Elasticity Imaging of Atheroma With Transcutaneous Ultrasound
Preliminary Study
Hiroshi Kanai, PhD; Hideyuki Hasegawa, PhD; Masataka Ichiki, MD;
Fumiaki Tezuka, MD; Yoshiro Koiwa, MD
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 elasticmodulus 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 thatof a mixture of smooth muscle and collagen fiber can be determined. On the basis of these reference parameters, eachpoint is statistically categorized as lipid, mixture, or other. Thus, the plaque is electronically stained usingtranscutaneous 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 insubjects with hyperlipidemia.
Conclusion—This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with highspatial resolution. (Circulation. 2003;107:3018-3021.)
Key Words: atherosclerosis 䡲 elasticity 䡲 plaque 䡲 ultrasonics

R

upture of atherosclerotic plaque is probably the mostimportant factor underlying the sudden onset of the acutecoronary 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 forreduction of cardiovascular events. MRI and intravascularultrasound 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 vulnerabilityof atherosclerotic plaque with sufficient accuracy has not yet
been reported. The purpose of the present study was todetermine the cross-sectional distribution of elasticity in thearterial wall using commercially available transcutaneous
ultrasound equipment.

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 intervalsof h0⫽375 ␮m 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 xm,n(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 decreaseof several tenths of a micrometer in wall thickness of the nth layer
resulting from the arrival of the pressure wave at the beginning of theejection period was determined by ⌬hm,n(t)⫽xm,n⫹1(t)⫺xm,n(t)⫺h0.
In the phased tracking method, for calculation of the autocorrelation 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 transmissioninterval ⌬T (⫽200 ␮s) can be accurately determined by introducing
a constraint, namely, that their waveforms are identical but theirphase values change.12,13 The lowest value of the change in thickness
was validated as being ⬇0.5 ␮m by expanding a rubber plate in awater tank.14 Such a minute change in thickness cannot be measured
by any other method. This method has already been applied to the invivo detection of regional instantaneous displacement and change inthickness, with sufficient reproducibility, in the interventricular
septum12,13,15 and in the common carotid artery (CCA).16

Methods
Measurement of Change in Thickness of theArterial Wall

Elasticity Estimation

An ultrasonic beam was sequentially scanned at M (⫽60) positions
with a linear-type ultrasonic probe of 7 MHz using conventional

From the ratio of the maximum decrease in thickness during one
heartbeat, ⌬hm,n,max⫽maxt|⌬hm,n(t)|, to the initial thickness h0 of theOriginal received March 6, 2002; de novo received March 14, 2003; revision received May 6, 2003; accepted May 7, 2003.
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@ecei.tohoku.ac.jp© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org

DOI: 10.1161/01.CIR.0000078633.31922.8A

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Kanai et al

Elasticity Imaging of Atheroma

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Figure 1. By referring to the stained image (2), the regions of lipid and of the mixture of smooth muscle and collagen fiber wereassigned in the spatial distribution of elasticity E␪,m,n measured in in vitro experiments (1). From the histogram of E␪,m,n for each region(3), the elasticity for each category was registered as a reference (4), from which each tissue was categorized as belonging to one of
the 3 categories.

nth layer, the maximum deformation of the nth layer was obtained by⌬␧m,n,max⫽⌬hm,n,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 eachlayer, the elastic modulus of the nth layer along the mth beam, E␪,m,n,is approximately given by17E␪,m,n⬵冉冊

Nm⫺n⫹11 ␳m,n,0⌬p⫹,2 h0 䡠 NmNm
⌬␧m,n,max(1)(n⫽1, . . . , Nm; m⫽1, . . . , M)
where ␳m,n,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 thearterial 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 E␪,m,n was estimated on the cross-sectional
image. Because the reflected ultrasound was received at a samplinginterval of 100 ns (⫽75 ␮m along depth direction) after thequadrature demodulation, we further divided each layer with athickness 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,E␪,m,n was estimated at intervals of 75 ␮m in the depth direction and300 ␮m 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 andin in vitro experiments (described below) after such extraction, theaverage elasticity was ⬇0.96⫾0.48 MPa and 0.89⫾0.31 MPa,
respectively, the difference between them being ⬇8%. Thus, theslight influence of assaying the artery through the skin waseliminated.
In separate in vivo experiments, when the pressure of theultrasonic 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 crosssection of the artery changes from a circular to an oval shape. We
confirmed that the measured elasticity is not influenced by thepressure on the ultrasonic probe to the skin surface as long as thepressure is ⱕ30 mm Hg. In our in vivo experiments, the ultrasonic probe was held on the skin surface with a pressure of30 mm Hg.

Results
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␪,m,n, was measured using the above method [Figure1(1)] under the same artificial circulation system to generate

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Circulation

June 24, 2003

Figure 2. CCAs of 2 healthy male subjects [(a) 24 years old and (b) 25 years old] and 2 male patients with hyperlipidemia [(c) 66 years
old and (d) 71 years old)]. The area outlined by green in each uppermost figure was analyzed in the middle and bottom of the figure.

a change in pressure so that it ranged from the diastolicpressure to the systolic pressure of the subjects. After eachin vitro measurement, elastica-Masson stain was applied.
Two typical results are shown in Figure 1(2). From thestain images, 10 regions with either lipid or a mixture ofsmooth muscle and collagen fiber were assigned in E␪,m,n ofthe 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)].

Kanai et al
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 invivo experiments, was statistically classified as one of 3
categories (lipid, mixture of smooth muscle and collagenfiber, 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, across-sectional image obtained by conventional ultrasounddiagnostic equipment is shown at the top. The cross-sectionalelasticity distribution of E␪,m,n was color-coded and superimposed on the reconstructed B-mode image as shown in themiddle. Finally, at the bottom, the categorized result isshown. The lipid and the mixture of smooth muscle andcollagen fiber are shown by yellow and cyan, respectively,
and the category of “other” is not colored.

Discussion
For the CCAs of normal subjects, the existence of thin fibrous
tissue along the arterial axis was clarified. For the plaque inthe subjects, soft inclusions of lipid surrounded by fibrous
tissue were found. With extrapolation of the results of an invitro study,19 we postulated that a thin layer constitutes afibrous cap surrounding the plaque. Iliac arteries were used todetermine 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, thecharacteristics of the collagen fiber itself and the lipid itself
do not differ between them. Thus, we employed the approachdescribed 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 byany other method.

Conclusion
Cross-sectional images of the elasticity around atherosclerotic plaques were transcutaneously obtained in this study.
This novel approach offers potential for diagnosis of thevulnerability of plaque in a clinical setting. Further study isElasticity Imaging of Atheroma

3021

being carried out to increase the number of elasticity
references.

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