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Related Experiment Video

Updated: Nov 19, 2025

Imaging and Quantification of the Area of Fast-Moving Microbubbles Using a High-Speed Camera and Image Analysis
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High-Frequency Array-Based Nanobubble Nonlinear Imaging in a Phantom and In Vivo.

Carly Pellow, Emmanuel Cherin, Eric C Abenojar

    IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
    |January 29, 2021
    PubMed
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    This study shows that high-frequency amplitude modulation (AM) imaging significantly improves contrast-enhanced ultrasound using nanobubbles (NBs). This advanced technique enhances NB detection sensitivity in both phantom and in vivo models.

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    Area of Science:

    • Biomedical Engineering
    • Acoustics
    • Nanotechnology

    Background:

    • Nanobubbles (NBs) show promise for ultrasound imaging and therapy.
    • Current NB imaging often uses low frequencies and high concentrations, lacking standardized protocols.
    • Previous work identified nonlinear scattering of NBs advantageous for amplitude modulation (AM) imaging.

    Purpose of the Study:

    • To implement pressure-calibrated high-frequency AM imaging for enhanced sensitivity to nonlinear NB scattering.
    • To evaluate the performance of three phospholipid-based NB formulations using this advanced imaging technique.

    Main Methods:

    • Utilized a commercial preclinical array system with pressure-calibrated amplitude modulation (AM) at high frequencies (e.g., 25, 30 MHz).
    • Investigated nonlinear scattering properties of porphyrin-lipid-encapsulated nanobubbles at low and high frequencies.
    • Assessed contrast-to-tissue ratio improvements in a tissue-mimicking phantom and in vivo.

    Main Results:

    • High-frequency AM imaging demonstrated enhanced sensitivity to nonlinear scattering from nanobubbles.
    • Significant improvements in contrast-to-tissue ratio were observed: 12.4–22.8 dB in phantoms and 6.7–14.8 dB in vivo compared to B-mode.
    • The pressure threshold-dependent nonlinear scattering of NBs was confirmed and leveraged for imaging.

    Conclusions:

    • Pressure-calibrated high-frequency AM imaging offers superior sensitivity for nanobubble-based ultrasound contrast imaging.
    • This method provides substantial contrast enhancement, paving the way for improved diagnostic and therapeutic ultrasound applications.
    • The findings support the development of standardized imaging protocols based on NB nonlinear scattering signatures.