Clinical Neurology and Neurosurgery 102 (2000) 9 – 12 www.elsevier.com/locate/clineuro
Contrast enhanced color duplex for diagnosis of subtotal stenosis or occlusion of the internal carotid artery Derk J. Hofstee a,*, Peter H. Hoogland b, Robert J. Schimsheimer a, Al W. de Weerd a a
Department of Clinical Neurophysiology, Medical Centre Haaglanden, Westeinde Hospital, Postbus 432, 2501 CK The Hague, The Netherlands b Department of Radiology, Medical Centre Haaglanden, Westeinde Hospital, Postbus 432, 2501 CK The Hague, The Netherlands Received 26 August 1999; received in revised form 13 December 1999; accepted 13 December 1999
Abstract Background and purpose. We initiated this prospective study to investigate the usefulness of contrast enhancement in combination with color Doppler-assisted duplex imaging (CDDI) for the distinction of subtotal internal carotid artery (ICA) stenosis and ICA occlusion. Methods. During 1 year all patients with a previously unknown subtotal ICA stenosis ( \ 90%) or ICA occlusion on routine CDDI were included in the study. These patients underwent a CDDI with and without intravenous contrast, Levovist® 300 mg/ml. Results. The study group consisted of 32 patients, 15 with subtotal stenosis and high velocity at the ICA stenosis, two with subtotal stenosis and minimal residual color flow and relative low velocity at the ICA stenosis and 15 with ICA occlusion. In all patients the diagnosis by CDDI without and with contrast were the same. Image quality was improved with contrast in 13 of the 17 patients at the subtotal ICA stenosis. There was no significant difference in mean velocities at the subtotal ICA stenoses without and with contrast. Conclusion. The usefulness of contrast enhancement with CDDI for differentiating subtotal ICA stenosis and ICA occlusion is limited. Possibly it is useful in patients with moderate image quality of the CCA and ICA and in patients with a subtotal stenosis with minimal residual color flow and relative low velocity at the ICA stenosis. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Carotid stenosis; Carotid artery occlusion; Contrast media; Duplex scanning; Ultrasonics
1. Introduction The differentiation between high-grade stenosis (\ 70% stenosis) and occlusion of the internal carotid artery (ICA) has major clinical consequences. The future risks for death or stroke are diminished by carotidendarterectomy in symptomatic patients with highgrade ICA stenosis [1,2]. Contrarily it is assumed that these future risks are not diminished by surgery in ICA occlusion. Ultrasonography and angiography are used to assess Abbre6iations: CCA, common carotid artery; CDDI, color Doppler-assisted duplex imaging; DSA, digital subtraction angiography; EDV, end diastolic velocity; ICA, internal carotid artery, PSV peak systolic velocity. * Corresponding author. Tel.: + 31-70-3302000; fax: + 31-703809459.
the degree of ICA stenosis. Angiography has long been considered to be superior to ultrasonography, especially in differentiating subtotal ICA stenosis (\ 90% stenosis) and ICA occlusion. However in the last decade’s ultrasonography technology developments have improved the sensitivity and specificity for diagnosis of subtotal ICA stenosis and ICA occlusion [3–5]. A relatively new development is the application of contrast enhancement in combination with color Doppler-assisted duplex imaging (CDDI) [6]. Contrast enhancing agents are intravenous administered transpulmonary stable agents that contain air micro bubbles. These air micro bubbles increase echogenicity of the arterial blood flow [6,7]. We initiated this prospective study to investigate the usefulness of contrast enhancement in combination with CDDI for the distinction of subtotal ICA stenosis and ICA occlusion.
0303-8467/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII: S 0 3 0 3 - 8 4 6 7 ( 9 9 ) 0 0 0 8 1 - 5
D.J. Hofstee et al. / Clinical Neurology and Neurosurgery 102 (2000) 9–12
10
Table 1 Subdivision of the study group based on routine CDDI Group
Diagnosis
Description
Patients
1 2 3 Total
Subtotal ICA stenosis PSV (ICA stenosis) \400 cm/s or ratio PSV (ICA stenosis)/EDV (distal CCA) \20 Subtotal ICA stenosis Minimal residual color flow with relative low PSV and EDV at the ICA stenosis ICA occlusion Absent color flow and no velocities in the ICA
15 2 15 32
2. Methods
2.4. Statistical analysis
2.1. Patients
The sensitivity and specificity of the CDDI without and with contrast for differentiating subtotal ICA stenosis and ICA occlusion were assessed with the DSA as gold standard. The differences of the CDDI mean PSV, EDV and PSV(ICA)/EDV(CCA) ratio without and with contrast enhancement were analysed with the student t-test with paired two samples.
In a period of 1 year 564 patients had a routine CDDI investigation in our laboratory. Those patients who had a previously unknown ICA subtotal stenosis or occlusion at routine CDDI were included in this study. The criteria for subtotal ICA stenosis (\90% stenosis) were peak systolic velocity (PSV)\ 400 cm/s at the ICA stenosis or a ratio of PSV at the ICA stenosis and end diastolic velocity (EDV) at the distal common carotid artery (CCA)\ 20 or a minimal residual color flow (string sign) with relative low PSV and EDV at the ICA stenosis. The criteria for ICA occlusion were absent color flow and no measurable velocities in the proximal and distal ICA. Finally 32 patients fulfilled the criteria for a subtotal stenosis or occlusion of the ICA.
2.2. CDDI measurements We used a Hewlett Packard Sonos 2000 CDDI machine with linear array 7.5, 5.5 and 5.0 MHz and 5.5, 5.5 and 5.0 MHz pulsed wave Doppler insonation. Experienced technicians did the investigations and all the examinations were video taped. All patients included in this study had a CDDI investigation of the relevant ICA without and with contrast enhancement. The CDDI investigation included measurement of PSV and EDV at the ICA stenosis and at the distal CCA and visualisation of residual color flow on the entire length of the ICA stenosis or in the presumed ICA occlusion. For contrast enhancement Levovist® 300 mg/ml was used with repeated intravenous bolus injections of 3 ml.
2.3. Angiography The decision to perform angiography was based on the clinical data and the routine CDDI, independent of this study. Angiography was performed by selective arterial digital subtraction angiography (DSA) and an experienced neuroradiologist assessed the results. The degree of ICA stenosis was assessed with the common carotid method [8].
3. Results
3.1. Patients The study group consisted of 32 patients and could be divided in three subgroups based on the routine CDDI results (Table 1). Group 1 consisted of 15 patients with presumed subtotal ICA stenosis and high PSV at the ICA stenosis. Group 2 consisted of two patients with presumed subtotal ICA stenosis and minimal residual color flow with relative low PSV and EDV at the ICA stenosis. Group 3 consisted of 15 patients with presumed ICA occlusion. In the patients with presumed subtotal ICA stenosis (group 1 and 2) there were ten men and seven women, the mean age was 62 years. (SD910 years), 13 had a stroke or TIA and four were asymptomatic. In the patients with presumed ICA occlusion (group 3) there were ten men and five women, the mean age was 57 years (SD 9 13 years), 12 had a stroke or TIA and three were asymptomatic.
3.2. CDDI diagnosis without and with contrast enhancement In group 1 the CDDI with contrast enhancement showed similar to the CDDI without contrast enhancement a subtotal ICA stenosis with high PSV at the stenosis and no occlusion. In group 2 the CDDI without and with contrast enhancement showed residual flow in the distal and proximal ICA and so excluded occlusion. In group 3 no residual flow in the proximal and distal ICA could be detected without and with contrast enhancement. Hence all 32 patients had the same diagnosis by CDDI without and with contrast enhancement (Table 2).
D.J. Hofstee et al. / Clinical Neurology and Neurosurgery 102 (2000) 9–12
11
Table 2 Diagnosis of subtotal ICA stenosis or occlusion with CDDI with and without contrast enhancement and with DSA Group
1 2 3 Total
CDDI without contrast ICA stenosis ICA occlusion
CDDI with contrast ICA stenosis ICA occlusion
DSA ICA stenosis
ICA occlusion
15 2 0
15 2 0
14 0 0
0 0 6
0 0 15 32
3.3. Image quality In all of the 32 CDDI examinations with contrast enhancement the gain could be decreased with about 50%. In group 1 subjective color image quality was improved in 12 of the 15 examinations with contrast enhancement. The color flow at the entire length of the ICA stenosis was better visualised. In group 2 subjective color image quality was improved in one of the two patients, the color flow at the stenosis was identified more easily. In group 3 image quality was improved at the CCA in one of the 15 patients, in all other patients image quality was already good without contrast enhancement.
3.4. Doppler 6elocities In group 1 the mean PSV and EDV at the ICA stenosis without contrast were 422 cm/s (SD 9 90), 167 cm/s (SD 9 77) and with contrast 448 cm/s (SD 9124), 162 cm/s (SD991). The differences in mean PSV and EDV at the ICA stenosis were not significant (P =0.23, P= 0.51). The mean ratio of PSV at the ICA stenosis and EDV at the distal CCA in the group 1 were 31 (SD 9 9) without contrast and 31 (SD9 15) with contrast. Hence there was no difference in the mean ratio (P = 0.97). In group 2 the PSV and EDV of the two patients at the ICA stenosis were without contrast 27, 0 and 154, 0 cm/s and with contrast 26, 5, 210 and 0 cm/s.
3.5. Comparison with angiography In group 1 a DSA was performed in 14 of the 15 patients, in group 3 a DSA was performed in six of the 15 patients. None of the patients in group 2 had a DSA. The mean degree of ICA stenosis assessed by DSA in group 1 was 88% (SD99%). All patients in group 3 who had a DSA showed, similar to the CDDI, an occlusion of the ICA. In the 20 patients who underwent a DSA the sensitivity and specificity for a subtotal ICA stenosis and ICA occlusion with CDDI without and with contrast enhancement was maximal. In the 12 patients who did not have a DSA, it was decided not to perform a DSA on
0 0 15 32
20
clinical motives, like major disability, asymptomatic stenosis or occlusion, concomitant systemic disease and high surgical risks.
4. Discussion To select patients with high-grade ICA stenosis for carotidendarterectomy ultrasonography and angiography are used. Some clinics screen patients with CDDI and perform subsequently a DSA when a high-grade ICA stenosis or ICA occlusion is suspected. Other clinics rely on CDDI alone for the indication of carotidendarterectomy. Two pitfalls with CDDI are a subtotal ICA stenosis that is mistaken for an ICA occlusion and vice versa. Mansour found a sensitivity and specificity with unenhanced CDDI for ICA occlusion of 96 and 99% [5]. Accuracy in differentiating ICA occlusion and subtotal ICA stenosis could possibly be improved by using contrast enhancement with CDDI. Sitzer suggested that the use of transpulmonary stable contrast improves the visualisation of high-grade ICA stenosis [6]. They examined 30 patients with a high-grade ICA stenosis (\ 70% stenosis) and two with an ICA occlusion. In our study 32 patients were included with subtotal ICA stenosis ( \ 90% stenosis) or ICA occlusion on routine CDDI, who were subdivided in 3 groups (Table 1). In all patients the diagnosis was not different between CDDI without and with contrast enhancement (Table 2). The mean PSV and EDV at the ICA stenosis in group 1 showed no significant difference without and with contrast enhancement. Color image quality at the ICA stenosis was improved in 12 of the 15 patients in group 1 and in one of the two patients in group 2. In group 3 contrast enhancement brought no substantial improvement of color image quality in the CCA. In 20 of the 32 patients in whom a DSA was performed CDDI showed no wrong diagnosis. We conclude that the contribution of the currently available contrast enhancer with CDDI in differentiating subtotal ICA stenosis and ICA occlusion is limited. The accuracy of CDDI without contrast enhancement for differentiating subtotal ICA stenosis and ICA occlusion is already high. Possibly contrast enhancement
12
D.J. Hofstee et al. / Clinical Neurology and Neurosurgery 102 (2000) 9–12
could further improve accuracy of CDDI results in patients with a marginal ICA and CCA color image quality, a minority group, and in patients with a minimal residual color flow and relative low PSV and EDV at the ICA stenosis, also a minority group.
[2]
[3]
Acknowledgements
[4]
We thank the technicans for their assistance and expertise: Ellen van’t Geloof, Margreet Staleman, Sabine Verschuren and Elna Vink (Department of Clinical Neurophysiology, Medical Centre Haaglanden, Westeinde Hospital, Postbus 432, 2501 CK The Hague, The Netherlands).
[5]
[6]
[7]
References [8] [1] North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symp-
.
tomatic patients with high-grade carotid stenosis. N Eng J Med 1991;325:445 – 53. European Carotid Surgery Trialists’ Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70 – 99%) or with mild (0 – 29%) carotid stenosis. Lancet 1991;337:1235– 43. Go¨rtler M, Niethammer R, Widder B. Differentiating subtotal carotid artery stenosis from occlusions by colour-coded duplex sonography. J Neurol 1994;241:301 – 5. Berman SS, Devine JJ, Erdoes LS, Hunter GC. Distinguishing carotid artery pseudo-occlusion with color-flow duplex. Stroke 1995;26:434 – 8. Mansour MA, Mattos MA, Hood DB, et al. Detection of total occlusion, string sign, and preocclusive stenosis of the internal carotid artery by color-flow duplex scanning. Am J Surg 1995;170:154 – 8. Sitzer M, Rose G, Fu¨rst G, Siebler M, Steinmetz H. Characteristics and clinical evaluation of high-grade internal carotid stenosis. J Neuroimag 1997;7(suppl 1):S22 – 5. Burns PN. Overview of echo-enhanced vascular ultrasound imaging for clinical diagnosis in neurosonology. J Neuroimag 1997;7(suppl 1):S2 – S14. Rothwell PM, Gibson RJ, Slattery J, Warlow CP. Prognostic value and reproducibility of measurements of carotid stenosis. Stroke 1994;25:2440 – 4.