Contrast imaging by non-overlapping dual frequency band transmit pulse complexes

SURF contrast imaging, as described previously in the literature, is a contrast agent detection technique achieved by processing of the received signals from transmitted dual frequency band pulse complexes with overlapping high-frequency (HF) and low-frequency (LF) pulses. The transmitted HF pulses are used for image reconstruction, whereas the transmitted LF pulses are used to manipulate the scattering properties of the contrast agent. As with harmonic contrast agent detection techniques, nonlinear wave propagation will, in most situations, also limit the specificity with the SURF contrast technique when transmitting overlapping HF and LF pulses. The present paper proposes an alternative SURF contrast imaging technique using transmit dual frequency band pulse complexes with non-overlapping HF and LF pulses. If the frequency of the LF manipulation pulse is close to the bubble resonance frequency, numerical simulations indicate a significant ring-down effect of the LF bubble radius response. Utilizing this bubble ring-down effect and transmitting the HF pulse just after the LF pulse, a contrast agent specificity approaching infinity accompanied by a contrast agent sensitivity only for contrast bubbles having resonance frequencies within a narrow frequency range may be obtained.     

SURF imaging: in vivo demonstration of an ultrasound contrast agent detection technique

A dual-band method for ultrasound contrast agent detection is demonstrated in vivo in an animal experiment using pigs. The method is named Second -order UltRasound Field Imaging, abbreviated SURF Imaging. It relies on simultaneously transmitting two ultrasound pulses with a large separation in frequency. Here, a low-frequency pulse of 0.9 MHz is combined with a high-frequency pulse of 7.5 MHz. The low-frequency pulse is used to manipulate the properties of the contrast agent, and the high frequency pulse is used for high-resolution contrast detection and imaging. An annular array capable of transmitting the low- and high-frequency pulses simultaneously was constructed and fitted to a mechanically scanned probe used in a GE Vingmed System 5 ultrasound scanner. The scanner was modified and adapted for the dual-band transmit technique. In-house software was written for post-processing of recorded IQ-data. Contrast-processed B-mode images of pig kidneys after bolus injections of 1 mL of Sonovuer are presented. The images display contrast detection with contrast-to-tissue ratios ranging from 15-40 dB. The results demonstrate the potential of SURF Imaging as an ultrasound contrast detection technique for clinically high ultrasound frequencies. This may allow ultrasound contrast imaging to be available for a wide range of applications.     

Radial modulation of microbubbles for ultrasound contrast imaging

Over the past few years, extensive research has been carried out in the field of ultrasound contrast imaging. In addition to the development of new types of ultrasound contrast agents, various imaging methods dedicated to contrast agents have been introduced, and some of them are now commercially available. In this study, we present results of an imaging technique that is capable of detecting echoes from microbubbles and eliminating those emanating from nonoscillating structures (tissue), thereby enhancing contrast imaging. The method is based on mixing a low frequency (LF) modulator signal and a high frequency (HF) imaging signal to effectively modulate the size of the contrast microbubble through its volumetric oscillations using the LF signal and to probe the radial motion using the HF imaging signal. To evaluate the performances and limitations of the method, high-speed optical observations and acoustic measurements were carried out on soft-shelled microbubbles. The results showed that, by incorporating the modulator signal, the bubbles respond differently compared to the HF excitation alone. The decorrelation between the signals obtained at the compression and expansion phase of the modulator signal is significantly high to be used as a parameter to detect contrast microbubbles and discriminate them from tissue. The echo received from a solid reflector shows identical responses during the compression and rarefaction phase of the LF signal. In conclusion, these results demonstrate the feasibility of this fully linear approach for improving the contrast detection.     

Post-processing enhancement of reverberation-noise suppression in dual-frequency SURF imaging

A post-processing adjustment technique to enhance dual-frequency second-order ultrasound field (SURF) reverberation-noise suppression imaging in medical ultrasound is analyzed. Two variant methods are investigated through numerical simulations. They both solely involve post-processing of the propagated high-frequency (HF) imaging wave fields, which in real-time imaging corresponds to post-processing of the beamformed receive radio-frequency signals. Hence, the transmit pulse complexes are the same as for the previously published SURF reverberation-suppression imaging method. The adjustment technique is tested on simulated data from propagation of SURF pulse complexes consisting of a 3.5-MHz HF imaging pulse added to a 0.5-MHz low-frequency soundspeed manipulation pulse. Imaging transmit beams are constructed with and without adjustment. The post-processing involves filtering, e.g., by a time-shift, to equalize the two SURF HF pulses at a chosen depth. This depth is typically chosen to coincide with the depth where the first scattering or reflection occurs for the reverberation noise one intends to suppress. The beams realized with post-processing show energy decrease at the chosen depth, especially for shallow depths where, in a medical imaging situation, a body-wall is often located. This indicates that the post-processing may further enhance the reverberation- suppression abilities of SURF imaging. Moreover, it is shown that the methods might be utilized to reduce the accumulated near-field energy of the SURF transmit-beam relative to its imaging region energy. The adjustments presented may therefore potentially be utilized to attain a slightly better general suppression of multiple scattering and multiple reflection noise compared with non-adjusted SURF reverberation-suppression imaging.     

Radial modulation of single microbubbles

Radial modulation imaging is a new promising technique to improve contrast-enhanced ultrasound images. The method is based on dual-frequency insonation of contrast agent microbubbles. A low-frequency (LF) pulse is used to modulate the responses of the microbubbles to a high-frequency (HF) imaging pulse. Inverting the LF pulse induces amplitude and phase differences in the HF response of contrast agent microbubbles, which can be detected using Doppler techniques. Although the technique has been successfully implemented, no consensus persists on parameter choice and resulting effects. In a separate study, "compression-only" behavior of coated microbubbles was observed. Compression-only behavior could be beneficial for radial modulation imaging. This was investigated using high-speed camera recordings and simulations. We recorded the vibrations of 78 single microbubbles in a dual-frequency ultrasound field. The results showed that the LF pulse induced significant compression-only behavior, which for microbubble sizes below and at HF resonance resulted in high radial amplitude modulation. It, however, also appeared that, for radial modulation imaging, microbubble size is more important than resonance and compression-only effects.     

A new ultrasound contrast imaging approach based on the combination of multiple imaging pulses and a separate release burst

A new ultrasound contrast imaging technique is described that optimally employs the rupture of the contrast agent. It is based on a combination of multiple high frequency, broadband, imaging pulses and a separate release burst. The imaging pulses are used to survey the target before and after the rupture and release of free gas bubbles. In this way, both processes (imaging and release) can be optimized separately. The presence of the contrast agent is simply detected by correlating or subtracting the signal responses of the imaging pulses. Because the time delay between the imaging pulses can be very short, the subtraction is less affected by tissue motion and can be done in real time. In vitro measurements showed that by using a release burst, the detection sensitivity increased 12 to 43 dB for different types of contrast agents. In the presence of a moving phantom, the increase in sensitivity was 22 dB. This new method is very sensitive for contrast agent detection in fundamental imaging mode and, therefore, non-linear propagation effects do not limit the maximum obtainable agent-to-tissue ratio. However, because of the inherent destruction of the contrast agent, it has to operate in an intermittent way. Through experiments, we have demonstrated the potential of the method to achieve simultaneous high sensitivity for contrast detection, i.e., high agent-to-tissue ratio, and high spatial resolution performance for different types of contrast agents     

Transmit beams adapted to reverberation noise suppression using dual-frequency SURF imaging

A method that uses dual-frequency pulse complexes of widely separated frequency bands to suppress noise caused by multiple scattering or multiple reflections in medical ultrasound imaging is presented. The excitation pulse complexes are transmitted to generate a second order ultrasound field (SURF) imaging synthetic transmit beam. This beam has reduced amplitude near the transducer, which illustrates the multiple scattering suppression ability of the imaging method. Field simulations solving a nonlinear wave equation are used to calculate SURF imaging beams, which are compared with beams for pulse inversion (PI) and fundamental imaging. In addition, a combined SURF and PI beam generation is described and compared with the beams mentioned above. A quality ratio, relating the energy within the near-field to that within the imaging region, is defined and used to score the multiple scattering and multiple reflection suppression abilities when imaging with the different beams. The realized combined SURF-PI beam scores highest, followed by SURF, PI (that score equally well), and the fundamental. The amplitude in the imaging region and therefore also the SNR is highest for the fundamental followed by SURF, PI, and SURF-PI. The work hence indicates that when substituting PI for SURF, one may trade increased SNR into use of increased imaging frequencies without loss of multiple scattering and multiple reflection noise suppression.     

Optical and acoustical interrogation of submicron contrast agents

Unlike conventional ultrasound contrast agents with a diameter of several microns, in this paper we explore the use of submicron contrast agents for the detection and localization of lymph nodes. The submicron agents are gas-filled, double-walled microspheres that rupture when exposed to ultrasound energy at megahertz frequencies. In this study, three experimental systems are combined with model predictions to assist in understanding the response of these unique agents to a range of signal transmission parameters. Optical experimental results for each agent delineate the relative expansion as a function of acoustical peak negative pressure, pulse length, and center frequency. The optical images demonstrate an order of magnitude expansion in radius during the pulse rarefaction, in which the expansion magnitude is dependent on the transmitted pressure and frequency. Simulations using a modified Rayleigh-Plesset model predict an increasing relative expansion for the microbubbles (initial bubble radius ranging from 0.3-1.3 /spl mu/m) with increasing pressure and decreasing initial radius. Acoustically recorded frequency spectra reveal the presence of harmonics for a range of transmitted pulses. In addition, in-vivo results from a normal canine model demonstrate marked contrast enhancement of first order lymph nodes. We hope to offer an alternative to present intra-operative procedures for sentinel node detection.     

Ultrasonic contrast agent shell rupture detected by inertial cavitation and rebound signals

Determining the rupture pressure threshold of ultrasound contrast agent microbubbles has significant applications for contrast imaging, development of therapeutic agents, and evaluation of potential bioeffects. Using a passive cavitation detector, this work evaluates rupture based on acoustic emissions from single, encapsulated, gas-filled microbubbles. Sinusoidal ultrasound pulses were transmitted into weak solutions of Optison at different center frequencies (0.9, 2.8, and 4.6 MHz), pulse durations (three, five, and seven cycles of the center frequencies), and peak rarefactional pressures (0.07 to 5.39 MPa). Pulse repetition frequency was 10 Hz. Signals detected with a 13-MHz, center-frequency transducer revealed postexcitation acoustic emissions (between 1 and 5 micros after excitation) with broadband spectral content. The observed acoustic emissions were consistent with the acoustic signature that would be anticipated from inertial collapse followed by "rebounds" when a microbubble ruptures and thus generates daughter/free bubbles that grow and collapse. The peak rarefactional pressure threshold for detection of these emissions increased with frequency (e.g., 0.53, 0.87, and 0.99 MPa for 0.9, 2.8, and 4.6 MHz, respectively; five-cycle pulse duration) and decreased with pulse duration. The emissions identified in this work were separated from the excitation in time and spectral content, and provide a novel determination of microbubble shell rupture.     

A low-cost bipolar pulse generator for high-frequency ultrasound applications

A design of a low-cost bipolar pulse generator for high-frequency (HF) ultrasound applications is presented. The pulse generator can produce N cycle (1-255 cycles) bipolar pulses with center frequency over 60 MHz. The measured pulse amplitude was over 160 Vpp, and the pulse ringing was less than 0.3 Vpp (i.e., signal-to-ring ratio is 55 dB). The pulser can be used in high-frequency ultrasound Doppler and B-mode imaging applications with arrays.     

The effect of the phase of transmission on contrast agent echoes

Ultrasound contrast agents consist of a gas bubble, encapsulated by a shell for stabilization. The shell dampens the fluctuations in the bubble radius when insonified. The detection of contrast microbubbles during a medical examination can indicate whether a region is perfused with blood. Here, the authors consider the effect of the phase of sonification signal on the backscatter by the bubble echo. By transmitting two short pulses of ultrasound with opposite phases, the authors demonstrate that a unique pair of echoes can be generated by a single microbubble, and that the properties of these echoes may be useful in the discrimination of bubble and tissue echoes. Specifically, the significant echo amplitude begins coincident with each transmitted rarefactional half-cycle, and the mean frequency of this echo depends on the transmitted phase. When rarefaction is transmitted first for a 2.25 MHz signal, the mean frequency is 0.8 MHz higher for an albumin-shelled bubble and 0.9 MHz higher for a lipid-shelled bubble. The experimental results agree with the predictions of the Gilmore-Akulichev equation.     

Subharmonic emissions from microbubbles: effect of the driving pulse shape

The aims of this work are to investigate the response of the ultrasonic contrast agents (UCA) insonified by different arbitrary-shaped pulses at different acoustic pressures and concentration of the contrast agent focusing on subharmonic emission. A transmission setup was developed in order to insonify the contrast agent contained in a measurement chamber. The transmitted ultrasonic signals were generated by an arbitrary wave generator connected to a linear power amplifier able to drive a single-element transducer. The transmitted ultrasonic pulses that passed through the contrast agent-filled chamber were received by a second transducer or a hydrophone aligned with the first one. The radio frequency (RF) signals were acquired by fast echographic multiparameters multi-image novel apparatus (FEMMINA), which is an echographic platform able to acquire ultrasonic signals in a real-time modality. Three sets of ultrasonic signals were devised in order to evaluate subharmonic response of the contrast agent respect with sinusoidal burst signals used as reference pulses. A decreasing up to 30 dB in subharmonic response was detected for a Gaussian-shaped pulse; differences in subharmonic emission up to 21 dB were detected for a composite pulse (two-tone burst) for different acoustic pressures and concentrations. Results from this experimentation demonstrated that the transmitted pulse shape strongly affects subharmonic emission in spite of a second harmonic one. In particular, the smoothness of the initial portion of the shaped pulses can inhibit subharmonic generation from the contrast agents respect with a reference sinusoidal burst signal. It also was shown that subharmonic generation is influenced by the amplitude and the concentration of the contrast agent for each set of the shaped pulses. Subharmonic emissions that derive from a nonlinear mechanism involving nonlinear coupling among different oscillation modes are strongly affected by the shape of the ultrasonic driving pulse.     

A new imaging strategy using wideband transient response of ultrasound contrast agents

High-resolution clinical systems operating near 15 MHz are becoming more available; however, they lack sensitive harmonic imaging modes for ultrasound contrast agent (UCA) detection, primarily due to limited bandwidth. When an UCA is driven to nonlinear oscillation, a very wideband acoustic transient response is produced that extends beyond 15 MHz. We propose a novel strategy using two separate transducers at widely separated frequencies and arranged confocally to simultaneously excite and receive acoustic transients from UCAs. Experiments were performed to demonstrate that this new mode shows similar resolution, higher echo amplitudes, and greatly reduced attenuation compared to transmission at a higher frequency, and superior resolution compared to transmission and reception at a lower frequency. The proposed method is shown to resolve two 200 microm tubes with centers separated by 400 microm. Strong acoustic transients were detected for rarefaction-first 1-cycle pulses with peak-negative pressures above 300 kPa. The results of this work may lead to uses in flow and/or targeted imaging in applications requiring very high sensitivity to contrast agents.     

Golay pulse encoding for microbubble contrast imaging in ultrasound

We present a technique that uses Golay phase encoding, pulse inversion, and amplitude modulation (GPIAM) for microbubble contrast agent imaging with ultrasound. This technique improves the contrast-to-tissue ratio (CTR) by increasing the time-bandwidth product of the insonating waveforms. A nonlinear pulse compression algorithm is used to compress the signal energy upon receive. A 6.5-dB improvement in CTR was observed using an 8-chip GPIAM sequence compared to a conventional pulse-inversion amplitude-modulation sequence. The CTR improvement comes at the cost of a reduction in frame rate: GPIAM coding uses four input pulses whereas most contrast imaging sequences require two or three pulses. Our results showed that the microbubble response can be phase encoded and subsequently compressed using a nonlinear matched-filtering algorithm, in order to enhance the signal from the contrast agent, while maintaining resolution and suppressing the tissue signal.     

Nonlinear propagation of ultrasound through microbubble contrast agents and implications for imaging

Microbubble contrast agents produce nonlinear echoes under ultrasound insonation, and current imaging techniques detect these nonlinear echoes to generate contrast agent images accordingly. For these techniques, there is a potential problem in that bubbles along the ultrasound transmission path between transducer and target can alter the ultrasound transmission nonlinearly and contribute to the nonlinear echoes. This can lead to imaging artefacts, especially in regions at depth. In this paper we provide insight, through both simulation and experimental measurement, into the nonlinear propagation caused by microbubbles and the implications for current imaging techniques. A series of investigations at frequencies below, at, and above the resonance frequency of microbubbles were performed. Three specific effects on the pulse propagation (i.e., amplitude attenuation, phase changes, and harmonic generation) were studied. It was found that all these effects are dependent on the initial pulse amplitude, and their dependence on the initial phase of the pulse is shown to be insignificant. Two types of imaging errors are shown to result from this nonlinear propagation: first, that tissue can be misclassified as microbubbles; second, the concentration of microbubbles in the image can be misrepresented. It is found that these imaging errors are significant for all three pulse frequencies when the pulses transmit through a microbubble suspension of 6 cm in path length. It also is found that the first type of error is larger at the bubble resonance frequency.     

Changes in the echoes from ultrasonic contrast agents with imaging parameters

Current harmonic imaging scanners transmit a narrowband signal that limits spatial resolution in order to differentiate the echoes from tissue from the echoes from microbubbles. Because spatial resolution is particularly important in applications, including mapping vessel density in tumors, we explore the use of wideband signals in contrast imaging. It is first demonstrated that microspheres can be destroyed using one or two pulses of ultrasound. Thus, temporal signal processing strategies that use the change in the echo over time can be used to differentiate echoes from bubbles and echoes from tissue. Echo parameters, including intensity and spectral shape for narrowband and wideband transmission, are then evaluated. Through these experiments, the echo intensity received from bubbles after wideband transmission is shown to be at least as large as that for narrowband transmission, and can be larger. In each case, the echo intensity increases in a nonlinear fashion in comparison with the transmitted signal intensity. Although the echo intensity at harmonic multiples of the transmitted wave center frequency can be larger for narrowband insonation, echoes received after wideband insonation demonstrate a broadband spectrum with significant amplitude over a very wide range of frequencies.     

High frequency coded imaging system with RF

Coded transmission is an approach to solve the inherent compromise between penetration and resolution required in ultrasound imaging. Our goal was to examine the applicability of the coded excitation to HF (20-35 MHz) ultrasound imaging. A novel real-time imaging system for research and evaluation of the coded transmission was developed. The digital programmable coder- digitizer module based on the field programmable gate array (FPGA) chip supports arbitrary waveform coded transmission and RF echo sampling up to 200 megasamples per second, as well as real-time streaming of digitized RF data via a high-speed USB interface to the PC. All RF and image data processing were implemented in the software. A novel balanced software architecture supports real-time processing and display at rates up to 30 frames/sec. The system was used to acquire quantitative data for sine burst and 16-bit Golay code excitation at 20 MHz fundamental frequency. SNR gain close to 14 dB was obtained. The example of the skin scan clearly shows the extended penetration and improved contrast when a 35-MHz Golay code is used. The system presented is a practical and low-cost implementation of a coded excitation technique in HF ultrasound imaging that can be used as a research tool as well as to be introduced into production.     

Three-stage approach to ultrasound contrast detection

A new method for detecting ultrasound contrast agents using a three-stage pulsing sequence is proposed. The method is based on observations showing that the scattering properties of contrast agents are modified by ultrasonic insonation at high power, but remain unchanged at low power. The objective of the first stage of the pulsing sequence is to use low power pulses to obtain a high resolution reference image without altering the agent. Higher power pulses in the second stage modify the contrast agent. The third stage detects the changes imposed to the contrast agent using low power pulses. A temporal filter is proposed to discriminate contrast response from clutter signal. The method is similar to power Doppler methods in that it uses several pulses to survey the target while destroying the agent. The new idea is to separate detection and destruction to circumvent a trade-off between sensitivity and resolution. Results from in vitro experiments with three different contrast agents are presented. The results are compared with harmonic power Doppler processed from the same data and show that an improvement in sensitivity is achievable by including the high power burst in the pulsing sequence. The results also show that the proposed filter reduces clutter artifacts from moving tissue     

Sonoluminescence generated by the interaction of two ultrasonic fields with strongly different frequencies

The phenomenon of luminescence under the action of ultrasound (sonoluminescence, SL) was studied in a liquid exposed to the field of a high-frequency (HF, 880 kHz) focusing radiator with simultaneous or preliminary action of a low-frequency (LF, 19.9 kHz) ultrasound on the sample. It is shown that a nonadditive increase in the SL intensity takes place for simultaneously operating radiators and is observed for a long time (up to several hours) after switching off the LF source. This is evidence of a long-term aftereffect of the LF ultrasound on the magnitude of SL induced by the HF oscillations. The possible mechanisms of the observed effect are discussed.     

Detection of ultrawide-band ultrasound pulses in optoacoustic tomography

A laser optoacoustic imaging system (LOIS) uses time-resolved detection of laser-induced pressure profiles in tissue in order to reconstruct images of the tissue based on distribution of acoustic sources. Laser illumination with short pulses generates distribution of acoustic sources that accurately replicates the distribution of absorbed optical energy. The complex spatial profile of heterogeneous distribution of acoustic sources can be represented in the frequency domain by a wide spectrum of ultrasound ranging from tens of kilohertz to tens of megahertz. Therefore, LOIS requires a unique acoustic detector operating simultaneously within a wide range of ultrasonic frequencies. Physical principles of an array of ultrawide-band ultrasonic transducers used in LOIS designed for imaging tumors in the depth of tissue are described. The performance characteristics of the transducer array were modeled and compared with experiments performed in gel phantoms resembling optical and acoustic properties of human tissue with small tumors. The amplitude and the spectrum of laser-induced ultrasound pulses were measured in order to determine the transducer sensitivity and the level of thermal noises within the entire ultrasonic band of detection. Spatial resolution of optoacoustic images obtained with an array of piezoelectric transducers and its transient directivity pattern within the field of view are described. The detector design considerations essential for obtaining high-quality optoacoustic images are presented.