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The value of studying carotid plaque morphology
Opinion The Value of Studying Carotid Plaque Morphology N. M. E1-Barghouti,PhD,FRCS Stroke is the most common disabling neurological disease of adult life, the third leading cause of death in the developed world, and an important cause of hospital admission and long-term morbidity in most industrialized populations. 1Advanced carotid atherosclerotic stenosis is the largest single etiological factor known to produce focal cerebral ischemia. 2 Because current medical treatment for acute stroke is underdeveloped, 3prevention is the key to the reduction of the morbidity and mortality. A number of clinical trials have been undertaken to evaluate the benefit of surgery, both in the symptomatic and the asymptomatic patients, in the prevention of disabling and fatal stroke. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) have clearly shown that symptomatic patients with severe 70% to 99% internal carotid artery stenosis carry a substantial risk of ipsilateral ischemic stroke and that surgery provides a six-fold reduction of this risk. 4,5 The effects of carotid endarterectomy in symptomatic patients with 30% to 70% stenosis remain to be determined. Because the incidence of stroke in medically treated patients with lower order stenosis is close to the combined perioperative morbidity and mortality rate, criteria other than the degree of stenosis may help to identify a subgroup at higher risk. The Asymptomatic Carotid Atherosclerosis Study (ACAS) has shown that relative stroke risk reduction in patients with asymptomatic advanced carotid stenosis (>60%) conferred by surgery is 55%.6 This study has provided the first scientific evidence that under certain circumstances carotid endarterectomy can reduce the incidence of stroke in patients with greater than 60% asymptomatic stenosis of the internal carotid artery. After successful carotid endarterectomy, the annual stroke rate was reduced from 2% in the medical group to 1% in the
From the Department of Surgery, South Cleveland Hospital, Middlesbrough, UK. ReceivedMarch 6, 1997;acceptedJuly 24, 1997. Address reprint requests to N. M. El-BarghoutLPhD, FRCS, 9 Woodhorn Gardens, Wide Open, Newcastleupon Tyne, NE13 6AG, UK. Copyright9 1998by National StrokeAssociation 1052-3057/98/0702-000253.00/0
surgical group. One important implication has emerged: to prevent one stroke at least 20 surgical procedures have to be performed. The cost of stroke prevention by these means is therefore high. Perhaps identifying a subgroup of this population at higher risk of stroke, using criteria such as plaque characterization in addition to the degree of stenosis, may spare others from unnecessary operation with consequent financial savings. 7 Duplex scanning has the ability to determine not only the degree of carotid stenosis based on flow characteristics, but also plaque structure. Thus, there is the potential to separate patients at high risk of developing stroke from those at low risk independent of the degree of stenosis. Because it is noninvasive, duplex scanning can be performed repeatedly in assessing the status of the carotid artery and may play an important role in determining when intervention would be appropriate. 8
The Importance of Ultrasonic Carotid Plaque Morphology to Cerebrovascular Events Advanced asymptomatic carotid stenosis (>75%) occurs in approximately 1% of subjects above the age of 50 years. 9 The majority of patients who develop stroke do so without warning symptoms. TM Although patients with asymptomatic high-grade carotid stenosis have an increased rate of spontaneous stroke, this risk remains low and perioperative mortality and morbidity may tilt the balance of risk benefit against surgery. The identification of a subgroup of patients with asymptomatic carotid stenosis who are at high risk of stroke based on plaque morphology and degree of carotid stenosis is therefore cruciaU 1 In advanced carotid stenosis, echolucent atherosclerotic plaques with a high lipid and hemorrhage content are unstable and more likely to embolize than echogenic fibrous plaques. 12There is a preponderance of echolucent plaques in patients with symptomatic cerebrovascular disease, whereas echogenic plaques are more common in asymptomatic patients. 13 Heterogenous and echolucent plaques are associated with increased risk of subsequent neurological events and a higher incidence of cerebral infarction: TM In asymptomatic patients with advanced
Journal of Stroke and Cerebrovascular Diseases, Vol. 7, No. 2 (March-April), 1998: pp 105-108
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106 carotid stenosis, echolucent plaques are associated with a higher incidence of intracranial embolic events detected by middle cerebral artery transcranial Doppler ultrasound, 15 supporting the hypothesis that echolucent plaques are unstable with a greater tendency to embolize than echogenic plaques. Cerebral infarcts on computerized tomography (CT) in patients with advanced carotid stenosis and transient ischemic attacks were associated with an increased risk of subsequent stroke and shorter survival time. Silent cerebral infarction in patients with asymptomatic carotid stenosis is considered to cause adverse prognosis and increased risk of subsequent neurological events. Thus carotid plaques associated with cerebral infarction are probably high-risk unstable plaques. 16 Carotid stenosis is more frequent and severe in patients with symptomatic cerebrovascular disease than in those who are asymptomaticF Asymptomatic patients with more than 75% carotid stenosis have a higher incidence of subsequent neurogenic events as compared with those with less than 75% stenosis, is In addition, the more severe the carotid stenosis, the higher the incidence of ipsilateral cerebral infarction. 19
Computerized Carotid Plaque Characterizations Most of the published studies of carotid plaque morphology on ultrasonography relied on subjective and qualitative visual characterization of the plaque ultrasound images. Objective and quantitative grading of plaque echogenicity and heterogeneity using computerized measurements may provide more accurate operatorindependent assessment of plaque echoic structure improving the detection of high-risk carotid plaque. Computer-based densitometric analysis of carotid plaque ultrasonic images allows enhanced differentiation of plaque composition. Beletsky et al 2~ analyzed B-mode images of nine carotid plaques using acoustic density of the moving column of blood as a reference point with which to compare the densities of various plaque components. Areas of plaque were identified that contained intraplaque hemorrhage, lipid fibrosis, and calcification. In another study, using radio frequency-based evaluation of the different echo zones within the carotid plaques, quantitative analysis of the integrated back scatter ultrasound signal distinguished lipid, fibrotic, and calcific components within the plaques. 2l Nevertheless, a more practical and simple method for objective evaluation of overall carotid plaque echogenicity which correlates well with plaque histological composition is needed for the routine use of such a method. Using image analysis programs, computerized ultrasonogram evaluation of overall carotid plaque echogenicity and heterogeneity has recently been developed. This was used to study patients with advanced carotid
N.M. EL-BARGHOUTI
stenosis. The median of the overall grey-scale content of the plaque image was used as a measure of echogenicity. The higher the grey-scale median, the more echogenic was the plaque. This method was reliable and reproducible. 22,23 Histological verification of plaque echogenicity was achieved by studying 52 patients undergoing carotid endarterectomy. The grey-scale median of each plaque was measured and correlated with fibrous, lipid, and hemorrhage content. A high lipid or hemorrhage content of the plaque was associated with a low grey-scale median, and a high fibrous and calcium content was associated with a high grey-scale median. This confirms that computer evaluation of plaque echogenicity as measured by the grey-scale median is of value in assessing plaque histology.24 To study the influence of plaque echogenicity measured in this manner on the incidence of cerebral infarction, 87 patients with 148 carotid plaques producing 50% to 99% stenosis were initially studied. Echolucent carotid plaques with low grey-scale medians were associated with a higher incidence of cerebral infarction, as compared with echogenic plaques. In addition, plaques with a grey-scale median below or equal to 32 were associated with a statistically significant higher incidence of cerebral infarction compared with those with a grey-scale median above that level; thus they may be considered high-risk unstable plaques. On the other hand, plaques with a grey-scale median above 32 might be considered as tow-risk stable plaques. 22 ;To test the validity of the above conclusions and the hypothesis that plaque morphology influences cerebral infarction, 190 patients with 329 carotid plaques producing 50% to 99% diameter stenosis of the internal carotid artery were studied. The results of the initial study were confirmed; the influence of plaque morphology on cerebral infarction applied to both symptomatic and asymptomatic plaques. Symptomatic plaques were more echolucent and associated with a higher incidence of cerebral infarction than asymptomatic plaques. The higher the degree of carotid stenosis, the higher the incidence of cerebral infarction and the higher the incidence of symptoms of cerebrovascular disease. Finally, logistic regression analysis showed that the most important factor that influenced the presence of ipsilateral cerebral infarction was plaque echogenicity measured as the grey-scale median. The most important factor that influenced the incidence of symptomatic cerebrovascular disease was the degree of internal carotid stenosis. 25
Carotid Plaque Heterogeneity The dilemma regarding carotid plaque heterogeneity is that several investigators have classified plaques as either homogenous or heterogenous. ~226 Close examination showed that plaques defined as heterogenous were predominantly echolucent and those defined as homogenous
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CAROTID PLAQUE MORPHOLOGY
were predominantly echogenic. Relying on visual subjective evaluation of the plaque ultrasound images, they concluded that heterogenous plaques were associated with a high incidence of subsequent neurogenic events and should be considered as high-risk unstable plaques. The problem classifying plaques as homogenous and heterogenous is that homogenous plaques may be interpreted either as homogenous and totally echolucent or homogenous and totally echogenic. The completely echolucent plaques are of higher risk than the completely echogenic ones. Also, heterogenous plaques might be interpreted either as heterogenous but predominantly echolucent or predominantly echogenic; the former are of higher risk than the latter. We have developed an objective way to evaluate the heterogeneity of the carotid plaques on ultrasonography, relying on the difference in the echogenicity between the most echogenic and the most echolucent within the plaque. Plaques associated with cerebral infarction are less heterogenous than those unassociated with infarction, and symptomatic plaques are less heterogenous than asymptomatic plaques. This shows that the more heterogenous the plaques, the more stable they are. Although both plaque echogenicity and heterogeneity influence the incidence of symptoms of cerebrovascular disease, complete plaque echogenicity is the most important factor influencing the incidence of ipsilateral cerebral infarction, and is thus the most sensitive predictor of high-risk plaques. 27
Future D i r e c t i o n s The study of carotid bifurcation plaque morphology on ultrasound and computerized evaluation of plaque echogenicity and heterogeneity may be effectively used together with the degree of carotid stenosis measured by duplex to identify high-risk carotid plaques, i.e., those associated with a high incidence of cerebral infarction. This is possible both in patients with symptomatic cerebrovascular disease and in individuals with asymptomatic carotid atherosclerotic stenosis. The relation between localized risk factors for stroke such as degree of carotid stenosis, plaque echogenicity and heterogeneity to symptoms of cerebrovascular disease, and the incidence of ipsilateral cerebral infarction can only be evaluated in a natural history study in which stroke is the end point. A 5-year multicenter natural history study is now under way in the United Kingdom,28 to identify a subgroup of patients with asymptomatic carotid stenosis with a high annual ipsilateral stroke rate. In the future, advances in image analysis technology should allow improved evaluation of carotid plaque images. The standardization of images obtained from different ultrasound scanners will be an important step toward the study of patients from different centers within multicenter trials. Another future application of computerized carotid plaque characterization is to identify pa-
tients who are more suitable for carotid stenting than for carotid endarterctomy. Patients with echolucent friable plaques are perhaps better managed by endarterectomy, whereas those with echogenic fibrous plaques are more suitable for stenting. 29
References 1. Robins M, Braum H. The national survey of stroke: The National Institute of Neurological and Communicative Disorders and Stroke, Office of Biometry and Field Studies Report. Stroke 1981;12:1-57, (suppl 1). 2. Gelabert H, Moore W. Carotid endarterectomy: current status. Curr Probl Surg 1991;28:187-262. 3. Kyriakides T, Middleton L. The magnitude of the problem: Stroke from carotid bifurcation disease without premonitory transient ischaemic attacks. In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:15. 4. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. N Engl J Med 1991;325:445. 5. 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;1:1255. 6. Executive committee for the asymptomatic carotid atherosclerosis study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995;273:1421-1428. 7. Nicolaides A. Asymptomatic carotid stenosis. "The doctor's dilemma." Int Angio11995;14:1-4. 8. Lusby R. Plaque characterisation: Does it identify high risk groups? In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:93. 9. Bornstein N, Norris J. Management of patients with asymptomatic neck bruits and carotid stenosis. Neurol Clin 1992:269. 10. Kannel W, Gordon T. An epidemiological investigation of cardiovascular disease. The Framingham Study, 18 year follow-up. Washington, DC: Dept of Health, Education and Welfare, 1974. 11. Geroulakos G, Sonecha T, Nicolaides A, et al. The management of patients with asymptomatic carotid stenosis. In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:565. 12. Langsfeld M, Grey-Weale AC, Lusby RJ. The role of plaque morphology and diameter reduction in the development of new symptoms in asymptomatic carotid arteries. J Vasc Surg 1989;9:548-557. 13. Geroulakos G, Ramaswami G, Nicolaides A, et al. Characterisation of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography. Br J Surg 1993;80:1274-1277. 14. Geroulakos G, Domjan J, Nicolaides A, et al. Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography. J Vasc Surg 1994;20: 263-266. 15. Srodon P, Geroulakos G, Lumley J. Asymptomatic intracranial embolic events are related to carotid plaque structure. Br J Surg 1997;84:166,suppl 2. 16. Evans G, Howard G, Kari P, et al. Cerebral infarction verified by cranial computed tomography and prognosis
108
17. 18. 19. 20.
21.
22.
23.
N.M. EL-BARGHOUTI
for survival following transient ischaemic attack. Stroke 1991;22:431-436. Zhu C, Norris J. Role of carotid stenosis in ischaemic stroke. Stroke 1990;21:1131-1134. Norris J, Zhu C, Bornstein N, et al. Vascular risks of asymptomatic carotid stenosis. Stroke 1991;22:1485-1490. Norris J, Zhu C. Silent stroke and carotid stenosis. Stroke 1992;23:483-485. Beletsky V, Kelly R, Fowler M, et al. Ultrasound densitometric analysis of carotid plaque composition. Stroke 1996;27:2173-2177. Urbani M, Picano E, Parenti G, et al. In vivo radio frequency-based ultrasonic tissue characterisation of the atherosclerotic plaque. Stroke 1993;24:1507-1512. El-Barghouti N, Geroulakos G, Androulakis A, et al. Computer assisted carotid plaque characterisation. Eur J Vasc Endovasc Surg 1995;9:389-393. Sanpaola A, Biasi G, Mingazzini P, et al. Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions. Eur J Vasc Endovasc Surg 1997 (in press).
24. E1-Barghouti N, Lavine T, Flanagan A, et al. Histological verification of computerised plaque characterisation. Eur J Vasc Endovasc Surg 1996;11:414-416. 25. E1-Barghouti N, Geroulakos G, Androulakis A, et al, The identification of the high risk carotid plaque. Eur J Vasc Endovasc Surg 1996;11:470-478. 26. Sterpetti A, Schultz R, Feldhaus R, et al. Ultrasonographic features of carotid plaques and the risk of subsequent neurologic deficits. Surgery 1988;104:652-660. 27. E1-Barghouti N, Nicolaides A, Tegos T, et al. The relative effect of carotid plaque heterogeneity and echogenicity on ipsilateral cerebral infarction and symptoms of cerebrovascular disease. Int Angio11997;15:300-306. 28. Nicolaides A. Asymptomatic carotid stenosis and risk of stroke. Identification of a high risk group (ACSRS). Int Angiol 1996;14:21-23. 29. Biasi G, Mingazzini P, E1-Barghouti N, et al. The importance of carotid plaque composition as an indication for carotid endarterectomy versus carotid stenting. J Vasc Surg 1997 (in press).
From the Department of Surgery, South Cleveland Hospital, Middlesbrough, UK. ReceivedMarch 6, 1997;acceptedJuly 24, 1997. Address reprint requests to N. M. El-BarghoutLPhD, FRCS, 9 Woodhorn Gardens, Wide Open, Newcastleupon Tyne, NE13 6AG, UK. Copyright9 1998by National StrokeAssociation 1052-3057/98/0702-000253.00/0
surgical group. One important implication has emerged: to prevent one stroke at least 20 surgical procedures have to be performed. The cost of stroke prevention by these means is therefore high. Perhaps identifying a subgroup of this population at higher risk of stroke, using criteria such as plaque characterization in addition to the degree of stenosis, may spare others from unnecessary operation with consequent financial savings. 7 Duplex scanning has the ability to determine not only the degree of carotid stenosis based on flow characteristics, but also plaque structure. Thus, there is the potential to separate patients at high risk of developing stroke from those at low risk independent of the degree of stenosis. Because it is noninvasive, duplex scanning can be performed repeatedly in assessing the status of the carotid artery and may play an important role in determining when intervention would be appropriate. 8
The Importance of Ultrasonic Carotid Plaque Morphology to Cerebrovascular Events Advanced asymptomatic carotid stenosis (>75%) occurs in approximately 1% of subjects above the age of 50 years. 9 The majority of patients who develop stroke do so without warning symptoms. TM Although patients with asymptomatic high-grade carotid stenosis have an increased rate of spontaneous stroke, this risk remains low and perioperative mortality and morbidity may tilt the balance of risk benefit against surgery. The identification of a subgroup of patients with asymptomatic carotid stenosis who are at high risk of stroke based on plaque morphology and degree of carotid stenosis is therefore cruciaU 1 In advanced carotid stenosis, echolucent atherosclerotic plaques with a high lipid and hemorrhage content are unstable and more likely to embolize than echogenic fibrous plaques. 12There is a preponderance of echolucent plaques in patients with symptomatic cerebrovascular disease, whereas echogenic plaques are more common in asymptomatic patients. 13 Heterogenous and echolucent plaques are associated with increased risk of subsequent neurological events and a higher incidence of cerebral infarction: TM In asymptomatic patients with advanced
Journal of Stroke and Cerebrovascular Diseases, Vol. 7, No. 2 (March-April), 1998: pp 105-108
105
106 carotid stenosis, echolucent plaques are associated with a higher incidence of intracranial embolic events detected by middle cerebral artery transcranial Doppler ultrasound, 15 supporting the hypothesis that echolucent plaques are unstable with a greater tendency to embolize than echogenic plaques. Cerebral infarcts on computerized tomography (CT) in patients with advanced carotid stenosis and transient ischemic attacks were associated with an increased risk of subsequent stroke and shorter survival time. Silent cerebral infarction in patients with asymptomatic carotid stenosis is considered to cause adverse prognosis and increased risk of subsequent neurological events. Thus carotid plaques associated with cerebral infarction are probably high-risk unstable plaques. 16 Carotid stenosis is more frequent and severe in patients with symptomatic cerebrovascular disease than in those who are asymptomaticF Asymptomatic patients with more than 75% carotid stenosis have a higher incidence of subsequent neurogenic events as compared with those with less than 75% stenosis, is In addition, the more severe the carotid stenosis, the higher the incidence of ipsilateral cerebral infarction. 19
Computerized Carotid Plaque Characterizations Most of the published studies of carotid plaque morphology on ultrasonography relied on subjective and qualitative visual characterization of the plaque ultrasound images. Objective and quantitative grading of plaque echogenicity and heterogeneity using computerized measurements may provide more accurate operatorindependent assessment of plaque echoic structure improving the detection of high-risk carotid plaque. Computer-based densitometric analysis of carotid plaque ultrasonic images allows enhanced differentiation of plaque composition. Beletsky et al 2~ analyzed B-mode images of nine carotid plaques using acoustic density of the moving column of blood as a reference point with which to compare the densities of various plaque components. Areas of plaque were identified that contained intraplaque hemorrhage, lipid fibrosis, and calcification. In another study, using radio frequency-based evaluation of the different echo zones within the carotid plaques, quantitative analysis of the integrated back scatter ultrasound signal distinguished lipid, fibrotic, and calcific components within the plaques. 2l Nevertheless, a more practical and simple method for objective evaluation of overall carotid plaque echogenicity which correlates well with plaque histological composition is needed for the routine use of such a method. Using image analysis programs, computerized ultrasonogram evaluation of overall carotid plaque echogenicity and heterogeneity has recently been developed. This was used to study patients with advanced carotid
N.M. EL-BARGHOUTI
stenosis. The median of the overall grey-scale content of the plaque image was used as a measure of echogenicity. The higher the grey-scale median, the more echogenic was the plaque. This method was reliable and reproducible. 22,23 Histological verification of plaque echogenicity was achieved by studying 52 patients undergoing carotid endarterectomy. The grey-scale median of each plaque was measured and correlated with fibrous, lipid, and hemorrhage content. A high lipid or hemorrhage content of the plaque was associated with a low grey-scale median, and a high fibrous and calcium content was associated with a high grey-scale median. This confirms that computer evaluation of plaque echogenicity as measured by the grey-scale median is of value in assessing plaque histology.24 To study the influence of plaque echogenicity measured in this manner on the incidence of cerebral infarction, 87 patients with 148 carotid plaques producing 50% to 99% stenosis were initially studied. Echolucent carotid plaques with low grey-scale medians were associated with a higher incidence of cerebral infarction, as compared with echogenic plaques. In addition, plaques with a grey-scale median below or equal to 32 were associated with a statistically significant higher incidence of cerebral infarction compared with those with a grey-scale median above that level; thus they may be considered high-risk unstable plaques. On the other hand, plaques with a grey-scale median above 32 might be considered as tow-risk stable plaques. 22 ;To test the validity of the above conclusions and the hypothesis that plaque morphology influences cerebral infarction, 190 patients with 329 carotid plaques producing 50% to 99% diameter stenosis of the internal carotid artery were studied. The results of the initial study were confirmed; the influence of plaque morphology on cerebral infarction applied to both symptomatic and asymptomatic plaques. Symptomatic plaques were more echolucent and associated with a higher incidence of cerebral infarction than asymptomatic plaques. The higher the degree of carotid stenosis, the higher the incidence of cerebral infarction and the higher the incidence of symptoms of cerebrovascular disease. Finally, logistic regression analysis showed that the most important factor that influenced the presence of ipsilateral cerebral infarction was plaque echogenicity measured as the grey-scale median. The most important factor that influenced the incidence of symptomatic cerebrovascular disease was the degree of internal carotid stenosis. 25
Carotid Plaque Heterogeneity The dilemma regarding carotid plaque heterogeneity is that several investigators have classified plaques as either homogenous or heterogenous. ~226 Close examination showed that plaques defined as heterogenous were predominantly echolucent and those defined as homogenous
107
CAROTID PLAQUE MORPHOLOGY
were predominantly echogenic. Relying on visual subjective evaluation of the plaque ultrasound images, they concluded that heterogenous plaques were associated with a high incidence of subsequent neurogenic events and should be considered as high-risk unstable plaques. The problem classifying plaques as homogenous and heterogenous is that homogenous plaques may be interpreted either as homogenous and totally echolucent or homogenous and totally echogenic. The completely echolucent plaques are of higher risk than the completely echogenic ones. Also, heterogenous plaques might be interpreted either as heterogenous but predominantly echolucent or predominantly echogenic; the former are of higher risk than the latter. We have developed an objective way to evaluate the heterogeneity of the carotid plaques on ultrasonography, relying on the difference in the echogenicity between the most echogenic and the most echolucent within the plaque. Plaques associated with cerebral infarction are less heterogenous than those unassociated with infarction, and symptomatic plaques are less heterogenous than asymptomatic plaques. This shows that the more heterogenous the plaques, the more stable they are. Although both plaque echogenicity and heterogeneity influence the incidence of symptoms of cerebrovascular disease, complete plaque echogenicity is the most important factor influencing the incidence of ipsilateral cerebral infarction, and is thus the most sensitive predictor of high-risk plaques. 27
Future D i r e c t i o n s The study of carotid bifurcation plaque morphology on ultrasound and computerized evaluation of plaque echogenicity and heterogeneity may be effectively used together with the degree of carotid stenosis measured by duplex to identify high-risk carotid plaques, i.e., those associated with a high incidence of cerebral infarction. This is possible both in patients with symptomatic cerebrovascular disease and in individuals with asymptomatic carotid atherosclerotic stenosis. The relation between localized risk factors for stroke such as degree of carotid stenosis, plaque echogenicity and heterogeneity to symptoms of cerebrovascular disease, and the incidence of ipsilateral cerebral infarction can only be evaluated in a natural history study in which stroke is the end point. A 5-year multicenter natural history study is now under way in the United Kingdom,28 to identify a subgroup of patients with asymptomatic carotid stenosis with a high annual ipsilateral stroke rate. In the future, advances in image analysis technology should allow improved evaluation of carotid plaque images. The standardization of images obtained from different ultrasound scanners will be an important step toward the study of patients from different centers within multicenter trials. Another future application of computerized carotid plaque characterization is to identify pa-
tients who are more suitable for carotid stenting than for carotid endarterctomy. Patients with echolucent friable plaques are perhaps better managed by endarterectomy, whereas those with echogenic fibrous plaques are more suitable for stenting. 29
References 1. Robins M, Braum H. The national survey of stroke: The National Institute of Neurological and Communicative Disorders and Stroke, Office of Biometry and Field Studies Report. Stroke 1981;12:1-57, (suppl 1). 2. Gelabert H, Moore W. Carotid endarterectomy: current status. Curr Probl Surg 1991;28:187-262. 3. Kyriakides T, Middleton L. The magnitude of the problem: Stroke from carotid bifurcation disease without premonitory transient ischaemic attacks. In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:15. 4. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. N Engl J Med 1991;325:445. 5. 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;1:1255. 6. Executive committee for the asymptomatic carotid atherosclerosis study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995;273:1421-1428. 7. Nicolaides A. Asymptomatic carotid stenosis. "The doctor's dilemma." Int Angio11995;14:1-4. 8. Lusby R. Plaque characterisation: Does it identify high risk groups? In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:93. 9. Bornstein N, Norris J. Management of patients with asymptomatic neck bruits and carotid stenosis. Neurol Clin 1992:269. 10. Kannel W, Gordon T. An epidemiological investigation of cardiovascular disease. The Framingham Study, 18 year follow-up. Washington, DC: Dept of Health, Education and Welfare, 1974. 11. Geroulakos G, Sonecha T, Nicolaides A, et al. The management of patients with asymptomatic carotid stenosis. In: Bernstein E, Callow A, et al, eds. Cerebral revascularisation. London: Med-Orion, 1993:565. 12. Langsfeld M, Grey-Weale AC, Lusby RJ. The role of plaque morphology and diameter reduction in the development of new symptoms in asymptomatic carotid arteries. J Vasc Surg 1989;9:548-557. 13. Geroulakos G, Ramaswami G, Nicolaides A, et al. Characterisation of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography. Br J Surg 1993;80:1274-1277. 14. Geroulakos G, Domjan J, Nicolaides A, et al. Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography. J Vasc Surg 1994;20: 263-266. 15. Srodon P, Geroulakos G, Lumley J. Asymptomatic intracranial embolic events are related to carotid plaque structure. Br J Surg 1997;84:166,suppl 2. 16. Evans G, Howard G, Kari P, et al. Cerebral infarction verified by cranial computed tomography and prognosis
108
17. 18. 19. 20.
21.
22.
23.
N.M. EL-BARGHOUTI
for survival following transient ischaemic attack. Stroke 1991;22:431-436. Zhu C, Norris J. Role of carotid stenosis in ischaemic stroke. Stroke 1990;21:1131-1134. Norris J, Zhu C, Bornstein N, et al. Vascular risks of asymptomatic carotid stenosis. Stroke 1991;22:1485-1490. Norris J, Zhu C. Silent stroke and carotid stenosis. Stroke 1992;23:483-485. Beletsky V, Kelly R, Fowler M, et al. Ultrasound densitometric analysis of carotid plaque composition. Stroke 1996;27:2173-2177. Urbani M, Picano E, Parenti G, et al. In vivo radio frequency-based ultrasonic tissue characterisation of the atherosclerotic plaque. Stroke 1993;24:1507-1512. El-Barghouti N, Geroulakos G, Androulakis A, et al. Computer assisted carotid plaque characterisation. Eur J Vasc Endovasc Surg 1995;9:389-393. Sanpaola A, Biasi G, Mingazzini P, et al. Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions. Eur J Vasc Endovasc Surg 1997 (in press).
24. E1-Barghouti N, Lavine T, Flanagan A, et al. Histological verification of computerised plaque characterisation. Eur J Vasc Endovasc Surg 1996;11:414-416. 25. E1-Barghouti N, Geroulakos G, Androulakis A, et al, The identification of the high risk carotid plaque. Eur J Vasc Endovasc Surg 1996;11:470-478. 26. Sterpetti A, Schultz R, Feldhaus R, et al. Ultrasonographic features of carotid plaques and the risk of subsequent neurologic deficits. Surgery 1988;104:652-660. 27. E1-Barghouti N, Nicolaides A, Tegos T, et al. The relative effect of carotid plaque heterogeneity and echogenicity on ipsilateral cerebral infarction and symptoms of cerebrovascular disease. Int Angio11997;15:300-306. 28. Nicolaides A. Asymptomatic carotid stenosis and risk of stroke. Identification of a high risk group (ACSRS). Int Angiol 1996;14:21-23. 29. Biasi G, Mingazzini P, E1-Barghouti N, et al. The importance of carotid plaque composition as an indication for carotid endarterectomy versus carotid stenting. J Vasc Surg 1997 (in press).