Quantifying Activation of Perfluorocarbon-Based Phase-Change Contrast Agents Using Simultaneous Acoustic and Optical Observation

Abstract

Phase-change contrast agents in the form of nanoscale droplets can be activated into microbubbles by ultrasound, extending the contrast beyond the vasculature. This article describes simultaneous optical and acoustical measurements for quantifying the ultrasound activation of phase-change contrast agents over a range of concentrations. In experiments, decafluorobutane-based nanodroplets of different dilutions were sonicated with a high-pressure activation pulse and two low-pressure interrogation pulses immediately before and after the activation pulse. The differences between the pre- and post-interrogation signals were calculated to quantify the acoustic power scattered by the microbubbles activated over a range of droplet concentrations. Optical observation occurred simultaneously with the acoustic measurement, and the pre- and post-microscopy images were processed to generate an independent quantitative indicator of the activated microbubble concentration. Both optical and acoustic measurements revealed linear relationships to the droplet concentration at a low concentration range <108/mL when measured at body temperature. Further increases in droplet concentration resulted in saturation of the acoustic interrogation signal. Compared with body temperature, room temperature was found to produce much fewer and larger bubbles after ultrasound droplet activation.

Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

“…10), probably because a greater number of Cy-droplets yielded more optical vaporisation events [22] producing a higher density of acoustic sources. Further study is required to determine the linearity and concentration range of this dependence.…”

“…The precursor Cy-microbubbles were produced via mechanical agitation. Finally, the Cy-droplet emulsion was obtained by condensing Cy-microbubbles using the method of Li et al [22].

Fig. 2Schematic showing the composition of Cy-droplet contrast agent.

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“…The ultrasound contrast enhancement was quantified using a custom designed ‘imaging-activation-imaging’ sequence [22], [32] on a Verasonics Vantage 256 research platform. Single cycle, low amplitude ultrasound at 4.5 MHz (plane-waves of 15-angle spatial compounding, 106.1 kPa, MI = 0.05) was used at each imaging step to estimate the ultrasound signal level from the contrast agent before and after Cy-droplet activation.…”

Notice of Removal: Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

“…The precursor Cy-microbubbles were produced via mechanical agitation. Finally, the Cy-droplet emulsion was obtained by condensing Cy-microbubbles using the method of Li et al [22].…”

“…For ultrasound imaging with acoustic vaporisation, focused pulses (8 MHz, 10-cycles, 3.39 MPa, mechanical index (MI) = 1.2, pulse-repetition-frequency = 14.3 kHz, total duration of exposure is 8.8 ms) transmitted from a clinical linear array probe L12-5 (ATL, USA) were applied to activate the Cy-droplets. The ultrasound contrast enhancement was quantified using a custom designed 'imaging-activation-imaging' sequence [22,32] on a Verasonics Vantage 256 research platform. Single cycle, low amplitude ultrasound at 4.5 MHz (plane-waves of 15-angle spatial compounding, 106.1 kPa, MI = 0.05) was used at each imaging step to estimate the ultrasound signal level from the contrast agent before and after Cy-droplet activation.…”