Phantom investigation of phase-inversion-based dual-frequency excitation imaging for improved contrast display.

OBJECTIVE: The goal of this work is to examine the effects of pulse-inversion (PI) technique in combination with dual-frequency (DF) excitation method to separate the high-order nonlinear responses from microbubble contrast agents for improvement of image contrast. DF excitation method has been previously developed to induce the low-frequency ultrasound nonlinear responses from bubbles by using the composition of two high-frequency sinusoids (f(1) and f(2)). MOTIVATION: Although the simple filtering was conventionally utilized to provide signal separation, the PI approach is better in the sense that it minimizes the mutual interferences among these high-order nonlinear responses in the presence of spectral overlap. The novelty of the work is that, in addition to the common PI summation, the PI subtraction was also applied in DF excitation method. METHODS: DF excitation pulses having an envelope frequency of 3MHz (i.e., f(1)=8.5MHz and f(2)=11.5MHz) with pulse lengths of 3-10µs and the pressure amplitudes from 0.5 to 1.5MPa were used to interrogate the nonlinear responses of SonoVue™ microbubbles in the phantom experiments. The high-order nonlinear responses in the DF excitation were extracted for contrast imaging using PI summation for even-order nonlinear components or PI subtraction for odd-order nonlinear ones. RESULTS: Our results indicated that, as compared to the conventional filtering technique, the PI processing effectively increases the contrast-to-tissue ratio (CTR) of the third-order nonlinear response at 5.5MHz and the fourth-order nonlinear response at 6MHz by 2-5dB. For these high-order nonlinear components, the CTR increase varies with the transmission pressures from 0.5 to 1.5MPa due to the microbubbles' displacement induced by the radiation force of DF excitation. CONCLUSIONS: For DF excitation technique, the PI processing can help to extract either the odd-order or the even-order nonlinear components for higher CTR estimates.

Coded excitation for photoacoustic imaging using a high-speed diode laser.

A Q-switched Nd:YAG laser providing nanosecond pulse durations and millijoule pulse energies is suitable for typical biomedical PA applications. However, such lasers are both bulky and expensive. An alternative method is to use a diode laser, which can achieve a higher pulse repetition frequency. Although the energy from a diode laser is generally too low for effective PA generation, this can be remedied by using high-speed coded laser pulses, with the signal intensity of the received signal being enhanced by pulse compression. In this study we tested a version of this method that employs coded excitation. A 20-MHz PA transducer was used for backward-mode PA detection. A frequency-coded PA signal was generated by tuning the interval between two adjacent laser pulses. The experimental results showed that this methodology improved the signal-to-noise ratio of the decoded PA signal by up to 19.3 dB, although high range side lobes were also present. These side lobes could be reduced by optimizing the compression filter. In contrast to the Golay codes proposed in the literature, the proposed coded excitation requires only a single stimulus.

Dual-high-frequency ultrasound excitation on microbubble destruction volume.

OBJECTIVE AND MOTIVATION: The goal of this work was to test experimentally that exposing air bubbles or ultrasound contrast agents in water to amplitude modulated wave allows control of inertial cavitation affected volume and hence could limit the undesirable bioeffects. METHODS: Focused transducer operating at the center frequency of 10 MHz and having about 65% fractional bandwidth was excited by 3 micros 8.5 and 11.5 MHz tone-bursts to produce 3 MHz envelope signal. The 3 MHz frequency was selected because it corresponds to the resonance frequency of the microbubbles used in the experiment. Another 5 MHz transducer was used as a receiver to produce B-mode image. Peak negative acoustic pressure was adjusted in the range from 0.5 to 3.5 MPa. The spectrum amplitudes obtained from the imaging of SonoVue contrast agent when using the envelope and a separate 3 MHz transducer were compared to determine their cross-section at the -6 dB level. RESULTS: The conventional 3 MHz tone-burst excitation resulted in the region of interest (ROI) cross-section of 2.47 mm while amplitude modulated, dual-frequency excitation with difference frequency of 3 MHz produced cross-section equal to 1.2mm. CONCLUSION: These results corroborate our hypothesis that, in addition to the considerably higher penetration depth of dual-frequency excitation due to the lower attenuation at 3 MHz than that at 8.5 and 11.5 MHz, the sample volume of dual-frequency excitation is also smaller than that of linear 3-MHz method for more spatially confined destruction of microbubbles.

Microbubble destruction by dual-high-frequency ultrasound excitation.

The efficiency of high-frequency destruction of microbubble-based contrast agent is limited by the high pressure threshold, while the difficulty of spatially confining destruction induced by low-frequency excitation to a small sample volume potentially increases the risk of adverse bioeffects. The dual-frequency excitation method involves the simultaneous transmission of 2 high-frequency sinusoids to produce an envelope signal at the difference frequency. The envelope signal provides the low-frequency driving force for oscillating the contrast-agent microbubbles to improve destruction efficiency, while the destruction sample volume remains small due to the high frequency of the carrier signal. Experimental results indicate that dual-frequency excitation consistently results in destruction of contrast-agent microbubbles that is superior to using a tone burst at the carrier frequency. With 1 micros pulse length, the acoustic pressure threshold for 95% microbubble destruction markedly reduces from 2.6 MPa to 0.9 MPa when the dual-frequency pulse having envelope frequency of 3 MHz is utilized instead of the 10-MHz sinusoidal pulse. In addition, the dual-frequency pulse having lower envelope frequency generally provides more efficient microbubble destruction, especially when the excitation waveform is long enough to guarantee sufficient envelope component.

Dual high-frequency difference excitation for contrast detection.

Stimulating high-frequency nonlinear oscillations of ultrasound contrast agents is helpful to distinguish microbubbles from background tissues. Nevertheless, inefficiency of such oscillations from most commercially available contrast agents and intense attenuation of the resultant high-frequency harmonics limit microbubble detection with high-frequency ultrasound. To avoid this high-frequency nature, we devised and explored a dual-frequency difference excitation technique to induce efficiently low-frequency, rather than high-frequency, nonlinear scattering from microbubbles by using high-frequency ultrasound. The proposed excitation pulse is comprised of 2 high-frequency sinusoids with frequency difference subject to the microbubble resonance frequency. Its envelope, with frequency being the difference between the 2 frequencies, is used to stimulate nonlinear oscillation of microbubbles for the consonant low-frequency harmonic generation, whereas high-imaging resolution is retained because of narrow high-frequency transmit beams. Hydrophone measurements and phantom experiments of speckle-generating flow phantoms were performed to demonstrate the efficacy of the proposed technique. The results show that, especially when the envelope frequency is near the microbubbleiquests resonance frequency, the envelope of the proposed excitation pulse can induce significant nonlinear scattering from microbubbles, the induced nonlinear responses tend to increase with the pulse pressures, and up to 26 dB and 36 dB contrast-to-tissue ratios with second- and fourth-order nonlinear responses, respectively, can be obtained. Potential applications of this method include microbubble fragmentation and cavitation with high-frequency ultrasound.

Effects of acoustic insonation parameters on ultrasound contrast agent destruction.

Ultrasound contrast agents (UCAs) are used to enhance the acoustic backscattered intensity of blood and thereby assist the assessment of blood perfusion. Characterization of UCA destruction provides important information for the design of contrast-assisted perfusion imaging. High-speed optical observation of single microbubble destruction during acoustic insonation has been performed in previous studies. The results identified that pressure, center frequency and transmission phase have significant effects on the fragmentation threshold. We proposed an acoustic-based experiment method to demonstrate the relationship between different acoustic exposure conditions and the degree of UCA destruction. The method also provides a simple and convenient way to determine the microbubble destruction threshold. The experiments introduced three insonation parameters, including acoustic pressure (0 to 1 MPa), pulse frequency (1, 2.25, 5 and 7.5 MHz) and pulse length (1 to 10 cycles). The term of surviving percentage (SP) was proposed to represent the ratio of UCA backscattered power with and without acoustic insonation. The results showed that the SP decreased with decreasing pulse frequency, but with increasing transmission acoustic pressure and pulse length. In addition, there was an exponential relationship between SP and acoustic pressure, and thus the UCA destruction pressure threshold could be predicted from the fitted exponential curve. The results also show that the degree of UCA destruction was not related to mechanical index (MI). Potential applications of this method include UCA high-resolution destruction/replenishment imaging model, microbubble cavitation, sonoporation in drug delivery and gene therapy.