Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

Abstract

Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through high-speed video microscopy and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be detected and differentiated from standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand and undergo unforced radial oscillation while settling to a final bubble diameter. The size-dependent oscillation phenomenon generates a unique acoustic signal that can be passively detected in both time and frequency domain using confocal piston transducers with an ‘activate high’ (8 MHz, 2 cycles), ‘listen low’ (1 MHz) scheme. Results show that the magnitude of the acoustic ‘signature’ increases as PFC boiling point decreases. By using a band-limited spectral processing technique, the droplet signals can be isolated from controls and used to build experimental relationships between concentration and vaporization pressure. The techniques shown here may be useful for physical studies as well as development of droplet-specific imaging techniques.

Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer

“…22 Ultra-high-speed camera observations published by our group demonstrated that this phenomenon is dictated by an overexpansion of the generated microbubble followed by exponentially decaying oscillations to final resting diameter. 22 The long oscillations (>5 cycles) represent the natural resonance of the generated microbubbles in the medium.…”

“…22 Ultra-high-speed camera observations published by our group demonstrated that this phenomenon is dictated by an overexpansion of the generated microbubble followed by exponentially decaying oscillations to final resting diameter. 22 The long oscillations (>5 cycles) represent the natural resonance of the generated microbubbles in the medium. Therefore, by examining the resulting acoustic a) Electronic mail: padayton@email.unc.edu signal, it is possible to determine physical properties of the contrast agents (e.g., size, shell material) and deduce information about the surrounding environment (e.g., ambient pressure, temperature, and viscosity).…”

“…Therefore, by examining the resulting acoustic a) Electronic mail: padayton@email.unc.edu signal, it is possible to determine physical properties of the contrast agents (e.g., size, shell material) and deduce information about the surrounding environment (e.g., ambient pressure, temperature, and viscosity). 22 Monitoring the vaporization of droplets in real-time would be also beneficial for droplet-mediated therapy in order to visualize and control the location of the treated area. 23 Very recently, a dual-frequency approach based on the "pulse high, listen low" scheme previously described by Sheeran et al 22 has been validated for isolating and extracting the droplet vaporization events.…”

“…22 Monitoring the vaporization of droplets in real-time would be also beneficial for droplet-mediated therapy in order to visualize and control the location of the treated area. 23 Very recently, a dual-frequency approach based on the "pulse high, listen low" scheme previously described by Sheeran et al 22 has been validated for isolating and extracting the droplet vaporization events. Using this approach, droplets are activated at high frequency (8 MHz) while the vaporization signal is detected by a second transducer centered at low frequency (1 MHz).…”

Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

“…From this lipid solution, 1.5 mL was pipetted into a 2 mL glass vial (Wheaton Industries, Millville, NJ), and the air headspace was then replaced with decafluorobutane (DFB) gas (Fluoromed, Round Rock, TX, USA). The microbubbles were then formed by mechanical agitation using a modified dental amalgamator (Lantheus Medical, New York, NY), resulting in a microbubble distribution ranging predominantly from 1 −10 μm with a concentration of 1-5 x 10 9 microbubbles per mL of solution [20]. The liquid microbubble is imaged using a tightly focused femtosecond laser beam, which is scanned across it.…”