Patent Grant
RE43048
This invention relates to ultrasonic diagnosis and imaging of the body with ultrasonic contrast agents and, in particular, to new methods and apparatus for ultrasonically detecting and imaging with contrast agents.
Ultrasonic diagnostic imaging systems are capable of imaging and measuring the physiology within the body in a completely noninvasive manner. Ultrasonic waves are transmitted into the body from the surface of the skin and are reflected from tissue and cells within the body. The reflected echoes are received by an ultrasonic transducer and processed to produce an image or measurement of blood flow. Diagnosis is thereby possible with no intervention into the body of the patient.
However materials known as ultrasonic contrast agents can be introduced into the body to enhance ultrasonic diagnosis. Contrast agents are substances which will strongly interact with ultrasonic waves, returning echoes which may be clearly distinguished from those returned by blood and tissue. One class of substances which has been found to be especially useful as an ultrasonic contrast agent is gases, in the form of tiny bubbles called microbubbles. Microbubbles present a significant acoustic impedance mismatch in comparison to tissue and fluids, and nonlinear behavior in certain acoustic fields which is readily detectable through special ultrasonic processing. In order to infuse bubbles into the body so that they will survive passage through the pulmonary system and circulate throughout the vascular system, gases have been stabilized in solutions in the form of tiny microbubbles. Microbubble contrast agents are useful for imaging the body's vascular system, for instance, as the contrast agent can be injected into the bloodstream and will pass through the veins and arteries of the body with the blood supply until filtered from the blood stream in the lungs, kidneys and liver.
One property of microbubble contrast agents currently under investigation is harmonic response. These harmonic contrast agents exhibit significant, detectable responses at frequencies which are harmonics of the transmitted ultrasonic frequency. This property is useful for clutter rejection of the received signals. When the transmitted frequency band is used as the received frequency band, echoes will be returned from the microbubbles, but also from surrounding tissue, the latter comprising clutter in the received echo signals. But with harmonic contrast agents, reception occurs at harmonic frequencies, where fundamental band clutter from tissue is ignored. Since tissue generally reflects very minimal harmonic components, the received harmonic band enables the microbubble echoes to be received with a high signal to noise ratio.
In accordance with the principles of present invention, a technique is provided for the detection and imaging of harmonic ultrasonic contrast agents. The harmonic contrast agent is insonified by alternate polarity transmitted pulses, and the echo signals received from the transmitted pulses are combined. The result is a suppression of harmonic components of the transmitted ultrasonic waves and the elimination of clutter.
In the drawings:
Referring to
In
Echoes received by the transducer array 112 are coupled through the T/R switch 114 and digitized by analog to digital converters 115. The sampling frequency fs of the A/D converters 115 is controlled by the central controller. The desired sampling rate dictated by sampling theory is at least twice the highest frequency fc of the received passband and, for the preceding exemplary frequencies, might be on the order of at least 8 MHz. Sampling rates higher than the minimum requirement are also desirable.
The echo signal samples from the individual transducer elements are delayed and summed by a beamformer 116 to form coherent echo signals. The digital coherent echo signals are then filtered by a digital filter 118. In this embodiment, the transmit frequency ftr is not tied to the receiver, and hence the receiver is free to receive a band of frequencies which is separate from the transmitted band. The digital filter 118 bandpass filters the signals in the passband bounded by frequencies fL and fc in
Filtered echo signals from tissue, generally filtered by a passband centered about or demodulated from the transmit frequency, are coupled to a B mode processor 37 for conventional B mode processing. Filtered echo signals of the harmonic contrast agent passband are coupled to a contrast signal detector 128 which performs pulse to pulse summation or integration of temporally discrete echoes from a given spatial location, amplitude or envelope detects the combined signals. Simple two pulse summation of the form P1+P2 may be employed where P1 represents the echoes received following one pulse and P2 represents the echoes received following another pulse. The combination of echoes from consecutive pulses may, if desired, be performed before the digital filter 118 rather than after, the decision being a matter of choice of system design.
The filtered echo signals from the digital filter 118 are also coupled to a Doppler processor 130 for conventional Doppler processing to produce velocity and power Doppler signals. The outputs of these processors are coupled to a 3D image rendering processor 132 for the rendering of three dimensional images, which are stored in a 3D image memory 134. Three dimensional rendering may be performed as described in U.S. patent application Ser. No. 08/638,710, and in U.S. Pat. Nos. 5,474,073 and 5,485,842, the latter two patents illustrating three dimensional power Doppler ultrasonic imaging techniques. The signals from the contrast signal detector 128, the processors 37 and 130, and the three dimensional image signals are coupled to a video processor 140 where they may be selected for display on an image display 50 as dictated by user selection. The video processor preferably includes persistence processing, whereby momentary intensity peaks of detected contrast agents can be sustained in the image. One technique for providing persistence is through frame averaging, whereby new image frames are combined with previous frame information on a spatial basis. The combination can be done by weighting the contributions of the old and new frame information and the frame information can be combined in a recursive manner; that is, old frame information is fed back for combining with new frame information. A preferred persistence technique is the fast attack, slow decay technique described in U.S. Pat. No. 5,215,094, which can be applied to both Doppler and contrast agent images.
The apparatus of
The echoes received from microbubbles in response to these alternate polarity transmissions are shown in
Following transmission of the ultrasonic pulse exhibiting the opposite polarity, the echo waveform 312 of
A mathematical analysis of this effect and response is as follows. To detect the harmonic response of microbubbles, the harmonic component in the incident pressure wave must be suppressed. Based on the analytical solution of the dynamic motion of microbubbles, the primary component of the backscattering pressure magnitude is linearly proportional to the incident pressure and the harmonic component is quadratically proportional to the incident pressure pi or ps(ω)αpi and ps(2ω)αpi2. Thus, neglecting the higher order terms, one may write the backscattering pressure magnitude pB(ω) from a microbubble in a generic form
PB(ω)=k1(ω)p+k2(ω)p2 (1)
where k1 and k2 are parametrically related to the acoustic properties of the microbubble such as size, viscosity, surface tension, ambient pressure, etc.
Now assume that the microbubble is excited by two narrow band signals at different times but with the same magnitude p and at the same frequency ω, but with opposite polarity: pi1=p cos ωt and pi2=−p cos ωt. Then the back-scattered pressure wave from pi1=p cos ωt is
pB1(ω,t)=k1(ω,t)p+k2(ω,t)p2 (2)
and from pi1=−p cos ωt is
pB2(ω,t+δt)=k1(ω,t+δt)p+k2(ω,t+δt)p2 (3)
Then the total backscattered pressure magnitude may be obtained by summing Equations (2) and (3),
S=pB1+pB2=(k1(ω,t)−k1(ω,t+δt))p+(k2(ω,t)+k2(ω,t+δt))p2 (4)
≈2k2(ω)p2
Equation (4) shows that the primary component is eliminated if k1(ω) and k2(ω) do not change substantially in the time duration δt, where δt is small.
Assume the backscattering from microbubbles is quasi-stationary over T, where T is the pulse repetition interval. Therefore, the average nonlinear acoustic properties are not changed over time T, or
E{k1(ω,t)}≅E{k1(ω,t+T)}
and
E{k2(ωt)}≅E{k2(ω,t+T)}.
The relationship of Equation (4) will hold by summing the pulse echoes from two pulses which are time-diverse in T. The quasi-stationary assumption is valid for slow perfused flow, such as myocardial perfusion.
When the bandwidth of the incident pressure wave is wide, the wideband excitation wave P(t) may be represented by a Fourier series
Thus the backscattered pressure magnitude of the microbubbles from P(t) may be written as
and the backscattered pressure magnitude of the microbubbles from −P(t) may be written as
Summing Equations (5) and (6), one may obtain
Again, the harmonic component is extracted and the primary component is eliminated.
Let us assume the nonlinearity in tissue is negligible. Since the backscattered pressure in a linear medium is linearly proportional to the incident pressure wave, the polarity of the backscattered wave will be changed as the polarity of the incident pressure wave is changed. Assuming the tissue is relatively stationary during the period of two consecutive pulses, summing the pulse echoes from consecutive pulses with opposite polarity will cancel the echo response from tissue. Thus, tissue clutter will be suppressed.
The concept of summing the pulse echoes from two pulses of opposite polarity may be generalized into processing echoes from multiple pulses with alternate polarity to maximize the sensitivity and minimize the variance, assuming the tissue is stationary during the pulsing interval. Let the pulse sequence be
P={p −p p− p p− p * *−p p}
and the pulse echoes be
E={E1 E2 E3 E4 E5 E6 · · · En}
Accumulating the partial sum of consecutive pairs of echoes results in
This application claims the benefit of U.S. Provisional Application No. 60/005,009, filed Oct. 10, 1995.
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| Number | Date | Country | |
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| Child | 09481814 | US |
