Elasticity Imaging of Atheroma
with Transcutaneous Ultrasound-Preliminary Study-Hiroshi Kanai, Ph.D.1; Hideyuki Hasegawa, Ph.D.1;
Masataka Ichiki, M.D.2; Fumiaki Tezuka, M.D.3;
Yoshiro Koiwa, M.D.4
1Graduate School of Engineering, Tohoku University, Sendai, Japan
2Sendai Hospital of East Railway Company, Sendai, Japan
3National Sendai Hospital, Sendai, Japan
4Tohoku University Graduate School of Medicine, Sendai, Japan

Dept of Electronic Eng, Tohoku University

Abstract This paper describes a noninvasive method for evaluating
regional elasticity in atheroma in which a novel measurement
method is applied to measure minute changes in thickness ofeach of the multiple layers of the arterial wall during one
heartbeat.
 By comparing the pathological findings with the elasticity
distribution, statistic parameters for lipid and a mixture of smoothmuscle and collagen fiber can be determined.
 By applying the method to the common carotid arteries (CCAs),
thin collagen fiber was clarified and soft inclusion of lipid inplaque was detected.
 This method offers potential for detection of plaque vulnerability
in a clinical setting.

Dept of Electronic Eng, Tohoku University

Clinical background Rupture of atherosclerotic plaque is probably the most importantfactor underlying the sudden onset of the acute coronary
syndrome.
 Direct characterization of the composition and vulnerability ofatherosclerotic plaque, rather than of the angiographic lumen,
may offer insight into the mechanisms of plaque regression andprogression and thereby promote evaluation of cholesterollowering therapy for reduction of cardiovascular events.

Dept of Electronic Eng, Tohoku University

Previous methods and purpose of this study MRI and intravascular ultrasound are promising technologies for
directly imaging plaque morphology.
 For the evaluation of dynamic mechanics, arterial elasticity has
been determined by measuring the pulse wave velocity (PWV)
and rough change in the diameter of the artery.
 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 crosssectional distribution of elasticity in the arterial wall using
commercially available transcutaneous ultrasound equipment.

Dept of Electronic Eng, Tohoku UniversityUsing conventional ultrasound diagnosis system
 An ultrasonic beam was sequentially scanned at M (=60) positions with alinear-type ultrasonic probe of 7 MHz using conventional ultrasound diagnostic
equipment, and multiple (Nm+1) points were preset from the luminal surface tothe adventitia along the m-th ultrasonic beam (m=1,…,M) with constantintervals of h0=375 µm at a time t0 just before the ejection period.
 By dividing the arterial wall into multiple layers, we defined the n-th layer(n=1,…,Nm) as being between two contiguous points, n and n+1, along eachbeam.
ultrasonic
skinprobe
surface

softcontrol ofpositions ofultrasonic beamhardcross-sectional imageof elasticity
spatial resolution
300 µm375 µm
(75 µm interval)

atherosclerotic plaquechange in thickness: 0.5 µm
Dept of Electronic Eng, Tohoku University

Measurement of change in thickness of arterial wall
 For measurement of change inthickness of each of the Nmlayers, the instantaneous depth
xm,n(t) of the n-th point along them-th beam was simultaneously
tracked by applying the phased
tracking method* to thereceived ultrasound.
 The minute decrease of several
tenths of a micrometer in wall
thickness of the n-th layer
resulting from the arrival of thepressure wave at the beginningof the ejection period wasdetermined byΔhm,n(t)=xm,n+1(t)-xm,n(t)-h0.

lumen

tracking results

M-mode
ECG
PCG
velocity in adventitia side
velocity in intima sidechange in thickness(36-year-old, normal, male)*Kanai H, Hasegawa H, Chubachi N, et al. IEEE Trans on UFFC. 1997;44:752-768.

Dept of Electronic Eng, Tohoku University

phased tracking method*1
 In the phased tracking method, for calculation of the autocorrelation function between the quadrature demodulated signalsof sequentially received echoes, minute phase change of about
0.4 degrees caused by movement of the n-th point during thepulse transmission interval ΔT (=200 µs) can be accurately
determined by introducing a constraint, namely, that theirwaveforms are identical but their phase values change.
 This method has already been applied to the in vivo detection ofregional instantaneous displacement and change in thickness,with sufficient reproducibility, in the interventricular
septum*1,*2,*3,*4 and in the CCA*5.
*1Kanai H, Sato M, Koiwa Y, et al. IEEE Trans on UFFC. 1996;43:791-810.
*2Kanai H, Hasegawa H, Chubachi N, et al. IEEE Trans on UFFC. 1997;44:752-768.
*3Kanai H, Koiwa Y. Ultrasound in Med & Biol. 2001;27:481-498.
*4Koiwa Y, Kanai H, Hasegawa H, et al. Ultrasound in Med & Biol. 2002;28:1395-1403.
*5Kanai H, Koiwa Y, Zhang J. IEEE Trans on UFFC. 1999;46:1229-1241.

Dept of Electronic Eng, Tohoku University

Accuracy evaluation* of measurement of change inthickness by phased tracking method The lowest value of the change in thickness was validated as
being about 0.5 µm by expanding a rubber plate in a watertank.* Such a minute change in thickness cannot be measured
by any other method.
・deciding rubber length from θ(t)・assuming that Poisson’s ratio σ=0.5
Theoretical value of change in thickness

θ(t)rubber platecompareMeasured value by the developed method
Evaluated accuracy: 0.5 µm（wavelength: 200 µm, 7.5MHz)*Kanai H, Sugimura K, Koiwa Y, et al. Electronics Letters. 1999;35:949-950.

Dept of Electronic Eng, Tohoku University

Application of phased tracking method
to measurement of heart wall vibrations in IVS
For a healthy subject, 5 heartbeats overlaid
systolediastole
ECG

Heart sound
RV sideLV sideUltrasonic beam

Measurement with reproducibility
even for high frequency
components (~200 Hz).
Difference between velocity
signals↓integration
change in thickness(0.5 µm accuracy)*Kanai H, Hasegawa H, Chubachi N, et al. IEEE Trans on UFFC. 1997;44:752-768.

Dept of Electronic Eng, Tohoku University

Elasticity estimation From the ratio of the maximum decrease in thickness
during one heartbeat, Δhm,n,max = maxt|Δhm,n(t)|, tothe initial thickness h0 of the n-th layer, the maximum
deformation of the n-th layer was obtained by
Δεm,n,max=Δhm,n,max/h0. Since 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 normal to eachlayer, the elastic modulus in the circumferential
direction of the n-th layer along the m-th beam, Eθ,m,n,
is approximately given by*1
N − n + 1  ∆p(t )1 ρ
Eθ,m ,n ≈  m ,n , 0 + mNm2  h0 ⋅ N m ∆ε m ,n ,max (t )(n = 1,..., N m ; m = 1,..., M )where ρθ,m,n is the initial radius of curvature of the nth layer.
 We assumed that the pressure in the arterial walldecreases linearly with the distance from the intimalside to the adventitia and that the arterial wall isalmost isotropic.*2*1 Hasegawa H, Kanai H, Hoshimiya N, et al. 2000 IEEE Ultrason Sympo Proc. 2000;1829-1832.
*2 Patel DJ, Janicki JS, Vaishnav RN, et al. Circ Res. 1973;32:93-107. Dept of Electronic Eng, Tohoku University

Spatial resolution in elasticity measurement
 For the region with a length of 18 mm along the axis of the artery, the regionalelasticity Eθ,m,n was estimated on the cross-sectional image.
 Since 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 depthof each layer by 1/5 of h0 and applied the above procedure to each depth.
 Thus, Eθ,m,n was estimated at intervals of 75 µm in the depth direction and300 µm in the axial direction.
ultrasonic
skin
probe
surfacesoft
control ofpositions ofultrasonic beamhardcross-sectional imageof elasticity
spatial resolution
300 µm375 µm
(75 µm interval)

atherosclerotic plaquechange in thickness

strainelasticity

change in thickness: 0.5 µm

blood pressure
Dept of Electronic Eng, Tohoku University

Accuracy confirmation* Using a silicone tube with two layers
set in an artificial circulation system,
the accuracy of the measurement ofregional elasticity for each layer has
already been validated to be about 0.1
MPa, that is, the error is about 8% of
the elasticity value obtained by aseparate static pressure-diameter test.

* Hasegawa H, Kanai H, Hoshimiya N, et al. 2000 IEEE Ultrason Sympo Proc. 2000;1829-1832.

Dept of Electronic Eng, Tohoku University

Slight influence of tissue surrounding the artery In in vivo experiments before the extraction of an iliac artery andin in vitro experiments (described below) after such extraction,
the average elasticity was about 0.96 ± 0.48 MPa and 0.89 ±0.31 MPa, respectively, the difference between them being
about 8%.
 Thus, the slight influence of assaying the artery through the skin
was eliminated.

Dept of Electronic Eng, Tohoku University

Effect of pressure of ultrasonic probe on skin surface
 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, and74.3 mmHg, the measured diameter ofthe 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, thecross section of the artery changes froma circular to an oval shape.
 We confirmed that the measured
elasticity is not influenced by thepressure on the ultrasonic probe to theskin surface as long as the pressure isequal to or less than 30 mmHg. In ourin vivo experiments, the ultrasonic probe
was held on the skin surface with apressure of 30 mmHg.

Dept of Electronic Eng, Tohoku University

In vitro measurements for determination of reference parameters*
 Immediately after 9 iliac arteries (25-40 mm in length and 4-24 mm in outer diameter) with plaques
were extracted from patients with embolism, cross-sectional elasticity distribution, Eθ,m,n, wasmeasured using the above method 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.
 From the stain images, each region with either lipid or a mixture of smooth muscle and collagen fiber
was assigned in Eθ,m,n. Each histogram of Eθ,m,n in the respective regions is shown.

* Kanai H, Hasegawa H, Ichiki M, et al. Circulation 2003;107,3018-3021.Dept of Electronic Eng, Tohoku UniversityReference parameters for elasticity library* For the respective categories of
the nine arteries, the average andthe standard deviation in elasticity
were determined to be 81 ± 40
kPa and 1.0 ± 0.63 MPa, whichwere registered as the reference
parameters.

* Kanai H, Hasegawa H, Ichiki M, et al. Circulation 2003;107,3018-3021.Dept of Electronic Eng, Tohoku University

Electronic staining* Based on these reference
parameters, each point in the
cross-sectional elasticity
distribution, which had been
noninvasively measured by
the above method inseparate in vivo
experiments, was statisticallyclassified as one of three
categories (lipid, mixture ofsmooth muscle and collagenfiber, or other). Thus, thearterial wall and theatherosclerotic plaque were
electronically stained.

* Kanai H, Hasegawa H, Ichiki M, et al. Circulation 2003;107,3018-3021.Dept of Electronic Eng, Tohoku University

in vivo measurements of the CCAs

The lipid and the mixture of smooth muscle and collagen fiber are shown by yellow and cyan, respectively, andthe category of "other" is not colored.

a healthy subject

two patients with hyperlipidemia having atherosclerotic plaques

lipid, mixture of smooth muscle & collagen fiber* Kanai H, Hasegawa H, Ichiki M, et al. Circulation 2003;107,3018-3021.Dept of Electronic Eng, Tohoku University

Discussion
 For the CCAs of normal subjects, the existence of thin fibrous tissue along thearterial axis was clarified. For the plaque in the subjects, soft inclusions oflipid surrounded by fibrous tissue were found. With extrapolation of theresults of an in vitro study,* we postulated that a thin layer constitutes afibrous cap surrounding the plaque.
 Iliac arteries were used to determine the reference parameters which werethen 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 collagenfiber 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 theelasticity around plaques, where large stress is concentrated, is displayed.
These results have not been previously obtained by any other method.
* Lee RT, Grodzinsky AJ, Frank EH, et al. Circulation. 1991;83:1764-1770.

Dept of Electronic Eng, Tohoku University

Conclusion
 Cross-sectional images of the elasticity around atherosclerotic
plaque were transcutaneously obtained in this study.
 This novel approach offers potential for diagnosis of thevulnerability of plaque in a clinical setting.
 Further study is being carried out to increase the number ofelasticity references.

Dept of Electronic Eng, Tohoku University