Phase-Dependent Dual-Frequency Contrast Imaging at Sub-Harmonic Frequency

Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
IEEE transactions on ultrasonics, ferroelectrics, and frequency control (Impact Factor: 1.51). 02/2011; 58(2):379-88. DOI: 10.1109/TUFFC.2011.1815
Source: PubMed


Sub-harmonic imaging techniques have been shown to provide a higher contrast-to-tissue ratio (CTR) at the cost of relatively low signal intensity from ultrasound contrast agents (UCAs). In this study, we propose a method of dual-frequency excitation to further enhance the CTR of subharmonic imaging. A dual-frequency excitation pulse is an amplitude-modulated waveform which consists of two sinusoids with frequencies of f₁ (e.g., 9 MHz) and f₂ (e.g., 6 MHz) and the resulting envelope component at (f₁ - f₂) (e.g., 3 MHz) can serve as a driving force to excite the nonlinear response of UCAs. In this study, the f₂, at twice of the resonance frequency of UCAs, is adopted to efficiently generate a sub-harmonic component at half of the f₂ frequency, and f₁ is included to enhance the high-order nonlinear response of UCAs at the sub-harmonic frequency. The second- and third-order nonlinear components resulting from the envelope component would spectrally overlap at the sub-harmonic frequency when f₁ and f₂ are properly selected. We further optimize the generation of the sub-harmonic component by tuning the phase terms between second- and third-order nonlinear components. The results show that, with dual-frequency excitation, the CTR at sub-harmonic frequency improves compared with the conventional tone-burst method. Moreover, the CTR changes periodically with the relative phase of the separate frequency component in the dual-frequency excitation, leading to a difference of as much as 9.1 dB between the maximal and minimal CTR at 300 kPa acoustic pressure. The echo produced from the envelope component appears to be specific for UCAs, and thus the proposed method has the potential to improve both SNR and CTR in sub-harmonic imaging. Nevertheless, the dual-frequency waveform may suffer from frequency-dependent attenuation that degrades the generation of the envelope component. The deviation of the microbubble's resonance characteristics from the selection of dual-frequency transmission may also decrease the CTR improvement.

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    • "Therefore, the generation of the subharmonic oscillations from UCAs is favorable in many applications such as; subharmonic imaging [9], [12], noninvasive blood pressure estimation [13]–[15], intravascular contrast imaging [16], molecular imaging [17], threedimensional ultrasound imaging [18]. For this reason, many detection methods have been proposed based on novel excitation techniques to enhance the subharmonic emission from microbubbles [19]–[23]. "
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    ABSTRACT: Subharmonic generation from ultrasound contrast agents depends on the spectral and temporal properties of the excitation signal. The subharmonic response can be improved by using wideband and long-duration signals. However, for sinusoidal tone-burst excitation, the effective bandwidth of the signal is inversely proportional to the signal duration. Linear frequency-modulated (LFM) and nonlinear frequencymodulated (NLFM) chirp excitations allow independent control over the signal bandwidth and duration; therefore, in this study LFM and NLFM signals were used for the insonation of microbubble populations. The amplitude modulation of the excitation waveform was achieved by applying different window functions. A customized window was designed for the NLFM chirp excitation by focusing on reducing the spectral leakage at the subharmonic frequency and increasing the subharmonic generation from microbubbles. Subharmonic scattering from a microbubble population was measured for various excitation signals and window functions. At a peak negative pressure of 600 kPa, the generated subharmonic energy by ultrasound contrast agents was 15.4 dB more for NLFM chirp excitation with 40% fractional bandwidth when compared with tone-burst excitation. For this reason, the NLFM chirp with a customized window was used as an excitation signal to perform subharmonic imaging in an ultrasound flow phantom. Results showed that the NLFM waveform with a customized window improved the subharmonic contrast by 4.35 ± 0.42 dB on average over a Hann-windowed LFM excitation.
    IEEE transactions on ultrasonics, ferroelectrics, and frequency control 12/2013; 60(12):2532-44. DOI:10.1109/TUFFC.2013.2852 · 1.51 Impact Factor
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    • "Ultrasound contrast agents are used extensively in medical ultrasound imaging (Chang et al. 1995; Burns 1996; Shi et al. 1999; Dayton and Ferrara 2002; Bhagavatheeshwaran et al. 2004; Goertz et al. 2005, 2006, 2007a; Forsberg et al. 2007; Ch erin et al. 2008; Masoy et al. 2008; Needles et al. 2010; Eisenbrey et al. 2011; Shen et al. 2011). An ultrasound contrast agent consists of small encapsulated microbubbles, which scatter the ultrasound very efficiently (De Jong 1993; Klibanov 2002). "
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    ABSTRACT: The dynamics of coated microbubbles was studied in an in vivo model. Biotinylated lipid-coated microbubbles were prepared in-house and were injected into a chick embryo chorioallantoic membrane (CAM) model on the fifth day of incubation. The microbubbles, ranging between 1.0 and 3.5 μm in diameter, were insonified in the frequency range of 4-7 MHz. Two amplitudes of acoustic pressure were applied: 300 kPa and 400 kPa. The fundamental and subharmonic responses were recorded optically with an ultra-fast camera (Brandaris 128) at 20 million frames per second. A subharmonic response was observed for 44% of the studied bubbles. From the data the frequency of the maximum fundamental and subharmonic response was derived for each individual bubble and resulted in the resonance curves of the microbubbles. All the bubbles showed shell (strain) hardening behavior for a higher acoustic pressure. We conclude that the subharmonic oscillations observed in this study belonged to the transmit at resonance (TR) regime.
    Ultrasound in medicine & biology 07/2012; 38(9):1608-17. DOI:10.1016/j.ultrasmedbio.2012.05.014 · 2.21 Impact Factor
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    • "Changing the phase between the transmitted signals of different frequencies modifies the envelope of the excitation burst. It has been shown that the phase between the two high-frequency transmit pulses in the dual-frequency excitation method, therefore the shape of the excitation burst, plays an important role in maximizing the amplitude response of the microbubbles at the SH frequency (Masotti et al 2007, Shen et al 2011). Zhang et al (2009) also compared an excitation technique, made up of dual-frequency, with the conventional single-frequency sinusoidal technique to enhance the SH emission from the UCA. "
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    ABSTRACT: Subharmonic (SH) emission from the ultrasound contrast agent (UCA) is of interest since it is produced only by the UCA and not by tissue, opposite to harmonic imaging modes where both tissue and microbubble show harmonics. In this work, the use of the self-demodulation (S-D) signal as a means of microbubble excitation at the SH frequency to enhance the SH emission of UCA is studied. The S-D wave is a low-frequency signal produced by the weak nonlinear propagation of an ultrasound wave. It is proportional to the second time derivative of the squared envelope of the transmitted signal. A diluted population of BR14 UCA (Bracco Research SA, Geneva, Switzerland) was insonified by a 10 MHz transducer focused at 76 mm firing bursts with different envelopes, durations and peak pressure amplitudes. The center frequency of the S-D signal changes from low frequencies (around 0.5 MHz) toward the transmitted frequency (10 MHz) by modifying the envelope function from gaussian to rectangular. For 6 and 20 transmitted cycles, the SH response is enhanced up to 25 and 22 dB, respectively, when using a rectangular envelope instead of a gaussian one. The experimental results are confirmed by the numerical simulation. The effects of the excitation duration and pressure amplitude are also studied. This study shows that a suitable design of the envelope of the transmit excitation to generate a S-D signal at the SH frequency can enhance the SH emission of UCA, and the SH imaging is feasible at high frequencies with a shorter transmit burst (six-cycle) and low acoustic pressure (∼100 KPa).
    Physics in Medicine and Biology 05/2012; 57(12):3675-91. DOI:10.1088/0031-9155/57/12/3675 · 2.76 Impact Factor
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