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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

A High-Resolution Technique for Ultrasound


Harmonic Imaging Using Sparse
Representations in Gabor Frames
Oleg Michailovich*, Student Member, IEEE and Dan Adam, Senior Member, IEEE

AbstractOver the last few decades there were dramatic


improvements in ultrasound imaging quality with the utilization
of harmonic frequencies induced by both tissue and echo-contrast agents. The advantages of harmonic imaging cause rapid
penetration of this modality to diverse clinical uses, among
which myocardial perfusion determination seems to be the most
important application. In order to effectively employ the information, comprised in the higher harmonics of the received signals,
this information should be properly extracted. A commonly
used method of harmonics separation is linear filtering. One of
its main shortcomings is the inverse relationship between the
detectability of the contrast agent and the axial resolution. In this
paper, a novel, nonlinear technique is proposed for separating the
harmonic components, contained in the received radio-frequency
images. It is demonstrated that the harmonic separation can
be efficiently performed by means of convex optimization. It
performs the separation without affecting the image resolution.
The procedure is based on the concepts of sparse signal representation in overcomplete signal bases. A special type of the sparse
signal representation, that is especially suitable for the problem
at hand, is explicitly described. The ability of the novel technique
to acquire un-masked, second (or higher) harmonic images is
demonstrated in series of computer and phantom experiments.
Index TermsGabor frames, harmonic imaging, sparse representations, ultrasound.

I. INTRODUCTION

HILE in conventional medical ultrasound only the


fundamental signal frequencies are used to construct an
image, in harmonic imaging the second (or higher) harmonics
echo signals are also acquired and displayed. The employment
of harmonic information has been proven to be a powerful tool,
remarkably extending the capabilities of the clinical ultrasound.
When the higher harmonics are not present in the transmitted
pulse, they are mostly caused either by nonlinear propagation of
the sound wave in the tissue or by the presence of a medium that
is capable of reflecting (or reradiating) the transmitted energy in
nonlinear manner, e.g., contrast agents [1]. As a consequence,

Manuscript received March 3, 2002; revised September 23, 2002. The work
of O. Michailovich was supported by the Israeli Planning and Budgeting Committee (VATAT) of the Council for Higher Education. The Associate Editor
responsible for coordinating the review of this paper and recommending its publication was M. W. Vannier. Asterisk indicates corresponding author.
*O. Michailovich is with the Department of Bio-Medical Engineering,
Technion-Israel Institute of Technology, 32000 Haifa, Israel (e-mail: bmoleg@
tx.technion.ac.il).
D. Adam is with the Department of Bio-Medical Engineering, TechnionIsrael Institute of Technology, 32000 Haifa, Israel.
Digital Object Identifier 10.1109/TMI.2002.806570

several imaging modalities have been developed during the last


decade, which are intended to acquire and process the harmonic
information, or even to separate one kind of such information
from another [2][6].
Although the harmonic imaging was originally developed for
processing echoes from ultrasound contrast agents, it has been
proven to be exceedingly productive to image the harmonics
within the ultrasound echoes (mainly the second harmonics)
even in the absence of contrast agents. This is commonly called
native harmonic or tissue harmonic imaging. The reason for the
generation of harmonics by the tissue is a slight nonlinearity of
the sound propagation, which results in gradual deformation of
the wave shape. It was recognized that the ultrasound images,
obtained in the second harmonic mode, have enhanced resolution and reduced acoustic noise [2], [7][10].
Unfortunately, harmonic imaging possesses a serious
problem of resolution-detectability tradeoff. It is an inevitable
consequence of the fact, that in most of the existing commercial
scanners, the harmonic selection is performed by linear filtering. An example of nonlinear harmonic separation method is
the recently proposed pulse-inversion technique for the second
harmonic enhancement [1][4], but even in this case the bubble
motion artifact results in retaining of a significant portion of
the first harmonic information in the resultant signal, necessitating application of a linear filtering to complete the task. In
this case, the improvement of the imaging resolution causes
unavoidable deteriorations of the measurement of the higher
harmonics, and vice versa. Indeed, the narrower the transmitted
frequency band is, the smaller is the spectral overlap between
the fundamental and harmonic frequencies and, thus, the
higher is the efficiency of the linear filtering for the harmonic
separation. Obviously, the narrowing of the frequency band
worsens the image resolution, putting limitations on image
quality. This situation is sketched in Fig. 1, demonstrating the
overlap of the fundamental and second harmonic bands. One
can formalize the condition for overlap as follow. Suppose
the support of the first frequency band belongs to the set
. Then it is easy to see, that the overlap
.
of the harmonic bands takes place whenever
The question, which the current paper is addressing, is
whether there exists a (possibly, nonlinear) technique that is
capable of separating the fundamental and harmonic frequencies of the received echo sequences, in which the bandwidths
significantly overlap. Moreover, such a technique must be
subjected to an additional constraint, requiring preservation of
the spectral bandwidths of fundamental and higher harmonics

0278-0062/02$17.00 2002 IEEE

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

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computer-based simulation results, while Section VIII provides


results from experiments done with a phantom. Section IX includes discussion of the main results of the study.
II. GENERAL FORMULATION

Fig. 1. A schematic diagram of an overlap between the fundamental and


second harmonic frequency bands.

after the separation. The advantage of such a harmonic-separation technique is self-evident: it could enhance the quality
of harmonic imaging, without the usual tradeoff between
harmonic detectability and imaging resolution.
The main contribution of the current paper is the proposal
of a nonlinear harmonic-separation method, which fulfills the
above requirements, and which can be efficiently implemented
by means of convex optimization. The approach is taken from
the field of sparse signal representations [11], which was successfully applied to the problem of blind source separation [12].
The superior ability of the sparse signal representation to separate components of signals, made up of a superposition of a few
disparate phenomena, was reported [13]. The results obtained
here confirm the advantages of the sparse decompositions over
the traditional linear approaches.
Since the harmonic separation procedure is iterative, the
complexity of the problem should be maximally reduced so as
to minimize the computational load. Such a reduction can be
achieved by means of the demodulation technique that is an
inherent part of almost all current commercial imaging systems.
In order to handle more efficiently the harmonic signals, a
slight modification of the standard demodulation scheme is
proposed here, which is explicitly explained in Section IV
below. It will be shown that the demodulated signals can be
efficiently represented using frames, derived from the familiar
Gabor frame by an appropriate modulation and bandwidth
adjustment (see Section V below).
The paper is organized as follows. Section II introduces theoretical preliminaries, which are necessary to form a basis for
the following derivations. Different models of the signals under
consideration and appropriate demodulation strategies are introduced in Sections III and IV, respectively, where also a proof
is provided that these procedures are optimal from the viewpoint of lossless reduction of the data size. Section V provides
a brief introduction to Gabor frames, with extension of its definition also to the discrete case. It also describes modifications
of standard Gabor frames, which are necessary for efficient representing the harmonic signals at hand. The algorithm structure
is summarized in Section VI. Section VII contains examples of

While methods of the blind source separation consider the


rather more complicated problem of separating a set of linear
mixtures onto a number of unknown source signals, the problem
of harmonics separation may be stated as follows. The acquired
radio-frequency (RF) sequence, that generally comprises the
first (fundamental) as well as higher harmonics, may be considered as a mixture of a few sources. The slightly simplified version is when only the first and the second harmonics are allowed
to exist, and the RF sequence is modeled as a sum of two signals, which represent activity of the first and second harmonic
components respectively, plus a noise term. Note that the model
does not require stationarity of these components, which cannot
be expected due to the process of dispersive (frequency-dependent) attenuation in biological tissues [14], [15]. Now, let ,
, denote a subspace of the Hilbert space of square inbe a sum
tegrable functions. Also let the received signal
,
,
, which are the first and second harof
monic components, and the noise, respectively. Also, suppose
,
, where
that there exists a set of functions,
is a set of indices, constituting a frame in the signal space
(i.e., a set of, generally, linearly dependent vectors, whose span
is dense in ). Then

(2.1)
and
be two subsets of , namely
,
Now, let
, and
, where denotes the space
of square summable sequences. Then, the harmonics separation
problem can be formulated as the following optimization task,
searching for:
(2.2)
and index sets
In words, one needs to find the sequence
, , such that the linear combination of the functions
,
,
with the coefficients, respectively given by
,
, will be as close as posthe subsequences
, correspondingly.
sible to the signal components ,
When the optimal solution is found, the desired signal components are estimated as
(2.3)
The in (2.3) denotes an estimate of the appropriate value.
Unfortunately, the minimization problem (2.2) cannot be
solved directly, until we are given an oracle, providing us with
and . Hence, it is useful to find another
the functions
(possibly sub-optimal) optimization procedure, which will
possess the following three important properties.
1) It must be solvable (that implies obtaining the solution in
finite time, without requiring either infeasible additional
information or conditions).

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

2) The solution obtained by this optimization algorithm,


should be as close as possible to that of the original
problem (2.2).
3) The computational burden of this procedure, should be
reasonable, implying a potential for real-time processing.
Such a procedure does exist and its applicability has been
demonstrated in [11][13] for superresolution representation of
sparse signal components and for the blind source separation.
Finding the sparse solution to (2.2) is a difficult, combinatorial problem. However, under certain conditions, which were recently reviewed in [16], it can be considered equivalent to the
constrained optimization problem, given by
s.t.

(2.4)

The problem (2.4) is commonly known as basis pursuit (BP)a


term, introduced in the pioneering works on this subject [11],
[13]. It is a convex, norm-minimization problem, which can be
efficiently solved by means of the linear programming (LP).
Note that when noise contaminates the signal to be decomposed, the problem (2.4) can be modified to the following unconstrained form:
(2.5)
A computationally efficient solution to (2.5), as well as the rules
for choosing the parameter , are given below.
The optimization problem (2.5) can be efficiently employed
to separate the fundamental and higher harmonics. Without any
loss of generality the formal procedure of harmonics separation, given below, will deal with the problem of first and
second harmonics separation, because its generalization is
straightforward.
The construction of is a crucial step, on which the success of the separation procedure depends in great degree, therefore, it requires some explanation. First, it is signal dependent.
In order to build maximally effectively, some a priori information about the signals and should be incorporated: knowledge of central frequency of the transducer in use and of its
fundamental bandwidth are sufficient, and this information can
be effortlessly obtained through a simple calibration procedure,
preceding the processing.
III. SIGNAL MODELS
In order to design a useful frame , it is required to first define a general model for the signals of interest, with as minimal
number of assumptions as possible. Such a model can be obtained by describing the signals as band-limited (or bandpass)
be a received RF signal,
signals [17, Ch. 7], as follows. Let
, which in
consisting of two components
the context of the present study are interpreted as the first and
second harmonic components of the signal. The noise term,
which should be added whenever actual signals are modeled, is
temporarily ignored for clarity. In most cases, these signals are
band-limited (bandpass), implying the following description:
where

(3.1)

Here
denotes the central frequency of the transmitted ultraare the description pasound pulse, and
and
are peaked
rameters. The two-sided spectra of
and
, correspondin the vicinity of the frequencies
ingly. While the spectrum of the fundamental harmonic can be
, namely
assumed to be enclosed within a band of width
Support
(3.2)
that of the second harmonic might have its support, enclosed in
an interval of rather different width.
Generally, there are two cases, which depend strongly on the
transmitted waveform and on a specific kind of the imposed
nonlinearity. In the first case, the bandwidth of the second harmonic component is approximately equal to that of the fundamental harmonic, formally
Support
(3.3a)
Such a situation frequently takes place, when the nonlinear
propagation of the ultrasound wave is of concern [18]. In the
second case, the spectrum of the second harmonics, when
received from disrupting contrast agents, can have even a
doubled width, as compared with the fundamental band [19].
In this case
Support
(3.3b)
Although the case (3.3a) is included in (3.3b), both these cases
will be treated separately throughout the paper, because they
lead to two distinct algorithms, which have considerably different complexity.
It is important to note, that basically the ultrasound pulse is
produced by a resonance system (the transducer piezoelectric
element), where its motion can be described by a second-order
differential equation. It implies an ultrasound pulse of an oscillatory nature and, hence, its fundamental spectrum should
. As a result,
converge to zero in the neighborhood of
. Regarding the overall signal
one can conclude, that
, one concludes that Support
for
for the case
the case (3.3a) and Support
(3.3b). It implies, that these signals are to be digitized at the samand
, respectively. Because the
pling rates
sampling rate is proportional to the bandwidth of the bandpass
signal, it is often convenient to represent it in terms of a low-pass
signal, whenever the latter can be sampled at a lower sampling
rate. It is performed through a cancellation of a high-frequency
component of the bandpass signals, known as demodulation. Its
modified versions, specially adapted to the harmonic separation
problem, are introduced in the next section.
IV. AUGMENTED DEMODULATION
Since the received RF sequences are real, their Fourier
transforms exhibit conjugate symmetry. It implies a possibility
to describe these signals in the Fourier domain only over the
. Consequently, the
positive semi-axis, i.e., for

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

signals
and
, when treated separately, can be completely characterized by the complex signals
and
, respectively, conditioned that
is known
in advance [17, Ch. 7]. It was found to be very useful to
execute the harmonics separation procedure in the domain
of low-pass signals. The reason for this is twofold. First, it
leads to efficient localization of the signal spectrum, and,
consequently, to optimal reduction of the problem size. Second,
this representation facilitates construction of a frame (as shown
in the section below), which is useful in the context of the
harmonics-separation problem.
in the low-pass domain, but
In order to express the signal
in an equivalent form, a technique similar to the familiar demodulation can be used. It differs from the standard procedure by the
requirement that the information, characterizing both harmonic
components, must be saved in the low-pass domain without loss
or aliasing. Slightly different demodulation schemes are used for
the two cases, when the bandwidth of the second harmonic is similar to that of the fundamental component, and when it is broader.
A. Equal Harmonic Bandwidths
In this case the demodulation is performed by the following
is multiplied by a complex expotwo simple steps. First,
and
, i.e.,
nent, whose frequency is the average of
. Second, the resultant (complex) signal is subjected
to a low-pass filter, whose passband is defined by the interval
. According to the assumption (3.3a), the signal,
so obtained, is given (accurate up to the error introduced by the
filtering) by
(4.1)
From the context of the problem it is obvious, that the complex
and
represent activities of the first and second
signals
harmonic components, correspondingly. Moreover all the original information is preserved by these signals, up to the error,
induced by the filtering. It should be noted that the frequency
is smaller by a factor of two, in
band, spanned by the signal
. The components of
have their
comparison to that of
frequency support included within the intervals, given by
Support
Support

(4.2)

The steps of this demodulation are depicted in Fig. 2. In Fig. 2(A)


and
are illustrated.
the power spectra of the signals
Note that these spectra are sketched schematically in order to
clearly describe their support in the frequency domain. In order
to distinguish between them, the spectrum of the second
is drawn at lower amplitude. The signals
harmonic signal
spectra, as obtained after the frequency shift and filtering, are
shown in Fig. 2(B). Finally, one can see that the spectra of
and
are supported in the interval
, where
they are positioned symmetrically around the origin. Supposing
that the applied low-pass filter has a narrow transition band, one
at the rate equal to
Hz.
can sample the analog signal
,
The sampling results in the complex sequence
and
,
consisting of the sequences

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which represent as before, the first and second harmonics,


respectively.1 In this case, according to the discussion above,
and
, within
the Fourier series of these sequences,
), are peaked in
one period (i.e., within the interval
, respectively, and supported within the
the vicinity of
intervals
Support
Support

(4.3)

to belong
It is possible now to consider the sequence
, which is a space of -seto the signal subspace
quences, whose Fourier series are supported within
. Analogously, one can consider the sequence
as being in the subspace
, which is comprised of the -sequences, having its Fourier series supported
.
within
B. Nonequal Harmonic Bandwidths
From purely theoretical point of view, the bandwidth of
the second harmonic component depends on the waveform
of the transmitted pulse and specific kind of the nonlinearity,
imposed by the insonified medium. To be as general as possible
under such circumstances, one can assume that the bandwidth
of the second harmonic component can be at most twice the
fundamental bandwidth. Consequently, in order to preserve
this component maximally undistorted in the low-pass domain,
and the
the frequency shift (demodulation) is set to be
subsequent low-pass filter has its passband defined by the
. In this case the resultant complex signal
interval
can be represented as
(4.4)
As in the previous case the resultant bandwidth is half the origand
are peaked around
inal, and the complex signals
and 0, respectively, and have their frequency bands supported within
Support
Support

(4.5)

Fig. 3 illustrates this demodulation procedure, where the content


of panels (A) and (B) are the same as those of Fig. 2.
Supposing the low-pass filter has a narrow transition band, the
can be sampled at the rate equal to
.
complex signal
and
have
Consequently, the sequences
their Fourier series supported within
Support
Support

(4.6)

Analogously to the previous case, one can define the signal suband
to which the sequences
spaces
and
are supposed to belong. The next
section addresses the construction of a frame that will be repreand .
sentative for the signal components included in
1In order to simplify the notation below, the same regular case characters will
denote both the sampled signals and the corresponding analog signals.

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

Fig. 2. Demodulation for the case of equal bandwidths of the first and second harmonics. (A) Power spectra of the signals f (t) and f (t). The spectrum of
f (t) has lower amplitude for convenience of visualization. Note that this sketch is merely schematic, intended to clarify the spectra supports. (B) Power spectra
of p (t) and p (t) (after demodulation). Note the symmetry around the origin.

V. GABOR FRAMES FOR HARMONIC SEPARATION


The ultrasound signals could be referred to as signals having
transitory characteristics, specifically when their echoes contain
higher harmonics of the transmitted frequency, e.g., when contrast agent imaging is performed. In such a case, the higher harmonics, radiated from the contrast agent, exhibit a local character, implying that these harmonics appear as transients in the
received RF lines. Thus, an optimal analysis of such a phenomenon may be done by an expansion of the signals into basis functions, which have a compact support both in time and frequency.
Among all possible choices of the basis functions, having a compact support both in time and frequency [20], Gabor functions
seem to be the most suitable in the context of the present study
for the reasons detailed below.

ultrasound signals are sequences of finite duration, the Gabor


frames for the space
are briefly introduced below to clarify
the following frame construction.
be a finite-duration sequence, representing a
Let
complex data signal. It can also be viewed as a vector in the
. Similarly, let
be a sequence,
Euclidian space
, a disreferred to below as a window. Given the window
is generated by shifting
both in
crete Gabor frame in
time and frequency (the inverted commas are used, since
the meaning of time and frequency is not obvious, when con). Let
,
denote the
cerning the vectors in
time-shift parameter, chosen such that is an integer multiple
. For the vectors in
one can define the circular shift
of
by
, where
, as
(5.1)

A. Gabor Frames for


Gabor theory treats expanding signals as linear combinations
of elementary signals that are obtained from a single function
(the window) by shifting it in time and frequency by integer
multiples of a time and a frequency shift parameter (detailed discussion may be found in [21][23]). Because in practice all the

significant shifts, so that the index


There are only
in (5.1) obtains values within the range
. The frequency sampling is characterized by a modulation
, where
. The modulation
parameter
by
of the vectors in
is defined as
(5.2)

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

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Fig. 3. Demodulation for the case of nonequal bandwidths of the first and second harmonics. (A) Power spectra of the signals f (t) and f (t). The spectrum
of f (t) has lower amplitude for convenience of visualization. (B) Power spectra of p (t) and p (t) (after demodulation).

Due

to

periodicity

of
the
Fourier
series
, there are only
significant shifts,
in (5.2). Now it is possible
implying
to define the following collection of vectors, obtained by
applying a composition of the shift and modulation operators
:
to

the condition number of the frame operator (which is the ratio


of the frame bounds and ) defines stability of the representation by the given frame [21].
The properties of the Gabor frames can be quite different, depending on the selection of the discrete window and the parameters and . The selection especially useful in the context of
the harmonics-separation is considered next.
B. Case 1: Equal Harmonic Bandwidths

(5.3)
It was explicitly investigated in [22], [23] that the collection,
with good timegiven by (5.3), can constitute a frame in
frequency localization properties, on condition that
(5.4)
must span all of
in order to be
The vector set
.
a frame in this space, implying that
.
This results in the requirement
matrix, whose columns are formed by
Let be a -by, as given by (5.3). Now,
,
all vectors
one has [24]
(5.5)
is known as a frame opwhere the symmetric matrix
erator, and and are minimal and maximal eigenvalues of ,
respectively. Consequently it can be concluded that every matrix with column rank uniquely represents a frame, where

We start by considering the case, when the bandwidths of the


fundamental and second harmonics are approximately equal. A
relative position of the harmonic components of a discrete seis shown in Fig. 2(B). For this specific case, the
quence
is chosen, as specified by (5.3), where the
frame
is fixed to be three, i.e.,
frequency-sampling parameter
. Let
,
, denote subsets,
applicable to a particular choice of a modulation phase. Conse,
quently, the entire vector set can be viewed as a union of
, namely for
(5.6)
,
It is important to emphasize that within each subset
, the vectors are identical up to a linear phase (i.e., circular shift).
The next parameter to be chosen is the form of the discrete
. It is defined in such a way that its
window

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

Fig. 4. Frame design for the case of equal bandwidths of the first and second harmonics. (A) Supports of the Fourier series of the first and second harmonic
[n] and g
[n], as given by (5.10).
components of the signal p[n], as given by (4.3). (B) Supports of the Fourier series of the vectors g

Fourier series will be a smooth function, compactly supported


in the interval, given by
(5.7)

Support

in its exact
The requirement for compact support of
sense may be too limiting, resulting in noncompactness of
(which is highly undesired). Thus, the rethe sequence
quirement is hereby relaxed, with the phrase supported in the
interval interpreted as having most of its energy concentrated
in the interval.
an operator of modulation by , one can
Denoting by
as follows:
obtain another vector set in

takes place between the supports of


and
, as
and
. This situation is
well as between those of
schematically depicted in Fig. 4, where (A) shows the supports
and
of
of the Fourier series of the components
the signal, representing the harmonics. On the other hand, the
and
supports of the Fourier series of the sequences
are shown in (B). The functions are drawn within the
.
interval of one period, i.e.,
C. Case 2: Nonequal Harmonic Bandwidths
For the case of nonequal harmonic bandwidths, we start the
, as given by (5.3),
frame design with the set
is equal to four,
where the frequency-sampling parameter
. Denoting, as previously, the subset of the frame
i.e.,
vectors, which are appropriate to a specific modulation phase
, one has
by

(5.8)
, this set also constitutes a frame
Due to the unitarity of
, and, moreover, it is characterized by the same frame
for
bounds. The new frame can also be considered as a union of
three subsets given by

where
(5.9)
It can be seen that for the specific choice

(5.11)
where
the window

. The support of the Fourier series of


is chosen to be

Support

(5.12)

In order to adapt this frame to the problem at hand we define a


new subset of vectors, which are given as follows. First, given
, lets
the Fourier series
to be Fourier
define a constricted window
,
coefficients of the dilated Fourier series
, i.e.,
where

Support
Support

(5.10)

efComparing (5.10) with (4.3) implies that


ficiently represents the fundamental (i.e., first) harmonic
represents the second harcomponent , while
monic component . This is because of the coincidence, which

(5.13)
by
Support

Denoting
Support
Support
Support

it is obvious that
, and, moreover,
Support
Support

(5.14)

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Fig. 5. Frame design for the case of nonequal bandwidths of the first and second harmonics. (A) Supports of the Fourier series of the first and second harmonic
components of the signal p[n], as given by (4.6). (B) Supports of the Fourier series of the vectors g [n], k = 1; 2; 3 and g [nj ], as given by (5.13). Note
that the parameter controls the bandwidths of g^ (!), and it should be set adaptively to fit optimally the support of p^ (! ).

Note that because of the choice (5.12) Support


,
, implying that the construction of
can be performed without aliasing.
Finally, the frame to be used for the harmonic separation is
obtained as

current study, because it is simple and accurate. After the discrete window is defined, all the frame vectors are computed and
stored as the columns of a -bymatrix , which will be
referred to as a frame matrix.
VI. SOLUTION BY CONVEX OPTIMIZATION

where

(5.15)

differs
Comparing (5.11) with (5.15) one can see that the set
from only by a subset, comprised of nonmodulated vectors
. Moreover the supports of their Fourier series
(which are continuously controlled by ) are larger or equal to,
, but never exceeding
as compared with those of
Support
. The advantage of the frame, as given by
(5.15), is illustrated in Fig. 5. On one hand, the coincidence of
and
is obvious, implying that
the supports of
the first harmonic component can be efficiently represented
. On the other hand, appropriately
in
choosing the parameter , one can achieve a coincidence
and
, implying that the
of the supports of
second harmonic component can be efficiently represented
. An optimal value of
might be
in
obtained by a calibration procedure, which may be needed for
each given case.
D. Choice of a Window
The last question to be addressed is the choice of the discrete
,
. One option is the envelope of
window
the ultrasound pulse, or its symmetric counterpart, which can
be more conveniently implemented. An important result of this
choice of the window is that the time-support of the pulse
envelope is equal to that of the pulse itself. It means that the
frame functions, derived from it, are ideally suited for the analysis of transient phenomena in the received RF lines, because
their time scale is similar to that of the pulse duration. The pulse
envelope is usually unknown, but can be estimated in a nonparametric manner as shown, for example, in [25]. A different, rather
simpler way to obtain the pulse envelope might be to measure
it directly before the scanning. This approach was used in the

A more concise notation of vectors in the appropriate Euclidean spaces, instead of sequences with indices, will be used
,
, and
be the acbelow. Let
quired RF sequence, the frame matrix [constructed according to
either (5.9) or (5.15)] and a vector of the representation coeffiimplies, that
cients, respectively. being a frame of
(6.1)
Due to the linear dependence of the vectors that comprise the
frame, the definition of the coefficients in (6.1) is not unique.
In the context of the problem of harmonic separation, the representation of by as few frame vectors as possible must be
found. Moreover, in most practical cases, the acquired signals
are contaminated by measurement noises. Since only analysis
of a noise-free part of the signals is of interest, it is tempting
to find a procedure, which can obtain the sparse representation
of the original (i.e., noise-free) signals, ignoring the noise. This
task can be performed by solving the following minimization
problem [13]:
(6.2)
The first term of the functional (6.2) penalizes the misadjustment of the model (6.1), while the second term forces the
solution to be as sparse as possible. Note that the tradeoff
parameter controls the influence of the sparseness penalty.
More about possible choices of , and its connection to the
Lagrange multiplier of the equivalent constrained problem
,
, where
is an
estimated standard deviation of the noise, can be found in
[26]. Note that the noise can be either measured before the
scanning or estimated from the data (see, for example [27]).
However, in this study a different approach to the selection
of was undertaken. It was shown in [11] and [13], that the
solution of (6.2) is closely related to the problem of de-noising

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by thresholding of the representation coefficients. This relation


facilitates the choice of the tradeoff parameter in (6.2),
, where is a
which was shown to be
standard deviation of the noise. Although this choice of the
threshold has been criticized as being of poor performance
for the problem of image de-noising (and more sophisticated
schemes have been proposed in [28]) we found this universal
threshold to be quite acceptable for the problem of harmonic
separation, as confirmed by the results of the computer and
phantom experiments (see the following sections).
It is interesting to note that an alternative method of finding
the representation coefficients in (6.1) might be the minimiza, where solves (6.1). This
tion of the Euclidian norm
method is known as method of frames (MOF) [11], and it possesses an analytic solution of the form
(6.3)
Solution (6.3) will be used for comparison during the evaluation
of the new method by computer and phantom experiments.
Finally, the minimization method should be selected. In
the current study, the FletcherReeves version [29, Ch. 1]
of the conjugate gradient algorithm is employed. Note that
this method cannot be directly applied to (6.2), because of
the nondifferentiability of the -norm. In order to overcome
this, the -norm was replaced by its smooth approximation,
, where
is sufficiently
small.
VII. SIMULATION STUDY
The performance of the harmonics-separation algorithm was
validated by simulations. In order to synthesize an input to
the algorithm, a model of the signal formation is defined by assuming the signal to contain two components. The first has its
energy concentrated around the fundamental frequency , as
might be measured from a biological tissue, assuming linear
wave propagation. The second has its energy lumped around
, mimicking a
both fundamental and double frequency, i.e.,
signal, which might be measured from nonlinear scatterers, e.g.,
contrast agents. The harmonic-free component can be modeled by the convolution of the ultrasound pulse with a function
representing the reflectivity properties of the interrogated tissue.
Since the statistic properties of the latter have no specific importance in the case of harmonics separation, it can be modeled as
an independent identically distributed (i.i.d.) random process,
obeying a Gaussian distribution. The convolution model is also
applicable for simulating the second nonlinear component.
Given a pressure wave, reflected (or reradiated) from a gas-filled
microbubble, this component can be obtained by convolving it
with a function, which accounts for the nonlinear scattering of
the interrogated tissue. Though this modeling might seem simplistic (indeed, all microbubbles cannot be assumed to reflect
identical pressure profile, because the later greatly depends on
their radii), it turns out to be quite useful during simulations,
allowing to investigate all the main features of the proposed
algorithm.
The choice of the reflectivity function for the nonlinear signal
component depends on the practical situation being described.

The problem of harmonics separation is considered here as part


of the problem of transient detection: within the time-dependant RF signal, the second harmonic component lasts a fraction
of the duration vs. the time the first harmonic component exists, and is referred to as a transient signal (or simply transient).
The goal is to detect the transient, which in medical ultrasound,
may be generated from contrast agent within a narrow vessel
(e.g., 23 mm) embedded in tissue. A reflectivity function, modeling such a transient, is synthesized by a Gaussian i.i.d. random
process, where most of the signal samples are zeroed, except
few at the location of the vessel. The latter was positioned,
for convenience of the analysis, at the centers of all the synthesized signals. The variances of both linear and nonlinear
reflectivity function were chosen to be equal. All the resultant
RF sequences were contaminated by a white noise, producing
SNR of 17 dB.
Two different nonlinear pulses were simulated, by solving
the RayleighPlesset equation for a 2.5- m microbubble in
water, where the driving pressure was 2- and 1-cycle sine
waveforms, with a central frequency of 2.2 MHz [18]. Other
parameters have been chosen such that the first and second
harmonic components of these pulses possess different degrees
of overlap between their spectra. Fig. 6 shows these pulses
in the time (left subplots) and the frequency (right subplots)
domains. Notice that in both cases the first-to-second harmonic
ration is about 12 dB.
The results are described in a joint time-frequency (TF) plane
by means of the short-time Fourier transform (STFT), implemented as described in [30, Ch. 4.2]. All the STFT are viewed in
a negative colormap, with the largest amplitudes drawn in dark
colors. Since the first harmonic component was approximately
similar for all the methods being applied, only the second harmonic components are compared. The transient, i.e., the second
harmonic components, appear in vicinity of 4.4 MHz (i.e., twice
the fundamental frequency), at times between roughly 5 and
11 s.
When analyzing the results obtained by a series of simulations, it was observed that the bandwidth of the second harmonic
component differs insignificantly from that of the fundamental
component. Hence, in the current section, the demodulation,
described in Section IV-A, is performed and the frame is constructed as specified in Section V-B. The window was set to be
a Gaussian function, scaled to have a frequency support, as re, thus,
quired by (5.7). Parameter was chosen to be
the frame can be considered as 1.5-fold oversampled.
Comparison is made to the method of frames (MOF) (see
(3.3), [11]) and the matched harmonic filtering (MHF). The
passband of the matching filter was adjusted to that of the second
harmonic.
After the representation coefficients have been obtained, they
were used to recover the components, depicted in Figs. 7 and
8, for RF lines having different degrees of overlap between the
first and second harmonic spectra. Note that all the sequences
were normalized to have a unit Euclidian norm before the visualization. In both figures, subplot (A1) shows the second harmonic component, recovered using MHF; subplot (A2) shows
the estimate of this harmonic component, obtained by MOF; and
subplot (A3) shows the second harmonic component, obtained

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

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Fig. 6. Examples of nonlinear pulses, used in the computer study for simulating the response of a nonlinear medium, e.g., contrast agent. (A) and (C) Pulses
in the time domain. (B) and (D) Spectra of the pulses (normalized to have peak values of 0 dB). Note that the pulses possess different degrees of overlap between
the first and the second harmonic bands.

Fig. 7. Estimates of the second harmonic component of the simulated RF lines, synthesized using the example of a nonlinear pulse, shown in Fig. 6(A) and
(B). (A1) Estimate obtained by MHF. (A2) Estimate obtained by MOF. (A3) Estimate obtained by sparse representation (BP). (B1)(B3) Appropriate estimates in
the time-frequency plane.

by the BP, i.e., through the sparse representation. The latter is


characterized by a significantly better reconstruction quality.
The estimates are also depicted in the time-frequency plane:
(B1)(B3) show the STFT of the results. The time-frequency
patterns of the second harmonic estimates are significantly dif-

ferent, when obtained either by MHF (subplots A1, B1), MOF


(subplots A2, B2), or BP (subplots A3, B3). In the first two cases
noticeable noise appears, while the latter case is noise-free and
well concentrated. Furthermore, when analyzing the detected
transients in the time-frequency plane, one can see that the fre-

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

Fig. 8. Estimates of the second harmonic component of the simulated RF lines, synthesized using the example of a nonlinear pulse, shown in Fig. 6 (C) and
(D). (A1) Estimate obtained by MHF. (A2) Estimate obtained by MOF. (A3) Estimate obtained by sparse representation (BP). (B1)(B3) Appropriate estimates in
the time-frequency plane.

quency bandwidth is preserved by the BP-bases method of harmonic separation.


VIII. PHANTOM EXPERIMENTS
Phantom experiments were made to study the applicability of
the proposed algorithm to the problem of harmonic imaging of
contrast agents. Contrast agents are used to assess perfusion of
tissue or tumor, since the slow flow rate in the smallest vessels
is not detected by Doppler ultrasound. The expectation to detect the contrast agent within the small vessels is mainly due
to the inherent nonlinearity of the gas micro-bubbles, which
was demonstrated to help detect the contrast agents [1][6],
[31][33].
Experiments were performed on a custom-made, tissue-mimicking phantom. The phantom was constructed of a suspension of Carborundum-1000 particles in agar (AgarAgar,
HISPANGAR, Spain) solution. It was observed, that the
phantoms produced in this way, reflect the acoustical energy
in a manner close to that of different biological soft tissues
[1], [4], [31]. The Carborundum-1000 is composed of silica
carbide particles having diameters ranging from 5 to 10 m
and acting as linear scatterers of ultrasound. The phantom was
obtained by rapid cooling of 1.8% of the Carborundum powder
suspension in 3.8% AgarAgar bed. This phantom is intended
to produce the background scattering level. Two hollow latex
tubes with inner diameter of 2 mm were embedded into the
phantom to mimic two coronary vessels. Diluted contrast agent
was made to flow through these tubes at flow velocity of about
2 cm/s The distance from the transducer to the outside surface

Fig. 9. Sketch of the phantom, used in the experimental study.

of the nearest tube was approximately equal to the focal length


(42 mm). The distance between the tubes was about 1 mm. A
sketch of the phantom is shown in Fig. 9.
The phantom was imaged by a focused, single-element,
3.5 MHz-transducer (Panametrics V383, Waltham, MA). Each
image was obtained from a set of RF sequences, gathered by

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

shifting the transducer in the lateral direction with an increment


of 1 mm. Each scanning resulted in 34 RF sequences. Note
that the scanning cross-section was chosen in such a way that
both tubes are positioned within it, i.e., the scanning direction
was carefully aligned with the coronary vessels (tubes). A
computer controllable transmitterreceiver (Advanced measurement system RAM-5000, RITEC), generating sine waves
with an adjustable number of sine periods and an adjustable
frequency, was used for driving the transducer and for acquiring
the RF lines. In order to use the transducer bandwidth during
reception as efficiently as possible for acquiring both the first
and the second harmonics, the transducer was excited at 2 MHz
by a sine wave of one period. The RF lines were sampled at
a rate of 25 MHz using CompuScope14100 (analog-to-digital
card for PCI bus, GAGE Applied, Inc.) The sampling resolution
was 14 bit. The data acquisition process was controlled through
GageScope software. All the acquired RF sequences were
truncated to the length of 1024 sample points, which provided
data from the phantom ranging from its surface to the depth of
approximately 63 mm.
The pressure amplitude of the transducer was set by a calibration procedure in such a way that before the injection of a contrast agent, there was no detectable second harmonics. In other
words, the pressure was chosen sufficiently small so that the
nonlinear propagation effect could not be measured. Under such
conditions, if when injecting contrast agent the second harmonic
component is generated, it is entirely ascribed to the contrast
agent. The method was tested with Optison (Molecular Biosystems, San Diego, CA). The Optison was diluted to a concentration of 0.2 ml in 500 ml of distilled water.
The Gabor frame, used in the phantom experiment, was
constructed, according to the description of Section V-C, following the appropriate demodulation procedure, presented in
Section IV-B. This frame was chosen, because it was observed
during preliminary analysis of the spectra of the received RF
lines, that the second harmonic bandwidth is slightly broader
than that of the fundamental harmonic. Frame design parameter
was chosen empirically (based on the observations of the
signals spectra) to be equal to 1.2.
A window function was obtained using the envelope of the
measured ultrasound pulse, as obtained in a water tank from a
planar reflector. This pulse was appropriately preprocessed so
that the resulting discrete window fulfills the conditions specwas chosen to
ified by (5.12). The frame design parameter
(where
is the length of the demodulated RF
be
lines), resulting in twofold oversampled Gabor frame. The increase of the overcompleteness did not result in any noticeable
improvement of the results. Thus, this choice can be viewed as
optimal, in the sense that it balances both the detection quality
and computation load. The harmonics separation algorithm was
executed using Matlab (The Mathworks, Inc., Natick, MA) on
a standard Pentium3 computer. The total execution time (for an
image as demonstrated below) was 21.2 s. The processing resulted in two images, corresponding to the first and the second
harmonic components of the RF image. Both images were transformed into the video format by standard I/Q demodulation
procedure, and visualized in the common 8-bit resolution. No
attenuation correction was performed and the dynamic range of

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the images was not optimized and, therefore, their quality may
be potentially improved.
Two other pairs of images were produced so as to compare
the MHF and MOF algorithms. In the MHF method two
matching filters were employed, where the first one was
adjusted to transfer the first harmonic frequencies, while the
second one transfers the second harmonic component. Note
that the matching harmonic filtering allows keeping the axial
resolution as high as possible. It is of importance, since the new
approach presented here has the advantage of retaining the axial
resolution, and, thus, the performance of all techniques should
be compared at the same resolution. The images obtained using
the MHF and MOF algorithms were subjected to the standard
I/Q demodulation, and visualized in 8-bit resolution, so that
all the images presented in this paper have the same dynamic
range.
The first harmonic images, obtained by all the algorithms
tested here, are very similar, thus, only one is shown, that is
obtained using MHF. This image is shown in Fig. 10(A), where
the effect of the contrast agent is demonstrated by an increase
of brightness inside the tubes. Fig. 10(B) shows a second-harmonic image, obtained by the MHF algorithm, while Fig. 10 (C)
shows this image, as obtained by the MOF. Note that in both
these cases the vessels are significantly masked by the portion
of the fundamental energy that leaks into the second harmonic
band. The second harmonic image, obtained by BP (sparse solution), is viewed in Fig. 10(D), where the only visible object is the
contrast agent, flowing in the two vessels. There is hardly any
masking by background reflections or strong reflections from
the tube-tissue interfaces.
IX. DISCUSSION AND CONCLUSION
In this paper a novel approach is presented to the problem
of separation of the harmonic components within an acquired
RF image. The proposed method differs from the conventional
approaches, which employ linear filtration. Linear filtration,
when applied to ultrasound harmonic processing, has several
shortcomings, among which is the inverse relation between
the transmitted bandwidth and the ability to detect the higher
harmonics. In such a case, the filter designed to extract the
second harmonics, allows significant energy related to the first
harmonics, to penetrate into the resultant signal. Since the
first harmonic component is typically stronger in comparison
with the second, this leakage tends to mask the second
harmonic component. In contrast imaging, where the higher
harmonics induced by the contrast agent are measured, it is
generally accepted that the second harmonics are masked by
native tissue harmonics produced by the nonlinear propagation
of the acoustic waves. However, when using linear filtration
during contrast agent imaging, the effect of the leakage of
the fundamental component into the frequency band of the
second harmonic component is much more destructive. It
considerably masks the information related to the nonlinearity
of the interrogated tissue or contrast agent. Consequently, in
order to obtain true harmonic images, this leakage must be
suppressed. It was reported [1], [31] that the higher harmonics
induced by contrast agents are often larger in amplitude than

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 21, NO. 12, DECEMBER 2002

Fig. 10. (A) First harmonic image of the phantom, as obtained by MHF. (B) Second harmonic image of the phantom, as obtained by MHF. (C) Second harmonic
image of the phantom, as obtained by MOF. (D) Second harmonic image of the phantom, as obtained by sparse decomposition (BP).

the amplitudes of the native tissue harmonics. Thus, when


leakage-free processing is used, the obtained second harmonic image can be very useful for imaging the contrast agent.
In this paper, the separation of the harmonic components is
based conceptually on the ideas of sparse representations of signals in over-complete bases, first introduced in [11], [13]. A special type of such bases, the Gabor Frames, which is particularly
suitable (after proper modifications) for the given problem, was
explicitly described. It was shown that it is capable of separating
the first harmonics from the second harmonics without any deterioration of the image resolution.
The proposed algorithm was specified for two different
cases: when the bandwidth of the second harmonic component
is larger than that of the fundamental harmonic component and
when these bandwidths are approximately equal. In both cases
the algorithm performance remains the same. Yet, for the case
of nonequal harmonic bandwidths, a higher sampling rate is
required. Moreover, it results in using a frame, characterized
by a higher overcompleteness. As a result, its computational
complexity is considerably higher than for the case of equal
bandwidths. Therefore, the latter case is preferred, whenever
the frequency supports of the first and second harmonics are
approximately equal. It should be noted, that though expected,
the broadening of the second harmonic bandwidth is frequently
insignificant in practice. Thus, using the harmonic separation
method, as proposed for the case of the equal bandwidths,
can result in significantly faster convergence, while hardly
worsening the resultant resolution.
The results obtained from computer simulations demonstrate
the advantages of the novel approach for transient harmonic detection. Its performance was compared with that of the MHF
and MOF algorithms. It was observed that the solutions by these

alternative methods, although preserving the axial resolution,


fail when additive noise is introduced. The solution by MOF,
in particular, tends to spread the energy evenly among all the
frame functions. It causes the noise within the frequency band of
the second harmonic component to be interpreted as the desired
transient. On the other hand, the BP (i.e. sparse representation)
is much more greedy, representing the signal with as few coefficients as possible. Consequently, the algorithm tends to ignore
the noise part of signal, which results in a robust estimation.
The proposed approach was additionally evaluated by
phantom experiments. These results were also compared with
those produced using the MHF and MOF methods. The experimental system was calibrated to have no native harmonics
in the reflected signals, so that the second harmonics, induced
by the contrast agent, appears on the background of the fundamental harmonic component. It was shown, that when the
MHF and MOF approaches are employed, the fraction of the
fundamental energy, leaking through the second harmonic
band, produces visible background reflections, which mask
the vessels. In contrast, the second-harmonic image, obtained
using the sparse-representation approach, is fairly free of this
artifact. These results also justify the hypothesis, concerning
the first harmonic leakage and its role in masking the contrast
agent (higher) harmonics. It is the most important result of
the current study. It implies that the novel technique provides
the possibility to acquire ultrasound images, which represent
only the nonlinear effects, without deterioration of the image
resolution. Moreover, these images are obtained as solutions of
the sparse frame problem by convex optimization.
Numerous reports describe different types of techniques intended to increase the contrast-to-native ratio within the acquired second harmonic component [3][6]. These techniques

MICHAILOVICH AND ADAM: A HIGH-RESOLUTION TECHNIQUE FOR ULTRASOUND HARMONIC IMAGING

have a common shortcoming, since they require transmitting


several pulses. In these cases the motion artifacts are crucial, and
the continuous motion of bubbles results in continuous alternations of the reflectivity function. Thus, when RF sequences,
generated by repeated transmits are compared, it is unknown
whether the changes are due to the nonlinearity of the contrast
agent or due to the alteration of the reflecting structure. The
method presented here does not require any change in the standard hardware structure of the imaging system. It requires as an
input a standard image and splits it onto two images, one for
each harmonic component.
The structure of the Gabor Frames used here, implies easy
extension to the separation of other frequency bands, e.g., the
second and third harmonics. Moreover, if the imaging system
in use has the required spectral properties, the algorithm can be
easily modified to simultaneously separate the first, second and
third harmonic components.

ACKNOWLEDGMENT
The authors would like to thank Prof. A. Ron from the University of Wisconsin-Madison for a helpful consultation. They
would like also to thank all the anonymous reviewers, whose
useful comments significantly improved the paper.

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