Dual-frequency acoustic droplet vaporization detection for medical imaging

Abstract

Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when vaporized into to gas-filled microbubbles using ultrasound. Here, we conducted a pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of droplet vaporization and investigate the effects of applied pressure and droplet concentration on image contrast and axial and lateral resolution. Control microbubble contrast agents were used for comparison. A confocal dual-frequency transducer was used to transmit at 8 MHz and passively receive at 1 MHz. Droplet signals were of significantly higher energy than microbubble signals. This resulted in improved signal separation and high contrast-to-tissue ratios (CTR). Specifically, with a peak negative pressure (PNP) of 450 kPa applied at the focus, the CTR of B-mode images was 18.3 dB for droplets and −0.4 for microbubbles. The lateral resolution was dictated by the size of the droplet activation area, with lower pressures resulting in smaller activation areas and improved lateral resolution (0.67 mm at 450 kPa). The axial resolution in droplet images was dictated by the size of the initial droplet and independent of the properties of the transmit pulse (3.86 mm at 450 kPa). In post-processing, time-domain averaging (TDA) improved droplet and microbubble signal separation at high pressures (640 kPa and 700 kPa). Taken together, these results indicate that it is possible to generate high-sensitivity, high-contrast images of vaporization events. In the future, this has the potential to be applied in combination with droplet-mediated therapy to track treatment outcomes or as a stand-alone diagnostic system to monitor the physical properties of the surrounding environment.

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

“…For example, it is difficult to achieve efficient drug concentration in tumor sites because of their limited capacity for loading therapeutic agents, short circulation time, and large micrometer size. To address these problems, phase-change perfluorocarbon (PFC) nanodroplets have been developed 18 , 20 , 24 - 27 in which the liquid in the core of nanodroplets can vaporize to gas phase upon activation by ultrasound energy, called acoustic droplet vaporization (ADV) 28 - 30 . The stability of nanodroplets is increased, and they can accumulate in tumor tissues by passive targeting due to their nano-scaled size.…”

“…Ultrasound is a form of the longitudinal mechanical wave that can be transmitted in the human body and is widely used in tumor imaging and therapy 30 - 35 . Different from the diagnostic ultrasound used in the clinic to force bubble elastic compression and expansion, more ultrasound energy is needed to induce conversion of nanodroplets into microbubbles and trigger local drug release 28 - 32 . However, it is difficult to induce droplet-to-bubble transition and destruction of hard-shelled (e.g.…”

Transcranial activation and imaging of low boiling point phase‐change contrast agents through the temporal bone using an ultrafast interframe activation ultrasound sequence

“…Vaporization detection image has been demonstrated to be quite effective when transmitting at a high frequency (≥5 MHz) and receiving at a low frequency (≤1.5 MHz). 45,55 In this study, in order to achieve transcranial activation of PCCAs, VDI was implemented at different transmit frequencies ranging from 2.5 to 3.5 MHz to investigate whether VDI could provide higher contrast than UIAU. Besides increased penetration, low frequency transmit would potentially favor the vaporization and cavitation of low boiling point PCCAs and thus enhance therapeutic effects.…”

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

“…This technique, requiring the use of two mechanically scanned confocal piston transducers, has been adapted to develop an imaging system for capturing droplet vaporization events and generating high-sensitivity, high-contrast images. 24 The large difference between the activation pulse frequency and the listening frequency results in a weak response from microbubbles and tissue. In vitro results showed that ADV imaging was capable of generating a contrast-to-tissue ratio (>18 dB), as good as standard contrast agent imaging techniques.…”

“…In vitro results showed that ADV imaging was capable of generating a contrast-to-tissue ratio (>18 dB), as good as standard contrast agent imaging techniques. 24 Imaging ADV at low frequency has several advantages. First, the penetration depth is increased because of the weak attenuation of low-frequency droplet content in tissue.…”