Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
  • G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
  • G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
  • G01S7/52017—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
  • G01S7/52019—Details of transmitters
  • G01S7/5202—Details of transmitters for pulse systems
  • G01S7/52022—Details of transmitters for pulse systems using a sequence of pulses, at least one pulse manipulating the transmissivity or reflexivity of the medium
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
  • G01S15/00—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
  • G01S15/88—Sonar systems specially adapted for specific applications
  • G01S15/89—Sonar systems specially adapted for specific applications for mapping or imaging
  • G01S15/8906—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques
  • G01S15/895—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques characterised by the transmitted frequency spectrum
  • G01S15/8952—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques characterised by the transmitted frequency spectrum using discrete, multiple frequencies
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
  • G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
  • G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
  • G01S7/52017—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
  • G01S7/52077—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging with means for elimination of unwanted signals, e.g. noise or interference
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
  • G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
  • G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
  • G01S7/52017—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
  • G01S7/52023—Details of receivers
  • G01S7/52036—Details of receivers using analysis of echo signal for target characterisation
  • G01S7/52038—Details of receivers using analysis of echo signal for target characterisation involving non-linear properties of the propagation medium or of the reflective target

Definitions

• This invention relates to methods and systems for ultrasonic detection and imaging of contrast agents located in soft tissue or tissue fluids.
• Ultrasound contrast agents are typically made as solutions of micro gas bubbles or nano lipid particles.
• the gas bubbles typically show strong and nonlinear scattering of the ultrasound, a phenomenon that is used to differentiate the contrast agent signal from the tissue signal.
• the increased scattering from the contrast agent within the transmitted frequency band was used to enhance the scattering from blood.
• second harmonic components in the nonlinearly scattered signal were used to further enhance the contrast agent signal above the tissue signal in methods generally referred to as nonlinear contrast harmonic imaging.
• CTR Contrast signal to Tissue signal Ratio. This gives the ratio of the signal power scattered from the contrast agent in a region to the signal power scattered from the tissue in that region. This ratio is often referred to as specificity.
• CNR Contrast signal to Noise Ratio. This gives the ratio of the signal power scattered from the contrast agent in a region to the noise power in that region. This ratio is often referred to as sensitivity.
• the CNR determines the maximum depth for imaging the contrast agent while the CTR describes the enhancement of the contrast agent signal above the tissue signal in the image and thus the capability of differentiating contrast signal from tissue signal. High values of both these ratios are therefore necessary for good imaging of the contrast agent.
• the nonlinear distortion of the signal scattered from the contrast agent is much stronger than for the tissue signal, a phenomenon that is extensively used to enhance the CTR.
• received tissue signal components in the transmitted frequency band are reduced by- combining the received signal from two transmitted pulses with different amplitudes.
• the second harmonic band of the nonlinearly scattered signal is obtained either by bandpass filtering or by combining the received signals from two or more transmitted pulses with different polarities.
• the contrast agent will typically undergo strong nonlinear oscillations with significant amount of energy scattered at higher harmonic components only if driven into oscillations well below its resonance frequency and the harmonic component used for detection and imaging is often obtained in a bandpass filtering process.
• the drive pulse typically has to be relatively narrowbanded. The consequence of a relatively narrowbanded and low frequency drive pulse is the low image resolution typically obtained with harmonic imaging.
• the received nonlinear harmonic component from the contrast agent typically has low amplitude which reduces the CNR and may require so high transmitted amplitude that the contrast agent bubbles are destroyed. This can cause a problem when the inflow rate of contrast agent to the tissue region is low.
• nonlinear contrast components scattered in the forward propagation direction will add in phase with the transmit field and hence accumulate.
• these nonlinear contrast components may be linearly back-scattered from the tissue and falsely interpreted as contrast agent signal, hence reducing the CTR.
• a limitation in all methods based on nonlinear harmonic detection is that nonlinear components in the tissue signal are preserved in the process, also limiting the CTR.
• the new method described does not require nonlinear harmonic imaging and is therefore not constricted by the above mentioned limitations encountered in nonlinear contrast harmonic imaging techniques.
• Ultrasound pulses containing both a low frequency band and a high frequency band overlapping in the time domain are transmitted towards the ultrasound contrast agent embedded in the tissue.
• the low frequency components are used to manipulate the acoustic scattering properties of the contrast agent for frequency components in the transmitted high frequency band, and the scattered bubble signal from the high frequency transmitted components is used for image reconstruction.
• the low frequency components in the received signals can for example be removed through bandpass filtering of the signals around the high frequency band.
• the tissue signal is suppressed by transmitting at least two such dual-band pulses for each radial image line with different phases and/or amplitudes between the low and high frequency components, and performing a linear combination of the back-scattered signals from the different pulses.
• the transmitted low frequency pulse will slightly influence the wave propagation of the transmitted high frequency pulse resulting in slightly different high frequency sound speeds when altering the phase and/or amplitude of the low frequency pulses.
• the resulting echoes may then have to be digitally interpolated and adjusted relative to each other before combination to adequately suppress the high frequency tissue echoes.
• non-moving, temporary stationary tissue With non-moving, temporary stationary tissue, one can for example transmit two pulses with different phase of the low frequency components and the same phase of the high frequency components, and perform a linear combination of the back- scattered signals from the two pulses.
• the scattered high frequency components from the contrast bubble will be manipulated differently than from the tissue by the two low frequency pulses of different phases and/or amplitudes, and the bubble signal can be preserved while the tissue signal is heavily suppressed in the combination of the two echoes.
• the back-scattered signals from these pulses are combined in a pulse to pulse high-pass filter as is commonly done in ultrasound imaging of blood velocities to suppress the tissue signal.
• Typical filtering schemes that are used are FIR-type filters or orthogonal decomposition using for example Legendre polynomials, with filtering along the pulse number coordinate for each depth.
• the present invention significantly increases the CNR relative to existing methods by using the total scattered high frequency signal, and in particular the strong linear components, from the contrast agent and not only nonlinear components of it.
• the present invention can use a more broadbanded transmit pulse and will hence achieve a higher range image resolution.
• a higher transmit frequency can be used resulting in a significant increase in both lateral and range resolution relative to nonlinear imaging methods.
• the performance of the present invention is less sensitive to the amplitude of the imaging pulses compared to nonlinear imaging methods. Together with the indicated suppression of received tissue signal with resulting increase in CNR, this facilitates non-destructive detection and imaging of single contrast agent bubbles.
• FIG.l displays the transfer functions from drive pressure to radial oscillation and to scattered pressure of a contrast bubble undergoing small amplitude oscillations.
• FIG.2 illustrates transmit pulses containing both a low frequency pulse and a high frequency pulse where the high frequency pulse is placed in the peak positive or peak negative period of the low frequency pulse.
• FIG.3 shows the radius responses from a bubble with resonance frequency around 4 MHz when driven by the pressure pulses in FIG.2.
• FIG.4 shows the far-field scattered pressure pulses from a bubble with resonance frequency around 4 MHz when driven by the pressure pulses in FIG.2.
• FIG.5 depicts the absolute value of the Fourier Transform of the pressure pulses in FIG.4.
• FIG.6 displays the result obtained by subtracting the two scattered contrast pulses in FIG.4 so that the high frequency tissue components can be suppressed.
• FIG.7 illustrates the method of digital sampling rate increase (interpolation) .
• FIG.8 shows a realization of the interpolation process by the use of polyphase filters.
• FIG.9 shows schematically the adjustment and combination of received echoes done in order to suppress the high frequency tissue components.
• ⁇ is the angular frequency and ⁇ 0 is the resonance frequency of the bubble while s is the stiffness of the gas and shell, m is the inertia of the surrounding liquid, and d is a damping factor of the resonant system.
• H 1 (Q) The absolute value and phase angle of H 1 (Q) is shown in the upper and lower panel in FIG.Ia, respectively.
• the displacement is ⁇ out of phase with the driving pressure.
• the bubble responds differently and the displacement and drive pressure are now in phase so that the bubble is increased in size when the drive pressure is positive and vice versa.
• the displacement is approximately ⁇ /2 out of phase with the drive pressure.
• the absolute value of the amplitude of the transfer function is seen in the upper panel of FIG.Ia.
• FIG.Ib displays the absolute value of H 2 (Cl) in the upper panel, while the phase angle of H 2 (Q) is shown in the lower panel.
• the dashed lines are results obtained setting the parameter d equal to 0.1 while the solid lines are obtained for d equal to 0.5.
• the amplitude of the scattered pressure as seen from the upper panel in FIG.Ib, significantly increases when going from drive frequencies below resonance towards resonance. For drive frequencies above resonance, the scattered amplitude approaches a constant level. In the lower panel of the figure, we see that for drive frequencies well below resonance, the scattered pressure is in phase with the driving pressure. This means that the bubble oscillation is dominated by s r the stiffness of the gas and shell.
• the bubble responds differently and the oscillation is now dominated by m, the inertia of the co- oscillating fluid mass.
• the scattered pressure and drive pressure are now ⁇ out of phase as seen in the lower panel of FIG.Ib.
• the scattered pressure is approximately ⁇ /2 out of phase with the drive pressure.
• the purpose of the present invention is to heavily suppress the high frequency tissue echoes in the image while maintaining the total high frequency contrast agent echoes, and the essence of the invention is now described by way of example through applying a simple two-pulse transmit scheme for each radial image line.
• the high frequency component 202 is placed in the positive peak of the low frequency component 201 as shown in FIG.2a, whereas in the second transmitted pulse, the high frequency component 213 is placed in the negative peak of the low frequency component 212 as shown in FIG.2b.
• FIG.2a and FIG.2b The difference between FIG.2a and FIG.2b is that the polarity of the transmitted low frequency components is inverted with respect to each other.
• the phases between the two low frequency pulses may vary with a different value ( ⁇ .O), with possible variation in the amplitude of the low frequency pulses between the two low frequency pulses, even without variation of the phase.
• FIG.3a shows the radius response from a contrast bubble with resonance frequency around 4 MHz when driven by the pulse in FIG.2a while the radius response from the same bubble when driven by the pulse in FIG.2b is seen in FIG.3b.
• the high frequency components (202 and 213) in the transmitted pulses are here around 5 MHz and hence chosen to be in the same area as the equilibrium resonance frequency of the contrast bubble. This is, however, done only for purpose of illustration and not a limitation in the present invention. From the bubble radius oscillations, it is seen that the high frequency component in the first transmitted pulse occurs when the bubble is compressed (204) by the low frequency pulse, whereas the high frequency component in the second transmitted pulse occurs when the bubble is expanded (214) by the low frequency pulse. When compressed, the bubble will increase its resonance frequency, while when expanded, it will reduce its resonance frequency.
• the resulting far-field scattered pressure from the contrast bubble when driven by the incident pressure pulse in FIG.2a is depicted in time domain in FIG.4a and in frequency domain in FIG.5a, while the scattered pressure obtained when driven by the incident pulse in FIG.2b is depicted in time domain in FIG.4b and in frequency domain in FIG.5b.
• the scattered high frequency fundamental component (209) in FIG.5a is somewhat weaker than the scattered high frequency fundamental component (220) in FIG.5b.
• Nonlinear scattered high frequency components (210 and 221) are also somewhat different.
• Scattered low frequency components (207 and 218) have low amplitude and are not meant to be used for image reconstruction. The purpose of the low frequency components is only to manipulate the scattering properties of the contrast agent, i.e. to make the bubble oscillate with such a low frequency that high frequency components can be used to interrogate it while manipulated by the low frequency pulses.
• the current method of enhancing the contrast agent signal while suppressing the tissue signal will however work in- such a situation also as the main essence is that the high frequency scattering properties of the bubbles are manipulated between transmitted pulses by the low frequency pulses, with limited change of the signal scattered from the tissue.
• the tissue When the tissue is moving, it may be advantageously to transmit more than two pulses for each radial image line to adequately suppress the received high frequency tissue signal. For example, one can transmit a set of M pulses, all with the same phase and amplitude of the high frequency components, but with different phases and/or amplitiudes of the low frequency components for each pulse.
• the back- scattered signals from these pulses are combined in a pulse to pulse high-pass filter as is commonly done in ultrasound imaging of blood velocities to suppress the tissue signal.
• Typical filtering schemes that are used are FIR-type filters or orthogonal decomposition using for example Legendre polynomials, with filtering along the pulse number coordinate for each depth.
• Ultrasound wave propagation in tissue is hence a weak nonlinear process for intensities commonly applied in medical imaging. Due to the nonlinear tissue elasticity, the high frequency components of the two dual-band pulses displayed in FIG.2 can have slightly different propagation velocities.
• the high frequency component (202) in FIG.2a occurring during the positive pressure swing of the low frequency component, will travel with a slightly higher sound speed than the high frequency component (213) in FIG.2b, occurring during the negative pressure swing of the low frequency component.
• C 0 equal to 1500 m/s
• FIG.7 displays schematically an interpolation method of sampling rate increase by a factor of J.
• the interpolation is here done by first introducing I - 1 zeros between each sample in the original sequence x(n) with a sampling rate of F x to obtain the desired sampling rate IF x .
• the sequence v(m) is then passed through a lowpass filter h (m) to obtain the desired output y(m) and this lowpass filter is typically implemented as a linear phase FIR-type filter where the z-transform of the filter is defined as
• This set of smaller filters are usually called polyphase filters and have unit sample responses
• the polyphase filters perform the computations at the original low sampling rate F x and the rate conversion results from the fact that I output samples are generated, one from each of the filters, for each input sample. Interpolation by use of polyphase filters are shown schematically in FIG.8.
• the polyphase filters are arranged as a parallel realization and the output of each filter is selected by a commutator rotating in the counterclockwise direction.
• the decomposition of h(m) into the set of I subfilters with impulse responses g k ⁇ m) results in filtering of the input samples x(n) by a periodically time-varying linear filter g(m,k) .
• FIG.9 shows schematically the adjustment and combination process done to suppress the received high frequency tissue signal components.
• the received echoes are first temporally interpolated and given a variable time adjustment (901) before the pulse to pulse combination (902) to heavily suppress the high frequency tissue components.
• the time delay effect of this variation in propagation velocity of the high frequency pulse is an integrating effect along the beam depth.
• the phase between the high and the low frequency pulses may even vary in sign along the beam depth for the same transmit pulse, as described above.
• the induced variation of the high frequency pulse propagation velocity by the low frequency pulse has less total effect on the delay of the high frequency pulses between different transmissions, compared to when the phase between the high and the low frequency components stays fairly constant along the beam.
• the separated contrast agent image is typically shown as an overlay with different color or pattern of the standard tissue image as obtained with only one of the transmit pulses for each radial image line.
• a weak tissue background in the ultrasound image can be obtained by using inaccurate or no time adjustments of the high frequency pulses with different phases of the low frequency pulses. Some of the tissue signal power can thus be brought to partly pass through the high pass filter for tissue signal cancellation.

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Citations (4)

• 2004
  • 2004-06-18 WO PCT/NO2004/000180 patent/WO2006001697A2/en active Application Filing
  • 2004-06-18 EP EP04748756A patent/EP1774361A2/de not_active Withdrawn

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