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Characterisation of carotid artery disease: comparison of duplex scanning with histology
Ultrasound in Med. & Biol. Vol. 1I, No. 6, pp. 835-840, 1985
0301-5629/85 $3.00 + .00 © 1985 Pergamon Press Ltd.
Printed in the U.S.A.
OOriginal Contribution I
CHARACTERISATION COMPARISON
OF
OF
DUPLEX
CAROTID SCANNING
ARTERY WITH
DISEASE: HISTOLOGY
D. A. RATLIFF, P. J. GALLAGHER, T. K. HAMES, K. N. HUMPHRIES, J. H . H . WEBSTER a n d A. D. B. CHANT Vascular Surgical Unit, Departments of Medical Physics and Pathology, Southampton, United Kingdom (Received 7 January 1985; in final form 24 May 1985) Abstract--The ability of duplex scanning to characterise the component tissue of atheromatous lesions of the internal carotid artery and to detect ulceration has been examined in a histological study of 42 carotid endarterectomy specimens. The results suggest that the only component of atheromatous lesions of the internal carotid artery which can be characterised from the B-scan is calcification. The presence of ulceration, intraluminal and intramural thrombns, fibrous intimai thickening and necrosiS are not related to the echogenic appearance of internal carotid stenoses and may not be detected reliably. B-mode imaging alone cannot reliably grade >50% internal carotid stenoses, but when this is combined with pulsed Doppler in the technique of duplex scanning, accurate results may be obtained.
Key Words: Carotid artery disease, Doppler ultrasound, Histology.
INTRODUCTION
use in diagnosis and the study of the natural history of carotid artery disease. The aim of this study is to establish if there is a relationship between the B-scan appearance of an internal carotid stenosis and its pathological composition, and the degree of stenosis on the B-mode image in comparison with that demonstrated by angiography.
The most widely accepted hypothesis for the pathogenesis of transient ischaemic attacks within the carotid territory is due to embolism of atheromatous and/or thrombotic material from ulcerated disease at the carotid bifurcation (Bartynski et al., 1981; Fields, 1979; Thiele et al., 1980; Moore and Hall, 1970). Potentially embolic lesions occur in up to 79% of patients with transient hemispheric symptoms and 75% of patients with amaurosis fugax (Thiele and Strandness, 1982). It is recognised that conventional angiography may fail to show disease of the carotid bifurcation and may incorrectly identify the degree or type of internal carotid stenoses (Croft et al., 1980; Ricotta et al., 1983; DeWeese et al., 1970). For example, in a series of fifty patients having carotid endarterectomy, 40% of twenty ulcers found at operation had been missed on angiography; a subintimal haematoma from intramural haemorrhage was found at operation in 34% of patients in whom ulceration had been reported on angiography (Edwards et al., 1979). With the development of duplex scanning as an accurate technique in the noninvasive assessment of carotid artery disease, there is now considerable interest in its ability to characterise the component tissue of atheromatous lesions and to detect ulceration. The presence or absence of ulceration in a given atheromatous lesion may be of importance clinically in patient management. Such information would also be of
MATERIALS AND M E T H O D S Duplex scans were obtained preoperatively in 39 patients having 42 carotid endarterectomies for symptomatic internal carotid artery disease using the Honeywell Ultra Imager. The operation was carried out by one of two experienced vascular surgeons (Chant and Webster) who made every effort to remove the specimen complete. The carotid endarterectomy specimen was fixed in formalin and sections were taken at multiple levels transversely so that the point of maximum stenosis was always included. The sections, which were not decalcified, were cut with disposable microtome knives and stained with both haematoxylin and eosin and Gomori's trichrome stain. They were then examined by a consultant pathologist with a special interest in atherosclerosis (Gallagher) for the principle pathological components of atheroma: calcification, fibrous intimal thickening, intramural thrombus and necrosis. Each feature was graded on a scale from 0 to III, scores of 0 or I representing a low content and II or III a high content of 835
836
Ultrasound in Medicine and Biology
the component, respectively. The criteria used for the grading o f calcification were as follows: grade 0 indicated that this feature was completely absent, whereas grade I indicated that only a single focus less than 3 m m in m a x i m u m microscopic dimension was present. More extensive deposits were assigned to grades II or III. All specimens were also examined for epithelial ulceration and intraluminal thrombus. The videotape recordings of the Duplex scanning examination were reviewed independently by the first author without knowledge of the duplex scanning or angiographic grading of stenosis or details of the pathological analysis. A real-time B-scan with 16 levels of grey was obtained which was updated at a rate of 30 frames per second. Multiple views of each carotid bifurcation and internal carotid artery were satisfactorily obtained in all cases using a standard protocol which we have previously described (Ratliff et aL, 1985). Longitudinal B-scans were used for analysis because, in our experience, they provided the best quality images for assessment. B-scans were obtained in transverse section in a proportion of cases but were not used for analysis. The B-scan appearances of the internal carotid stenoses were graded on a scale from I to V. In the final analysis grade I, II, and III lesions were grouped together into 27 heterogeneous lesions of low echogenicity, and grade IV and V lesions into 15 homogeneous lesions of high echogenicity (see Figs. 1 and 2, respectively). The degree of stenosis on the real-time B-scan alone was estimated without use of the pulsed Doppler information and graded in the same way as angiography on a quartile basis. The figures reproduced in this paper were obtained from a captured freeze-frame on a videorecorder and their quality does not, therefore, represent that seen during a real-time examination.
Fig. 1. B-scan appearance of heterogeneous internal carotid stenosis of low echogenicity. The common carotid artery and bifurcation are shown on the left with the internal carotid artery on the right below the external carotid artery.
November/December1985, Volume 11, Number 6
Fig. 2. B-scan appearance of a homogeneous internal carotid stenosis of high echogenicity. The common carotid artery is shown on the left with the internal carotid artery on the right. Comparison was available for 39 biplanar angiograms. The degree of each internal carotid stenosis on angiography was graded independently by a consultant radiologist (S.B.) into one of the following six categoriee normal, 1-24%, 25-49%, 50-74%, and 75-99% diameter reduction, and occlusion. RESULTS Epithelial ulceration was present in 31 (74%) o f 42 cases and intraluminal thrombus was present in 25 (60%) cases. Twenty-four (77%) of 31 cases of epithelial ulceration had associated intraluminal thrombus. Neither parameter could be diagnosed reliably by B-mode imaging or duplex scanning. A high content of calcification was found in 11 of 15 stenoses of high echogenicity, and 21 of 27 cases of low echogenicity had a low calcification content. The echogenicity of the lesion on the B-scan was significantly related to its calcification content (x 2 with Yates's correction = 8.4, p > 0.005). Ten of 15 lesions of high echogenicity had a low content of intramural thrombus, but only 13 of 27 lesions of low echogenicity had a high proportion of intramural thrombus (X2 with Yates's correction = 0.37, N.S.). Similarly the degree of fibrous intimal thickening and necrosis were not significantly related to the B-mode characteristics of the lesion. From our experience with duplex scanning we felt that >50% internal carotid stenoses may have variable B-scan appearances, as illustrated in Figs. 3 and 4. Both are examples of >75% internal carotid stenosis. In Fig. 3 a mass of disease can clearly be seen at the origin of the internal carotid artery with posterior acoustic shadowing, but in Fig. 4 disease of only 1-24% severity is visualised on the B-scan and the diagnosis was made by obtaining a high frequency shift of the internal carotid signal >4 K H z using the pulsed Doppler.
Characterisationof carotidarterydisease• D. A. RATLIFFel al.
837
et al., 1982), not only between plaques but also between
Fig. 3. B-scan appearance of a >50% internal carotid stenosis with posterior acoustic shadowing. The common carotid artery is shown on the left with a mass of disease at the origin of the internal carotid artery which appears to have almost completely obliterated its lumen as its courses away down and to the right. It was therefore decided to compare the grading of percentage diameter stenosis by B-mode imaging alone and also by duplex scanning in comparison with biplanar angiography. The results are shown in Tables 1 and 2, respectively. There was very poor agreement between the percentage diameter stenosis by B-mode imaging and that by biplanar angiography (r = 0.18). When the degree of stenosis was graded from the Bscan alone, 13 of 19 cases of 75-99% stenosis were underestimated and 7 cases were graded as of <50% severity (see Table l). The sensitivity of B-mode imaging was 71% and specificity 72% in comparison with angiography in the detection of >50% internal carotid stenosis. In contrast there was good agreement between the results of duplex scanning and biplanar angiography (K -- 0.60). There were no false positive results and only one false negative result in which a case of 5074% stenosis by angiography was graded to be of 2549% severity by duplex scanning. Duplex scanning correctly identified 15 of 19 cases of 75-99% stenosis and the remaining four cases were graded 50-74% stenosis (see Table 2). The sensitivity of duplex scanning was 97% and specificity 100% in comparison with angiography in the detection of >50% internal carotid stenosis.
areas of the same lesion. There is a spectrum of echogenicity of internal carotid stenoses from the highly echogenic, homogeneous lesion accompanied by posterior acoustic shadowing to lesions of very low echogenicity which may be barely visible. Although plaques may be of uniform echogenicity there is more frequently variation within lesions which gives rise to heterogeneous appearances of intermediate echogenicity. Whilst this may be expected because of the differing pathological constituents of atheroma, it has not been clear how these relate to the varying B-scan appearances of internal carotid stenoses. These results suggest that lesions of high echogenicity, often with posterior acoustic shadowing, contain a high content of calcium but heterogeneous lesions of low echogenicity contain other components of atheromatous material in varying proportions. The degree of intramural thrombus, fibrous intimal thickening and necrosis were not significantly related to the B-scan appearance although they were shown to be present histologically. It is known from previous work on the aorta that calcium deposits within intimal plaque are responsible for marked attenuation to transmitted ultrasound (Hartley and Strandness, 1969). However, these are interesting findings because collagen and fibrous tissue are also associated with increased echogenicity in tissue (Fields and Dunn, 1973), and the dark areas in heterogeneous lesions might be interpreted as intraplaque haemorrhage by some observers. The problem of detecting ulceration by duplex scanning is shown in Fig. 5. Two lesions of high echogenicity are seen at the origin of the internal carotid artery with a gap between them. There are three possible interpretations of this situation: (i) that the gap
DISCUSSION Duplex scanning is an accurate technique in the direct noninvasive assessment of carotid artery disease by means of its B-mode imaging and pulsed Doppler facilities (Langiois et al., 1983; Fell et al., 1981). Considerable variation in the B-scan appearances of atheroma has been reported (Zwiebel, 1982; Cooperberg
Fig. 4. B-scan appearance of >50% internal carotid stenosis. The common carotid artery is shown on the left with barely any disease visible in the internal carotid artery on the right.
838
Ultrasound in Medicineand Biology
November/December1985, Volume 11, Number6
Table 1. Accuracy of B-mode imaging in comparison with angiography(39 carotid endarterectomies) Diameter stenosis by biplanar angiography 1-24%
25-49%
50-74%
75-99%
Total
3
4
I
2
4
10
Diameter
1-24%
1
stenosis
25-49%
3
by B-mode
50-74%
2
8
6
16
imagin 9
75-99%
-
3
6
9
3
13
19
39
Total
4
kappa = 0.18
the reliability of ulcer detection by duplex scanning of the carotid bifurcation. Hennerici has found that ulcerative lesions may be confidently identified (Hennerici and Freund, 1984; Hennerici et al., 1984), whilst others have not found this to be the case (Zweibel et al., 1983; Calhoun and MacErlean, 1984; Herring et al., 1984; Cooperberg et aL, 1979). Wolverson et al. (1983a) reported that localised or abrupt interruption of the intimal surface with marked irregularity and excavations were reliable indicators of ulceration. This is a rare finding in our experience. In this study there was no relation between the B-mode appearance of an internal carotid stenosis and the demonstration that it was ulcerated pathologically. A change in the echogenicity of the surface of a lesion from an area of high to low echogenicity can in itself give rise to the impression of a loss of intimal continuity. An apparently large
represents an ulcer; (ii) that the two lesions are two separate plaques; or (iii) this is one contiguous plaque with two areas of high echogenicity separated by an area containing material of low echogenicity such as thrombus or necrosis. In theory it might be possible to correctly identify the third situation from the first two by the careful positioning of the pulsed Doppler sample in the area of low echogenicity, but this is not helpful in practice. Furthermore, the exact position of the pulsed Doppler sample in the third dimension on a two-dimensional image is not known. Paradoxically the only way of detecting thrombus is by use of pulsed Doppler since it has the same ultrasound characteristics as moving blood. This difficulty in diagnosis is compounded by the knowledge that ulceration was present in 74% of the cases in this study. There is controversy in the literature concerning
Table 2. Accuracy of duplex scanning in comparison with angiography (39 carotid endarterectomies) Diameter stenosis by biplanar angiography 1-24%
Diameter
25-49%
1-24%
3
I
1
2
50-74%
75-99%
Total
4
stenosis
25-49g
by Duplex
50-74%
9
4
13
scannin 9
75-99%
3
15
18
13
19
39
Tota]
4
3
kappa = 0 . 6 0
I
4
Characterisation of carotid artery disease• D. A. RATLIFFel al.
Fig. 5. B-scan appearance of an internal carotid stenosis. The common carotid artery is shown on the left with two lesions of high echogenicity at the origin of the intemal carotid artery with a gap between them. The internal carotid artery courses away to the right. ulcer between two highly echogenic lesions may be composed of material of low echogenicity in one contiguous lesion. It has recently been reported that some unusual types of carotid pathology including Takayashu's arteritis, carotid dissection and diverticula within a plaque may be readily diagnosed by real-time B-mode imaging (Dean et al., 1984). We agree with these authors that careful attention must be paid to the gain controls for maximum shades of grey in order to show pathology optimally and with their conclusion that accurate diagnosis is achieved by persistence and careful evaluation. However, we have had only isolated experiences of these rare conditions to date and are therefore unable to comment with confidence on their findings. The images in this study were obtained by a 5 MHz short-focus probe which gave high quality images with good grey-scale resolution and sensitivity suitable for detailed analysis. One possible limitation of this study is that a higher frequency imaging probe of 7.5 or 10 MHz was unavailable and not used. Whilst these may produce images of better resolution, the claim that there use results in improved accuracy is not yet proven. Because of some of the problems which have been discussed above, it is not at all certain whether ulceration is likely to be diagnosed more reliably by their use. In addition to the imaging frequency, however, another important facto~ which determines the sensitivity of a given probe in a particular system is its ability to detect changes in the "characteristic impedance" of the components of soft tissue. The characteristic impedance of a tissue refers to its ability to reflect sound waves and to generate an echo, and is directly propor-
839
tional to the density of the tissue (McDicken, 1981). For a structure to be detected, it must produce an echo of adequate magnitude which then must be visualised on the display with sufficient dynamic range of grey scale. The sensitivity of individual systems in this respect and the a m o u n t of variation between them are not known at the present time. Further work now needs to be done to assess and quantify this capability for individual probes in different systems and to determine their respective resolutions when a tissue phantom is used. This may help to explain differing results which have been reported in the literature. The results of comparison of B-mode imaging alone with angiography confirm the consensus of previous work that it may not be used reliably in the accurate diagnosis of internal carotid stenosis (Comerota et al., 1981; James et al., 1982), despite the findings of some authors that there is close agreement between sonographic and angiographic estimates of disease (Wolverson et al., 1983b). Historically there has been a direct progression from B-mode imaging of the carotid bifurcation to duplex scanning with greatly improved accuracy (Zweibel et al., 1983; Leopold et al., 1982), which we have been able to confirm by a direct comparison in this study. CONCLUSIONS The results of this histological study suggest that the only component of atheromatous lesions of the intemal carotid artery which can be characterised from the B-scan is calcification. The presence of ulceration, intraluminal and intramural thrombus, fibrous intimal thickening and necrosis are not related to the echogenic appearance of internal carotid stenoses and may not be detected reliably. B-mode imaging alone cannot reliably grade >50% internal carotid stenoses, but when this is combined with pulsed Doppler in the technique of duplex scanning, accurate results may be obtained. Acknowledgment--We are verygrateful to Dr. S. Birch, Consultant Radiologist, for reviewingand interpretingthe angiograms. REFERENCES
Bartynski W. S., Darbouze P. and Nemir P. (1981) Significanceof ulcerated plaque in transient cerebral ischaemia. Am. J. Surg. 141, 353-357. Colhoun E. and MacErlean D. (1984) Carotid artery imaging using duplex scanning and bidirectional arteriography: a comparison. Clin. Radiol. 35, 101-106. Comerota A. J., Cranley J. J. and Cook S. E. (1981) Real-time Bmode carotid imaging in diagnosis of cerebrovasculardisease. Surgery89, 718-729. Cooperberg P. L., Robertson W. D., Fry P. and SweeneyV. (1982) High resolution real-time ultrasound of the carotid bifurcation. A.J.N.R. 3, 13-17. CooperbergP. L., Robertson W. D., Fry P. and SweeneyV. (1979)
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High resolution real-time ultrasound of the carotid bifurcation. J. Clin. Ultrasound 7, 13-17. Croft R. J., Ellam L. D. and Harrison M. J. G. (1980) Accuracy of carotid angiography in the assessment ofatheroma of the internal carotid artery. Lancet 1, 997-999. Dean M., Crew J. and Knighton D. (1984) Identification of unusual carotid artery pathology by real-time imaging. Bruit 8, 279-286. DeWeese J. A., May A. G., Lipchik E. O. and Rob C. (1970) Anatomic and haemodynamic correlations in carotid artery stenosis. Stroke 1, 149-157. Edwards J. H., Kricheff I. I., Riles T. and Imparato A. (1979) Angiographically undetected ulceration of the carotid bifurcation as a cause of embolic stroke. Radiology 132, 369-373. Fell G., Phillips D. J., Chikos P. M., Harley J. D., Thiele B. L. and Strandness D. E., Jr. ( 1981) Ultrasonic duplex scanning for disease of the carotid artery. Circulation 64, 1191-1195. Fields W. S. (1979) Selection of patients with ischaemic cerebrovascular disease for arterial surgery. World J. Surg. 3, 147-154. Fields S. and Dunn F. (1973) Correlation ofechographic visualizability of tissue with biological composition and physiological state. J. Acoust. Soc. Am. 54, 809-812. Hartley C. J. and Strandness D. E., Jr. (1969) The effects of atherosclerosis on the transmission of ultrasound. J. Surg. Res. 9, 575581. Hennerici M., Reifschneider G., Trockel U. and Aulich A. (1984) Detection of early atherosclerotic lesions by duplex scanning of the carotid artery. J. Clin. Ultrasound 12, 455-464. Hennerici M. and Freund H-J. (1984) Efficacy of CW-Doppler and duplex system examinations for the evaluation of extracranial carotid disease. J. Clin. Ultrasound 12, 155-161. Herring M. B., Russ M., Benge C. and Gardner A. L. (1984) A comparison of Doppler flow measurements, ultrasonic and arteriographic imaging in the evaluation of stenoses of the carotid artery. Surg. Gyn. Obstet. 159, 67-69. James E. M., Earnest F., IV, Forbes G. S., Reese D. F., Houser O. W. and Folger W. N. (1982) High-resolution dynamic ultrasound imaging of the carotid bifurcation: a prospective evaluation. Radiology 144, 853-858. Langlois Y., Roederer G. O., Chan A., Phillips D. J., Beach K. W., Martin D., Chikos P. M. and Strandness D. E., Jr. (1983) Evaluating carotid artery disease. The concordance between pulsed Doppler/spectrum analysis and angiography. Ultrasound in Med. & Biol. 9, 51-63.
November/December 1985, Volume 1l, Number 6 Leopold G. R., Bemstein E. F., Humber P. R. and Wickbom I. (1982) Ultrasonic imaging for occlusive carotid disease. In Noninvasive Diagnostic Techniques in Vascular Disease, 2nd Edn (Edited by E. F. Bernstein), pp. 256-272. C. V. Mosby, London. McDicken W. N. (198 l) Ultrasound in tissue. In Diagnostic Ultrasonics, Principles and Use of Instruments, 2nd Edn, pp. 56-60. John Wiley, New York. Moore W. S. and Hall A. D. (1970) Importance of emboli from carotid bifurcation in pathogenesis of cerebral ischaemic attacks. Arch. Surg. 101,708-716. Ratliff D. A., Hames T. K., Humphries K. N., Birch S. and Chant A. D. B. (1985) The reliability of Doppler ultrasound techniques in the assessment of carotid disease. Angiology 36, 333-341. Ricotta J. J., Fiore W. M., Holen J., Gramiak R. A., Green R. M. and DeWeese J. A. (1983) Definition of extracranial carotid disease: comparison of oculopneumoplethysmography, continuous wave Doppler angiography and measurement at operation. In Progress in Stroke Research 2 (Edited by R. M. Greenhalgh and F. C. Rose), pp. 91-102. Pitman, London. Thiele B. L. and Strandness D. E., Jr. (1982) Distribution of intracranial and extracranial arterial lesions in patients with symptomatic cerebrovascular disease. In Noninvasive Diagnostic Techniques in Vascular Disease, 2nd Edn (Edited by E. F. Bernstein). C. V. Mosby, London, pp. 193-199. Thiele B. L., Young J. V., Chikos P. M., Hirsch J. H. and Strandness I~. E., Jr. (1980) Correlation of arteriographic findings and symptoms in cerebrovascular disease. Neurology 30, 1041-1046. Wolverson M. K., Bashiti H. M. and Peterson G. J. (1983a) Ultrasonic tissue characterization of atheromatous plaques using a high resolution real time scanner. Ultrasound in Med. & Biol. 9, 599609. Wolverson M. K., Heiberg E., Sundaram M., Tantanasirviongse S. and Shields J. B. (1983b) Carotid atherosclerosis: high-resolution real-time sonography correlated with angiography. A.J.R 140, 355-361. Zwiebel W. J., Austin C. W., Sackett J. F. and Strother C. M. (1983) Correlation of high-resolution, B-mode and continuous-wave Doppler sonography with arteriography in the diagnosis of carotid stenosis. Radiology 149, 523-532. Zwiebel W. J. (1982) High-resolution B-mode and duplex carotid sonography. In Introduction to Vascular Ultrasonography, pp. 103-149. Grune and Stratton, New York.
0301-5629/85 $3.00 + .00 © 1985 Pergamon Press Ltd.
Printed in the U.S.A.
OOriginal Contribution I
CHARACTERISATION COMPARISON
OF
OF
DUPLEX
CAROTID SCANNING
ARTERY WITH
DISEASE: HISTOLOGY
D. A. RATLIFF, P. J. GALLAGHER, T. K. HAMES, K. N. HUMPHRIES, J. H . H . WEBSTER a n d A. D. B. CHANT Vascular Surgical Unit, Departments of Medical Physics and Pathology, Southampton, United Kingdom (Received 7 January 1985; in final form 24 May 1985) Abstract--The ability of duplex scanning to characterise the component tissue of atheromatous lesions of the internal carotid artery and to detect ulceration has been examined in a histological study of 42 carotid endarterectomy specimens. The results suggest that the only component of atheromatous lesions of the internal carotid artery which can be characterised from the B-scan is calcification. The presence of ulceration, intraluminal and intramural thrombns, fibrous intimai thickening and necrosiS are not related to the echogenic appearance of internal carotid stenoses and may not be detected reliably. B-mode imaging alone cannot reliably grade >50% internal carotid stenoses, but when this is combined with pulsed Doppler in the technique of duplex scanning, accurate results may be obtained.
Key Words: Carotid artery disease, Doppler ultrasound, Histology.
INTRODUCTION
use in diagnosis and the study of the natural history of carotid artery disease. The aim of this study is to establish if there is a relationship between the B-scan appearance of an internal carotid stenosis and its pathological composition, and the degree of stenosis on the B-mode image in comparison with that demonstrated by angiography.
The most widely accepted hypothesis for the pathogenesis of transient ischaemic attacks within the carotid territory is due to embolism of atheromatous and/or thrombotic material from ulcerated disease at the carotid bifurcation (Bartynski et al., 1981; Fields, 1979; Thiele et al., 1980; Moore and Hall, 1970). Potentially embolic lesions occur in up to 79% of patients with transient hemispheric symptoms and 75% of patients with amaurosis fugax (Thiele and Strandness, 1982). It is recognised that conventional angiography may fail to show disease of the carotid bifurcation and may incorrectly identify the degree or type of internal carotid stenoses (Croft et al., 1980; Ricotta et al., 1983; DeWeese et al., 1970). For example, in a series of fifty patients having carotid endarterectomy, 40% of twenty ulcers found at operation had been missed on angiography; a subintimal haematoma from intramural haemorrhage was found at operation in 34% of patients in whom ulceration had been reported on angiography (Edwards et al., 1979). With the development of duplex scanning as an accurate technique in the noninvasive assessment of carotid artery disease, there is now considerable interest in its ability to characterise the component tissue of atheromatous lesions and to detect ulceration. The presence or absence of ulceration in a given atheromatous lesion may be of importance clinically in patient management. Such information would also be of
MATERIALS AND M E T H O D S Duplex scans were obtained preoperatively in 39 patients having 42 carotid endarterectomies for symptomatic internal carotid artery disease using the Honeywell Ultra Imager. The operation was carried out by one of two experienced vascular surgeons (Chant and Webster) who made every effort to remove the specimen complete. The carotid endarterectomy specimen was fixed in formalin and sections were taken at multiple levels transversely so that the point of maximum stenosis was always included. The sections, which were not decalcified, were cut with disposable microtome knives and stained with both haematoxylin and eosin and Gomori's trichrome stain. They were then examined by a consultant pathologist with a special interest in atherosclerosis (Gallagher) for the principle pathological components of atheroma: calcification, fibrous intimal thickening, intramural thrombus and necrosis. Each feature was graded on a scale from 0 to III, scores of 0 or I representing a low content and II or III a high content of 835
836
Ultrasound in Medicine and Biology
the component, respectively. The criteria used for the grading o f calcification were as follows: grade 0 indicated that this feature was completely absent, whereas grade I indicated that only a single focus less than 3 m m in m a x i m u m microscopic dimension was present. More extensive deposits were assigned to grades II or III. All specimens were also examined for epithelial ulceration and intraluminal thrombus. The videotape recordings of the Duplex scanning examination were reviewed independently by the first author without knowledge of the duplex scanning or angiographic grading of stenosis or details of the pathological analysis. A real-time B-scan with 16 levels of grey was obtained which was updated at a rate of 30 frames per second. Multiple views of each carotid bifurcation and internal carotid artery were satisfactorily obtained in all cases using a standard protocol which we have previously described (Ratliff et aL, 1985). Longitudinal B-scans were used for analysis because, in our experience, they provided the best quality images for assessment. B-scans were obtained in transverse section in a proportion of cases but were not used for analysis. The B-scan appearances of the internal carotid stenoses were graded on a scale from I to V. In the final analysis grade I, II, and III lesions were grouped together into 27 heterogeneous lesions of low echogenicity, and grade IV and V lesions into 15 homogeneous lesions of high echogenicity (see Figs. 1 and 2, respectively). The degree of stenosis on the real-time B-scan alone was estimated without use of the pulsed Doppler information and graded in the same way as angiography on a quartile basis. The figures reproduced in this paper were obtained from a captured freeze-frame on a videorecorder and their quality does not, therefore, represent that seen during a real-time examination.
Fig. 1. B-scan appearance of heterogeneous internal carotid stenosis of low echogenicity. The common carotid artery and bifurcation are shown on the left with the internal carotid artery on the right below the external carotid artery.
November/December1985, Volume 11, Number 6
Fig. 2. B-scan appearance of a homogeneous internal carotid stenosis of high echogenicity. The common carotid artery is shown on the left with the internal carotid artery on the right. Comparison was available for 39 biplanar angiograms. The degree of each internal carotid stenosis on angiography was graded independently by a consultant radiologist (S.B.) into one of the following six categoriee normal, 1-24%, 25-49%, 50-74%, and 75-99% diameter reduction, and occlusion. RESULTS Epithelial ulceration was present in 31 (74%) o f 42 cases and intraluminal thrombus was present in 25 (60%) cases. Twenty-four (77%) of 31 cases of epithelial ulceration had associated intraluminal thrombus. Neither parameter could be diagnosed reliably by B-mode imaging or duplex scanning. A high content of calcification was found in 11 of 15 stenoses of high echogenicity, and 21 of 27 cases of low echogenicity had a low calcification content. The echogenicity of the lesion on the B-scan was significantly related to its calcification content (x 2 with Yates's correction = 8.4, p > 0.005). Ten of 15 lesions of high echogenicity had a low content of intramural thrombus, but only 13 of 27 lesions of low echogenicity had a high proportion of intramural thrombus (X2 with Yates's correction = 0.37, N.S.). Similarly the degree of fibrous intimal thickening and necrosis were not significantly related to the B-mode characteristics of the lesion. From our experience with duplex scanning we felt that >50% internal carotid stenoses may have variable B-scan appearances, as illustrated in Figs. 3 and 4. Both are examples of >75% internal carotid stenosis. In Fig. 3 a mass of disease can clearly be seen at the origin of the internal carotid artery with posterior acoustic shadowing, but in Fig. 4 disease of only 1-24% severity is visualised on the B-scan and the diagnosis was made by obtaining a high frequency shift of the internal carotid signal >4 K H z using the pulsed Doppler.
Characterisationof carotidarterydisease• D. A. RATLIFFel al.
837
et al., 1982), not only between plaques but also between
Fig. 3. B-scan appearance of a >50% internal carotid stenosis with posterior acoustic shadowing. The common carotid artery is shown on the left with a mass of disease at the origin of the internal carotid artery which appears to have almost completely obliterated its lumen as its courses away down and to the right. It was therefore decided to compare the grading of percentage diameter stenosis by B-mode imaging alone and also by duplex scanning in comparison with biplanar angiography. The results are shown in Tables 1 and 2, respectively. There was very poor agreement between the percentage diameter stenosis by B-mode imaging and that by biplanar angiography (r = 0.18). When the degree of stenosis was graded from the Bscan alone, 13 of 19 cases of 75-99% stenosis were underestimated and 7 cases were graded as of <50% severity (see Table l). The sensitivity of B-mode imaging was 71% and specificity 72% in comparison with angiography in the detection of >50% internal carotid stenosis. In contrast there was good agreement between the results of duplex scanning and biplanar angiography (K -- 0.60). There were no false positive results and only one false negative result in which a case of 5074% stenosis by angiography was graded to be of 2549% severity by duplex scanning. Duplex scanning correctly identified 15 of 19 cases of 75-99% stenosis and the remaining four cases were graded 50-74% stenosis (see Table 2). The sensitivity of duplex scanning was 97% and specificity 100% in comparison with angiography in the detection of >50% internal carotid stenosis.
areas of the same lesion. There is a spectrum of echogenicity of internal carotid stenoses from the highly echogenic, homogeneous lesion accompanied by posterior acoustic shadowing to lesions of very low echogenicity which may be barely visible. Although plaques may be of uniform echogenicity there is more frequently variation within lesions which gives rise to heterogeneous appearances of intermediate echogenicity. Whilst this may be expected because of the differing pathological constituents of atheroma, it has not been clear how these relate to the varying B-scan appearances of internal carotid stenoses. These results suggest that lesions of high echogenicity, often with posterior acoustic shadowing, contain a high content of calcium but heterogeneous lesions of low echogenicity contain other components of atheromatous material in varying proportions. The degree of intramural thrombus, fibrous intimal thickening and necrosis were not significantly related to the B-scan appearance although they were shown to be present histologically. It is known from previous work on the aorta that calcium deposits within intimal plaque are responsible for marked attenuation to transmitted ultrasound (Hartley and Strandness, 1969). However, these are interesting findings because collagen and fibrous tissue are also associated with increased echogenicity in tissue (Fields and Dunn, 1973), and the dark areas in heterogeneous lesions might be interpreted as intraplaque haemorrhage by some observers. The problem of detecting ulceration by duplex scanning is shown in Fig. 5. Two lesions of high echogenicity are seen at the origin of the internal carotid artery with a gap between them. There are three possible interpretations of this situation: (i) that the gap
DISCUSSION Duplex scanning is an accurate technique in the direct noninvasive assessment of carotid artery disease by means of its B-mode imaging and pulsed Doppler facilities (Langiois et al., 1983; Fell et al., 1981). Considerable variation in the B-scan appearances of atheroma has been reported (Zwiebel, 1982; Cooperberg
Fig. 4. B-scan appearance of >50% internal carotid stenosis. The common carotid artery is shown on the left with barely any disease visible in the internal carotid artery on the right.
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Table 1. Accuracy of B-mode imaging in comparison with angiography(39 carotid endarterectomies) Diameter stenosis by biplanar angiography 1-24%
25-49%
50-74%
75-99%
Total
3
4
I
2
4
10
Diameter
1-24%
1
stenosis
25-49%
3
by B-mode
50-74%
2
8
6
16
imagin 9
75-99%
-
3
6
9
3
13
19
39
Total
4
kappa = 0.18
the reliability of ulcer detection by duplex scanning of the carotid bifurcation. Hennerici has found that ulcerative lesions may be confidently identified (Hennerici and Freund, 1984; Hennerici et al., 1984), whilst others have not found this to be the case (Zweibel et al., 1983; Calhoun and MacErlean, 1984; Herring et al., 1984; Cooperberg et aL, 1979). Wolverson et al. (1983a) reported that localised or abrupt interruption of the intimal surface with marked irregularity and excavations were reliable indicators of ulceration. This is a rare finding in our experience. In this study there was no relation between the B-mode appearance of an internal carotid stenosis and the demonstration that it was ulcerated pathologically. A change in the echogenicity of the surface of a lesion from an area of high to low echogenicity can in itself give rise to the impression of a loss of intimal continuity. An apparently large
represents an ulcer; (ii) that the two lesions are two separate plaques; or (iii) this is one contiguous plaque with two areas of high echogenicity separated by an area containing material of low echogenicity such as thrombus or necrosis. In theory it might be possible to correctly identify the third situation from the first two by the careful positioning of the pulsed Doppler sample in the area of low echogenicity, but this is not helpful in practice. Furthermore, the exact position of the pulsed Doppler sample in the third dimension on a two-dimensional image is not known. Paradoxically the only way of detecting thrombus is by use of pulsed Doppler since it has the same ultrasound characteristics as moving blood. This difficulty in diagnosis is compounded by the knowledge that ulceration was present in 74% of the cases in this study. There is controversy in the literature concerning
Table 2. Accuracy of duplex scanning in comparison with angiography (39 carotid endarterectomies) Diameter stenosis by biplanar angiography 1-24%
Diameter
25-49%
1-24%
3
I
1
2
50-74%
75-99%
Total
4
stenosis
25-49g
by Duplex
50-74%
9
4
13
scannin 9
75-99%
3
15
18
13
19
39
Tota]
4
3
kappa = 0 . 6 0
I
4
Characterisation of carotid artery disease• D. A. RATLIFFel al.
Fig. 5. B-scan appearance of an internal carotid stenosis. The common carotid artery is shown on the left with two lesions of high echogenicity at the origin of the intemal carotid artery with a gap between them. The internal carotid artery courses away to the right. ulcer between two highly echogenic lesions may be composed of material of low echogenicity in one contiguous lesion. It has recently been reported that some unusual types of carotid pathology including Takayashu's arteritis, carotid dissection and diverticula within a plaque may be readily diagnosed by real-time B-mode imaging (Dean et al., 1984). We agree with these authors that careful attention must be paid to the gain controls for maximum shades of grey in order to show pathology optimally and with their conclusion that accurate diagnosis is achieved by persistence and careful evaluation. However, we have had only isolated experiences of these rare conditions to date and are therefore unable to comment with confidence on their findings. The images in this study were obtained by a 5 MHz short-focus probe which gave high quality images with good grey-scale resolution and sensitivity suitable for detailed analysis. One possible limitation of this study is that a higher frequency imaging probe of 7.5 or 10 MHz was unavailable and not used. Whilst these may produce images of better resolution, the claim that there use results in improved accuracy is not yet proven. Because of some of the problems which have been discussed above, it is not at all certain whether ulceration is likely to be diagnosed more reliably by their use. In addition to the imaging frequency, however, another important facto~ which determines the sensitivity of a given probe in a particular system is its ability to detect changes in the "characteristic impedance" of the components of soft tissue. The characteristic impedance of a tissue refers to its ability to reflect sound waves and to generate an echo, and is directly propor-
839
tional to the density of the tissue (McDicken, 1981). For a structure to be detected, it must produce an echo of adequate magnitude which then must be visualised on the display with sufficient dynamic range of grey scale. The sensitivity of individual systems in this respect and the a m o u n t of variation between them are not known at the present time. Further work now needs to be done to assess and quantify this capability for individual probes in different systems and to determine their respective resolutions when a tissue phantom is used. This may help to explain differing results which have been reported in the literature. The results of comparison of B-mode imaging alone with angiography confirm the consensus of previous work that it may not be used reliably in the accurate diagnosis of internal carotid stenosis (Comerota et al., 1981; James et al., 1982), despite the findings of some authors that there is close agreement between sonographic and angiographic estimates of disease (Wolverson et al., 1983b). Historically there has been a direct progression from B-mode imaging of the carotid bifurcation to duplex scanning with greatly improved accuracy (Zweibel et al., 1983; Leopold et al., 1982), which we have been able to confirm by a direct comparison in this study. CONCLUSIONS The results of this histological study suggest that the only component of atheromatous lesions of the intemal carotid artery which can be characterised from the B-scan is calcification. The presence of ulceration, intraluminal and intramural thrombus, fibrous intimal thickening and necrosis are not related to the echogenic appearance of internal carotid stenoses and may not be detected reliably. B-mode imaging alone cannot reliably grade >50% internal carotid stenoses, but when this is combined with pulsed Doppler in the technique of duplex scanning, accurate results may be obtained. Acknowledgment--We are verygrateful to Dr. S. Birch, Consultant Radiologist, for reviewingand interpretingthe angiograms. REFERENCES
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