(Circulation. 2000;102:766.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Quantitative Ultrasonic Tissue Characterization Can Identify High-Risk Atherosclerotic Alteration in Human Carotid Arteries
From the Department of Geriatric Medicine (S.T., H.R., Y.Y., K.M., A.O., J.H., T.O.), Division of Legal Medicine (K.H.), Department of Internal Medicine and Therapeutics (T.M.), and Department of Surgery, Course of Interventional Medicine (N.H.), Osaka University Graduate School of Medicine, Suita, Japan; and Division of Cardiology (H.I., K.S.), Sakurabashi Watanabe Hospital, Osaka, Japan.
Correspondence to Jitsuo Higaki, MD, Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail higaki{at}geriat.med.osaka-u.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images.
Methods and Results—We performed B-mode measurement and IBS
signal analysis with acoustic densitometry with a 7.5-MHz
linear-array transducer in freshly excised human aortas (n=58) (normal,
atheromatous, and fibrous tissue) obtained at autopsy.
Atheromatous and fibrous tissue had a similar
intima-media thickness (IMT), but the IBS value in
atheromatous specimens was lower than that in fibrous
specimens. We further applied this method to human carotid
ultrasonography. The subjects were young (80 regions), middle aged with
1 or no coronary risk factors (low risk) (120 regions), middle
aged with 
2 coronary risk factors (high risk) (240 regions),
or elderly (80 regions) or were patients with myocardial infarction
(MI) with multivessel disease (90 regions). The IMT was similar in
middle-aged, elderly, and MI subjects. In contrast, the IBS value was
significantly higher in elderly subjects and lower in high-risk
middle-aged and MI subjects compared with that in low-risk middle-aged
subjects. The percent of regions diagnosed as
atheromatous (IBS less than mean minus 2-SD
value of IBS in young subjects) was 11% in low-risk middle-aged
subjects, 29% in high-risk middle-aged subjects, and 63% in the MI
group.
Conclusions—In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.
Key Words: atherosclerosis • ultrasonics • plaque • arteries • myocardial infarction
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Diagnostic ultrasonography is increasingly used as a noninvasive method to study atherosclerosis in the carotid and femoral arteries. The thickness of the carotid intima-media complex has been shown to be related to cardiovascular risk factors in cross-sectional studies1 and to the occurrence of coronary artery disease.2 3 The ulcerative formation of atherosclerotic lesions is thought to be related to the incidence of cerebrovascular disease.4 Thus, a conventional diagnostic ultrasound system that includes B-mode and color and pulsed Doppler imaging provides excellent clinical information about the vessel wall in terms of characterization of the dimension and flow pattern of the arteries. However, structural alterations of the vessel wall, such as fibrosis, calcification, or deposition of lipids, cannot be accurately identified with these methods. The development of occlusive or mural thrombi, which are associated with fissured atherosclerotic plaques, is the most common cause of acute cerebral and myocardial infarction, and plaque rupture is dependent on the content of lipid in the atheroma and the thickness of the fibrous cap.5 6
One approach to quantitative evaluation of the composition of plaque is to define its acoustic propagation properties through the estimation of native radiofrequency signals from the tissue. The measurement of integrated backscatter (IBS) is based on an analysis of unprocessed radiofrequency signals to derive quantitative ultrasonic indexes with which to differentiate normal from pathological myocardial structures.7 8 Quantitative ultrasonic tissue characterization of the biophysical composition of plaque and the vessel wall has been performed with high-frequency, high-resolution acoustic microscopy in vitro9 10 11 12 and with a single focused transducer.13 14 However, these tools are available only in an experimental setting and cannot be used to clinically detect vascular signals in humans.
Acoustic densitometry is a clinically applicable ultrasonic backscatter imaging technology that provides an integrated on-line capability to measure, display, and analyze the average acoustic image intensity within a region of interest (ROI). In the present study, we examined the use of this technology in the clinical setting by comparing its results with pathological findings. First, we compared ultrasonic tissue characterization data of excised specimens of human aorta with histological findings. Then, we carried out ultrasonic tissue characterization of the human carotid arterial wall in the clinical setting to compare IBS among different age groups and to investigate the effect of coronary risk factors and the existence of coronary artery disease on IBS.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Experimental Specimens
Fifty-eight fresh samples of arterial wall were obtained from human aortas at autopsy. The average time from autopsy to ultrasonic examination was
6 hours. Sections of thoracic and
abdominal aorta were opened longitudinally, and full-thickness samples
(1x3 cm) were excised. The samples were mounted flat with the
endothelial side up between 2 echo pads (Aquaflex;
Parker Laboratories, Inc) that adhered to each other, placed on a steel
plate, and positioned at the focus of the transducer. The thickness of
the echo pad was 1.5 cm. The institutional ethics committee approved
the study protocol, and informed consent was obtained from the
relatives of each patient.
Subjects for Carotid Ultrasonography
The study group consisted of 61 subjects. Eight of these
subjects were young healthy volunteers (mean±SD age 28±1 years old, 6
men and 2 women), 36 were middle-aged patients (46±2 years old, 26 men
and 10 women), 8 were elderly patients without a history of
cardiovascular disease or stroke (79±2 years old, 4
men and 4 women), and 9 were patients with angiographically documented
multivessel disease who had had a myocardial infarction (MI) within the
past 3 months (MI group, 63±3 years old, 6 men and 3 women). We
evaluated the incidence of the following coronary risk factors
in each subject: high blood pressure (3 measurements of systemic
blood pressure during 3 months >160/95 mm Hg or taking
antihypertensive medication), diabetes mellitus (fasting blood glucose
of >110 mg/dL or hemoglobin A1C of >6.5%),
dyslipidemia (total cholesterol of >220
mg/dL), and current smoking (1 pack/d). The middle-aged subjects were
divided into 2 groups according to the number of risk factors. Twelve
low-risk middle-aged subjects (48±2 years old, 9 men and 3 women) were
identified as having 1 or no coronary risk factors. Twenty-four
high-risk middle-aged subjects (43±1 years old, 17 men and 7 women)
were identified as having 2 risk factors. All elderly patients had
<2 coronary risk factors. Patients with MI had >2 risk
factors. The average duration between the examination and the onset of
MI was 1.5±0.2 months. Patient characteristics for each group are
shown in Table 1
. An excellent
image of the bilateral common carotid arteries was obtained in all
patients, and all showed no obvious atherosclerotic plaques or
calcified lesion. The hospital ethics committee approved the study
protocol, and informed consent was obtained from each patient.
|
Fundamentals of Acoustic Densitometry
We used a special software package, acoustic
densitometry, that is available as an option with the Hewlett-Packard
SONOS 5500 equipped with a 7.5-MHz linear-array transducer (axial
resolution 0.1 mm). This system is capable of providing either
conventional 2-dimensional envelope-detected
echocardiographic images or IBS images in which the
gray level is displayed proportional to the integrated backscattered
power. A maximum of 60 frames displayed at a real-time frame rate of
30 Hz (30 frames/s) are captured into cine-loop memory and
subsequently stored on optical disk in a digital format with the same
resolution as the scan converter memory (512x512, 8 bits). The return
echoes that impinge on the individual elements of the phased-array
transducer are amplified, mixed to the intermediate frequency, and
summed with appropriate time delays to obtain a focused beam. This
intermediate frequency signal, which is uniquely related to the
radiofrequency signal, is sent to either a standard ultrasound video
processing chain or a special IBS processor before scan conversion.
With the use if specialized hardware, the IBS processor computes the
IBS power along each scan line before scan conversion and real-time
display on the ultrasound monitor. The resulting image is relatively
free of random acoustic speckle (noise) because of the local averaging
or integration of the backscatter signal power along each scan line.
The IBS image is internally calibrated in dB and has a dynamic range of
64 dB in the SONOS 5500 system. This system has a unique feature in
which the transmit power, log compression, and time-gain compensation
values are displayed on a screen (and can be stored with the images),
which allows an operator to adjust the system to the same values at
every examination.15
Acquisition and Analysis of IBS Data in the
Experimental Setting
For each specimen, conventional B-mode images of optimal image
quality were first obtained with the 7.5-MHz linear-array probe, and
then 60 two-dimensional IBS images were acquired into cine-loop memory
and stored on optical disk. The image preprocessing, transmit power,
focus, and time-gain compensation settings were adjusted to yield
optimal images from the specimens, and the system controls were
unchanged for measurements of all specimens. For an analysis of
the image data, the backscatter images were first retrieved from disk
into the system memory. In this study, we used 11x11 or 21x21 pixel
rectangular-shaped ROIs and placed them in the intima-media complex of
the vessels. The average power of the IBS signal contained within the
ROI was measured and displayed in dB for a total of 60 time frames. The
system automatically calculated the average value of the IBS signal,
which was also displayed in dB.16 In advanced plaque
specimens, IBS data were sampled from the ROI, with care taken to
exclude calcified regions, which were more readily identified with
conventional B-mode ultrasound. The relative IBS values of the
adventitia of pathologically different samples were almost the same
when those values were calibrated with the IBS value of a fixed
reference object beside each sample. Therefore, we adopted the
adventitia as the reference object. We then expressed the relative IBS
value of the intima-media complex as the difference from the IBS value
obtained from a reference ROI placed within the adventitia (calibrated
IBS value [dB]).
Acquisition and Analysis of IBS Data in Clinical
Setting
We obtained data of intima-medial thickness (IMT) in 5
consecutive regions every 5 mm from the bifurcation of the common
carotid artery with use of the 7.5-MHz linear-array probe. A total of
10 regions from the bilateral carotid arteries were examined in each
person. IBS data were also sampled in the same regions in which IMT was
measured. We also used 11x11 or 21x21 pixel rectangular-shaped ROIs
and placed them in the intima-media complex of the vessels. Data
analysis was performed with Acoustic Densitometry in the
same manner. In the present study, the same relative TGC profile
was used for all subjects. We also expressed the relative IBS value of
the intima-media complex as the difference from the IBS value obtained
from a reference ROI placed within the adventitia (calibrated IBS value
[dB]). Absolute IBS values of the adventitia were between 52 and 55
dB, which were within the dynamic range of the SONOS 5500 system.
Reproducibility of Data
We determined the intraobserver and interobserver variabilities
of IBS value of the tissue in 10 randomly selected recordings
twice by the same observer and once each by 2 independent observers.
Intraobserver and interobserver variabilities of IBS value were
2.3±0.3% and 2.5±0.2% in the experimental study and 2.3±0.1% and
2.0±0.2% in the clinical study, respectively.
Histological Analysis
Representative tissue specimens were fixed in
formalin and sectioned through the midpoints of lesions where
radiofrequency data were recorded. The tissue was embedded in
paraffin, and 5-µm sections of each sample were studied
histologically with hematoxylin and eosin, and
Masson’s trichrome stains. The structural composition of the aortic
wall at each site of ultrasonic interrogation was determined through
sequential examination of the subserial sections of each specimen. Two
experienced pathologists who were blinded to the echographic results
evaluated each tissue sample of arterial wall and
characterized them histologically into 1 of 3
categories: (1) normal tissue specimen, (2) fibrous tissue
specimen (wall thickened by connective tissue), and (3)
atheromatous tissue specimen (characterized by
accumulation of lipid in the intima or by a fibrous cap and a lipid
core). Moreover, we measured the IMT with the photographs of each
specimen. Specimens with significant necrosis and hemorrhage
were not considered. Thickness was measured at 5 points in the center
of each specimen to obtain the average value. With a thin steel wire as
a spatial marker, the transducer was oriented toward the center of the
specimen. Thus, only the central part of the specimen was
histologically characterized.
Statistical Analysis
Data were expressed as mean±SEM. For all statistical
analyses, we used a computer software application, StatView
(Abacus Concepts Inc). Values expressed as percent incidence were
compared by 
2 test when the minimum expected
value was >5. Values expressed as mean±SEM were compared by 1-way
ANOVA, followed by Fisher’s protected least significant difference
test. Values of P<0.05 were considered statistically
significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Experimental Study
IBS Analysis of Excised Aortas and Comparison With Histological Findings
Histological examination showed that 58 samples consisted of 16 normal regions, 18 atheromatous lesions, and 24 fibrous lesions. The mean values of IBS and IMT for the 3 histological categories are shown in Table 2
. The mean IMT was significantly thinner
in normal regions than in atheromatous and fibrous
lesions (P<0.01). The mean IMT of the fibrous and
atheromatous lesions was the same. The mean value of
calibrated IBS in normal regions was significantly lower than that in
fibrous lesions (P<0.01). The mean value of calibrated IBS
in atheromatous lesions was significantly lower than
that in fibrous lesions (P<0.001) and normal regions
(P<0.01) (Table 2). IBS in
atheromatous lesions differed from that in fibrous
lesions, although IMT values were identical. Figure 1 shows the data for calibrated IBS
values and IMT in each specimen in the 3 histological
groups. We classified most specimens as 1 of the 3 categories of tissue
according to ultrasonic tissue characterization in conjunction with
thickness measurement.
|
|
, Normal segment. x,
Atheromatous segment. 
, Fibrous segment.
In Vivo Study
Carotid IMT and IBS Data In Vivo
Mean IMT and calibrated IBS values are depicted in Figure 2. IMT gradually thickened with age, and
IMT in the MI group was significantly thicker than that in young and
middle-aged subjects. In the middle-aged group, IMT in patients with
fewer risk factors was similar to that in patients with more risk
factors. Of interest, the calibrated IBS values in the high-risk
middle-aged group and MI groups were significantly lower than those in
the young and low-risk middle-aged groups. In contrast, the calibrated
IBS value in elderly patients was significantly higher than that in any
other group.
|
To investigate the distribution of calibrated IBS values in each group,
we defined the normal range of calibrated IBS according to the IBS
value in young healthy subjects. The values for mean-2 SDs and mean+2
SDs of IBS in young healthy subjects were -14.3 and -9.0 dB,
respectively. As presented earlier with the
histological comparison, it is likely that relatively
fatty tissue shows a lower IBS value than -14.3 dB and that fibrous
tissue shows a higher IBS value than -9.0 dB. Figure 3 shows the distribution of calibrated
IBS values in each group. Lesions with a higher IBS value were more
frequent and lesions with a lower IBS value were less frequent in
elderly patients than in middle-aged patients. In the high-risk
middle-aged patients and MI patients, there were more lower-IBS lesions
than in the low-risk middle-aged patients. MI patients showed more
frequent lower-IBS lesions than did high-risk middle-aged patients.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The results of the present study confirm that IBS analysis is indeed an effective ultrasonic technique with which to distinguish atheromatous (fibrofatty) tissue from fibrous tissue in experimental settings and further demonstrated that acoustic densitometry with a 7.5-MHz linear-array transducer can quantitatively identify high-risk patients with unstable atherosclerosis in a clinical setting.
According to the ultrasonic diagnosis of vascular composition, conventional B-mode analysis was applied first. Grønholdt et al17 demonstrated that triglyceride-rich lipoprotein level in the fasting and postprandial state can be used to predict carotid plaque echolucency and that echolucency was associated with a high lipid content of plaque. Beletsky et al18 performed densitometric analysis of the B-mode images of carotid plaques in patients who underwent endarterectomy. Digital densitometric evaluation in both studies allowed differentiation of the various possible components of carotid plaques, but densitometric analysis was subject to inherent nonlinear transformations in the ultrasound imaging chain that resulted from log compression and postprocessing functions.
There also are several reports on the usefulness of IBS in the
determination of tissue composition of atherosclerotic plaques through
the use of experimental methods.9 10 Wickline et
al10 reported that the IBS of intimal fatty plaques was
10-fold less than that of intimal fibrous plaques, according to
ultrasonic microscopy. Picano et al14 and Barzilai et
al13 examined human aortas with complex plaques that had a
lower frequency and lower resolution ultrasonic systems (10 MHz) and
measured IBS within a 2-µs window (1.5-mm tissue thickness). They
reported that arterial segments with extensive
calcification demonstrated greater backscatter than predominantly
fibrofatty, fibrous, or normal aortas. Although the sensitivity of the
system used in the present study was lower due to lower axial
resolution, we could distinguish these 3 types of aortic tissue from
each other with acoustic densitometry in conjunction with IMT
assessment through conventional B-mode imaging. Acoustic densitometry
appeared to provide reliable information about plaque composition in
the clinical setting.
Of more interest, the present technique in the clinical setting revealed that risk factors for coronary heart disease were related to the incidence of atheromatous plaque in the carotid arteries. This is quite important because previous reports have shown that weak reflection of ultrasound from a carotid atherosclerotic plaque is associated with a high lipid content, as well as with an increased risk of cerebral infarction.19 20 Several studies have suggested that plaque rupture is related to the lipid content of plaques. Ultrasonic parameters of the carotid artery (IMT, presence of plaque) are considered to be sensitive markers of the earliest stage of systemic atherosclerosis.1 2 3 21 22 23 In the present study, thick IMT lesions were observed in middle-aged and elderly patients, but a wide distribution of IBS data (especially lower values) was seen only in the high-risk middle-aged group. In addition, the same trend was clearly observed in patients with multivessel disease who had recently had an MI. These findings indicate that it is possible to identify a high-risk group with systemic atherosclerosis, which is a high risk factor for coronary heart attack and stroke, through the use of IBS analysis in conjunction with conventional IMT measurement.
The extrapolation of these findings to in vivo conditions is fraught with several technical problems, including the necessity for perfect alignment of the ultrasound beam, the necessity to account for tissue anisotropy, variable attenuation introduced by anatomic structures between the skin surface (transducer) and the arterial wall, and insufficient dynamic range (signal sensitivity). The present system does not have a sufficient dynamic range to measure the absolute value of IBS (ie, backscatter of plaque/tissue with reference to the backscatter from an adjacent blood pool or vascular cavity). In the present study, we adopted the adventitia of the carotid artery as a reference object to calculate calibrated IBS value. There has not been an established standard reference tissue for quantitative ultrasonic tissue characterization with IBS analysis in vivo. Some investigators used the IBS signal from the vessel lumen or left ventricular cavity as a reference object. However, the relative IBS values of the adventitia of pathologically different samples in our ex vivo study were almost same when those values were calibrated with the IBS value of a fixed reference object beside each sample (data not shown). Therefore, adventitia could be one appropriate candidate for a reference object in this study. We could not recognize a difference between IBS of the intima and media due to insufficient axial resolution of the present system. Our data reflect the sum of backscatter signal from the intima-media complex. Improvement in the axial resolution will increase the sensitivity to distinguish atheromatous plaque and fibrous plaque.
At the present time, we can estimate the IBS value of the intima-media complex for a follow-up examination of antiatherosclerotic therapy, and if the acoustic densitometry analysis package were transferred to an intravascular ultrasound system with >1 order of magnitude improvement in resolution, we could potentially evaluate the stability of the plaque and obtain important information to determine the treatment strategy. This relatively simple, repeatable, and quantitative data analysis will enable us to evaluate the biological and pathophysiological status of an atherosclerotic lesion in the long-term follow-up of vascular structure as a "noninvasive ultrasonic biopsy."
|
Acknowledgments |
|---|
We are indebted to Alwyn D’sa (Hewlett-Packard) and Kenji Kikuda (Kikuda Ltd) for helpful discussion.
Received February 2, 2000; revision received March 9, 2000; accepted March 13, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Heiss G, Sharrett AR, Barnes R, et al. Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol. 1991;134:250–256.
2.
O’Leary DH, Polak JF, Kronmal RA, et al. Distribution
and correlates of sonographically detected carotid artery disease in
the Cardiovascular Health Study: the CHS Collaborative
Research Group. Stroke. 1992;23:1752–1760.
3.
Salonen JT, Salonen R. Ultrasonographically assessed
carotid morphology and the risk of coronary heart disease.
Arterioscler Thromb. 1991;11:1245–1249.
4.
Handa N, Matsumoto M, Maeda H, et al. Ultrasonic
evaluation of early carotid atherosclerosis.
Stroke. 1990;21:1567–1572.
5.
Lee RT, Grodzinsky AJ, Frank EH, et al.
Structure-dependent dynamic mechanical behavior of fibrous caps from
human atherosclerotic plaques. Circulation. 1991;83:1764–1770.
6. Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56–62.[Abstract]
7. Miller JG, Perez JE, Sobel BE. Ultrasonic characterization of myocardium. Prog Cardiovasc Dis. 1985;28:85–110.[Medline] [Order article via Infotrieve]
8. Perez JE, Barzilai B, Madaras EI, et al. Applicability of ultrasonic tissue characterization for longitudinal assessment and differentiation of calcification and fibrosis in cardiomyopathy. J Am Coll Cardiol. 1984;4:88–95.[Abstract]
9. Shepard RK, Miller JG, Wickline SA. Quantification of atherosclerotic plaque composition in cholesterol-fed rabbits with 50-MHz acoustic microscopy. Arterioscler Thromb. 1992;12:1227–1234.[Abstract]
10.
Wickline SA, Shepard RK, Daugherty A. Quantitative
ultrasonic characterization of lesion composition and remodeling in
atherosclerotic rabbit aorta. Arterioscler Thromb. 1993;13:1543–1550.
11.
Recchia D, Sharkey AM, Bosner MS, et al. Sensitive
detection of abnormal aortic architecture in Marfan syndrome with
high-frequency ultrasonic tissue characterization.
Circulation. 1995;91:1036–1043.
12. de Kroon MG, van der Wal LF, Gussenhoven WJ, et al. Backscatter directivity and integrated backscatter power of arterial tissue. Int J Card Imaging. 1991;6:265–275.[Medline] [Order article via Infotrieve]
13.
Barzilai B, Saffitz JE, Miller JG, et al. Quantitative
ultrasonic characterization of the nature of atherosclerotic plaques in
human aorta. Circ Res. 1987;60:459–463.
14.
Picano E, Landini L, Distante A, et al. Angle
dependence of ultrasonic backscatter in arterial tissues: a
study in vitro. Circulation. 1985;72:572–576.
15. Recchia D, Wickline SA. Ultrasonic tissue characterization of blood during stasis and thrombosis with a real-time linear-array backscatter imaging system. Coron Artery Dis. 1993;4:987–994.[Medline] [Order article via Infotrieve]
16.
Takiuchi S, Ito H, Iwakura K, et al. Ultrasonic tissue
characterization predicts myocardial viability in early stage of
reperfused acute myocardial infarction. Circulation. 1998;97:356–362.
17.
Gronholdt ML, Nordestgaard BG, Wiebe BM, et al.
Echo-lucency of computerized ultrasound images of carotid
atherosclerotic plaques are associated with increased levels of
triglyceride-rich lipoproteins as well as increased plaque
lipid content. Circulation. 1998;97:34–40.
18.
Beletsky VY, Kelley RE, Fowler M, et al. Ultrasound
densitometric analysis of carotid plaque composition:
pathoanatomic correlation. Stroke. 1996;27:2173–2177.
19. El-Barghouty NM, Levine T, Ladva S, et al. Histological verification of computerised carotid plaque characterisation. Eur J Vasc Endovasc Surg. 1996;11:414–416.[Medline] [Order article via Infotrieve]
20. European Carotid Plaque Study Group. Carotid artery plaque composition: relationship to clinical presentation and ultrasound B-mode imaging: European Carotid Plaque Study Group. Eur J Vasc Endovasc Surg. 1995;10:23–30.[Medline] [Order article via Infotrieve]
21. Blankenhorn DH, Rooney JA, Curry PJ. Noninvasive assessment of atherosclerosis. Prog Cardiovasc Dis. 1984;26:295–307.[Medline] [Order article via Infotrieve]
22.
Ebrahim S, Papacosta O, Whincup P, et al. Carotid
plaque, intima media thickness, cardiovascular risk
factors, and prevalent cardiovascular disease in men
and women: the British Regional Heart Study. Stroke. 1999;30:841–850.
23.
Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid
intima-media thickness and risk of stroke and myocardial infarction:
the Rotterdam Study. Circulation. 1997;96:1432–1437.
This article has been cited by other articles:
 |
|
 |
|
  F. Piscione, G. Iaccarino, G. Galasso, E. Cipolletta, M. A. Rao, G. Brevetti, R. Piccolo, B. Trimarco, and M. Chiariello Effects of Ile164 Polymorphism of Beta2-Adrenergic Receptor Gene on Coronary Artery Disease J. Am. Coll. Cardiol., October 21, 2008; 52(17): 1381 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kozakova, C. Palombo, M. Paterni, C.-H. Anderwald, T. Konrad, M.-P. Colgan, A. Flyvbjerg, J. Dekker, and on behalf of the Relationship between Insulin Sens Body Composition and Common Carotid Artery Remodeling in a Healthy Population J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3325 - 3332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bernini, F. Galetta, F. Franzoni, M. Bardini, C. Taurino, A. Moretti, M. Bernini, P. Berti, P. Miccoli, and A. Salvetti Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling Eur. J. Endocrinol., August 1, 2008; 159(2): 137 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mahmud, J. J. Cavendish, and A. Salami Current Treatment of Peripheral Arterial Disease: Role of Percutaneous Interventional Therapies J. Am. Coll. Cardiol., August 7, 2007; 50(6): 473 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Roman, T. Z Naqvi, J. M Gardin, M. Gerhard-Herman, M. Jaff, and E. Mohler American Society of Echocardiography Report: Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology Vascular Medicine, August 1, 2006; 11(3): 201 - 211. [PDF]
|
|
|
|
|
|
G. Bernini, F. Franzoni, F. Galetta, A. Moretti, C. Taurino, M. Bardini, G. Santoro, L. Ghiadoni, M. Bernini, and A. Salvetti Carotid Vascular Remodeling in Patients with Pheochromocytoma J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1754 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Watanabe, S. Sugiyama, K. Kugiyama, O. Honda, H. Fukushima, H. Koga, Y. Horibata, T. Hirai, T. Sakamoto, M. Yoshimura, et al. Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease J. Am. Coll. Cardiol., December 6, 2005; 46(11): 2022 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawasaki, K. Sano, M. Okubo, H. Yokoyama, Y. Ito, I. Murata, K. Tsuchiya, S. Minatoguchi, X. Zhou, H. Fujita, et al. Volumetric Quantitative Analysis of Tissue Characteristics of Coronary Plaques After Statin Therapy Using Three-Dimensional Integrated Backscatter Intravascular Ultrasound J. Am. Coll. Cardiol., June 21, 2005; 45(12): 1946 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Honda, S. Sugiyama, K. Kugiyama, H. Fukushima, S. Nakamura, S. Koide, S. Kojima, N. Hirai, H. Kawano, H. Soejima, et al. Echolucent carotid plaques predict future coronary events in patients with coronary artery disease J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1177 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Wickline Plaque characterization: surrogate markers or the real thing? J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1185 - 1187. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yamagami, K. Kitagawa, Y. Nagai, H. Hougaku, M. Sakaguchi, K. Kuwabara, K. Kondo, T. Masuyama, M. Matsumoto, and M. Hori Higher Levels of Interleukin-6 Are Associated With Lower Echogenicity of Carotid Artery Plaques Stroke, March 1, 2004; 35(3): 677 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Giannattasio, M. Failla, G. Emanuelli, A. Grappiolo, L. Boffi, D. Corsi, and G. Mancia Local Effects of Atherosclerotic Plaque on Arterial Distensibility Hypertension, November 1, 2001; 38(5): 1177 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Mathiesen, K. H. Bonaa, and O. Joakimsen Low Levels of High-Density Lipoprotein Cholesterol Are Associated With Echolucent Carotid Artery Plaques: The Tromso Study Stroke, September 1, 2001; 32(9): 1960 - 1965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawasaki, H. Takatsu, T. Noda, Y. Ito, A. Kunishima, M. Arai, K. Nishigaki, G. Takemura, N. Morita, S. Minatoguchi, et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: Comparison between histology and integrated backscatter images J. Am. Coll. Cardiol., August 1, 2001; 38(2): 486 - 492. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||