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Screening test for carotid disease
Screening Test for Carotid Disease Edward I. Bluth Because cardiovascular disease is the leading cause of death in the United States, the identification of a screening test to reduce the risk of stroke has been a long-term goal of those interested in public health. The recent European and North American randomized carotid endarterectomy trials have demonstrated that both symptomatic and asymptomatic patients with internal carotid artery stenosis may experience a reduction of stroke risk when treated with endarterectomy. Thus the detection of occult carotid stenosis has been proposed as a stroke-reducing method. US has been studied both as a solitary screening method and in conjunction with hypertension and cardiac arrhythmia screening. This article reviews the methods proposed for US carotid artery screening, the reported accuracy of these methods, and issues of cost- and clinical effectiveness.
Copyright 2003, Elsevier Science (USA). All rights reserved.
he identification of a screening test to reduce the risk of stroke has been a long-term goal of those interested in public health. Cardiovascular disease is the leading cause of death in the United States (Fig 1). Of that group, 18% or 160,000 deaths per year are attributed to stroke (Fig 2). Perhaps more importantly, approximately 500,000 individuals per year suffer morbidity from a new or recurrent stroke. A very large number, if not the majority of these strokes, occur in the carotid distribution, a common site for atherosclerosis formation. The recent European and North American randomized control trials have demonstrated that symptomatic patients with a greater then 70% carotid stenosis have a significant benefit, and patients with greater then 50% stenosis have a moderate benefit, from surgical intervention, compared to conservative medical therapy) '2 Additionally, the Asymptomatic Carotid Atherosclerosis Study 3 has shown that asymptomatic patients with a greater then 60% stenosis would also benefit from endarterectomy, compared to medical antiplatelet treatment, in centers with perioperative morbidity and mortality less then 3%. Over two milfion people over the age of 50, it is estimated, have asymptomatic carotid artery stenosis of at least 50% of the luminal diameter. Considering the number of individuals at risk for stroke, and the significant economic implications associated with providing short and long term care for this group, it is no wonder then that there has been considerable attention directed at developing an accurate, low risk, economical, and rapid stroke screening test.
T
SCREENING TESTS
At first, there was considerable enthusiasm that a complete carotid duplex Doppler ultrasound could be the desired screening test, but it was soon noted that this strategy was not cost effective. 4 The complete duplex examination, although accurate, was too long and complicated and was better suited
as a diagnostic test. In fact, in many centers it is now used as a final test before carotid intervention. Levenson 5 proposed a new protocol for stroke screening, including obtaining blood pressures in both arms, assessing the cardiac rhythm EKB (for atrial fibulation), and rapidly scanning the carotid arteries with ultrasound. The ultrasound (US) evaluation consisted of rapid color flow imaging of the carotid arteries with the patient sitting in a chair. Although this study of 176 participants did not include comparison with a "gold standard," 26 patients (15%) were found to have a greater then 50% carotid stenosis, 16 had previously unknown cardiac arrhythmias, and 104 had hypertension. Since there was no comparison "gold standard," there was no measure of efficacy such as sensitivity, specificity, and positive or negative predictive value. In 1999, Carsten et al 6 proposed a limited colorflow duplex carotid screening examination. This method involves identifying the carotid bulb and obtaining an immediate, single, angle corrected Doppler-derived velocity of the segment of the internal carotid artery (ICA) with the most turbulent flow. They used a peak systolic velocity of at least 125 cm/sec as a determinant of at least a 50% ICA stenosis. They compared their screening test to a complete duplex examination and achieved 86% sensitivity, 98% specificity, 95% positive predicative value (PPV), and 93% negative predictive value (NPV). Using ROC curves they could
From the Chairman, Department of Radiology, Ochsner Clinic Foundation, New Orleans, LA Address reprint requests to Edward L Bluth, MD, FACR, Department of Radiology, Ochsner Clinic, 1514 Jefferson Hwy, New Orleans, LA 70124; e-mail: [email protected]. Copyright 2003, Elsevier Science (USA). All rights reserved. 0887-2171/03/2401-166530.00/0 do# l O.lO53/sult.2003.S0887-2171(03)O0004-O
Seminars in Ultrasound, CT, and MRI, Vol 24, No 1 (February), 2003: pp 55-61
55
56
EDWARD I. BLUTH
Fig 1.
Five leading causes of death in the United States.
achieve a 91% sensitivity, 95% specificity, 89% PPV and 96% NPV if they used a 115 cm/sec "cut point." The time required to perform the study was less then 5 minutes; however, to achieve this level of speed and accuracy, the study, was performed by only the two senior registered vascular technologists in the laboratory. It is uncertain whether similar speed and accuracy could be achieved if the method was used at other centers or performed by less experienced vascular technologists. Additionally, it appears that the same examiners may have performed both the screening and comparison "gold standard" examinations, potentially leading to some bias. POWER DOPPLER IMAGING
In 1997, Bluth et al reported at the annual meeting of the Radiological Society of North America7 and subsequently published in Radiology, s another methodology for rapid screening employing only power Doppler imaging (PDI). This test fit the criteria of being accurate, low risk, economical and rapid. The idea was to apply the concepts of screening mammography to the carotid
arteries. Examinations would be interpreted as either normal or abnormal. If normal, the patient would return for routine screening at intervals to be determined; if abnormal, the patient would be directed for further evaluation at a different time, using either a complete duplex Doppler examination, magnetic resonance angiography (MRA), computed tomographic angiography (CTA), or catheter angiography as the follow-up test. The PDI test simply consists of a series of transverse and sagittal images of the right and left common and internal carotid arteries obtained using a high frequency transducer matched to the patient's size. Usually, five-to-six representative images per side are all that are required for documentation. The diameter of the narrowest segment is compared to the diameter of the unobstructed portion of the ICA, similar to the NASCET methodology (Fig 3). An estimated narrowing of greater then 40% diameter reduction is considered positive (Fig 4). If calcifications prevent full visualization, particularly of the bulb, the test should be interpreted as positive. The PDI screening test was developed at one
SCREENING TEST FOR CAROTID DISEASE
Fig 2.
57
Stroke deaths as a percent of all cardiovascualr deaths in the United States.
center and its methodology was successfully transferred and used at another medical center with a different group of examiners and interpreters. In the principal pilot test, 100 patients were screened before or after the complete duplex Doppler study, which was their "gold standard." In the validation pilot test, 20 patients were screened after a selective fight and left intrarterial digital subtraction angiogram (DSA). Each imaging study was independently performed by different groups of technologists and interpreted by different radiologists, without knowledge of the other results. In the principal study, the sensitivity was 76%, specificity 88%, PPV 51%, and NPV 96%. The AUC value for the empirical ROC curve was 0.84. At the validation site, the sensitivity was 75% and specificity 90% for detection of 40% or greater stenosis. Combining both studies the AUC was 0.87, and the sensitivity 91%. Based on ROC analysis, it was felt that the screening test could function at 91% sensitivity and 79% specificity for detecting a greater then 40% stenosis. By comparison, the AUC for screening mammography is 0.845 for a large sam-
ple of radiologists accredited by the ACR. Thus, the PDI screening test compares favorably. A cost effectiveness analysis of the PDI screening test was also performed by Bluth et al, 8 following the methodology of Lee et al, 4 which had previously been used to show that a complete duplex Doppler carotid study was not cost effective as a screening test. It is generally accepted by health service researchers that interventions costing up to $50,000 per quality-adjusted life (QALY) are acceptable. Interventions costing between $50,000 to $100,000 are borderline, and those exceeding $100,000 are unacceptable. For a screening population older than 65, Bluth et al 8 calculated that the QALY would be $47,000 and as such clearly acceptable. This was based on a charge for the examination of $80. If the charge were reduced to $40, the QALY would be $43,000. Additionally, if more selective parameters for screening were used, such as screening only those who were hypertensive or smoked, the QALY would be reduced $15,000 to $32,000. Clearly, the PDI test fits the
58
EDWARD I. BLUTH
Fig 3.
Normal PDI screening test. (A) Sagittal, (B} transverse, and (C) duplex Doppler showing normal ICA velocity.
SCREENING TEST FOR CAROTID DISEASE
59
Fig 4. Positive PDI screening test. (A) Sagittal, and (B). transverse images, show substantial ICA narrowing. Cursors indicate location of vessel w a l l (C) Doppler invsetigation shows elevated peak systolic- (442 cm/sec) and end diastolic velocity (168 cm/sec), consistent with 80% to 99% stenosis.
60
EDWARD I. BLUTH
Fig 5. Positive PDI screening test (A) Sagittal image of the right iCA. (B) Sagittal image of the left ICA. Note the asymmetry. The left ICA lumen is much bigger than the stenotic right. ICA. (C) Duplex Doppler shows elevated flow velocity in the right ICA corresponding to 50% to 79% stenosis (peak systolic- and end diastolic velocity 171 and 57 cm/sec, respectively). Normal velocity {not shown) was found in the left ICA.
SCREENING TEST FOR CAROTID DISEASE
61
economic parameters of health service researchers as an acceptable screening test. As in all tests, pitfalls in the PDI test have been noted. These include the presence of calcifications, which can obscure visualization of the narrowest segments of the ICA. Also, diffuse narrowing of a vessel can confuse the unwary. Those used to evaluating only a focal narrowing might fail to appreciate a long diffuse narrowed segment of disease. Because the normal carotids are usually symmetric in size, comparing both sides can avoid this error, leading to more accurate interpretations (Fig 5). The technical expertise of those using PDI is also an important factor in avoiding pitfalls. PDI is not as simple a tool as it appears. Inappropriately increasing gain leads to overestimation of the lumen size and underestimation of stenosis. Inappropriately increasing the wall filter or the PRF can lead to an underestimation of flow, and therefore, an overestimation of stenosis. 3-DIMENSIONAL
POWER DOPPLER
In 2000, German researchers, Keberle et al 9, reported in the Journal of Ultrasound in Medicine a carotid screening method similar to the PDI technique described above, but this method used real time, 3-dimensional power Doppler sonography as the screening tool. Color Doppler sonography, in conjunction with spectral Doppler was the "gold standard," using the peak systolic velocity of the ICA as the stenosis-discriminating factor. In this study, 75 patients were screened. There was good correlation between the degrees of stenosis measured by 3D power Doppler sonography and that measured with color Doppler/spectral sonog-
raphy (r = 0.982; P < 0.01). For detecting ICA stenosis greater than 50%, these authors reported 97.9% sensitivity, 100% specificity, 100% PPV, and 99% NPV. In addition, they postulated that 3D volume and reconstructions would facilitate remote interpretations. CONCLUSIONS
If centers for stroke screening are developed, it would be wise to include screening for hypertension, atrial fibrillation, and carotid stenosis, because these three disorders represent the most common etiologies of strokes. The US screening component is the most difficult to perform, and therefore, must be the most carefully considered. Several US screening tests have been proposed, all of which are fast and accurate. Since they are all noninvasive and take less than 5 minutes, these tests would be readily acceptable to the general public. Only one US test, the PDI method, has been shown to be cost effective. At a proposed charge of $40 to $80, PDI is also affordable. While a limited color and spectral Doppler examination could have a similar low charge and could be shown to be cost effective, there is probably a greater degree of operator dependence and variability with this method, since angle-corrected Doppler measurements are required. PDI is thought to be less angle dependent than standard color Doppler, and therefore, may be more easily performed and learned. PDI is also widely available on most modem duplex Doppler instruments, while 3-D US imaging is not. At the present time, two studies using PDI have shown acceptable ranges of sensitivity, specificity, and positive and negative predictive values.
REFERENCES 1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325:445, 1991 2. European Carotid Surgery Trialists' Collaborative Group. MRC European Carotid SurgeryTrial; interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet 337:1235, 1991 3. Executive Committee for the AsymptomaticCarotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421, 1995 4. Lee TT, Solomon NA, Heidenreich PA, Oehlert J, Barber AM: Cost-effectiveness of screening for carotid stenosis in asymptomatic patients. Ann Intern Med 126:337, 1997 5. Lavenson GS Jr: A new accurate, rapid and cost-effective
protocol for sn'oke-preventionscreening. Cardiovasc Surg 6(6): 590-593, 1998 6. Carsten CG III, Elmore JR, Franklin DP, Thomas DD, Mordan F, Wood GC: Use of limited color-flow duplex for a carotid screening project. Am J Surg 178(2):173-176, 1999 7. Bluth E, Merritt C, Sullivan M, Smetherman D, Champagne J, Sunshine J: A screening test for carotid stenosis: A preliminary feasibility study (abs). Radiology 205:545, 1997 8. Bluth EI, Sunshine JH, Lyons JB, et aI: Power Doppler imaging: Initial evaluation as a screening examination for carotid artery stenosis. Radiology 215(3):791-800, 2000 9. Keberle M, Jenett M, Beissert M, Jahns R, Haerten R, Hahn D. Three-dimensional power Doppler sonography in screening for carotid artery disease. J Clin Ultrasound 28(9): 441-451, 2000
Copyright 2003, Elsevier Science (USA). All rights reserved.
he identification of a screening test to reduce the risk of stroke has been a long-term goal of those interested in public health. Cardiovascular disease is the leading cause of death in the United States (Fig 1). Of that group, 18% or 160,000 deaths per year are attributed to stroke (Fig 2). Perhaps more importantly, approximately 500,000 individuals per year suffer morbidity from a new or recurrent stroke. A very large number, if not the majority of these strokes, occur in the carotid distribution, a common site for atherosclerosis formation. The recent European and North American randomized control trials have demonstrated that symptomatic patients with a greater then 70% carotid stenosis have a significant benefit, and patients with greater then 50% stenosis have a moderate benefit, from surgical intervention, compared to conservative medical therapy) '2 Additionally, the Asymptomatic Carotid Atherosclerosis Study 3 has shown that asymptomatic patients with a greater then 60% stenosis would also benefit from endarterectomy, compared to medical antiplatelet treatment, in centers with perioperative morbidity and mortality less then 3%. Over two milfion people over the age of 50, it is estimated, have asymptomatic carotid artery stenosis of at least 50% of the luminal diameter. Considering the number of individuals at risk for stroke, and the significant economic implications associated with providing short and long term care for this group, it is no wonder then that there has been considerable attention directed at developing an accurate, low risk, economical, and rapid stroke screening test.
T
SCREENING TESTS
At first, there was considerable enthusiasm that a complete carotid duplex Doppler ultrasound could be the desired screening test, but it was soon noted that this strategy was not cost effective. 4 The complete duplex examination, although accurate, was too long and complicated and was better suited
as a diagnostic test. In fact, in many centers it is now used as a final test before carotid intervention. Levenson 5 proposed a new protocol for stroke screening, including obtaining blood pressures in both arms, assessing the cardiac rhythm EKB (for atrial fibulation), and rapidly scanning the carotid arteries with ultrasound. The ultrasound (US) evaluation consisted of rapid color flow imaging of the carotid arteries with the patient sitting in a chair. Although this study of 176 participants did not include comparison with a "gold standard," 26 patients (15%) were found to have a greater then 50% carotid stenosis, 16 had previously unknown cardiac arrhythmias, and 104 had hypertension. Since there was no comparison "gold standard," there was no measure of efficacy such as sensitivity, specificity, and positive or negative predictive value. In 1999, Carsten et al 6 proposed a limited colorflow duplex carotid screening examination. This method involves identifying the carotid bulb and obtaining an immediate, single, angle corrected Doppler-derived velocity of the segment of the internal carotid artery (ICA) with the most turbulent flow. They used a peak systolic velocity of at least 125 cm/sec as a determinant of at least a 50% ICA stenosis. They compared their screening test to a complete duplex examination and achieved 86% sensitivity, 98% specificity, 95% positive predicative value (PPV), and 93% negative predictive value (NPV). Using ROC curves they could
From the Chairman, Department of Radiology, Ochsner Clinic Foundation, New Orleans, LA Address reprint requests to Edward L Bluth, MD, FACR, Department of Radiology, Ochsner Clinic, 1514 Jefferson Hwy, New Orleans, LA 70124; e-mail: [email protected]. Copyright 2003, Elsevier Science (USA). All rights reserved. 0887-2171/03/2401-166530.00/0 do# l O.lO53/sult.2003.S0887-2171(03)O0004-O
Seminars in Ultrasound, CT, and MRI, Vol 24, No 1 (February), 2003: pp 55-61
55
56
EDWARD I. BLUTH
Fig 1.
Five leading causes of death in the United States.
achieve a 91% sensitivity, 95% specificity, 89% PPV and 96% NPV if they used a 115 cm/sec "cut point." The time required to perform the study was less then 5 minutes; however, to achieve this level of speed and accuracy, the study, was performed by only the two senior registered vascular technologists in the laboratory. It is uncertain whether similar speed and accuracy could be achieved if the method was used at other centers or performed by less experienced vascular technologists. Additionally, it appears that the same examiners may have performed both the screening and comparison "gold standard" examinations, potentially leading to some bias. POWER DOPPLER IMAGING
In 1997, Bluth et al reported at the annual meeting of the Radiological Society of North America7 and subsequently published in Radiology, s another methodology for rapid screening employing only power Doppler imaging (PDI). This test fit the criteria of being accurate, low risk, economical and rapid. The idea was to apply the concepts of screening mammography to the carotid
arteries. Examinations would be interpreted as either normal or abnormal. If normal, the patient would return for routine screening at intervals to be determined; if abnormal, the patient would be directed for further evaluation at a different time, using either a complete duplex Doppler examination, magnetic resonance angiography (MRA), computed tomographic angiography (CTA), or catheter angiography as the follow-up test. The PDI test simply consists of a series of transverse and sagittal images of the right and left common and internal carotid arteries obtained using a high frequency transducer matched to the patient's size. Usually, five-to-six representative images per side are all that are required for documentation. The diameter of the narrowest segment is compared to the diameter of the unobstructed portion of the ICA, similar to the NASCET methodology (Fig 3). An estimated narrowing of greater then 40% diameter reduction is considered positive (Fig 4). If calcifications prevent full visualization, particularly of the bulb, the test should be interpreted as positive. The PDI screening test was developed at one
SCREENING TEST FOR CAROTID DISEASE
Fig 2.
57
Stroke deaths as a percent of all cardiovascualr deaths in the United States.
center and its methodology was successfully transferred and used at another medical center with a different group of examiners and interpreters. In the principal pilot test, 100 patients were screened before or after the complete duplex Doppler study, which was their "gold standard." In the validation pilot test, 20 patients were screened after a selective fight and left intrarterial digital subtraction angiogram (DSA). Each imaging study was independently performed by different groups of technologists and interpreted by different radiologists, without knowledge of the other results. In the principal study, the sensitivity was 76%, specificity 88%, PPV 51%, and NPV 96%. The AUC value for the empirical ROC curve was 0.84. At the validation site, the sensitivity was 75% and specificity 90% for detection of 40% or greater stenosis. Combining both studies the AUC was 0.87, and the sensitivity 91%. Based on ROC analysis, it was felt that the screening test could function at 91% sensitivity and 79% specificity for detecting a greater then 40% stenosis. By comparison, the AUC for screening mammography is 0.845 for a large sam-
ple of radiologists accredited by the ACR. Thus, the PDI screening test compares favorably. A cost effectiveness analysis of the PDI screening test was also performed by Bluth et al, 8 following the methodology of Lee et al, 4 which had previously been used to show that a complete duplex Doppler carotid study was not cost effective as a screening test. It is generally accepted by health service researchers that interventions costing up to $50,000 per quality-adjusted life (QALY) are acceptable. Interventions costing between $50,000 to $100,000 are borderline, and those exceeding $100,000 are unacceptable. For a screening population older than 65, Bluth et al 8 calculated that the QALY would be $47,000 and as such clearly acceptable. This was based on a charge for the examination of $80. If the charge were reduced to $40, the QALY would be $43,000. Additionally, if more selective parameters for screening were used, such as screening only those who were hypertensive or smoked, the QALY would be reduced $15,000 to $32,000. Clearly, the PDI test fits the
58
EDWARD I. BLUTH
Fig 3.
Normal PDI screening test. (A) Sagittal, (B} transverse, and (C) duplex Doppler showing normal ICA velocity.
SCREENING TEST FOR CAROTID DISEASE
59
Fig 4. Positive PDI screening test. (A) Sagittal, and (B). transverse images, show substantial ICA narrowing. Cursors indicate location of vessel w a l l (C) Doppler invsetigation shows elevated peak systolic- (442 cm/sec) and end diastolic velocity (168 cm/sec), consistent with 80% to 99% stenosis.
60
EDWARD I. BLUTH
Fig 5. Positive PDI screening test (A) Sagittal image of the right iCA. (B) Sagittal image of the left ICA. Note the asymmetry. The left ICA lumen is much bigger than the stenotic right. ICA. (C) Duplex Doppler shows elevated flow velocity in the right ICA corresponding to 50% to 79% stenosis (peak systolic- and end diastolic velocity 171 and 57 cm/sec, respectively). Normal velocity {not shown) was found in the left ICA.
SCREENING TEST FOR CAROTID DISEASE
61
economic parameters of health service researchers as an acceptable screening test. As in all tests, pitfalls in the PDI test have been noted. These include the presence of calcifications, which can obscure visualization of the narrowest segments of the ICA. Also, diffuse narrowing of a vessel can confuse the unwary. Those used to evaluating only a focal narrowing might fail to appreciate a long diffuse narrowed segment of disease. Because the normal carotids are usually symmetric in size, comparing both sides can avoid this error, leading to more accurate interpretations (Fig 5). The technical expertise of those using PDI is also an important factor in avoiding pitfalls. PDI is not as simple a tool as it appears. Inappropriately increasing gain leads to overestimation of the lumen size and underestimation of stenosis. Inappropriately increasing the wall filter or the PRF can lead to an underestimation of flow, and therefore, an overestimation of stenosis. 3-DIMENSIONAL
POWER DOPPLER
In 2000, German researchers, Keberle et al 9, reported in the Journal of Ultrasound in Medicine a carotid screening method similar to the PDI technique described above, but this method used real time, 3-dimensional power Doppler sonography as the screening tool. Color Doppler sonography, in conjunction with spectral Doppler was the "gold standard," using the peak systolic velocity of the ICA as the stenosis-discriminating factor. In this study, 75 patients were screened. There was good correlation between the degrees of stenosis measured by 3D power Doppler sonography and that measured with color Doppler/spectral sonog-
raphy (r = 0.982; P < 0.01). For detecting ICA stenosis greater than 50%, these authors reported 97.9% sensitivity, 100% specificity, 100% PPV, and 99% NPV. In addition, they postulated that 3D volume and reconstructions would facilitate remote interpretations. CONCLUSIONS
If centers for stroke screening are developed, it would be wise to include screening for hypertension, atrial fibrillation, and carotid stenosis, because these three disorders represent the most common etiologies of strokes. The US screening component is the most difficult to perform, and therefore, must be the most carefully considered. Several US screening tests have been proposed, all of which are fast and accurate. Since they are all noninvasive and take less than 5 minutes, these tests would be readily acceptable to the general public. Only one US test, the PDI method, has been shown to be cost effective. At a proposed charge of $40 to $80, PDI is also affordable. While a limited color and spectral Doppler examination could have a similar low charge and could be shown to be cost effective, there is probably a greater degree of operator dependence and variability with this method, since angle-corrected Doppler measurements are required. PDI is thought to be less angle dependent than standard color Doppler, and therefore, may be more easily performed and learned. PDI is also widely available on most modem duplex Doppler instruments, while 3-D US imaging is not. At the present time, two studies using PDI have shown acceptable ranges of sensitivity, specificity, and positive and negative predictive values.
REFERENCES 1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325:445, 1991 2. European Carotid Surgery Trialists' Collaborative Group. MRC European Carotid SurgeryTrial; interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet 337:1235, 1991 3. Executive Committee for the AsymptomaticCarotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421, 1995 4. Lee TT, Solomon NA, Heidenreich PA, Oehlert J, Barber AM: Cost-effectiveness of screening for carotid stenosis in asymptomatic patients. Ann Intern Med 126:337, 1997 5. Lavenson GS Jr: A new accurate, rapid and cost-effective
protocol for sn'oke-preventionscreening. Cardiovasc Surg 6(6): 590-593, 1998 6. Carsten CG III, Elmore JR, Franklin DP, Thomas DD, Mordan F, Wood GC: Use of limited color-flow duplex for a carotid screening project. Am J Surg 178(2):173-176, 1999 7. Bluth E, Merritt C, Sullivan M, Smetherman D, Champagne J, Sunshine J: A screening test for carotid stenosis: A preliminary feasibility study (abs). Radiology 205:545, 1997 8. Bluth EI, Sunshine JH, Lyons JB, et aI: Power Doppler imaging: Initial evaluation as a screening examination for carotid artery stenosis. Radiology 215(3):791-800, 2000 9. Keberle M, Jenett M, Beissert M, Jahns R, Haerten R, Hahn D. Three-dimensional power Doppler sonography in screening for carotid artery disease. J Clin Ultrasound 28(9): 441-451, 2000