(Stroke. 1995;26:1517-1519.)
© 1995 American Heart Association, Inc.
Articles |
Microembolic Signal Detection Using Ultrasound
From the University Department of Neurology, King's College Hospital School of Medicine and Dentistry and the Institute of Psychiatry (H.S.M.), and the Rita Lila Weston Institute of Neurological Studies, University College London Medical School (M.J.H.), London, UK.
Correspondence to Dr Hugh Markus, University Department of Neurology, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK.
Key Words: carotid artery diseases • embolism • heart valve prosthesis • ultrasonics • cerebral ischemia
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Introduction |
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 Top Introduction References |
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It is 5 years since Spencer and colleagues1 described in this journal the detection of embolic signals thought to represent solid material released from carotid plaques during the dissection phase of carotid endarterectomy. There has been a rapid spread of interest in this technique. A number of reports have demonstrated the detection of embolic signals in patients with a wide variety of potential embolic sources, and it has been suggested that this detection may already form an important clinical investigational tool. Others have cautioned skepticism.2
The principles underlying ultrasonic detection of cerebral emboli are relatively simple. Being both larger than the surrounding red blood cells and of a different material with different acoustic impedance than the surrounding blood, the incident ultrasound beam is both reflected and scattered at the interface between the embolus and blood. This results in an increase in the intensity of the received signal which, as the embolus is in the sample volume for a short time only, is of short duration. It has been clearly demonstrated in both animal models3 4 and flow models5 that platelet, thrombus, atheroma, and fat emboli result in the expected short-duration, high-intensity signal, usually within the Doppler flow spectrum. In these experimental studies, emboli smaller than 200 to 400 µm could not be reliably introduced, but it is likely that much smaller emboli can be detected using this technique. The intensity increase tends to be unidirectional, and frequency or velocity focused. In contrast, artifact results in predominantly bidirectional signals that can usually, but not always, be easily distinguished.6
Preliminary studies have reported the detection of similar signals in patients with carotid stenosis,7 8 9 10 11 12 prosthetic cardiac valves,13 14 15 16 myocardial infarction,17 atrial fibrillation,18 19 and native cardiac valve disease. In addition, perioperative monitoring has revealed signals during carotid endarterectomy,1 20 21 carotid angiography,22 23 24 carotid angioplasty,25 and cardiopulmonary bypass.26 A worrying feature of the initial reports is a wide variation both in the proportion of patients with embolic signals and in the number of events per hour in patients with similar embolic sources.
A striking early finding was the frequency of signals in patients with mechanical prosthetic cardiac valves. This finding has been replicated by a number of groups, and although there is some variation in the proportion of individuals with embolic signals, reasonable agreement has been found. Embolic signals are much more common in patients with mechanical cardiac valves than with porcine cardiac valves, and in the former group some patients have many thousands per day.13 14 15 Differences have been found in the characteristics of the embolic signals compared with those found in patients with other potential solid embolic sources, such as carotid stenosis.27 Signals recorded from prosthetic heart valve patients tend to be more intense and of longer duration, and experimental evidence would suggest that they therefore result from either larger solid emboli or from emboli composed of a more echogenic material. The lack of any correlation with clinical events14 makes the former less likely, and it has been suggested that these signals may result from gaseous bubbles formed by a cavitation process. Although this remains to be proven, it would be consistent with the lack of association found between embolic signals and degree of anticoagulation, coagulation parameters (D-dimer, antithrombin, and thrombin-antithrombin III complex),28 and antithrombotic and antiplatelet therapy29 in this patient group. Further studies are required to determine whether they relate to clinical outcome in any way, and these would need to include detection of more subtle neurological deficits, possibly with neuropsychological assessment as has been performed in cardiopulmonary bypass.26
Despite the obvious potential applications in atrial fibrillation, both in selecting patients for anticoagulation and for monitoring the effectiveness of anticoagulation and antiplatelet therapy in individual patients, there have been few studies of this condition. Tegeler et al18 found embolic signals in 13 of 44 patients with recent stroke and atrial fibrillation when recording from the common carotid artery for 15 to 60 minutes. The incidence of embolic signals may be lower in patients with atrial fibrillation but no recent neurological event, and initial small studies suggest an incidence of approximately 10% during a short single recording.19 30 Further studies are required to determine the prevalence of embolic signals in patients with atrial fibrillation with and without neurological events, the response to warfarin and aspirin, and ultimately the prognostic significance of the embolic signals.
Carotid stenosis has received more study. Although all studies have reported embolic signals in some patients with symptomatic carotid stenosis (recording from the ipsilateral middle cerebral artery), the proportion of signal-positive patients has varied from 20% to over 90%.7 8 9 10 11 12 These differences may reflect differences in the patient populations studied, including anticoagulation and antithrombotic treatment, degree of stenosis, and time since last symptom. As would be expected from clinical natural history studies, embolic signals appear to be more frequent soon after a stroke or transient ischemic attack in patients with carotid stenosis.11 12 31 However, it is difficult to account for all the differences in the reported frequency of embolic signals in initial studies by these clinical parameters alone, and this has led some to question the validity of the technique. Embolic signals in patients with carotid stenosis tend to be of lower amplitude and shorter duration than those found in patients with prosthetic cardiac valves,15 27 and there may be less interobserver agreement in their identification than for the more intense signals found in patients with mechanical cardiac valves. Random fluctuations in the background Doppler signal, or "Doppler speckle," occur in normal individuals, and both these and artifact have to be differentiated from true embolic signals. With use of defined criteria and intensity thresholds, good intraobserver variability has been reported within individual centers.15 31 In contrast, a recent consensus examination at the International Symposium on Haemodynamics in Munster found relatively poor interobserver agreement. Many publications to date have given little information on the criteria used for embolic signal detection and no estimate of interobserver or intraobserver reproducibility. It is vital that a consensus on the optimal definition be developed and validated using both signals resulting from known emboli in models and embolic signals in patients and then applied by different centers. A further worrying feature has been the lack of blinded evaluation of data. In most studies, identification of embolic signals has been made by a trained observer during a recording from a patient or control subject, with the presence of the embolic source being known at the time the identification of an embolic signal is made. Using such protocols, it is difficult to exclude unintentional bias influencing the identification of an intensity increase as representing an embolic signal. Now that this technique has passed its pilot stage, in future clinical studies recordings of the Doppler signal should be made and evaluated blinded to the clinical diagnosis. It is of note that where this blinded evaluation has been applied, the prevalence of embolic signals was found to be at the lower end of the reported range.12 An important further potential difficulty is that the sensitivity of detection may vary with different equipment and even with the same equipment if different settings are used. In an experimental model, it has been demonstrated that embolic signals are easier to detect with a low gain and sample volume.32 Temporal resolution, or time-window overlap, of current machines using a fast Fourier transform may be insufficient to detect all transient increases in signal intensity.31 The characteristics of the high-intensity signal produced by the same embolus may vary with alteration in the angle of insonation, the transducer frequency, and the depth of the vessel. Yet few studies mention either recording parameters or computing characteristics of the equipment used. These parameters need to be established by the manufacturers for each transcranial Doppler machine, particularly if they are specifically marketed for embolic signal detection.
The clinical significance of embolic signals remains uncertain. Almost all signals reported to date have been asymptomatic, although a recent case report describes multiple middle cerebral artery embolic signals occurring during ipsilateral common carotid artery compression at the same time at which a contralateral hemiparesis developed, and fundoscopy revealed retinal cholesterol emboli.33 It is likely that the prognostic significance of embolic signals may differ between different clinical groups. Preliminary data suggest that they may have limited significance in patients with prosthetic cardiac valves, as discussed above. In contrast, preliminary evidence suggests a potential clinical importance in carotid artery disease. In this condition, they are more common in symptomatic rather than asymptomatic carotid stenosis,7 10 12 they are reduced in frequency after carotid endarterectomy,31 they are more common with plaques showing intraluminal thrombus and plaque ulceration,34 and in individual cases, they appear to have responded to anticoagulation35 36 and antiplatelet treatment.12 Future prospective clinical studies are needed to evaluate the importance of these signals in each individual clinical subgroup separately, and it is likely that multicenter studies will be needed. Prior to this step, standard recording protocols need to be developed. Short periods of the order of 30 minutes may be sufficient for patients with mechanical prosthetic cardiac valves,37 whereas repeating recordings on more than one occasion may be necessary for carotid stenosis, in which preliminary studies suggest more temporal variability.12
Detection of asymptomatic embolic signals may have a number of important clinical applications, including the localization of the embolic source in individual patients, the monitoring of the effectiveness of antithrombotic and antiplatelet therapy in individual patients, perioperative monitoring, and the selection of a high-risk group for appropriate prophylactic pharmacological and surgical treatment. Prior to these studies, additional baseline information is required. Uniform consensus criteria for the identification of embolic signals need to be determined to allow comparison of data among centers. These criteria can then be evaluated by determining interobserver variability in detecting specific embolic signals by operators in different centers. A better understanding of the effect of recording with different equipment needs to be determined. Optimal recording protocols then will need to be determined by studying the variability of embolic signals over time; these protocols are likely to differ for the different disease states. This will allow power calculations to be performed, and the feasibility of large-scale, multicenter prognostic studies to evaluate the clinical significance of embolic signals can then be determined.
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Acknowledgments |
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We are grateful to Dr Patrick Hill of the Medical Physics Department, Middlesex Hospital, for helpful discussions.
Received May 4, 1995; revision received May 30, 1995; accepted May 30, 1995.
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References |
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TopIntroductionReferences |
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