin, 136 cm/s). D, Spectral Doppler waveform shows tardus appearance in intervertebral segment of left vertebral artery. velocity at the origin ( ) and intervertebral segments (PSV IV ), and end-diastolic velocity at the origin and intervertebral segments of the vertebral artery. In addition, the values (D O and were calculated. DSA Examination Within 2 weeks after the ultrasound examinations, the patients underwent a DSA examination for evaluation of cerebral arterial stenosis. DSA was the reference standard in this study. Complete cerebral angiography, including the vertebral artery, common carotid artery, internal carotid artery, external carotid artery, and cerebral arteries, was performed with a double C-arm angiographic system (Neurostar Plus/ TOP, Siemens Healthcare) according to a protocol described previously [6]. The results of DSA were interpreted, and the narrowest lumen of the vertebral artery was measured by experienced neurosurgeons. According to the method of assessing carotid arterial stenosis in the North American Symptomatic Carotid Endarterectomy Trial [7], the degree of stenosis at the proximal vertebral artery was stratified as < 50%, 50 69%, and 70 99% stenosis and occlusion. The patients with < 50%, 50 69%, or 70 99% stenosis of the proximal vertebral artery or a normal vertebral artery were included in this study. Statistical Analysis SPSS software (version 11.5, SPSS) was used for statistical analysis. The optimal thresholds AJR:193, November 2009 1435

Hua et al. of various parameters for 50 69% and 70 99% stenosis were determined with receiver operating characteristics (ROC) analysis [8]. The sensitivity, specificity, and accuracy of sonography versus angiography were estimated. A value of p < 0.05 was considered a significant difference. Results DSA measurement of the narrowed lumen of the proximal vertebral artery showed that 25 subjects (10.1%) had < 50% stenosis; 76 subjects (30.8%), 50 69% stenosis; 116 subjects (47.0%), 70 99% stenosis; and 30 subjects (12.1%), normal vertebral arteries. DSA and CDI showed several features of vertebral artery stenosis. These features included luminal narrowing; increased velocity at the site of the lesion; and a tardus waveform (waveform with acceleration time delayed at systolic phase) and significantly reduced velocity in the intervertebral segment of the vertebral artery compared with the origin (Fig. 1). The ROC curves and the area under the ROC curve of various hemodynamic parameters and the morphologic parameters A for evaluating < 50%, 50 69%, and 70 99% stenosis of the origin of the vertebral artery are shown in Figure 2 and Table 1. According to the results of ROC analysis, the optimal cutoff values for < 50% stenosis were 85 cm/s, 1.3, and end-diastolic velocity at the origin 27 cm/s; for 50 69% stenosis were 140 cm/s, 2.1, and enddiastolic velocity at the origin 35 cm/s; and for 70 99% stenosis were 210 cm/s, 4.0, and end-diastolic velocity at the origin 50 cm/s. Tables 2 4 show the sensitivity, specificity, and accuracy of the hemodynamic parameters in the evaluation of stenosis of the origin of the vertebral artery origin compared with the DSA findings. was the most useful hemodynamic parameter, having a sensitivity of 92.0%, specificity of 96.7%, and accuracy of 94.5% for < 50% stenosis; sensitivity of 96.1%, specificity of 96.4%, and accuracy of 96.2% for 50 69% stenosis; and a sensitivity of 86.2%, specificity of 90.8%, and accuracy of 88.7% for 70 99% Fig. 2 Graphs show receiver operating characteristics curves for peak systolic velocity (PSV) at origin of vertebral artery (red), ratio of PSV at origin to intervertebral PSV (green), end-diastolic velocity at origin (blue), and ratio of difference between normal and narrowest luminal diameter to normal luminal diameter (purple) in evaluation of < 50% (A), 50 69% (B), and 70 99% (C) stenosis at origin of vertebral artery. Black line indicates reference values. stenosis. As shown in the scatterplot of the of three categories of stenosis (Fig. 3), variable degrees of stenosis can be differentiated with values. The morphologic measurement of the vascular lumen ([D O ] / D O ) was the optimal indicator for evaluating < 50% stenosis, but it was the poorest indicator in assessment of 50 69% and 70 99% stenosis compared with the other parameters. TABLE 1: Results of Receiver Operating Characteristics Analysis of Parameters for Evaluating Stenosis of Origin of Vertebral Artery Parameter < 50% Stenosis 50 69% Stenosis 70 99% Stenosis AUC 95% CI p AUC 95% CI p AUC 95% CI p 0.974 0.935 1.013 < 1 0.986 0.966 6 < 1 0.950 0.924 0.977 < 1 0.953 0.903 4 < 1 0.972 0.949 0.994 < 1 0.907 0.870 0.944 < 1 End diastolic velocity at origin 0.640 0.492 0.788 < 1 0.834 0.765 0.904 < 1 0.858 0.813 0.904 < 1 (D O 0.993 0.977 9 < 1 0.949 0.916 0.981 < 1 0.850 0.803 0.897 < 1 Note AUC = area under the receiver operating characteristics curve, PSV = peak systolic velocity, IV = intervertebral segment, DO = diameter of distal normal lumen, DS = narrowest diameter of lumen. B (cm/s) 600 500 400 300 200 100 0 <50% 50 69% 70 99% Degrees of Stenosis Fig. 3 Scatterplot shows peak systolic velocity at origin of vertebral artery ( ) for mild (< 50%), moderate (50 69%), and severe (70 99%) stenosis. C 1436 AJR:193, November 2009

Color Doppler Imaging of Proximal Vertebral Artery Stenosis TABLE 2: Optimal Cutoff Values of Peak Systolic Velocity at the Origin of the Vertebral Artery in the Evaluation of Stenosis Degree of Stenosis Cutoff Value (cm/s) (%) (%) Accuracy (%) < 50% 75 96.0 60.0 76.3 80 92.0 93.3 92.7 85 92.0 96.7 94.5 90 84.0 96.7 90.9 50 69% 130 98.7 89.1 94.7 135 97.4 92.7 95.4 140 96.1 96.4 96.2 145 92.1 98.2 94.6 70 99% 190 93.1 80.9 86.6 200 90.5 85.5 87.8 210 86.2 90.8 88.7 220 78.4 96.2 87.8 TABLE 3: Optimal Cutoff Values of the Ratio of Peak Systolic Velocity at the Origin to Intravertebral Peak Systolic Velocity in the Evaluation of Stenosis Degree of Stenosis Cutoff value (%) (%) Accuracy (%) < 50% 1.1 92.0 73.3 81.8 1.3 80.0 96.7 89.1 1.5 72.0 100 87.2 50 69% 2.0 94.7 83.6 90.1 2.1 92.1 89.1 90.8 2.2 88.2 90.9 89.3 70 99% 3.5 91.4 73.3 81.8 4.0 88.8 80.9 84.6 4.5 75.9 86.3 81.3 TABLE 4: Optimal Cutoff Values of End-Diastolic Velocity at the Origin of the Vertebral Artery in the Evaluation of Stenosis Degree of Stenosis Cutoff Value (cm/s) (%) (%) Accuracy (%) < 50% 23 84.0 26.7 52.7 25 72.0 46.7 58.2 27 56.0 63.0 60.0 29 36.0 76.7 58.2 50 69% 34 76.3 81.8 78.7 35 73.7 87.3 79.3 36 71.1 87.3 77.8 37 69.7 89.1 77.9 70 99% 45 77.6 71.0 74.1 50 76.7 78.6 77.7 55 69.8 84.0 77.3 60 62.9 87.8 76.2 Discussion Although DSA is considered the reference standard for evaluation of arterial stenosis, CT angiography, MR angiography, and sonography are three noninvasive techniques also used for evaluating vertebral artery stenosis. Although the sensitivity and specificity of CT angiography and MR angiography are comparable with those of sonography [9], sonography has its own advantages, including low cost, greater availability, absence of contraindications compared with CT angiography and MR angiography, and suitability for long-term surveillance. Thus, it is essential to establish the optimal diagnostic criteria for evaluation of vertebral arterial stenosis with sonography. Since the 1980s, several studies [10 15] of duplex sonography in the assessment of the origin of the vertebral artery have been conducted. Some studies, however, relied solely on diameter measurement, and others did not differentiate moderate stenosis (50 69%) from severe stenosis (70 99%). As did we, Koch et al. [15] found that is the most accurate diagnostic parameter for detecting proximal vertebral arterial stenosis. Koch et al., however, recommended a relatively low cutoff value (114 cm/s) for the diagnosis of 50 99% stenosis and did not subdivide the category 50 99% stenosis. It should be pointed out that differences in values among their subjects were large (175 ± 109 cm/s), possibly because of the relatively small sample size (36 subjects with 50 99% stenosis versus 192 subjects with 50% stenosis in our study). In our study, the mean ± SD values of for 50 69% and 70 99% stenosis were 182.7 ± 40.4 cm/s and 280.5 ± 75.9 cm/s, which may better reflect the actual stenosis of the vessels. It is important clinically to differentiate 50 69% stenosis from 70 99% stenosis because patients with 50 69% stenosis need regular follow-up examinations, but patients with 70 99% stenosis may need intervention. In our study, 50 69% stenosis was differentiated from 70 99% stenosis because the management strategies for these two categories of stenosis are different. Thus all of the patients with 70 99% stenosis diagnosed according to sonographic criteria underwent surgical intervention, and the patients with 50 69% stenosis underwent medical treatment with regular follow-up CDI to monitor the progress of the lesion. These patients may undergo surgical intervention when the degree of stenosis reaches 70 99%. AJR:193, November 2009 1437

Hua et al. Because of the anatomic characteristics and small diameter of the vertebral artery, it is often difficult to precisely measure the diameter at the origin when the artery is stenosed [16]. Therefore, direct measurement of the diameter for estimating mild and severe stenosis is unreliable, as confirmed in our study. As shown by the areas under the ROC curves of the four parameters in Table 1 and the severity of the degree of stenosis, (D O turned out to be the poorest indicator of stenosis among the four parameters. On the other hand, was the most reliable hemodynamic parameter no matter the degree of stenosis, the accuracy rates being 94.5%, 96.2%, and 88.7% for < 50%, 50 69%, and 70 99% stenosis. In this study, with DSA as the reference standard, we established a set of Doppler parameters and thresholds for evaluating mild, moderate, and severe degrees of stenosis of the origin of the vertebral artery. The recommended Doppler thresholds are as follows: of 85 cm/s or greater and less than 140 cm/s, of 1.3 or greater and less than 2.1, or end-diastolic velocity at the origin of 27 cm/s or greater for defining < 50% stenosis; of 140 cm/s or greater and less than 210 cm/s, of 2.1 or greater and less than 4.0, or end-diastolic velocity at the origin of 35 cm/s or greater for defining 50 69% stenosis; and of 210 cm/s or greater, of 4.0 or greater, or end-diastolic velocity of 50 cm/s or greater at the origin for defining 70 99% stenosis. According to the data shown in Tables 2 4, the parameters with highest sensitivity should be selected for patients with 50 69% stenosis (because follow-up may be needed), whereas parameters with higher accuracy and specificity should be used for patients with 70 99% stenosis (because treatment decisions may rely on the CDI results). We conclude that CDI is a reliable method for evaluation of proximal vertebral arterial stenosis. 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