Study of Acoustic Nonlinearity Parameter Imaging Methods in Reflection Mode For Biological Tissues

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Study of acoustic nonlinearity parameter imaging methods

in reflection mode for biological tissues


Xiufen Gong,a) Dong Zhang, Jiehui Liu, Huanlei Wang, Yongsheng Yan, and Xiaochen
Xu
State Key Lab of Modern Acoustics, Institute of Acoustics, Nanjing University, Nanjing 210093, China
Received 10 February 2004; revised 16 June 2004; accepted 22 June 2004
Three novel methods for acoustic nonlinearity parameter B/A imaging in reflection mode are
developed in this paper. They are: 1 the acoustic nonlinearity parameter B/A tomography by
detecting reflective second harmonic wave, 2 the B/A tomography in reflection mode via the
measurement of the difference frequency wave generated by a parametric array, and 3 the C-scan
imaging of B/A via the measurement of the echo second-harmonic signal. A theoretical analysis and
the experimental imaging of normal and pathological biological tissues by using these methods are
also present and discussed. Results show that using the acoustic nonlinearity parameter imaging we
can more easily distinguish the diseased tissue from the normal one than using the linear acoustic
parameters. 2004 Acoustical Society of America. DOI: 10.1121/1.1781709
PACS numbers: 43.80.Ev, 43.80.Cs FD Pages: 18191825

I. INTRODUCTION on the insert-substitution method have been developed,16 18


e.g., B/A tomography via the measurement of the second-
The ultrasound B-scan imaging has been widely used in harmonic detection, and B/A tomography via the measure-
a modern hospital for clinical ultrasound diagnosis because it ment of the sum or difference frequency wave produced by
can provide important information on the diseased state of the parametric effect. The obtained experimental images
the tissues in a human body noninvasively and nondestruc- showed that the difference between healthy and pathological
tively. The principle of this technique is based on the as- tissues could be determined quite well by using the acoustic
sumption of linear acoustics. However, many reports indicate nonlinearity parameter.
that the nonlinear acoustical effects must be considered in Up to now, few works on B/A image using echo
the range of biomedical frequencies and intensities.13 Due signals19 have been reported. Considering that the ultrasound
to these nonlinear effects, a monochromatic sound wave will medical diagnostic instruments operate mostly in reflection
be distorted progressively and harmonics will be generated. mode, it is necessary to investigate the B/A imaging in re-
Considering that the second harmonics has a better direc- flection mode. Besides, the B/A imaging via the measure-
tional performance and spatial resolution compared with the ment of the second harmonics is limited by high sound at-
fundamental wave, the most current B-scanning has the func- tenuation. Hence, development of novel techniques for
tion of the second-harmonic imaging.4 6 It is well known in reducing the frequency and obtaining lower sound attenua-
nonlinear acoustics that as a measure of nonlinearity of a tion in the reconstruction of B/A tomography is needed.
medium, the acoustic nonlinearity parameter B/A determines In this paper we present three versions of B/A imaging
the pressure amplitude of the second harmonics generated. methods in reflection mode, which are: 1 the acoustic non-
Also, since this parameter reflects the dynamic properties of linearity parameter B/A tomography by detecting the reflec-
the medium, it can give more important messages about the tive second-harmonic wave, 2 B/A tomography in reflec-
structural features and the pathological change of the tissues tion mode via the measurement of the low difference
than the linear ultrasonic parameters.711 Therefore, the non- frequency wave generated by a parametric array, and 3 the
linearity parameter B/A can become a new and useful pa- nonlinearity parameter B/A imaging in reflection mode at a
rameter in biological tissue characterization. constant depth named C-scan imaging of B/A) via the mea-
Owing to the inhomogeneous features of biological tis- surement of the echo signals of second harmonics. A theo-
sues, most efforts have worked on the B/A imaging in the retical analysis and the experimental images of normal and
fields of ultrasound biomedicine and nonlinear acoustics. pathological biological tissues obtained by using these meth-
Ichida et al.12 presented a phase shift method, and Nakagawa ods are presented and discussed.
et al.13 reported methods using the second-harmonic wave
and parametric array for nonlinearity parameter imaging. II. METHODS AND RESULTS
Cain14 theoretically studied the ultrasonic imaging of the
A. Tomography of the nonlinearity parameter B A via
nonlinearity parameter B/A in reflection mode. Fatemi and
the second harmonics in reflection mode
Greenleaf proposed a method for read-time assessment of
tissue nonlinearity.15 In our laboratory, several B/A imaging 1. Theory
techniques in transmission mode for biological tissues based A compound PZT transducer T, as shown in Fig. 1, is
used to transmit the primary wave at frequency and also to
a
Electronic mail: dzhang@nju.edu.cn receive the reflective second-harmonic wave at 2 2 . An

J. Acoust. Soc. Am. 116 (3), September 2004 0001-4966/2004/116(3)/1819/7/$20.00 2004 Acoustical Society of America 1819
FIG. 1. Propagation path of generated second harmonics in reflection mode.

aluminum plate is fixed at position L from the transducer to


enhance the reflective signal. The test sample is inserted into
the water as a reference medium at distance x from T with FIG. 2. Geometry of ultrasonic tomography in reflection mode.
xL. When a wave with the finite amplitude P 1 (0) is trans-
mitted from the transducer at x0, P 1 P 1 (0)sin t, the
wave will be distorted along the path of propagation and the where w is the i of distilled water, whose B/A5.2. The
second harmonics generated. ratio of Eq. 2 to Eq. 3 will be


The pressure amplitudes of the reflected second harmon- p 2s L 1 L
ics received by the compound transducer consist of two p i x
parts, one of which is the reflected second harmonics gener- p 2w L 1R w L 0

ated on the forward path and the other is the second harmon-
ics generated on the backward path of the reflected primary
wave from the plate and can be expressed as

exp
0
x
2 1 x dx L

x
2 x dx

P 2s L R
2 2
P 0 L
i x dxR L
i Lx dx ,
L

0
2 x dx R exp Lx

0
2 1 x dx
4 1


0 0

where i (x) (x)/ 0 (x)c 30 (x),


(x)1 (B/2A)(x) .
1
L

Lx
2 x dx
0
L
2 1 x dx dx. 4

0 (x), c 0 (x) and (B/A)(x) are the density, velocity, and the Figure 2 shows a conventional CT scanning system. The
nonlinearity parameter at x. R is the reflection coefficient of sample rotates from 0 to 360 at an equal interval angle
the plate. Considering the sound attenuation of the sample, 2 /K K is the number of rotating steps, and at each
Eq. 1 is rewritten as angle j j2 /K ( j0,1,...,K1) the compound trans-


ducer sweeps step by step along one fixed direction u axis.
p 2s L R
2 2
P 0
4 1

0
L
i x exp
0
x
2 1 x dx Assuming that the linear scan is uL/N L and N are the
distance and the step number of the linear scan respectively,


the projection data are sampled at u i iu (iN/2,
x
L
2 x dx L

0
2 x dx
N/21,...,0,1,...,N/2). Thus, a K(N1) projection data
matrix will be obtained for each specimen.


Lx L The ratio of P 2s (L)/ P 2w (L) can be regarded as the pro-
R exp 2 1 x dx 2 x dx jection data p(u, ) in the CT technique
0 Lx

L
2 1 x dx dx, 2
p u,
1
0L
V

V
i x,y d v , 5
0
where VL/2, i (x,y) i (x,y)C(x,y), C(x,y) is the ma-
where 1 (x) and 2 (x) are the attenuation coefficients of the trix of the attenuation correction and determined by Eq. 521
primary and second-harmonic waves.
In order to avoid the measurement of the absolute sound
pressure amplitude for the second harmonics, the finite- C x,y
1
2

2

0
exp
V
v
2 1 x,y d v

amplitude insert-substitute method16,20 is used. When the


sample is absent, the pressure amplitude of the second har-
monics in the water reflected from the plate is
V

v
2 x,y d v R exp
V/2 v

V
2 1 x,y d v

P 2w L
L 2
P 0 R 1R w ,
2 1
3 V

V/2 v
2 x,y d v d .

1820 J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging
FIG. 4. B/A tomography via second-harmonic wave in reflection mode for
a three layers tissue sample: a sample model, b experimental tomogra-
FIG. 3. Block diagram of experimental system for B/A tomography via phy.
second-harmonic wave in reflection mode.

can be determined by the gray scale of their images as fol-


Equation 4 shows that p(u, ) is a linear integral of
lows: for the fatty tissue B/A10.9, for the normal porcine
i (x,y) along the propagation path of the wave, therefore
liver B/A7.3, and for the hepatonecrosis liver B/A10.5.
the i (x,y) image can be reconstructed by using the filtered
These obtained values coincide well with the results in
convolution method in the CT technique. Then, the nonlin-
literatures.7,18 Furthermore, the hepatonecrosis liver can be
earity parameter B/A tomography can be obtained after the
discerned according as its B/A value is higher than that of
correction of sound attenuation.
the normal liver, therefore, they can be distinguished more
easily by means of B/A tomography.
2. Experimental system and results
The block diagram of the experimental system is shown B. Tomography of the acoustic nonlinearity
in Fig. 3. The outer annular ring of the compound transducer parameter B A via the difference frequency wave
with a resonance frequency of 2.0 MHz is used as the trans- from a parametric array in reflection mode
mitter and the central disk with a resonance frequency of 4.0
MHz as the receiver to detect the second harmonics. A 2.0 1. Theory and method
MHz tone-burst signal is generated by a programmable func-
When two primary waves with angular frequencies 1
tion generator Agilent 33250A, USA. After passing
and 2 and the initial sound pressure amplitudes P 1 (0) and
through a broad-band power amplifier ENI 2100L, USA,
P 2 (0) are transmitted from a transducer simultaneously, sev-
this signal is sent to the transmitter. The second-harmonic
eral frequency components will be generated during the
signals of 4 MHz cumulated in the path of propagation
sound propagation due to the nonlinear interaction of these
through the sample will be reflected by the aluminum plate
two waves in a medium. If only the quadratic effects are
and then detected by the receiver. By using a frequency-
considered, the second harmonics 2 1 and 2 2 as well as
selective amplifier with a central frequency of 4 MHz, the
the parametric signals with sum and difference frequencies
reflected second-harmonic wave is amplified and recorded by
components 1 2 will be generated.22
a digital oscilloscope Lecroy 9310A, USA. The amplitude
As shown in Fig. 6, an aluminum plate with rhe reflec-
of the reflected second harmonics in the reference medium
tive coefficient R used as a reflector is located at distance L
water P 2w can also be measured. Then the value of
away from a compound transducer T. Considering only the
P 2s (L)/ P 2w (L) is used as the projection data. The two-
difference frequency component P d , the reflected sound
dimensional mechanical scanning system motor 1 for
pressure amplitude of the difference frequency wave re-
sample rotating and motor 2 for linear scanning is controlled
ceived by the compound transducer is
via the GP-IB interface by a computer.
A cylindrical sample container with diameter of 30 mm
is surrounded by a polythene membrane. The excised fresh
soft tissues taken from a slaughter house are carefully packed
into the container and the unoccupied space is filled with a
0.9% saline solution to avoid the influence of gas bubbles.
The cross section of a three-layer sample model is shown in
Fig. 4a. The internal layer is the porcine liver tissue, the
intermediate layer the porcine fatty tissue and the external
layer water. The corresponding experimental B/A tomogra-
phy is shown in Fig. 4b. The second sample model consists
of two half-cylindrical tissues with normal liver tissue and
hepatonecrosis tissue as shown in Fig. 5a. The correspond-
FIG. 5. B/A tomography via second-harmonic wave in reflection mode for
ing experimental tomography of B/A is shown in Fig. 5b. normal and hepatonecrosis livers: a sample model, b experimental to-
The averaged values of B/A for the above-mentioned tissues mography.

J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging 1821
FIG. 6. Propagation path of generated difference-frequency wave via a para-
metric array in reflection mode.

d
P dw R 1R P 0 P 2 0 w L, 6
2 1

where w 2(B/A) w /2 w c w3 , d 2 1 , w , c w are


the density and velocity of the reference medium distilled
water, respectively.
For an inhomogeneous medium biological tissue the
nonlinear coefficient i (x) is dependent on the position.
Then Eq. 6 will be rewritten as

P ds R 1R
d
2 1
P 0 P 2 0
L

0
i x dx. 7 FIG. 7. Block diagram of experimental system for B/A tomography via a
parametric array in reflection mode.

Considering the sound attenuation of the sample, this equa-


tion is modified as 2. Experimental arrangement

P ds R
d
2 1
P 0 P 2 0
0
L
i x,y C x,y dl, 8 The block diagram of the experimental system is shown
in Fig. 7. A compound transducer is employed as both the
transmitter and the receiver. The external circular PZT ring
where C(x,y) is the attenuation matrix defined as
with an outer diameter of 2.2 cm and with a resonance fre-

C x,y
1
2
2

0
exp
0
L
1 x,y 2 x,y dl
quency of 4 MHz is used as a transmitter of two primary
waves. The internal PZT disk with a diameter of 0.7 cm and
with a resonance frequency of 1 MHz is used as a receiver of


l
L
d x,y dl
L

0
d x,y dl the difference frequency wave. Two function generators
Philips PM5193 and Agilent 33250A transmit sine waves


at 3.5 and 4.5 MHz, respectively. These two signals are
L
added by an adder, then modulated by a pulse generator
R exp 1 x,y 2 x,y dl
0 HP8110A, USA. The modulated burst signal is amplified


l
by a power amplifier ENI A150, USA and then excites the
d x,y dl d . 9 external PZT of the transducer. The reflected signal of differ-
0 ence frequency is received by the internal PZT disk and re-
corded by a digital oscilloscope Lecroy 9310, USA. The
In order to avoid measuring the absolute value of the sound
pressure, the finite amplitude insert-substitution method is amplitudes of the difference frequency wave at 1 MHz are
introduced and the distilled water is used as the reference measured with and without inserting the sample ( P ds and
medium. Using Eqs. 6 and 8, we define p P ds / P dw as P dw ). The ratio of P ds / P dw is considered as the projection
the projection data in the conventional CT technique, the data. In the mechanical scanning, the rotating interval angle
procedure of which is similar to that shown in Fig. 2. is 15, so 24 angles are needed in one circle. At each angle,
The two-dimensional image of i (x,y)C(x,y) is recon- the projection data is sampled at the step of 1.25 mm. All
structed by using the filtered convolution algorithm to deal projection data are collected in the range of 8 cm and a
with the projection data. Then the i (x,y) tomography is 2465 projection matrix is obtained. The B/A tomography
obtained by correction of C(x,y). Finally the B/A tomogra- is displayed after reconstruction and correction by attenua-
phy is imaged with algebraic transformation. tion C(x,y).

1822 J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging
FIG. 10. B/A tomography via parametric array in reflection mode for nor-
mal and diseased tissues: a sample model normal and hepatocirrhosis
livers, b experimental tomography.

images, the averaged values of B/A are obtained as follows:


B/A11 for the porcine fat; B/A6.5 for the normal por-
FIG. 8. Comparison of beam patterns at 1 MHz between generation directly cine liver and B/A8.3 for the hepatocirrhosis liver. These
from a transducer and that from a parametric array. results are consistent with those presented in Refs. 7 and 18.
The second-harmonic imaging has been successful for
3. Experimental results years due to its better lateral resolution and improved clarity
of the image quality. However, the second harmonics has
a. The beam pattern of the difference frequency wave. higher attenuation because of the doubling of the fundamen-
The beam pattern of the difference frequency wave at 1 MHz tal frequency. The difference frequency scheme is needed
for a distance of 8 cm generated by the nonlinear interaction because it provides the low frequency wave corresponding
of the two primary waves at 3.5 and 4.5 MHz is shown in to the low sound attenuation with a high directionality.
Fig. 8 as closed circles. For comparison, the beam pattern at
the same distance from the transmitter excited directly at 1
MHz is also shown in this figure as open circles. It can be C. Nonlinearity parameter imaging in C-scan mode
found that the difference frequency wave has a better direc-
tional performance, which will be conducive to improve the 1. Theory and method
resolution of imaging.
The nonlinearity parameter C-scan image is constructed
b. B/A tomography for biological tissues.B/A tomogra-
by the echo signal of the reflected second harmonics at a
phy was performed for several biological tissues including
constant depth of a biological specimen. Assume that a finite
normal and diseased ones. As shown in Figs. 9a and 10a,
amplitude plane wave P 1 (0) with frequency f 0 is emitted at
the two sample models in different tissue combinations are
z0 and travels through the medium. The biological speci-
studied. In Fig. 9a the porcine fatty tissue is located in the
men can be regarded as a layered medium distributed in the
external ring and the internal part is the normal porcine liver
uniform media. At distance z from the source, the reflected
tissue. In Fig. 10a, the left side is the normal porcine liver
echo signal of the second harmonics 2 f 0 is
tissue and the right side is a kind of pathological porcine
liver tissue hepatocirrhosis. The corresponding experimen-
tal images are shown in Figs. 9b and 10b, respectively.
P 12r 2 f 0 ,z P 12 2 f 0 ,z R 2 f 0 ,z exp 2 2 f 0 ,z dz ,
The obtained experimental images coincide well with 10
their sample models and the gray levels represent the B/A where R(2 f 0 ,z) is the reflection coefficient at z, 2 (2 f 0 ,z)
values of biological tissues. Based on the gray levels of the is the sound attenuation at 2 f 0 , and P 12(2 f 0 ,z) is the pres-
sure amplitude of the cumulated second harmonics at dis-
tance z and should satisfy
d P 12 2 f 0 ,z
dz

K z P 21 f 0 ,0 exp 2 1 f 0 ,z dz
2 2 f 0 ,z P 12 2 f 0 ,z , 11
where K(z) /4 0 c 30 B/A(z)2 .
If an infinitesimal ultrasound wave P i (0) with fre-
quency 2 f 0 is transmitted into the medium, the reflected sig-
nal of this fundamental wave at z will be

FIG. 9. B/A tomography via parametric array in reflection mode for two
kinds of normal tissues, a sample model normal liver and fatty tissues,

P ir 2 f 0 ,z P i 2 f 0 ,z R 2 f 0 ,z exp 2 2 f 0 ,z dz ,
b experimental tomography. 12

J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging 1823
FIG. 11. Block diagram of experimental system for B/A imaging by C-scan
method.

where P i (2 f 0 ,z) P i (2 f 0 ,0)exp 2(2f 0 ,z)dz. Dividing


Eq. 10 by Eq. 12 and eliminating R(2 f 0 ,z) and
exp 2(2f 0 ,z)dz, we get
P i 2 f 0 ,z P ir 2 f 0 ,z
. 13
P 12 2 f 0 ,z P 12r 2 f 0 ,z
FIG. 12. Sample models and experimental results in B/A imaging by C-scan
Differentiating Eq. 13 with respect to variable z and con- mode: a sample with half liver and half fat tissues, b sample with liver in
sidering the relationship of Eq. 11, we obtain inner circle and fat in outer ring, c sample with liver in central square and
fat in outside.


d P 12 2 f 0 ,z
dz P i 2 f 0 ,z
K z
P 21 f 0 ,z
P i 2 f 0 ,0
exp 2 1 f 0 ,z
writing the B/A value into the image file. Then the 2D image


of (B/A)(x,y), perpendicular to the z axis, is obtained by
2 2 f 0 ,z dz . 14 grating the C-scan method.
Biological samples in the different combinations of nor-
For biological tissues, 2 1 ( f 0 ,z) 2 (2 f 0 ,z), then Eq. 14 mal porcine liver and fat tissues are studied. Figure 12 shows
will be reduced to the sample models and corresponding experimental results.


In sample a, liver and fat tissues are located in the right and
d P 12r 2 f 0 ,z P 21 f 0 ,0
K z . 15 left half parts, respectively. With a sampling interval of 0.4
dz P ir 2 f 0 ,z P i 2 f 0 ,0 mm and a sampling number of 6464, the imaging area is
Parameter z can be converted to t by zc 0 t/2. Hence, the 2.562.56 cm2. In sample b, the central square is a liver
distribution of the nonlinearity parameter B/A is obtained as tissue with a border of 2.0 cm and the outer part is a fat
tissue. In sample c, the ring area is a liver tissue and the
B
A
z
8 c 2 P i 0 d P 12r 2 f 0 ,z
P 21 0 dt P ir 2 f 0 ,z
2. 16
other area is a fat tissue. The inner-radius and outer-radius of
the ring are 0.6 cm and 1.1 cm, respectively. For samples b
and c, the sampling interval is 0.5 mm and the sampling
From this equation, we can image the B/A distribution of the number is 6464, so the imaging area is 3.23.2 cm2. In
biological specimen by measuring the ratio of P 12r (2 f 0 ,z) experimental images, black and gray areas correspond to the
and P ir (2 f 0 ,z). porcine liver and fat tissues, the B/A values of which are 6.9
and 9.6, respectively. The obtained B/A values coincide well
2. Experiment and results with those obtained by other imaging methods. Figure 13a
Figure 11 shows an automatic mechanical system for the demonstrates a sample model with a half normal porcine
B/A C-scan imaging in pulse reflection mode with high pre- liver and a half diseased fatty liver. Figure 13b shows the
cision, which consists of a Newport MM3000 motion con-
troller, a pulse generator, a frequency synthesizer PM5193, a
wideband power amplifier ENI A150, a digital oscilloscope
HP54502A and a compound PZT transducer used both as a
transmitter for 2 MHz and a receiver for 4 MHz. The 3D
mechanical scanning system is used to construct the image at
a constant depth of the tissue. The reflected signals are de-
tected and measured by the following procedures: 1 pass-
ing the signal through the delay switch of the digital oscillo-
scope and adjusting the imaging depth of the sample, 2
segmenting the wave form, taking FFT and obtaining the
pressure amplitude of the reflected second harmonics
P 12r (2 f 0 ,z) and the reflected fundamental component
FIG. 13. B/A imaging by C-scan mode for a sample with half normal
P ir (2 f 0 ,z) respectively, 3 calculating the ratio P 12r / P ir , porcine liver and half diseased fatty liver: a sample model b experimental
the slope (d/dt) P 12r / P ir and the value of (B/A)(z), 4 result.

1824 J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging
TABLE I. Linear and nonlinear parameters of several biological tissues. ACKNOWLEDGMENTS
Density Velocity Attenuation The Authors wish to thank Professor F. Dunn for his
Sample g/cm3 m/s 2 MHz, dB/cm B/A B/A Ref. valuable suggestions and comments. This work was sup-
Porcine fat 0.95 1455 1.11 10.9 10.8a
ported by Natural Science Foundation of China and JiangSu
Porcine liver 1.06 1588 1.08 6.9 6.8b Province.
Fatty liver 1.05 1598 1.20 8.3 8.3b
1
Hepatocirrhosis 1.05 1600 1.26 8.3 8.1b T. G. Muir and E. L. Carstensen, Prediction of nonlinear acoustic effects
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357 1980.
2
a
See Ref. 16. E. L. Carstensen, W. K. Law, N. D. Mckay, and T. G. Muir, Demonstra-
b
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16
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18
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J. Acoust. Soc. Am., Vol. 116, No. 3, September 2004 Gong et al.: Reflective nonlinearity parameter imaging 1825

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