Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2002-11-01
2004-08-31
Imam, Ali M (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06783496
ABSTRACT:
BACKGROUND OF THE INVENTION
Certain embodiments of the present invention relate to ultrasound imaging of the human anatomy for the purpose of medical diagnosis. In particular, certain embodiments of the present invention relate to methods and apparatus for improving the ratio of contrast signals to tissue signals in ultrasound contrast imaging.
Contrast agents may be used with ultrasound imaging to enhance the clinical evaluation of blood flow and perfusion, which is the circulation of blood to an organ or tissue. The contrast agents comprise microbubbles which are typically 1-10 um in size. When injected into a patient's blood, the contrast microbubbles generate nonlinear signals and increase the ultrasound echo strength in comparison to the echo strength of blood without contrast. Tissue also generates nonlinear signals, but the nonlinear tissue signals are generally weaker than the nonlinear contrast signals.
In order to visualize blood flow or perfusion of tissue, the tissue echo strength must be significantly reduced relative to the contrast echo strength. One way to suppress the tissue signal is to image second or high harmonics of the nonlinear signals generated by the microbubbles. In basic harmonic imaging, a narrowband signal is transmitted at a frequency, f
0
. In U.S. Pat. Nos. 5,724,979 and 5,733,527, the returned echoes are band pass filtered at 2f
0
in order to image a second harmonic signal generated by the microbubbles and tissue. Alternatively, in U.S. Pat. Nos. 5,632,277, 5,706,819, and 6,3719,914, pulse inversion permits overlap of the fundamental and harmonic bands for better spatial resolution by using two phase inverted transmit pulses to cancel the fundamental (linear) component which leaves the nonlinear components to be imaged.
For each of the aforementioned conventional methods, the ratio of contrast to tissue signal strength is still insufficient for imaging tissue perfusion. One method to improve the contrast-to-tissue ratio (CTR) is to reduce the transmit mechanical index (MI), because the nonlinear signal of tissue falls faster than the nonlinear signal of contrast as the MI decreases. This method, however, experiences signal-to-noise ratio (SNR) limitations.
Compared to techniques which use second or high harmonics, subharmonic imaging has the advantage that tissue does not produce significant subharmonic content, and thus a high CTR can be maintained. (see U.S. Pat. No. 6,117,082; James Chomas et al., “Subharmonic Phase-Inversion for Tumor Perfusion Estimation”; P. M. Shankar et al., “Advantage of Subharmonic Over Second Harmonic Backscatter for Contrast-to-Tissue Echo Enhancement”) Subharmonic imaging involves transmitting a pulse at a fundamental frequency, f
0
, and filtering the received echoes to reject echoes at f
0
, while receiving echoes at a subharmonic frequency of f
0
, e.g. f
0
/2, f
0
/3, and the like. However, the subharmonic signal level is generally much lower than the second harmonic and fundamental signal. Another problem experienced while generating the subharmonic response is that a pressure threshold exists which may be too high for low MI real-time perfusion imaging.
Subharmonic generation is a positive feed back loop. In U.S. Pat. No. 6,117,082, a seed signal at a subharmonic frequency is introduced to induce the positive feed back of the subharmonic signal generation during the pulsing time. To avoid tissue signal generated by the seed signal, the seed signal is put almost 40 dB down compared to the fundamental signal. The low amplitude of the seed signal limits the speed for generating a high level subharmonic signal. Thus, high pressure and a long transmit pulse are needed to generate a strong subharmonic signal.
Recently, a phase inverted subharmonic imaging method was developed to further enhance the CTR. It was found that the threshold to generate subharmonic vibration could be low when the transmit frequency is at two times the microbubble resonance frequency. (James Chomas et al., “Subharmonic Phase-Inversion for Tumor Perfusion Estimation”). However, a seed subharmonic signal is not employed, so a high pressure is still needed to generate enough subharmonic signal for imaging.
For many contrast applications, and especially for perfusion imaging, bubble destruction has to be avoided. Contrast microbubbles are destroyed by high-MI ultrasound pulses, therefore, low-MI pulses are desired in order to not destroy contrast agents and in order to maintain a longer duration over which the contrast agents may be imaged.
Therefore, a need exists for a method to perform ultrasound imaging using contrast which generates a strong subharmonic signal and which improves the ratio of contrast echo signals to tissue echo signals, while not destroying the contrast microbubbles for continued imaging of microbubbles. It is an object of certain embodiments of the present invention to meet these needs and other objectives that will become apparent from the description and drawings set forth below.
BRIEF SUMMARY OF THE INVENTION
A method for improving contrast-to-tissue ratio while imaging contrast infused tissue and blood vessels is provided. The method includes infusing a subject with contrast medium having microbubbles having a fundamental frequency. A first transmit pulse comprising first and second signals is transmitted into the subject. The first signal has a first frequency based on the fundamental frequency and the second signal has a second frequency based on the first frequency and is lower than the first frequency. A second transmit pulse comprising third and fourth signals having the first and second frequencies, respectively, is transmitted into the subject. The third and fourth signals are phase inverted with respect to the first and second signals.
A method of imaging a patient using diagnostic ultrasound is provided including generating first and second signals having first and second frequencies, respectively. The second frequency is a subharmonic frequency with respect to the first frequency. The method further includes combining the first and second signals to create a first transmit pulse. Third and fourth signals are generated with the first and second frequencies, respectively, and the third and fourth signals are phase inverted with respect to the first and second signals. The third and fourth signals are combined to create a second transmit pulse.
A system for improving a contrast-to-tissue ratio while imaging contrast infused tissue and blood vessels is provided. The system includes a seeded waveform generator generating first and second transmit pulses comprising basic and seed signals. The basic signal has a first frequency and the seed signal has a second frequency which is a subharmonic frequency of the first frequency. The first and second transmit pulses are phase inverted with respect to each other. The system further includes a transmitter transmitting the first and second transmit pulses into a patient having tissue and blood vessels infused with contrast agent comprising microbubbles. A receiver receives first and second sets of echoes based on the first and second transmit pulses, respectively. A filter being centered at a frequency based on the second frequency filters the first and second sets of echoes to create filtered signals representing a response from the microbubbles.
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Cheri X. Deng, et al., “A Review of Physical Phenomena Associated With Ultrasonic Contrast Agents and Illustrative Clinical Applications,” Ultrasound in Medicine and Biology, vol. 28, No. 3, pp. 227-286, 2002.
David Hope Simpson et. al, “Pulse Inversion Doppler: Anew Method for Detecting Nonlinear Echoes from Microbub
Chiao Richard Yun
Hao Xiaohui
Dellapenna Michael A.
GE Medical Systems Global Technology Company LLC
Imam Ali M
McAndrews Held & Malloy Ltd.
Vogel Peter J.
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