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Optimisation of Subharmonic Generation by Native and Altered Populations of the Ultrasound Contrast Agent SonoVue

A Ivory1*, J Browne2 , A Fagan3 , (1) University of Dublin, Dublin 8, Ireland, (2) Dublin Institute of Technology, Dublin 8, Ireland, (3) Mayo Clinic, Rochester, MN


(Tuesday, 7/31/2018) 4:30 PM - 6:00 PM

Room: Room 207

Purpose: Dynamic Contrast-Enhanced Ultrasound using ultrasound contrast agents(UCA) is a non-invasive method of imaging the microvasculature, typically employing harmonic imaging. Subharmonic imaging, detects signals which are generated by the UCAs but not by tissue and holds potential for improving quantification accuracy. However, optimal transmission parameters have not yet been established. The aim of this work was to establish the optimum transmit beam parameters for subharmonic signal generation with ‘native’ and ‘altered’ populations of SonoVue® (Bracco, Switzerland).

Methods: SonoVue® was acoustically characterized using a narrowband through-transmission system. The subharmonic response of ‘native’ and ‘altered’ UCA, altered through decantation, was investigated at transmit center frequencies 1.8–5 MHz and pulse lengths 1-8 cycles. Three independent samples were measured 30 times at each set of transmit parameters. Frequency spectra were determined with the Welch Periodogram and corrected for transmit and receive sensitivities of the single-element transducers (Olympus, USA). The subharmonic amplitude was measured at bandwidths defined at half the transmit frequency full-width half-maximum and full-width tenth-maximum.

Results: The ‘altered’ UCA had reduced polydispersity (1–4µm; 99%/82% bubble count/volume, respectively), compared to ‘native’ (57% bubble volume 4–10µm). Both UCA generated the highest subharmonic signal when insonated at a pulse length of 3-cycles. The maximum measured native subharmonic signal peaked at a transmit frequency of 1.9MHz, corresponding to subharmonic at 0.95MHz. This frequency increased in the altered population, to the range 2.3–2.5MHz, bringing the subharmonic center frequency above 1 MHz. Results supported that there is a lower subharmonic generation threshold when insonated near the resonance frequency, measured at 2.1/2.4MHz for native/altered populations.

Conclusion: Optimal transmit beam parameters have been established for maximizing subharmonic generation from SonoVue®. Furthermore, altering the size distribution shifted the frequency of maximum subharmonic to a more clinically-useful detection range (typically curvilinear probes used in abdominal contrast imaging have highest sensitivities > 1 MHz).

Funding Support, Disclosures, and Conflict of Interest: The authors acknowledge funding from the Irish Research Council and experimental support from Bracco Suisse, Switzerland.


Optimization, Contrast Agent, Quantitative Imaging


IM- Ultrasound : Contrast imaging

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