This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hatsukami, T. S. Articles by Strandness, D. E. Search for Related Content PubMed PubMed Citation Articles by Hatsukami, T. S. Articles by Strandness, D. E.

(Stroke. 1997;28:95-100.)
© 1997 American Heart Association, Inc.

Articles

Carotid Plaque Morphology and Clinical Events

Thomas S. Hatsukami, MD; Marina S. Ferguson, MT(ASCP); Kirk W. Beach, PhD, MD; David Gordon, MD; Paul Detmer, PhD; David Burns, PhD; Charles Alpers, MD D. Eugene Strandness, Jr, MD

the Surgical Service, Seattle Veterans Affairs Medical Center (T.S.H.); Departments of Pathology (M.S.F., C.A.) and Surgery (K.W.B., P.D., D.E.S.), University of Washington, Seattle; Department of Pathology, University of Michigan, Ann Arbor (D.G.); and Department of Chemistry, McGill University, Toronto, Canada (D.B.).

Correspondence to Thomas S. Hatsukami, Seattle VA Medical Center, Surgical Service (112), 1660 S Columbian Way, Seattle, WA 98108. E-mail tomhat@u.washington.edu.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Studies have suggested that B-mode ultrasonography can be used to determine carotid plaque composition and that specific plaque characteristics are associated with a worse clinical outcome. However, histological studies examining the relationship between carotid plaque morphology and clinical outcome have reported conflicting findings. Furthermore, few investigators have described plaque morphology in quantifiable terms. This study examines the association between the volume of carotid plaque constituents and preoperative ischemic neurological symptoms. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound or MRI.

Methods Atherosclerotic plaques from 43 patients undergoing carotid endarterectomy were examined histologically, with sections obtained every 0.5 to 1 mm. The lesions were examined for the presence and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic plaque core, and calcification. The quantity of each constituent was compared in plaques removed from symptomatic patients with those excised from asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov statistic.

Results There was no difference between plaques removed from asymptomatic and symptomatic patients with regard to the presence and volume of fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic core, or calcification.

Conclusions In patients with highly stenotic carotid lesions who are undergoing carotid endarterectomy, gross plaque composition is similar regardless of preoperative symptom status. Given this similarity, it is unlikely that differences in the volume of intraplaque hemorrhage, lipid core, necrotic core, or calcification in atherosclerotic carotid plaques explain their embolic history.

Key Words: atherosclerosis • carotid arteries • histology • magnetic resonance imaging • ultrasonics

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
A number of investigators have observed that the majority of patients with highly stenotic, atherosclerotic carotid plaques remain asymptomatic. For example, in the Asymptomatic Carotid Atherosclerosis Study (ACAS), unoperated patients with a greater than 60% diameter reducing carotid artery stenosis had only an 11.0% risk for ipsilateral hemispheric stroke at 5 years and a 19.2% 5-year risk for ipsilateral transient ischemic attack or stroke.¹ Factors other than the degree of stenosis must also be important in determining whether the carotid lesion will remain clinically silent. Plaques that are more prone to disruption, fracture, or fissuring may be at higher risk for embolization, occlusion, and consequent ischemic neurological events. Glagov and Zarins² suggest that differences in plaque structure, composition, and consistency may account for the relative instability of some atherosclerotic lesions.

Several investigators have proposed the use of diagnostic imaging techniques, such as B-mode ultrasonography, to characterize plaque composition and to identify the higher-risk, unstable carotid lesion.^{3 4 5} O'Holleran et al⁵ suggested that carotid plaques with a "soft" appearance on ultrasound correlated with lesions containing intraplaque hemorrhage or lipid and that these lesions were at higher risk for stroke than "dense" lesions that were primarily fibrous tissue. Furthermore, plaques exhibiting sonographic findings consistent with calcification were found to have the lowest risk for subsequent stroke or transient ischemic attack.

However, the literature on histological studies examining the association between carotid plaque composition and neurological symptoms is inconsistent. Imparato et al⁶ found that macroscopic intraplaque hemorrhage was the only feature that was significantly more common in plaques removed from symptomatic patients. Similarly, Lusby et al⁷ noted acute or recent intraplaque hemorrhage in 49 of 53 plaques (92%) from symptomatic patients compared with 7 of 26 plaques (27%) from asymptomatic patients. Avril et al⁸ classified carotid plaques as "hard" (predominantly composed of collagen or calcium) or "soft" (containing atheromatous debris or intraplaque hemorrhage). Soft plaques were significantly more common in symptomatic carotid lesions.

In contrast to these reports, in a postmortem study involving individuals who had asymptomatic carotid disease, Svindland and Torvik⁹ noted that small recent and old hemorrhages were a common finding in carotid plaques that resulted in a greater than 60% stenosis. Furthermore, numerous healed ulcerations and organized thrombi were seen. The authors concluded that plaque complications are frequent in cases with stenosis and that most of them apparently heal without giving rise to symptoms. Bassiouny et al¹⁰ similarly concluded that intraplaque hemorrhage was commonly seen in carotid plaques, including those without severe stenosis, and did not discriminate between symptomatic and asymptomatic stenotic lesions.

Factors that may account for these conflicting findings include the use of differing techniques of tissue examination, sampling errors, and differences in the definition of specific histological features. Some studies report gross macroscopic findings, while others examine the tissue microscopically. Many studies that incorporate histological examination do not examine the lesion in its entirety. Furthermore, there is a lack of standardization of histological definitions. For example, Lusby et al⁷ made a distinction between acute, recent hemorrhage and old hemorrhage, while others did not. Lastly, most of the previous studies have noted the presence or absence of specific features, but not in quantifiable terms.

The aim of this study was to determine whether there is a quantifiable difference in the composition of plaques in symptomatic and asymptomatic patients undergoing carotid endarterectomy. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound, CT, or MRI.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patient Population
Forty-three consecutive patients undergoing carotid endarterectomy at the University of Washington and Seattle Veterans Affairs Medical Centers were recruited after informed consent was obtained. The consent forms and protocol were approved by each facility's institutional review board. Median age was 70 years (range, 48 to 89 years). Of the 43 patients, 33 were male. Twenty-one patients underwent carotid endarterectomy for symptomatic, high-grade carotid stenosis. Ten of the patients had a recent ipsilateral hemispheric stroke with some recovery, 7 patients had an ipsilateral hemispheric transient ischemic attack, and 4 patients had transient monocular blindness. The median interval between symptoms and carotid endarterectomy was 3.6 weeks. Twenty-two patients underwent carotid endarterectomy for an asymptomatic high-grade carotid stenosis.

Histological Analysis and Outlining Procedure
Endarterectomy specimens were fixed in 10% neutral buffered formalin and subsequently decalcified in formic acid. The plaques were dehydrated in graded alcohols and embedded in paraffin. Cross sections (6 µm thick) were obtained every millimeter throughout the length of the plaque. Additional sections were obtained every 0.5 mm in the region of the carotid bifurcation. The resulting sections were mounted on glass slides and stained with hematoxylin and eosin. A digitized image was created for each section with a Matrox video frame grabber and printed on a laser printer. Specific plaque constituents were traced on a transparency overlying the print. These constituents were identified under the microscope and outlined under the direct supervision of experienced cardiovascular pathologists who were unaware of the patient's clinical status.

Plaque constituents were defined as follows: (1) fibrous intimal tissue: plaque regions rich in collagen bundles (Fig 1a); (2) intraplaque hemorrhage: regions of fibrin deposits and lysed red blood cells with some surrounding inflammatory cell infiltrate (Fig 1b). These areas are in contradistinction to hemorrhage caused by operative manipulation, in which intact red blood cells without surrounding tissue reaction are seen; (3) lipid core: distinct regions containing diffusely distributed clefts from which cholesterol crystals have been extracted (Fig 1c); (4) necrotic core: discrete regions with loosely aggregated necrotic debris, no viable cells, and without admixed collagen (Fig 1d); and (5) calcification: aggregates of prominent calcification, usually of either necrotic cellular debris or collagenous stroma, but devoid of cells (Fig 1e).

View larger version (745K): [in this window] [in a new window]   Figure 1. Photomicrographs of fibrous intimal tissue (a), intraplaque hemorrhage (b), lipid core (c), necrotic core (d), and calcification (e). Feature of interest is marked with arrow. Lu indicates lumen; FC, fibrous cap.

The histological tracings on transparency were then converted to a computer-assisted drawing format with a Gateway 486 33-MHz personal computer with a Matrox video frame grabber, digitizing pad, and modified software developed on Optimas (BioScan). The outlines were then joined as a complete three-dimensional drawing with the use of SilverScreen (Schroff Development Corp) (Fig 2).¹¹

View larger version (22K): [in this window] [in a new window]   Figure 2. Simplified representation of histological reconstruction with outlines generated in Silverscreen.

Output from the SilverScreen outlines provided the distribution of each constituent within the excised specimen and the area of each constituent per 0.5- to 1.0-mm section. The volume of each constituent was estimated with the stereological method described by Cavalieri¹² :

where V(obj)=volume of the object, t=the distance between parallel sections, and a=area of the object in each cross section.

The reproducibility of our pathologists for estimating plaque constituent volumes with this technique has been previously published by Thackray et al.¹¹ In that study, the total volume for each constituent was measured in three adjacent sets of cross sections, offset by 10 µm. The technique has an average standard deviation of 2.17 mm³ over a range of constituent volumes from 250 mm³ to 0.3 mm³. For constituent volumes greater than 1 mm³, the variability was acceptable.

Statistical Analysis
The estimated volumes of each constituent in the symptomatic and asymptomatic groups were displayed in box/whisker charts and cumulative distribution plots. Kolmogorov-Smirnov statistics were calculated with Statview 4.01 statistical software (Abacus Concepts, Inc) to compare differences between the two groups.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Degree of Stenosis
The severity of internal carotid artery stenosis was similar between the symptomatic and asymptomatic groups of patients. By duplex spectral waveform criteria,^{13 14} 7 symptomatic patients had a 50% to 79% diameter reducing internal carotid stenosis, and 14 patients had an 80% to 99% stenosis. In the asymptomatic group, 5 patients had a 50% to 79% diameter reducing internal carotid stenosis, and 17 patients had an 80% to 99% stenosis. The peak systolic velocity was similar in the symptomatic and asymptomatic groups (mean±SEM, 433±25 and 433±41 cm/s, respectively).

Volumes
The estimated volume of each plaque constituent is displayed in Figs 3 through 7. The graphs in the left panels (panel a) demonstrate the median estimated volume, the top and bottom quartiles, and the top and bottom deciles. The top, bottom, and line through the middle of each box correspond to the 75th percentile (top quartile), 25th percentile (bottom quartile), and 50th percentile (median), respectively. The whiskers extend from the 10th percentile (bottom decile) to the 90th percentile (top decile). The cumulative distribution plots in the right panels (panel b) document each data point in the asymptomatic and symptomatic groups. If there is a significant difference in the volume of a constituent between the two groups, one would expect a separation of the lines connecting the data points in each group. There was no difference in fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic core, or calcification volumes when we compared plaques removed from symptomatic and asymptomatic individuals.

View larger version (17K): [in this window] [in a new window]   Figure 3. Box plot chart (a) and corresponding cumulative distribution plot (b) of the estimated volume of fibrous intimal tissue in plaques harvested from asymptomatic and symptomatic individuals. The top, bottom, and line through the middle of the box in panel a correspond to the 75th percentile (top quartile), 25th percentile (bottom quartile), and 50th percentile (median), respectively. The whiskers extend from the 10th percentile (bottom decile) and to the 90th percentile (top decile). There was no difference between asymptomatic and symptomatic plaques with regard to the volume of fibrous intimal tissue (P=.28).

View larger version (15K): [in this window] [in a new window]   Figure 4. Box plot chart (a) and corresponding cumulative distribution plot (b) of the estimated volume of intraplaque hemorrhage in plaques harvested from asymptomatic and symptomatic individuals. There was no difference between asymptomatic and symptomatic plaques with regard to the volume of intraplaque hemorrhage (P>.99).

View larger version (14K): [in this window] [in a new window]   Figure 5. Box plot chart (a) and corresponding cumulative distribution plot (b) of the estimated volume of the lipid core in plaques harvested from asymptomatic and symptomatic individuals. There was no difference between asymptomatic and symptomatic plaques with regard to the lipid core volume (P=.47).

View larger version (15K): [in this window] [in a new window]   Figure 6. Box plot chart (a) and corresponding cumulative distribution plot (b) of the estimated volume of the necrotic core in plaques harvested from asymptomatic and symptomatic individuals. There was no difference between asymptomatic and symptomatic plaques with regard to the necrotic core volume (P>.99).

View larger version (15K): [in this window] [in a new window]   Figure 7. Box plot chart (a) and corresponding cumulative distribution plot (b) of the estimated volume of the calcification in plaques harvested from asymptomatic and symptomatic individuals. There was no difference between asymptomatic and symptomatic plaques with regard to the volume of calcification (P=.29).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In recent years, considerable attention has been devoted to atherosclerotic plaque characterization with imaging techniques such as ultrasound and MRI.^{3 15 16 17 18 19 20 21 22 23} A reliable, preferably noninvasive method of quantitatively characterizing these lesions in vivo would provide several benefits. First, imaging methods that better characterize plaque structure and composition would help determine which factors lead to the development of unstable atherosclerotic lesions and aid in identifying patients at increased risk for plaque disruption. Second, it would permit the performance of serial examinations. Histological analysis of excised arterial specimens provides accurate data on plaque composition, but from only a single point in time. Quantitative in vivo assessment of the plaque would allow prospective studies that serially monitor the progression or regression of atherosclerosis. Third, direct in vivo assessment of atherosclerotic plaque would permit smaller, less time-consuming epidemiological studies and clinical trials. The ACAS trial demonstrated that the majority of atherosclerotic carotid lesions remain clinically silent.¹ In such circumstances, studies that use adverse clinical outcomes as end points would require large numbers of subjects followed for many years. Quantitative imaging would provide a more direct evaluation of the effect of atherosclerotic risk factors on plaque progression. Similarly, quantitative imaging would provide direct assessment of the efficacy of interventions intended to halt the progression or cause regression of atherosclerotic disease.

Advancements in ultrasound and MRI technology continually improve the prospects for precise quantitative imaging of arterial wall pathology. In this histological study, the volumes of the lipid core, necrotic plaque core, intraplaque hemorrhage, and calcification failed to discriminate lesions removed from patients who had clinically recognizable ischemic neurological events from those who were asymptomatic. These findings suggest that in highly stenotic plaques, identification and quantification of these features by MRI or ultrasound will be unlikely to distinguish lesions that are at high risk for ischemic events from those that are likely to remain clinically silent.

Characterizing the nature of the fibrous cap that overlies the lipid-rich plaque core may be more productive. For example, a thinned fibrous cap may be more prone to plaque rupture. Defining the surface morphology of the lesion may also be important. In a review of patients enrolled in the North American Carotid Endarterectomy Trial, Eliasziw et al²⁴ found a higher risk for subsequent stroke if angiographic evidence of a plaque ulcer was demonstrated. In unoperated patients with a nonulcerated 85% carotid stenosis, the risk for ipsilateral stroke at 24 months was 21.3% compared with 43.9% in patients with an ulcerated 85% stenosis. In patients with a 95% carotid stenosis, the 2-year risk for ipsilateral stroke was 21.3% in patients without evidence of ulcer and 73.2% in patients with ulcerated lesions.

However, the inability of angiography to detect plaque ulceration is well documented, in part because of the limited number of views that are typically obtained.^{25 26} In a review of the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial, Streifler et al²⁶ found that the sensitivity and specificity of detecting ulcerated plaques were only 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%.

Characterization of the fibrous cap and plaque surface morphology remains a significant challenge for ultrasound and MRI. As with angiography, physical restrictions limit the number of views obtainable with transcutaneous B-mode ultrasonography. As a result of anisotropic effects, the plaque surface morphology can be reliably characterized only where the ultrasound beam is orthogonal to the plaque-lumen interface.²⁷ Difficulties with MRI include flow and motion artifacts, for example, from patient movement and pulsation of the arterial wall.

Unfortunately, the surface morphology of the excised carotid plaques could not be well characterized in this study because of artifacts introduced during the removal of the lesion. During endarterectomy, the full thickness of the plaque was incised, thereby disrupting the luminal surface of the lesion. Future studies examining surface morphology will require excision of the plaque intact, without incising through to the luminal surface.

Another plaque feature that may be of interest is the age of intraplaque hemorrhage and mural thrombus. Lusby et al⁷ noted evidence of recent hemorrhage in a significantly greater proportion of plaques removed from symptomatic individuals. However, evidence of remote hemorrhage was noted in 18 of 20 asymptomatic patients with a greater than 50% stenosis. If one were to assume that lesions with recent hemorrhage are acutely unstable, as opposed to plaques with remote hemorrhage, where the lesion has undergone a process of healing as suggested by Svindland and Torvik,⁹ then distinguishing recent from remote hemorrhage would be another important goal for diagnostic imaging.

In conclusion, this study found that intraplaque hemorrhage, the lipid core, necrotic core, and calcification are commonly found in highly stenotic carotid plaques. Furthermore, the volumes of these materials are similar in plaques removed from asymptomatic and symptomatic individuals. From an imaging perspective, it is unlikely that identification of these plaque features will distinguish severe carotid stenoses that are at higher risk for developing ischemic neurological symptoms.

	Acknowledgments

 
This study was supported by the National Institutes of Health Specialized Center for Organized Research, grant P50HL42270. The authors gratefully acknowledge Randy Small, Department of Neuropathology, University of Washington, for the excellent histological sectioning of this difficult material, and Brett Thackray, MSE, for his assistance in developing the image processing software.

Received July 1, 1996; revision received September 5, 1996; accepted September 5, 1996.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Executive Committee for Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421-1428.[Abstract/Free Full Text]

2. Glagov S, Zarins CB. What are the determinants of plaque instability and its consequences? J Vasc Surg. 1989;9:389-390.

3. Reilly LM, Lusby RJ, Hughes L, Ferrell LD, Stoney RJ, Ehrenfeld WK. Carotid plaque histology using real-time ultrasonography: clinical and therapeutic implications. Am J Surg. 1983;146:188-193.[Medline] [Order article via Infotrieve]

4. O'Donnell TFJ, Erdoes L, Mackey WC, McCullough J, Shepard A, Heggerick P, Isner J, Callow AD. Correlation of B-mode ultrasound imaging and arteriography with pathologic findings at carotid endarterectomy. Arch Surg. 1985;120:443-449.[Abstract/Free Full Text]

5. O'Holleran LW, Kennelly MM, McClurken M, Johnson JM. Natural history of asymptomatic carotid plaque: five year follow-up study. Am J Surg. 1987;154:659-662.[Medline] [Order article via Infotrieve]

6. Imparato AM, Riles TS, Mintzer R, Baumann FG. The importance of hemorrhage in the relationship between gross morphologic characteristics and cerebral symptoms in 376 carotid artery plaques. Ann Surg. 1983;197:195-203.[Medline] [Order article via Infotrieve]

7. Lusby RJ, Ferrell LD, Ehrenfeld WK, Stoney RJ, Wylie EJ. Carotid plaque hemorrhage: its role in production of cerebral ischemia. Arch Surg. 1982;117:1479-1488.[Abstract/Free Full Text]

8. Avril G, Batt M, Guidoin R, Marois M, Hassen-Khodja R, Daune B, Gagliardi JM, Le-Bas P. Carotid endarterectomy plaques: correlations of clinical and anatomic findings. Ann Vasc Surg. 1991;5:50-54.[Medline] [Order article via Infotrieve]

9. Svindland A, Torvik A. Atherosclerotic carotid disease in asymptomatic individuals: an histological study of 53 cases. Acta Neurol Scand.. 1988;78:506-517.[Medline] [Order article via Infotrieve]

10. Bassiouny HS, Davis H, Massawa N, Gewertz BL, Glagov S, Zarins CK. Critical carotid stenoses: morphologic and chemical similarity between symptomatic and asymptomatic plaques. J Vasc Surg. 1989;9:202-212.[Medline] [Order article via Infotrieve]

11. Thackray BD, Burns DH, Ferguson MS, Gordon D, Beach KW, Hatsukami TS, Detmer PR, Primozich JF, Strandness DE Jr. A new method for studying plaque morphology. Am J Card Imaging.. 1995;9:149-156.[Medline] [Order article via Infotrieve]

12. Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS. 1988;96:379-394.[Medline] [Order article via Infotrieve]

13. Roederer GO, Langlois YE, Chan AW, Primozich JF, Lawrence RJ, Chikos PM, Strandness DE Jr. Ultrasound duplex scanning of extracranial carotid arteries: improved accuracy using new features from the common carotid artery. J Cardiovasc Ultrasonography. 1982;1:373-379.

14. Roederer GO, Langlois YE, Jager KA, Lawrence RJ, Primozich JF, Phillips DJ, Strandness DE Jr. A simple spectral parameter for accurate classification of severe carotid disease. Bruit. 1984;8:174-178.

15. Bendick PJ, Glover JL, Hankin R, Reilly MK, Dalsing MC, Waller BF. Carotid plaque morphology: correlation of duplex sonography with histology. Ann Vasc Surg. 1988;2:6-13.[Medline] [Order article via Infotrieve]

16. Hatsukami TS, Thackray BD, Primozich JF, Ferguson MS, Burns DH, Beach KW, Detmer PR, Alpers C, Gordon D, Strandness DE Jr. Echolucent regions in carotid plaque: preliminary analysis comparing three-dimensional histologic reconstructions to sonographic findings. Ultrasound Med Biol. 1994;20:743-749.[Medline] [Order article via Infotrieve]

17. Bluth EI, Kay D, Merritt CRB. Sonographic characterization of carotid plaque: detection of hemorrhage. AJR Am J Roentgenol. 1986;146:1061-1065.[Abstract/Free Full Text]

18. Gray-Weale AC, Graham JC, Burnett JR, Byrne K, Lusby RJ. Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology. J Cardiovasc Surg (Torino). 1988;29:676-681.[Medline] [Order article via Infotrieve]

19. European Carotid Plaque Study Group. Carotid artery plaque composition: relationship to clinical presentation and ultrasound B-mode imaging. Eur J Vasc Endovasc Surg. 1995;9:1-8.[Medline] [Order article via Infotrieve]

20. Vinitski S, Consigny PM, Shapiro MJ, Janes N, Smullens SN, Rifkin MD. Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque. Invest Radiol. 1991;26:703-714.[Medline] [Order article via Infotrieve]

21. Yuan C, Tsuruda JS, Beach KN, Hayes CE, Ferguson MS, Alpers CE, Foo TK, Strandness DE. Techniques for high-resolution MR imaging of atherosclerotic plaque. J Magn Reson Imaging. 1994;4:43-49.[Medline] [Order article via Infotrieve]

22. Mohiaddin RH, Longmore DB. MRI studies of atherosclerotic vascular disease: structural evaluation and physiological measurements. Br Med Bull.. 1989;45:968-990.[Abstract/Free Full Text]

23. Gold GE, Pauly JM, Glover GH, Moretto JC, Macovski A, Herfkens RJ. Characterization of atherosclerosis with a 1.5-T imaging system. J Magn Reson Imaging.. 1993;3:399-407.[Medline] [Order article via Infotrieve]

24. Eliasziw M, Streifler JY, Fox AJ, Hachinski VC, Ferguson GG, Barnett HJ. Significance of plaque ulceration in symptomatic patients within high-grade carotid stenosis. Stroke. 1994;25:304-308.[Abstract]

25. Wechsler LR. Ulceration and carotid artery disease. Stroke. 1988;19:650-653.[Free Full Text]

26. Streifler JY, Eliasziw M, Fox AJ, Benavente OR, Hachinski VC, Ferguson GG, Barnett HJ. Angiographic detection of carotid plaque ulceration: comparison with surgical observations in a multicenter study. Stroke. 1994;25:1130-1132.[Abstract]

27. Rubin JM, Carson PL, Meyer CR. Anisotropic ultrasonic backscatter from the renal cortex. Ultrasound Med Biol. 1988;14:507-511.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				W. Peeters, W.E. Hellings, D.P.V. de Kleijn, J.P.P.M. de Vries, F.L. Moll, A. Vink, and G. Pasterkamp Carotid Atherosclerotic Plaques Stabilize After Stroke: Insights Into the Natural Process of Atherosclerotic Plaque Stabilization Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 128 - 133. [Abstract] [Full Text] [PDF]

				T. Y. Tang, S. P. Howarth, S. R. Walsh, M. E. Gaunt, and J. H. Gillard Contralateral Carotid Intraplaque Hemorrhage May Reduce the Predictive Value of Fat-Suppressed T1-Weighted MRI in Symptomatic Carotid Disease Stroke, December 1, 2007; 38(12): e156 - e157. [Full Text] [PDF]

				P. Gao, Z.-q. Chen, Y.-h. Bao, L.-q. Jiao, and F. Ling Correlation Between Carotid Intraplaque Hemorrhage and Clinical Symptoms: Systematic Review of Observational Studies Stroke, August 1, 2007; 38(8): 2382 - 2390. [Abstract] [Full Text] [PDF]

				M Kumagai, T Yamagishi, N Fukui, and M Chiba Carotid artery calcification seen on panoramic dental radiographs in the Asian population in Japan Dentomaxillofac. Radiol., February 1, 2007; 36(2): 92 - 96. [Abstract] [Full Text] [PDF]

				N. Yamada, M. Higashi, R. Otsubo, T. Sakuma, N. Oyama, R. Tanaka, K. Iihara, H. Naritomi, K. Minematsu, and H. Naito Association between Signal Hyperintensity on T1-Weighted MR Imaging of Carotid Plaques and Ipsilateral Ischemic Events AJNR Am. J. Neuroradiol., February 1, 2007; 28(2): 287 - 292. [Abstract] [Full Text] [PDF]

				T. Saam, J. Cai, L. Ma, Y.-Q. Cai, M. S. Ferguson, N. L. Polissar, T. S. Hatsukami, and C. Yuan Comparison of Symptomatic and Asymptomatic Atherosclerotic Carotid Plaque Features with in Vivo MR Imaging. Radiology, August 1, 2006; 240(2): 464 - 472. [Abstract] [Full Text] [PDF]

				G. Stoll and M. Bendszus Inflammation and Atherosclerosis: Novel Insights Into Plaque Formation and Destabilization Stroke, July 1, 2006; 37(7): 1923 - 1932. [Abstract] [Full Text] [PDF]

				G. Sangiorgi, A. Mauriello, E. Bonanno, C. Oxvig, C. A. Conover, M. Christiansen, S. Trimarchi, V. Rampoldi, D. R. Holmes Jr, R. S. Schwartz, et al. Pregnancy-Associated Plasma Protein-A Is Markedly Expressed by Monocyte-Macrophage Cells in Vulnerable and Ruptured Carotid Atherosclerotic Plaques: A Link Between Inflammation and Cerebrovascular Events J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2201 - 2211. [Abstract] [Full Text] [PDF]

				J.N.E. Redgrave, J.K. Lovett, P.J. Gallagher, and P.M. Rothwell Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms: The Oxford Plaque Study Circulation, May 16, 2006; 113(19): 2320 - 2328. [Abstract] [Full Text] [PDF]

				M. Ouhlous, H. Z. Flach, T. T. de Weert, J. M. Hendriks, M. R. H. M. van Sambeek, D. W. J. Dippel, P. M. T. Pattynama, and A. van der Lugt Carotid Plaque Composition and Cerebral Infarction: MR Imaging Study AJNR Am. J. Neuroradiol., May 1, 2005; 26(5): 1044 - 1049. [Abstract] [Full Text] [PDF]

				A. Mohr, F. Roemer, H. Genant, A. C. Langheinrich, and R. M. Bohle Analysis of Atherosclerosis with Micro-CT * Drs Langheinrich and Bohle respond: Radiology, April 1, 2005; 235(1): 338 - 339. [Full Text] [PDF]

				R. E. Zierler Characterization of Carotid Artery Plaques Using Real-Time Compound B-Mode Ultrasound Perspectives in Vascular Surgery and Endovascular Therapy, March 1, 2005; 17(1): 59 - 60. [Abstract] [PDF]

				A. Kampschulte, M.S. Ferguson, W.S. Kerwin, N. L. Polissar, B. Chu, T. Saam, T.S. Hatsukami, and C. Yuan Differentiation of Intraplaque Versus Juxtaluminal Hemorrhage/Thrombus in Advanced Human Carotid Atherosclerotic Lesions by In Vivo Magnetic Resonance Imaging Circulation, November 16, 2004; 110(20): 3239 - 3244. [Abstract] [Full Text] [PDF]

				L. G. Spagnoli, A. Mauriello, G. Sangiorgi, S. Fratoni, E. Bonanno, R. S. Schwartz, D. G. Piepgras, R. Pistolese, A. Ippoliti, and D. R. Holmes Jr Extracranial Thrombotically Active Carotid Plaque as a Risk Factor for Ischemic Stroke JAMA, October 20, 2004; 292(15): 1845 - 1852. [Abstract] [Full Text] [PDF]

				K. C. Wang, D. Saloner, and J. H. Rapp Characteristics of Carotid Plaque as Risk Factors for Stroke Perspectives in Vascular Surgery and Endovascular Therapy, September 1, 2004; 16(3): 193 - 199. [Abstract] [PDF]

				B. Chu, A. Kampschulte, M. S. Ferguson, W. S. Kerwin, V. L. Yarnykh, K. D. O'Brien, N. L. Polissar, T. S. Hatsukami, and C. Yuan Hemorrhage in the Atherosclerotic Carotid Plaque: A High-Resolution MRI Study Stroke, May 1, 2004; 35(5): 1079 - 1084. [Abstract] [Full Text] [PDF]

				R. Kern, K. Szabo, M. Hennerici, and S. Meairs Characterization of Carotid Artery Plaques Using Real-time Compound B-mode Ultrasound Stroke, April 1, 2004; 35(4): 870 - 875. [Abstract] [Full Text] [PDF]

				P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]

				J. Alvarez-Linera, J. Benito-Leon, J. Escribano, J. Campollo, and R. Gesto Prospective Evaluation of Carotid Artery Stenosis: Elliptic Centric Contrast-Enhanced MR Angiography and Spiral CT Angiography Compared with Digital Subtraction Angiography AJNR Am. J. Neuroradiol., May 1, 2003; 24(5): 1012 - 1019. [Abstract] [Full Text] [PDF]

				J. L. Stork, K. Kimura, C. R. Levi, B. R. Chambers, A. L. Abbott, and G. A. Donnan Source of Microembolic Signals in Patients With High-Grade Carotid Stenosis Stroke, August 1, 2002; 33(8): 2014 - 2018. [Abstract] [Full Text] [PDF]

				L. J. Walker, A. Ismail, W. McMeekin, D. Lambert, A. D. Mendelow, and D. Birchall Computed Tomography Angiography for the Evaluation of Carotid Atherosclerotic Plaque: Correlation With Histopathology of Endarterectomy Specimens Stroke, April 1, 2002; 33(4): 977 - 981. [Abstract] [Full Text] [PDF]

				J.Y. Streifler, N. Rosenberg, A. Chetrit, R. Eskaraev, B.A. Sela, R. Dardik, A. Zivelin, B. Ravid, J. Davidson, U. Seligsohn, et al. Cerebrovascular Events in Patients With Significant Stenosis of the Carotid Artery Are Associated With Hyperhomocysteinemia and Platelet Antigen-1 (Leu33Pro) Polymorphism Stroke, December 1, 2001; 32(12): 2753 - 2758. [Abstract] [Full Text] [PDF]

				C. D. Liapis, J. D. Kakisis, and A. G. Kostakis Carotid Stenosis: Factors Affecting Symptomatology Stroke, December 1, 2001; 32(12): 2782 - 2786. [Abstract] [Full Text] [PDF]

				B. D. Coombs, J. H. Rapp, P. C. Ursell, L. M. Reilly, and D. Saloner Structure of Plaque at Carotid Bifurcation: High-Resolution MRI With Histological Correlation Stroke, November 1, 2001; 32(11): 2516 - 2521. [Abstract] [Full Text] [PDF]

				X.-Q. Zhao, C. Yuan, T. S. Hatsukami, E. H. Frechette, X.-J. Kang, K. R. Maravilla, and B. G. Brown Effects of Prolonged Intensive Lipid-Lowering Therapy on the Characteristics of Carotid Atherosclerotic Plaques In Vivo by MRI: A Case-Control Study Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1623 - 1629. [Abstract] [Full Text] [PDF]

				B. Randoux, B. Marro, F. Koskas, M. Duyme, M. Sahel, A. Zouaoui, and C. Marsault Carotid Artery Stenosis: Prospective Comparison of CT, Three-dimensional Gadolinium-enhanced MR, and Conventional Angiography Radiology, July 1, 2001; 220(1): 179 - 185. [Abstract] [Full Text] [PDF]

				K. J. Hunt, G. W. Evans, A. R. Folsom, A. R. Sharrett, L. E. Chambless, C. H. Tegeler, and G. Heiss Acoustic Shadowing on B-Mode Ultrasound of the Carotid Artery Predicts Ischemic Stroke : The Atherosclerosis Risk in Communities (ARIC) Study Stroke, May 1, 2001; 32(5): 1120 - 1126. [Abstract] [Full Text] [PDF]

				T. J. Tegos, E. Kalodiki, S.-S. Daskalopoulou, and A. N. Nicolaides Stroke: Epidemiology, Clinical Picture, and Risk Factors: Part I of III Angiology, October 1, 2000; 51(10): 793 - 808. [Abstract] [PDF]

				T. S. Hatsukami, R. Ross, N. L. Polissar, and C. Yuan Visualization of Fibrous Cap Thickness and Rupture in Human Atherosclerotic Carotid Plaque In Vivo With High-Resolution Magnetic Resonance Imaging Circulation, August 29, 2000; 102(9): 959 - 964. [Abstract] [Full Text] [PDF]

				B. Axisa, A. R. Naylor, N. London, P. R. F. Bell, and M. M. Thompson The Influence of Carotid Plaque Morphology on the Development of Cerebral Symptoms Vascular and Endovascular Surgery, July 1, 2000; 34(4): 309 - 318. [Abstract] [PDF]

				J. Golledge, R. M. Greenhalgh, and A. H. Davies The Symptomatic Carotid Plaque Stroke, March 1, 2000; 31(3): 774 - 781. [Abstract] [Full Text] [PDF]

				A. Mauriello, G. Sangiorgi, G. Palmieri, R. Virmani, D. R. Holmes Jr, R. S. Schwartz, R. Pistolese, A. Ippoliti, and L. G. Spagnoli Hyperfibrinogenemia Is Associated With Specific Histocytological Composition and Complications of Atherosclerotic Carotid Plaques in Patients Affected by Transient Ischemic Attacks Circulation, February 22, 2000; 101(7): 744 - 750. [Abstract] [Full Text] [PDF]

				S. Meairs and M. Hennerici Four-Dimensional Ultrasonographic Characterization of Plaque Surface Motion in Patients With Symptomatic and Asymptomatic Carotid Artery Stenosis Stroke, September 1, 1999; 30(9): 1807 - 1813. [Abstract] [Full Text] [PDF]

				M.-L. M. Gronholdt Ultrasound and Lipoproteins as Predictors of Lipid-Rich, Rupture-Prone Plaques in the Carotid Artery Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 2 - 13. [Abstract] [Full Text] [PDF]

				T. J. DeGraba, A.-L. Siren, L. Penix, R. M. McCarron, R. Hargraves, S. Sood, K. D. Pettigrew, and J. M. Hallenbeck Increased Endothelial Expression of Intercellular Adhesion Molecule-1 in Symptomatic Versus Asymptomatic Human Carotid Atherosclerotic Plaque Stroke, July 1, 1998; 29(7): 1405 - 1410. [Abstract] [Full Text] [PDF]

				O. Joakimsen, K. H. Bonaa, and E. Stensland-Bugge Reproducibility of Ultrasound Assessment of Carotid Plaque Occurrence, Thickness, and Morphology : The Tromso Study Stroke, November 1, 1997; 28(11): 2201 - 2207. [Abstract] [Full Text]

				C. Yuan, L. M. Mitsumori, K. W. Beach, and K. R. Maravilla Carotid Atherosclerotic Plaque: Noninvasive MR Characterization and Identification of Vulnerable Lesions Radiology, November 1, 2001; 221(2): 285 - 299. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hatsukami, T. S. Articles by Strandness, D. E. Search for Related Content PubMed PubMed Citation Articles by Hatsukami, T. S. Articles by Strandness, D. E.