Published online before print June 16, 2003, doi: 10.1161/01.CIR.0000078633.31922.8A
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:3018.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Elasticity Imaging of Atheroma With Transcutaneous Ultrasound
Preliminary Study
From the Graduate School of Engineering, Tohoku University (H.K., H.H.); Sendai Hospital of East Railway Company (M.I.); National Sendai Hospital (F.T.); and Tohoku University Graduate School of Medicine (Y.K.), Sendai, Japan.
Correspondence to Hiroshi Kanai, PhD, Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan. E-mail hkanai{at}ecei.tohoku.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Background— Knowledge of the physical properties of atherosclerotic plaque is essential when evaluating its vulnerability in a clinical setting. Such knowledge, however, is still difficult to obtain with the various approaches developed to date.
Methods and Results— This article describes a noninvasive method for evaluating the regional elasticity (the elastic modulus in the circumferential direction) of tissue surrounding atherosclerotic plaque in which a novel phased tracking method is applied to measure minute changes in thickness of each of the multiple layers of the arterial wall during one heartbeat. By comparing the pathological findings with the distribution of elasticity, average elasticity of lipid and that of a mixture of smooth muscle and collagen fiber can be determined. On the basis of these reference parameters, each point is statistically categorized as lipid, mixture, or other. Thus, the plaque is electronically stained using transcutaneous ultrasound. By applying the method to the common carotid arteries, the presence of thin collagen fiber was clarified along the arterial axis for normal subjects, whereas soft inclusion of lipid was found for every plaque in subjects with hyperlipidemia.
Conclusion— This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.
Key Words: atherosclerosis • elasticity • plaque • ultrasonics
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Rupture of atherosclerotic plaque is probably the most important factor underlying the sudden onset of the acute coronary syndrome.1 Direct characterization of the composition and vulnerability of atherosclerotic plaque, rather than of the angiographic lumen,2 may offer insight into the mechanisms of plaque regression and progression3,4 and thereby promote evaluation of cholesterol-lowering therapy5,6 for reduction of cardiovascular events. MRI and intravascular ultrasound are promising technologies for directly imaging plaque morphology.7,8 For the evaluation of dynamic mechanics, arterial elasticity has been determined by measuring the pulse wave velocity9 and rough change in the diameter of the artery.10,11 However, a method to detect the vulnerability of atherosclerotic plaque with sufficient accuracy has not yet been reported. The purpose of the present study was to determine the cross-sectional distribution of elasticity in the arterial wall using commercially available transcutaneous ultrasound equipment.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Measurement of Change in Thickness of the Arterial Wall
An ultrasonic beam was sequentially scanned at M (=60) positions with a linear-type ultrasonic probe of 7 MHz using conventional ultrasound diagnostic equipment (Toshiba SSH-140A), and multiple (Nm+1) points were preset from the luminal surface to the adventitia along the mth ultrasonic beam (m=1,..., M) with constant intervals of h0=375 µm at a time t0 just before the ejection period. By dividing the arterial wall into multiple layers, we defined the nth layer (n=1,..., Nm) as being between two contiguous points, n and n+1, along each beam. For measurement of change in thickness of each of the Nm layers, the instantaneous depth xmn(t) of the nth point along the mth beam was simultaneously tracked by applying the phased tracking method12,13 to the received ultrasound. The minute decrease of several tenths of a micrometer in wall thickness of the nth layer resulting from the arrival of the pressure wave at the beginning of the ejection period was determined by
hmn(t)=xmn+1(t)-xmn(t)-h0.
In the phased tracking method, for calculation of the auto-correlation function between the quadrature-demodulated signals of sequentially received echoes, minute phase change of 
0.4 degrees caused by movement of the nth point during the pulse transmission interval T (=200 µs) can be accurately determined by introducing a constraint, namely, that their waveforms are identical but their phase values change.12,13 The lowest value of the change in thickness was validated as being 0.5 µm by expanding a rubber plate in a water tank.14 Such a minute change in thickness cannot be measured by any other method. This method has already been applied to the in vivo detection of regional instantaneous displacement and change in thickness, with sufficient reproducibility, in the interventricular septum12,13,15 and in the common carotid artery (CCA).16
Elasticity Estimation
From the ratio of the maximum decrease in thickness during one heartbeat, hmn,max=maxt|hmn(t)|, to the initial thickness h0 of the nth layer, the maximum deformation of the nth layer was obtained by 
mn,max=hmn,max/h0. Because the deformation was sufficiently small and was in the linear regime, it showed incremental strain in the radial direction. By assuming that the arterial wall is incompressible and that the blood pressure is applied perpendicularly to each layer, the elastic modulus of the nth layer along the mth beam, E
mn, is approximately given by17
|
|
where 
mn,0 is the initial inner radius of curvature of the nth layer along the mth beam at a time t0. We assumed that the pressure in the arterial wall decreases linearly with the distance from the intimal side to the adventitia and that the arterial wall is almost isotropic.18
For the region with a length of 18 mm along the axis of the artery, the regional elasticity Emn was estimated on the cross-sectional image. Because the reflected ultrasound was received at a sampling interval of 100 ns (=75 µm along depth direction) after the quadrature demodulation, we further divided each layer with a thickness of h0 into 5 points, shifted the initial depth of each layer by one fifth of h0, and applied the above procedure to each depth. Thus, Emn was estimated at intervals of 75 µm in the depth direction and 300 µm in the axial direction. Using a silicone tube with two layers set in an artificial circulation system,17 the accuracy of the measurement of regional elasticity for each layer has already been validated to be 0.1 MPa17—that is, the error is 8% of the elasticity value obtained by a separate static pressure-diameter test.
In in vivo experiments before the extraction of an iliac artery and in in vitro experiments (described below) after such extraction, the average elasticity was 0.96±0.48 MPa and 0.89±0.31 MPa, respectively, the difference between them being 8%. Thus, the slight influence of assaying the artery through the skin was eliminated.
In separate in vivo experiments, when the pressure of the ultrasonic probe on the skin surface of a healthy subject was set as 8.0, 14.0, 33.2, 40.7, 54.5, and 74.3 mm Hg, the measured diameter of the same point of the CCA changed as 6.8, 6.8, 6.6, 6.1, 6.0, and 5.4 mm, respectively. For higher pressure, the cross section of the artery changes from a circular to an oval shape. We confirmed that the measured elasticity is not influenced by the pressure on the ultrasonic probe to the skin surface as long as the pressure is ≤30 mm Hg. In our in vivo experiments, the ultrasonic probe was held on the skin surface with a pressure of 30 mm Hg.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Electronic Staining
Immediately after 9 iliac arteries (25 to 40 mm in length and 4 to 24 mm in outer diameter) with plaques were extracted from patients with embolism, cross-sectional elasticity distribution, E
,mn, was measured using the above method [Figure 1(1)] under the same artificial circulation system to generate a change in pressure so that it ranged from the diastolic pressure to the systolic pressure of the subjects. After each in vitro measurement, elastica-Masson stain was applied. Two typical results are shown in Figure 1(2). From the stain images, 10 regions with either lipid or a mixture of smooth muscle and collagen fiber were assigned in E,mn of the 9 specimens. Each histogram of E,m,n in the respective regions is shown in Figure 1(3). For the respective categories of the 9 arteries, the average and the standard deviation in elasticity were determined to be 81±40 kPa and 1.0±0.63 MPa, which were registered as the reference parameters [Figure 1(4)].
|
On the basis of these reference parameters, each point in the cross-sectional elasticity distribution, which had been noninvasively measured by the above method in separate in vivo experiments, was statistically classified as one of 3 categories (lipid, mixture of smooth muscle and collagen fiber, or other). Thus, the arterial wall and the atherosclerotic plaque were electronically stained.
For CCAs
The proposed method was applied to in vivo measurements of the CCAs of 2 healthy subjects [Figure 2, (a) and (b)] and 2 patients with hyperlipidemia having atherosclerotic plaques [Figure 2, (c) and (d)]. In Figure 2, for each subject, a cross-sectional image obtained by conventional ultrasound diagnostic equipment is shown at the top. The cross-sectional elasticity distribution of E,mn was color-coded and superimposed on the reconstructed B-mode image as shown in the middle. Finally, at the bottom, the categorized result is shown. The lipid and the mixture of smooth muscle and collagen fiber are shown by yellow and cyan, respectively, and the category of "other" is not colored.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
For the CCAs of normal subjects, the existence of thin fibrous tissue along the arterial axis was clarified. For the plaque in the subjects, soft inclusions of lipid surrounded by fibrous tissue were found. With extrapolation of the results of an in vitro study,19 we postulated that a thin layer constitutes a fibrous cap surrounding the plaque. Iliac arteries were used to determine the reference parameters, which were then applied to CCAs in the in vivo experiments. Although the composition of the iliac artery and that of the CCA differ, the characteristics of the collagen fiber itself and the lipid itself do not differ between them. Thus, we employed the approach described above. Whether this composition is closely related to the rupture of atherosclerotic plaque should be investigated. However, the spatial heterogeneity of the elasticity around plaques, where large stress is concentrated, is displayed. These results have not been previously obtained by any other method.
|
Conclusion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Cross-sectional images of the elasticity around atherosclerotic plaques were transcutaneously obtained in this study. This novel approach offers potential for diagnosis of the vulnerability of plaque in a clinical setting. Further study is being carried out to increase the number of elasticity references.
Received March 6, 2002; revision received May 6, 2003; accepted May 7, 2003.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
1. Moreno PR, Falk E, Palacios IF, et al. Macrophage infiltration in acute coronary syndromes: implication for plaque rupture. Circulation. 1994; 90: 775–778.
2. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988; 78: 1157–1166.
3. Loree HM, Kamm RD, Stringfellow RG, et al. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res. 1992; 71: 850–858.
4. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995; 92: 657–671.
5. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990; 323: 1289–1298.[Abstract]
6. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995; 333: 1301–1307.
7. McConnell MV, Aikawa M, Maier SE, et al. MRI of rabbit atherosclerosis in response to dietary cholesterol lowering. Arterioscler Thromb Vasc Biol. 1999; 19: 1956–1959.
8. Potkin BN, Bartorelli AL, Gessert JM, et al. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation. 1990; 81: 1575–1585.
9. Hallock P. Arterial elasticity in man in relation to age as evaluated by the pulse wave velocity method. Arch Intern Med. 1934; 54: 770–798.
10. Peterson RH, Jensen RE, Parnell R. Mechanical properties of arteries in vivo. Circ Res. 1960; 8: 622–639.
11. Hansen F, Mangell P, Sonesson B, et al. Diameter and compliance in the human common carotid artery: variations with age and sex. Ultrasound Med Biol. 1995; 21: 1–9.[Medline] [Order article via Infotrieve]
12. Kanai H, Sato M, Koiwa Y, et al. Transcutaneous measurement and spectrum analysis of heart wall vibrations. IEEE Trans Ultrason Ferroelectr Freq Control. 1996; 43: 791–810.[CrossRef]
13. Kanai H, Hasegawa H, Chubachi N, et al. Noninvasive evaluation of local myocardial thickening and its color-coded imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 1997; 44: 752–768.[CrossRef]
14. Kanai H, Sugimura K, Koiwa Y, et al. Accuracy evaluation in ultrasonic-based measurement of microscopic change in thickness. Electronics Letters. 1999; 35: 949–950.[CrossRef]
15. Kanai H, Koiwa Y. Myocardial rapid velocity distribution. Ultrasound Med Biol. 2001; 27: 481–498.[CrossRef][Medline] [Order article via Infotrieve]
16. Kanai H, Koiwa Y, Zhang J. Real-time measurements of local myocardium motion and arterial wall thickening. IEEE Trans Ultrason Ferroelectr Freq Control. 1999; 46: 1229–1241.[Medline] [Order article via Infotrieve]
17. Hasegawa H, Kanai H, Hoshimiya N, et al. A method for evaluation of regional elasticity of the arterial wall with non-uniform wall thickness by measurement of its change in thickness during an entire heartbeat. 2000 IEEE Ultrason Sympo Proc. 2000; 1829–1832.
18. Patel DJ, Janicki JS, Vaishnav RN, et al. Dynamic anisotropic viscoelastic properties of the aorta in living dogs. Circ Res. 1973; 32: 93–107.
19. 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.
This article has been cited by other articles:
 |
|
 |
|
  A. Paini, P. Boutouyrie, D. Calvet, M. Zidi, E. Agabiti-Rosei, and S. Laurent Multiaxial Mechanical Characteristics of Carotid Plaque: Analysis by Multiarray Echotracking System Stroke, January 1, 2007; 38(1): 117 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cinthio, A. R. Ahlgren, J. Bergkvist, T. Jansson, H. W. Persson, and K. Lindstrom Longitudinal movements and resulting shear strain of the arterial wall Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H394 - H402. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||