DIGITAL SUBTRACTION ANGIOGRAPHY IN CAROTID ARTERY STENOSIS
A. Srinivasan and M. Goyal
Department of Diagnostic Imaging, University of Ottawa, Ottawa, Canada
Introduction
Atherosclerotic disease of the craniocervical vessels is the underlying basis for cerebral thromboembolic stroke in more than 90% of cases in industrialized nations [19]. Craniocervical atherosclerotic vascular disease most commonly and severely affects the in- ternal carotid artery (ICA) origin and the distal bas- ilar artery [19]. The clinical symptoms and morbid- ity that result from carotid artery disease, the primary cause of stroke, are mainly due to plaque ul- ceration, thrombosis, intraplaque hemorrhage, and thinned fibrous caps [24]. Clinical benefit of treat- ing symptomatic, severe carotid stenosis has been demonstrated in a number of trials [18], [10]. There- fore the goals of imaging in atherosclerotic cranio- cervical disease are to determine the degree of ca- rotid stenosis, identify ‘tandem’ lesions in the carotid siphon or intracranial circulation and to evaluate the existing and potential collateral circulation [27].
Conventional catheter angiography remains the standard technique against which other non-invasive modalities (CT, MR) are assessed.
Experimental and clinical knowledge
Measuring carotid stenosis
Both the North American Symptomatic Endarterec- tomy Trial (NASCET) and European Carotid Sur- gery Trial (ECST) demonstrated definite benefit of carotid endarterectomy (CEA) in symptomatic pa- tients with severe stenosis (70–99%) of the ICA [18], [10]. The Asymptomatic Carotid Atherosclerosis Study (ACAS) also showed benefit of surgery for asymptomatic stenosis greater than 60% [10]. In an
analysis published in 1998 by the NASCET collab- orators, they showed that CEA yielded only a mo- derate reduction in the risk of stroke in patients with symptomatic moderate (50–69%) carotid stenosis whereas patients with severe stenosis ( 70 percent) had a durable benefit from CEA at eight years of follow-up [2]. They suggested that decisions about treatment for patients in the moderate stenosis cate- gory must take into account recognized risk factors, and that exceptional surgical skill was obligatory if CEA was to be performed. As a result, it is essential to determine accurately the degree of stenosis in an individual patient since this has an impact on man- agement decisions.
In both the NASCET and ECST trials, the degree of stenosis was determined using digital sub- traction angiography (DSA), which has since be- come the reference standard. In the NASCET trial, the stenosis was calculated from the ratio of the li- near luminal diameter of the narrowest segment of the diseased portion of the artery to the diameter of the artery beyond any poststenotic dilatation (%
stenosis [1 minimum residual lumen/normal distal cervical internal carotid artery diameter]
100) [18] (Fig. 1). The ECST trial measured the percentage diameter stenosis on the best angiogra- phic view of the point of maximum narrowing, using as the denominator an estimate of the original width of the artery at this narrowest point and bearing in mind the slight widening of the normal ICA origin, which is where most of the stenoses were found [10].
The reproducibility of these measurements was also internally validated in both the studies. Gagne et al.
prospectively studied the reliability of carotid stenosis measurements performed by practicing physicians of different specialties and different levels of clinical ex- perience and concluded that physicians could easily
learn the NASCET technique for quantification of carotid stenosis and reliably implement it for appro- priate identification of candidates for CEA [12].
Limitations of measurement techniques
There are, however, limitations with both the NAS- CET and ECST angiographic methods [1], [5], [11]. With the NASCET method, the distal ICA may be obscured by overlying vessels or inadequate contrast enhancement. It is often difficult to decide the appropriate segment of distal ICA on which to base a measurement. With severe stenosis, there is the risk of underestimation of stenosis since the ICA beyond the stenosis may be significantly narrow- ed. Furthermore, minor degrees of stenosis (50%
bulb diameter reduction) may result in a “negative stenosis” because the carotid bulb is larger than the distal ICA [1]. For ECST measurements, variations in anatomy or irregular stenoses can make it diffi- cult, even for the experienced observer, to predict the normal position of the carotid bulb.
Also, significant discrepancies between the NAS- CET and the ECST angiographic methods may arise such that a 50% stenosis by NASCET is equivalent to approximately 70% by ECST [3], [23]. For a clini- cian considering CEA in an individual symptomatic patient, this could cause management dilemmas. This is due to the fact that CEA has a proven benefit in severe stenosis and may only be moderately beneficial in moderate stenosis [2]. The principal difficulty, there- fore, with both methods is establishing the diameter of the normal ICA. An alternative approach is to use the well-established physiological and anatomic relationship between the common carotid artery (CCA) and proximal ICA, so that the normal ICA diameter can be derived from measurement of the CCA. For example, duplex ultrasound studies have consistently shown normal ICA/CCA peak blood flow velocity ratios of 0.7 [3], [23], and studies of
Fig. 1. Lateral common carotid angiogram in a 50-year-old male patient reveals severe stenosis involving the internal carotid artery bulb (arrow) with a ‘string-sign’ (arrowheads) noted distal to the stenosis. DSA still remains the best modality for distinguishing complete ICA occlusion from the ‘string-sign’ due to 99% stenosis.
In another study, Rothwell et al. [20] concluded that there was little difference in the ability of the three angiographic methods (NASCET, ECST and CC) to predict ipsilateral carotid distribution ische- mic stroke but found the CC method to be consis- tently the most reproducible of the three, particu- larly for stenosis in the clinically important range of 50–90%. Hence, they recommended that the CC method of measurement should be adopted as the standard method of measuring the degree of carotid stenosis on angiograms [20].
However, other authors have felt that CC meth- od is neither superior nor easier to calculate than the NACSET method [8]. They also point out that benefits of CEA have been established in patients with 70–99% carotid stenosis using the NASCET criteria in a clinical trial (unlike the CC method which has not figured in any major clinical trial) and hence did not recommend conversion from the NASCET method to the CC method [8].
Role of rotational angiography
DSA measurement techniques used traditionally in- volve the anterior-posterior, lateral and oblique views of the carotid bifurcation. However, these pro- jections may not always be optimal for demon- strating the maximum stenosis. Three-dimensional reformations of CT angiogram and MR angiogram can provide visualization from any angle desired and may be as or more accurate than DSA for determin- ing the degree of stenosis. Newer techniques like 3D computed rotational angiography (CRA) can provide a larger number of views than DSA, which may in- fluence the estimated degree of stenosis. CRA pro- vides stenosis grades equivalent to DSA, as well as absolute measurements, providing a comparison for newer 3D techniques [16].
In a study comparing depiction of ICA stenosis on rotational angiography and DSA and its impact on patient treatment, both rotational angiography and DSA were performed in 47 stenotic ICAs. In three ICAs, rotational angiography was non-diagnostic. In 28 of the remaining 44 ICAs, the degree of stenosis was categorized similarly with DSA and rotational normal angiograms [25] have shown the ICA/CCA
diameter ratio is 1:1.19 (0.09).
Alternate methods of quantifying stenosis
Thus there are different methods for estimating the stenosis of the ICA proposed in the literature. The use of various methods, which produce different val- ues on the same angiograms, has caused confusion and reduced the generalizability of the results of re- search. If the results of future studies are to be properly applied to clinical practice, and if noninvasive meth- ods of imaging are to be properly validated against angiography, a single, standard method of measure- ment of stenosis on angiograms should be adopted.
This standard method should be selected on the bases of its ability to predict risk of ipsilateral carotid distri- bution ischemic stroke and its reproducibility.
Bladin et al. compared stenosis measurements using the NASCET and ECST methods and, two new techniques, the Common Carotid (CC) and Ca- rotid Stenosis Index (CSI) [4]. The CC method was based on a direct comparison of the residual lumen to the distal CCA diameter adjacent to the bulb. The CSI was based on the known relationship between the proximal CCA and ICA (1.2 CCA diameter proximal ICA diameter). Of the different angiogra- phic techniques, CSI was found to be the most reliable validated method of measuring carotid stenosis.
Hence the authors proposed CSI as a bridge between results of carotid surgery trials, and to validate nonin- vasive modalities against angiography [4].
Staikov et al. compared three angiographic meth- ods for grading of carotid stenosis (ECST, NAS- CET, and CC methods) and also examined the cor- relation between angiographic and ultrasound findings [21]. They concluded that measurements using the CC method were the most reproducible and those using the NASCET method the least.
Also, interobserver reproducibility was found to be best for the CC and ECST methods and least for the NASCET method. Ultrasound provided an ac- curacy of 94% compared to ECST and CC methods and 84% compared to the NASCET method in this study [21].
angiography, whereas with rotational angiography, 15 ICAs were classified one category higher and one ICA was classified two categories higher, owing to the increased number of projections available. Seventy percent to 99% stenosis was demonstrated in 18 ICAs with DSA and in 25 ICAs with rotational angiogra- phy. The authors concluded that rotational angiogra- phy frequently depicts more severe ICA stenosis and that rotational angiography could have facilitated a change in the optimal treatment (from non-surgical treatment to CEA) in seven ICAs [7].
Interobserver variability
Interobserver variability in the measurement of ca- rotid stenoses from DSA displayed in different ways (non-magnified or magnified, white or black arter- ies) was studied by Chow et al., who also compared human readers with computer-generated densito- metric measurements of vessel stenosis [6]. The most reliable measurements of stenosis were obtain- ed from the non-magnified black and white artery images. The interobserver variability in the measure- ment of internal carotid stenoses using non-magni- fed images was small and increased with magnified images. Also, the computer-generated stenosis mea- surements were consistently much higher than those of the radiologists. The authors concluded that read- ers of digital angiographic images must determine the most reliable, reproducible images generated by their equipment, as these measurements significantly affect treatment of patients with symptomatic ICA stenosis [6].
Another study evaluating the interobserver vari- ability for carotid artery stenosis measurements resulted in good overall interrater agreement using the NASCET/ACAS and ECST criteria [22]. However, the authors found that the agreement for therapeutic decisions on carotid surgery was less strong and concluded that accurate stenosis measurement alone may not suffice for reliable treatment decisions in patients with high grade carotid artery stenosis [22].
Young et al. evaluated the reporting of carotid stenosis using four different techniques (three tech- niques with caliper measurements and the fourth was visual assessment) on both DSA and MRA [28].
The variability in reporting and the number of clini- cally significant differences arising as a result were similar for each of the four techniques using DSA.
While the typical measurement errors for each of the techniques studied were on the order of 5%, each technique produced some sizable individual differ- ences for the same angiogram, with resultant wide 95% limits of agreement. Also, the observer variability for reporting MRA was generally a little greater than for DSA. Compared with the caliper techniques, the visual impression of stenosis technique performed well, particularly for MRA. The authors concluded that although observer variability in reporting can be considerable, no important differences were found among the different techniques widely used for mea- suring carotid stenosis [28].
Advantages of DSA
Distinction between near-occlusion and occlusion of the ICA is crucial because patients can benefit from a surgical treatment in the former scenario [27]. DSA is the best neuroimaging technique for this distinc- tion since other non-invasive modalities may fail to show antegrade flow in severely stenotic vessels [27].
An example of ‘string sign’ is depicted in Fig. 1.
Detection of tandem lesions (or distal stenosis) is important since some patients may be included from CEA or endovascular therapy depending on the sever- ity of the individual lesions. DSA is probably the best test to reliably demonstrate tandem lesions compared to other non-invasive modalities [27] (Fig. 2).
DSA also provides information about acces- sibility from the femoral route, demonstrates any aortic pathology (e.g., dissection, aneurysm) that may preclude endovascular therapy or make it diffi- cult and assesses feasibility of using present day angiographic equipment to access tortuous vessels.
Complications of angiography
Hankey et al. prospectively evaluated 382 patients with symptomatically mild carotid ischemia who had cerebral angiography to visualize a potentially resect- able lesion at the carotid bifurcation [13]. They en- countered complications in 14 angiograms done in 13
Fig. 2. A 47-year-old female patient presented with right middle cerebral artery territory stroke. CT angiogram (a) revealed focal stenosis at the right ICA bulb and a long segment narrowing involving the cervical ICA starting from the bulb upwards (arrows). Carotid angioplas- ty and stenting was planned. However, on the common carotid angiogram (b), there was tandem stenosis detected with a proximal in- ternal carotid stenosis (curved arrow) and a significant distal intracranial stenosis in the supraclinoid segment (arrow), which was difficult to appreciate even retrospectively on the CTA due to adjacent bone.
patients (3.4%) with two local complications (0.5%), two systemic complications (0.5%) and 10 neurologi- cal complications (2.6%). Of the neurological compli- cations 2 (0.5%) were transient (transient ischemic attack 1, generalized seizure 1), 3 (0.8%) were revers- ible strokes and 5 (1.3%) resulted in permanent strokes. There were no deaths encountered [13].
Hankey et al. also evaluated eight prospective and seven retrospective studies from which it was possible to derive the complication rate of conven- tional cerebral angiography for patients with mild ischemic cerebrovascular disease, who were potential candidates for carotid endarterectomy [14]. Three studies of intravenous and one of intra-arterial digital subtraction angiography were also examined. They reported that angiography carries a 4% risk of minor stroke or transient ischemic attacks, 1% risk of major stroke and a less than 1% risk of even death [14].
In another study evaluating the neurological com- plications in cerebral angiography, the authors en- countered 39 (1.3%) neurologic complications in 2,899 procedures; 20 were transient (0.7%), five (0.2%) were reversible, and 14 (0.5%) were permanent [26].
These studies suggest that the risk of an angiogra- phic procedure is not negligible and therefore the po- tential benefit to symptomatic patients may be dimi- nished by the invasive nature of DSA. There is also the additional risk of contrast reactions and contrast indu- ced nephropathy with DSA. Amongst the non-inva- sive modalities, CTA shares the same risks as DSA whereas these risks are avoided with US and MRA.
Thus there is still ongoing work about determin- ing the best way of measuring ICA stenosis and its clinical application. However, it suffices to say that till a proper trial with the other mentioned methods are performed, the NASCET method would proba- bly be the most commonly used technique due to its simplicity of use and its well established clinical role.
Aspects to the future
Carotid plaque instability is considered an impor- tant determinant of stroke risk [17]. There are now various imaging techniques that can provide infor- mation on carotid plaque morphology. Some charac-
teristics that may reflect a high risk of vulnerability are outward, abluminal plaque remodelling, the pres- ence of intra-plaque haemorrhage, inflammation, severe flow disturbances around the encroaching le- sion, plaque cap thinning and ulceration, and abnor- mal plaque motion [15]. While non-invasive modal- ities like US and MRI have shown potential in assessment of plaque morphology, DSA may not have the capability of demonstrating the above men- tioned plaque characteristics. Non-invasive tests may, therefore, play an increasing role in carotid imaging in the near future due to potential implica- tions in predicting stroke risk.
Conclusion
DSA has long since been established as the gold standard for assessment of vascular disease. Clinical trials using DSA for measurement of carotid artery stenosis have been found DSA to be reasonably re- producible and reliable. But ultrasound Doppler, CTA and MRA are replacing DSA in most centers as the initial tool for assessment of vascular disease in the neck and intracranial circulation. Not only do these modalities have the obvious advantage of being non-invasive unlike DSA, they also have dem- onstrated good sensitivity in detecting and grading carotid artery stenosis in multiple studies. Also dem- onstration of plaque morphology may be better with MRI and US and this may play a key role in predic- ting stroke risks. However, DSA is still the modality of choice for distinguishing between near occlusion and occlusion and will continue to be used for prob- lem solving purposes.
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