Investigating the Subharmonic Response of Individual Phospholipid Encapsulated Microbubbles at High Frequencies: A Comparative Study of Five Agents

Helfield, Brandon; Chérin, Emmanuel; Foster, F. Stuart; Goertz, David E.

doi:10.1016/j.ultrasmedbio.2012.01.011

Cited by 69 publications

(80 citation statements)

References 52 publications

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“…Kwan and Borden 35 and Kooiman et al 23 present convincing microscopic images of heterogeneous lipid domains and ascribe this phenomenon to phase separation of the different lipid species on the bubble surface. Similar variations in the local lipid concentration on the shell have been found to affect the nonlinear behavior of DSPC microbubbles at high frequencies, 45 although no clear relation between the nonlinear response and shell microstructure was evident. Hosny et al 7 quantified the spatial distribution of viscosity in the microbubble shell using a fluorescence lifetime imaging technique and also found a large variation in viscosity that was correlated to differences in the ultrasound response of microbubbles of similar size.…”

Section: Shell Viscositymentioning

confidence: 72%

“…During calibration, a 0.2 -lm needle-type hydrophone (Precision Acoustics) was positioned approximately 2 mm from the sample holder membrane (a modified OptiCell V R with one membrane removed), such that the hydrophone location corresponded to the location of the ELIP during the optical measurement. The transmitted acoustic pressure amplitude in situ was attenuated by a factor of 3 dB relative to the free-field pressure due to the presence of the membrane and the 45 angle of incidence of the acoustic wave. The in situ pressure waveform and power spectrum for a 250 kPa peak pressure amplitude excitation pulse are shown in Fig.…”

Section: B Acoustic Excitation Pulsementioning

confidence: 99%

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Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-highspeed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 Â 10 À8 to 2.5 Â 10 À9 kg/s, was observed with increasing dilatation rate, from 0.5 Â 10 6 to 1 Â 10 7 s À1 . This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [j s ¼ (2.1 6 1.0) Â 10 À8 kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

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Section: Shell Viscositymentioning

confidence: 72%

Section: B Acoustic Excitation Pulsementioning

confidence: 99%

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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“…S6 A and B). majority of USCAs can only be used at frequencies < 5 MHz; as such, there is an increasing interest in extending contrast imaging to high frequencies useful for superficial tissue, such as carotid and breast (26,27). For this reason, we would like to emphasize that for all data reported above, we did ultrasound scans using a 12.5-MHz frequency, applying the tissue harmonic imaging (THI) modality.…”

Section: Resultsmentioning

confidence: 99%

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Delogu

Vidili

Venturelli

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

144

102

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Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.

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“…For contrast-enhanced ultrasound imaging, the chirp excitation also enhances the ultrasound scattering from microbubble populations and can achieve a better CTR. Even though phospholipid coated commercial UCAs and in-house produced microbubbles have different behavior, subharmonic emission efficiency, and disruption threshold [25]; their response to wideband excitation will be stronger since UCAs have a polydisperse size distribution. More microbubbles can be excited close to their resonance frequency, which also increases the nonlinear behavior of microbubbles.…”

Section: Discussionmentioning

confidence: 99%

The effect of amplitude modulation on subharmonic imaging with chirp excitation

Harput

Arif

McLaughlan

et al. 2013

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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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 with the signal duration. Linear frequency modulated (LFM) and nonlinear frequency modulated (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 to 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.

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Investigating the Subharmonic Response of Individual Phospholipid Encapsulated Microbubbles at High Frequencies: A Comparative Study of Five Agents

Cited by 69 publications

References 52 publications

Impulse response method for characterization of echogenic liposomes

Impulse response method for characterization of echogenic liposomes

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

The effect of amplitude modulation on subharmonic imaging with chirp excitation

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