Chapter 1.3 SONOGRAPHIC EVALUATION IN CAROTID ARTERY STENOSIS B. K. Lal Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA

Introduction Over three decades ago, Doppler was introduced as the first ultrasonographic method for evaluation of cerebrovascular disease. Since then, the development of new ultrasound techniques has revolutionized the clinical applications for extracranial carotid disease. Interpretation of pulse wave Doppler signals involves an analysis of audio signals and the frequency spectrum. It is based on the Doppler frequency shift resulting from moving red blood cells in the carotid artery. In experienced hands, pulse wave Doppler ultrasound can identify significant luminal narrowing based on increased velocity of blood flow across a stenotic lesion. High-resolution B-mode ultrasound scanning uses linear array transducers (7–12 MHz) to display morphological features of the arterial wall. Duplex ultrasonography (DUS) combines integrated PW Doppler spectrum analysis and B-mode sonography. The B-mode image offers information about morphology in addition to serving as a guide for accurate PW Doppler velocity measurement. Color Doppler flow imaging based on the direction of flow superimposes color-coded blood flow patterns over the B-mode image. Power Doppler imaging color codes blood flow according to the amplitude of the Doppler signal. Both these modalities afford greater sensitivity to blood flow detection allowing improved detection of near-occlusive stenoses, tortuosity, and other morphological abnormalities in the arterial wall. The noninvasive nature of DUS makes this testing modality more attractive than the “gold standard” of cervical angiography. If the diagnosis of significant carotid stenosis can be accurately made with DUS, the risk of stroke inherent in angiography (1.2% in the Asymptomatic Carotid Atherosclerosis Study [9]) can be avoided. Cur-

rently, many patients (90% at the authors’ institution) undergo carotid revascularization based solely on a duplex examination.

Indications for testing Symptomatic patients Prospective randomized trials have documented the efficacy of carotid endarterectomy (CEA) in reducing stroke in symptomatic carotid stenosis. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) confirmed that CEA offered a 65% relative risk reduction compared to best medical therapy in patients with 70-99% carotid stenosis who present with transient ischemic attack (TIA) or non-disabling stroke [23]. Similarly, symptomatic patients with a 50–69% carotid stenosis derived a 29% relative risk reduction at 5 years [4]. Therefore all patients with hemispheric neurological symptoms attributable to the carotid circulation should undergo carotid imaging. This test should be performed even in the absence of a carotid bruit because NASCET data revealed that over one third of patients with high-grade carotid stenosis lacked a carotid bruit [28]. Testing in asymptomatic patients with hemispheric infarcts identified on computed tomographic (CT) or magnetic resonance (MR) is also indicated to rule out carotid disease. Patients with non-lateralizing symptoms such as dizziness or lightheadedness cannot be assumed to be caused by carotid stenosis. Other symptoms such as cranial nerve dysfunction (e.g., dysphasia, double vision, or blurred vision) and drop attacks are more likely to be vertebro-basilar in origin.

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Asymptomatic patients with a carotid bruit The Asymptomatic Carotid Atherosclerosis Study (ACAS) documented a 53% relative risk reduction in ipsilateral stroke and any perioperative stroke or death at 5 years when comparing CEA with medical therapy for asymptomatic  60% carotid stenosis [9]. Controversy continues regarding who best to screen since widespread imaging of all asymptomatic patients is unlikely to be cost-effective. Most physicians have adopted a selective approach; however, it is clear that additional studies are necessary to clarify this issue. The most commonly used selection criteria include the presence of a carotid bruit. Carotid bruits, expected to be found in up to 8.2% of patients  75 years of age [14] have been associated with a threetimes increased risk of stroke in a population-based prospective cohort study [33]. One third of patients with an asymptomatic carotid bruit can be expected to harbor a carotid stenosis  50% when studied with DUS [27]. Of note, 21% of patients with a bruit ultimately progressed to 50–79% stenosis; while 27% of patients with 50–79% stenosis progressed to  80% stenosis at 7 years [17]. It is clear that the presence of a carotid bruit should prompt a carotid duplex ultrasound to screen for carotid stenosis and the patients must be followed regularly for possible disease progression in case their disease is not severe enough to warrant revascularization.

Asymptomatic patients without a bruit Significant carotid stenosis can exist in the absence of cervical bruit. For this reason, recommendations for carotid duplex scanning have been made based on specific risk factors such as age, hypertension, smoking, coronary artery disease (CAD), and peripheral arterial occlusive disease (PAD). Significant carotid stenosis was present in 17.5% of patients aged  50 years with CAD, tobacco abuse, and PAD [12]. Claudication and decreased ankle-brachial index have both been found to be predictive of carotid stenosis [21]. In a prospective evaluation of 1087 patients undergoing coronary artery bypasses, 17% had carotid stenoses  50% and 5% had steno-

Chapter 1.3

ses  80%. Age  60 years, hypertension, diabetes mellitus, and smoking, increase the risk of significant carotid stenosis in patients undergoing cardiac surgery [3]. Based on these data, duplex scanning can be recommended selectively based on the presence of several risk factors.

Post-carotid revascularization surveillance Carotid duplex scanning has been used as a surveillance tool for carotid restenosis. Widely varying protocols exist for the follow-up of patients after carotid revascularization. In addition, despite the absence of conclusive cost-effectiveness data, it is likely that carotid duplex scanning for surveillance in this setting will continue to be a common indication, given the restenosis rates associated with CEA [8] and carotid artery stenting [20]. Data supporting surveillance of the contralateral carotid artery after ipsilateral revascularization is more forthcoming since a substantial number of contralateral arteries have been observed to progress to high-grade stenoses on follow-up [29]. The optimal frequency of this surveillance has not been defined but the author follows patients with  50% stenoses once a year; and those with  50% disease twice a year.

Quantifying the degree of carotid stenosis Arteriography is the standard against which all non-invasive assessments of carotid luminal narrowing are commonly compared. While several methodologies have been proposed for the angiographic quantification of stenosis, the Committee on Standards for Noninvasive Vascular Testing of the Joint Council of the Vascular Societies recommended that percent diameter reduction should be determined relative to the distal uninvolved internal carotid artery (ICA) [30]. Doppler measures that have been correlated with angiographic stenosis include ICA peak systolic velocity (PSV), and end-diastolic velocity (EDV), as well as ratios of ICA PSV and CCA PSV [1].

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Initially, ICA PSV and the relative distribution of velocities within the spectral profile based on PW Doppler measurements, were used to define the degree of narrowing of the ICA [5]. The University of Washington criteria were subsequently refined with the addition of EDV [28]. Accordingly, stenoses were classified as mild (1–15%), moderate (16–49%), severe (50–99%) and occluded. These criteria remained useful until the publication of the results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) [23], [4], and the Asymptomatic Carotid Atherosclerosis Study (ACAS) [9]. The NASCET demonstrated an early and significant benefit associated with carotid endarterectomy (CEA) in symptomatic patients with an ipsilateral ICA stenosis  70%, and a significant benefit over a longer follow-up in symptomatic patients with ICA stenosis of 50–69%. Additionally, the ACAS concluded that asymptomatic patients with an ICA stenosis  60% could also benefit from CEA. These new criteria did not correspond to the categories previously defined by researchers at the University of Washington. Using receiver operator characteristic (ROC) curves to compare sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for new criteria to define degrees of stenosis relevant to clinical management, Faught et al. [10] concluded that the combination of a PSV  130 cm/s and an EDV  100 cm/s defined a stenosis of 70–99%. Using a similar approach, Moneta et al. [22] concluded that an ICA PSV/common carotid artery PSV ratio  4.0 provided optimal accuracy for the diagnosis of a stenosis of 70–99%. Yet a third set of criteria for the same degree of stenosis were proposed by Carpenter et al. [7] such that a combination of PSV  210 cm/s, EDV  70 cm/s, ICA PSV/CC PSV  3.0, and ICA EDV/CCA EDV  3.3 was most accurate. It is clear that DUS results are more accurate when a single cutoff point for stenosis is used (e.g.,  50% or  60%), or when a broad category is used rather than a small range of stenosis (e.g., 50–99% vs. 60–69%). Recent studies demonstrate that Doppler criteria are influenced by equipment used [11], laboratories [2] and the technologist performing the test [24]. Additionally, contralateral disease has been associated

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with increased carotid volume flow resulting in an overestimation of the severity of disease [31]. Most diagnostic laboratories simply use the well-established criteria of others to diagnose severe carotid stenosis. However, for the reasons cited above, it is recommended that each laboratory validate its own Doppler criteria for clinically relevant stenoses [18]. One such methodology is to subject the vascular laboratory to certification by an independent auditing organization such as the Intersocietal Commission for Accreditation of Vascular Laboratories (ICAVL) [6], [16]. Studies comparing the accuracy of duplex ultrasound examinations have noted consistently superior results from accredited versus non-accredited laboratories [6]. A group of experts from different medical specialties met in October 2002 to arrive at a consensus document with regard to the use of DUS in the diagnosis of ICA [13]. Table 1 illustrates their recommendations when using grayscale imaging and Doppler ultrasound. Technical considerations, diagnostic stratification, imaging and Doppler parameters, Doppler diagnostic thresholds, structure and content of the final report, and quality assessment issues were all discussed and suggestions were made. Recommendations were also made for follow-up of patients at high risk or with asymptomatic carotid stenosis, and research topics were suggested for the future. Ideally, each center should perform its own validation; however, in the absence of such validation, the criteria suggested in Table 1 may serve as a useful guideline.

Ultrasound and carotid artery stenting Carotid artery stenting (CAS) has emerged as an alternative to CEA in the management of carotid stenosis under specific high-risk circumstances [32]. The ultimate value of CAS when compared with CEA will be based upon ongoing prospective randomized clinical trials [15]. In the interim, however, the number of patients undergoing CAS is increasing rapidly and these patients require intensive follow-up to monitor for instent restenosis [20]. US velocity criteria have not been well established for patients undergoing CAS. We have

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Chapter 1.3

Table 1. Representative Doppler ultrasound velocity criteria for the diagnosis of internal carotid artery stenosis Primary parameters

Additional parameters

Degree of stenosis (%)

ICA PSV (cm/sec)

ICA/CCA PSV ratio

ICA EDV (cm/sec)

Normal  50 50–69 70–99 Near occlusion Occlusion

 125  125 125–230  230 High/low/undetectable Undetectable

 2.0  2.0 2.0–4.0  4.0 Variable Not applicable

 40  40 40–100  100 Variable Undetectable

Adapted from: Grant EG et al.: Carotid artery stenosis: Gray-scale and Doppler ultrasound diagnosis. Society of Radiologists in Ultrasound consensus conference. Radiology 229: 340–346 (2003).

reported that the introduction of a stent into the ICA alters arterial biomechanical properties such that the resultant stent-arterial complex has decreased compliance [19]. Additional studies have demonstrated that when velocity criteria for non-stented ICAs were used in stented ICAs, several normal diameters were diagnosed as having in-stent stenosis [25], [26]. We have also reported that normal luminal diameters in recently stented ICAs were most accurately defined by revised velocity criteria: PSV  150 cm/sec with ICA PSV/CCA PSV ratio  2.16 [19]. Correlation studies with evolving in-stent restenosis (ISR) and angiographic diameter reduction will help define velocity criteria for increasing grades of stenosis in the stented ICA. Meanwhile, the author’s laboratory routinely registers baseline velocities immediately post-CAS, and utilizes a combination of planimetric measurements on B-mode imaging and rising intra or peri-stent velocities as indicators of evolving ISR during follow-up.

Testing procedure The DUS examination must include a blood pressure measurement in both arms. A blood pressure differential of  20 mmHg is indicative of possible brachiocephalic, subclavian or axillary artery stenosis. Testing proceeds with the patient in the supine position with the head turned away from the side being examined. The carotid sheath travels along the anterior border of the sternocleidomastoid muscle and this is where imaging can commence. The common carotid artery is identified at its origin in the

base of the neck just above the clavicle and followed to the carotid bifurcation usually located below the mandible. Abnormal locations of the bifurcation must be reported since they impact on the extent of surgical exposure (mandibular subluxation during CEA for high bifurcations) or decision regarding the type of revascularization to be offered (CAS for extremely high bifurcations). The transducer may be placed anterior, medial, or posterior to the sternocleidomastoid muscle to optimize flow visualization. Any luminal or wall abnormalities should be reported. Velocity measurements are recorded with an angle of insonation of 60°. Commonly, velocity measurements are obtained at the proximal and distal common carotid artery (CCA), external carotid artery (ECA); ICA (proximal, middle, and distal); and vertebral. Every effort should be made to follow the ICA as far cephalad as possible. The location of the distal extent of the plaque should be reported since this again impacts on the revascularization procedure. If the plaque continues cephalad into the distal ICA it entails extensive surgical dissection in the distal carotid triangle. The vertebral arteries can be found posterior to the CCA between the vertebral bodies. While the tortuous course of these arteries makes diagnosis of a stenosis difficult; every effort must be made to report antegrade versus retrograde (i.e., reverse) flow.

Validation The standard technique of validating DUS is through comparison to angiography. The goal for a definitive

B. K. Lal

examination would be a high positive predictive value (PPV) to minimize the number of patients who would undergo an unnecessary operation. A high PPV is achieved by missing the diagnosis in some patients with a stenosis (decreased sensitivity). The laboratory at the authors’ institution has a high PPV, and thus diagnostic angiography may be avoided before recommending revascularization. In elderly, asymptomatic patients, the few patients under-diagnosed would be at a low risk for stroke which is why such an approach is utilized by all participating centers in large multicenter trials for carotid revascularization (e.g., NASCET). A younger, otherwise healthy patients with a bruit, TIA, or an atherosclerotic carotid artery on a B-mode scan, who does not meet the flow criteria of a significant stenosis, should have additional diagnostic studies (e.g., contrast angiography, MRA, or CTA). The patient’s physician needs to ensure that a potential stroke-prone lesion is not left untreated. Other diagnostic laboratories may use DUS as a screening test only. They wish to have a high negative predictive value (NPV) so that few patients with a stenosis are under-diagnosed. A high NPV is achievable by decreasing the specificity. Many patients will be over-diagnosed so that few are missed. Thus all patients in this setting will need an additional study before proceeding to revascularization.

Planimetric evaluation As the discussion above indicates, velocity criteria for equivalent degrees of stenosis may vary between different centers. Conversely diameter and percent area stenosis measurements do not have this disadvantage. In addition, unlike ipsilateral velocity measurements, area and diameter measurements remain unaffected by contralateral stenosis/occlusion, ipsilateral proximal or distal stenosis/occlusion, or low cardiac output/cardiac arrhythmia. However, planimetry has not gained universal popularity since the measurements are hindered by heavy arterial calcification or tortuosity leading to inadequate B-mode imaging of the stenosis. This may occur in as high as 10–15% of all arteries imaged. These issues affect velocity recordings

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much less because the highest velocities are seen at the exit of the stenosis. Planimetry, however, complements velocity measurements and these methods should be used together. It is an especially important adjunct in the follow-up of stented carotid arteries.

Conclusions Carotid DUS is the established method for diagnosing a cervical carotid artery stenosis. In medical centers with a vascular laboratory that has established an excellent PPV, angiography may be avoided before embarking on carotid revascularization. Other laboratories may emphasize the screening aspect of their testing and will have a higher NPV. Patients diagnosed in this setting must undergo a confirmatory study prior to undergoing revascularization. The criteria used for diagnosing specific categories of stenoses vary between laboratories. The hallmark of a good laboratory is one that establishes its own criteria and continually validates them in an ongoing quality assurance program.

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40 [7] Carpenter JP, Lexa FJ, Davis JT: Determination of duplex Doppler ultrasound criteria appropriate to the North American Symptomatic Carotid Endarterectomy Trial. Stroke 27: 695–699 (1996). [8] DeGroote RD, Lynch TG, Jamil Z et al.: Carotid restenosis: long-term noninvasive follow-up after carotid endarterectomy. Stroke 18: 1031–1036 (1987). [9] Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273: 1421–1428 (1995). [10] Faught WE, Mattos MA, van Bemmelen PS et al.: Color-flow duplex scanning of carotid arteries: new velocity criteria based on receiver operator characteristic analysis for threshold stenoses used in the symptomatic and asymptomatic carotid trials. J Vasc Surg 19: 818– 827; discussion 827–818 (1994). [11] Fillinger MF, Baker RJ Jr, Zwolak RM et al.: Carotid duplex criteria for a 60% or greater angiographic stenosis: variation according to equipment. J Vasc Surg 24: 856–864 (1996). [12] Fowl RJ, Marsch JG, Love M et al.: Prevalence of hemodynamically significant stenosis of the carotid artery in an asymptomatic veteran population. Surg Gynecol Obstet 172: 13–16 (1991). [13] Grant EG, Benson CB, Moneta GL et al.: Carotid artery stenosis: gray-scale and Doppler US diagnosis— Society of Radiologists in Ultrasound Consensus Conference. Radiology 229: 340–346 (2003). [14] Heyman A, Wilkinson WE, Heyden S et al.: Risk of stroke in asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia. N Engl J Med 302: 838–841 (1980). [15] Hobson RW 2nd: Rationale and status of randomized controlled clinical trials in carotid artery stenting. Semin Vasc Surg 16: 311–316 (2003). [16] ICAVL: The Intersocietal Commission for the Accreditation of Vascular Laboratories: Standards for Accreditation in Noninvasive Vascular Testing. Columbia, MD: ICAVL (2005). [17] Johnson BF, Verlato F, Bergelin RO et al.: Clinical outcome in patients with mild and moderate carotid artery stenosis. J Vasc Surg 21: 120–126 (1995). [18] Kuntz KM, Polak JF, Whittemore AD et al.: Duplex ultrasound criteria for the identification of carotid stenosis should be laboratory specific. Stroke 28: 597–602 (1997). [19] Lal BK, Hobson RW 2nd, Goldstein J et al.: Carotid artery stenting: is there a need to revise ultrasound velocity criteria? J Vasc Surg 39: 58–66 (2004). [20] Lal BK, Hobson RW 2nd, Goldstein J et al.: In-stent recurrent stenosis after carotid artery stenting: life table analysis and clinical relevance. J Vasc Surg 38: 1162– 1168; discussion 1169 (2003).

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