Sustaining Microbubbles Derived from Phase Change Nanodroplet by Low-Amplitude Ultrasound Exposure

Abstract

To improve the short lifetime of microbubbles induced upon application of triggering ultrasound pulse to a phase change nanodroplet (PCND), the effect of low-pressure continuous ultrasound for sustaining microbubbles was studied in a gel phantom. A pulse with 100 cycles of 1.1 MHz ultrasound with a peak negative pressure of 2.4 MPa was used for the generation of microbubbles while superimposing a bubble-sustaining ultrasound at a frequency of 1.1 MHz with a relatively low-pressure amplitude. It was found that a peak negative pressure in the range from 0.01 to 0.1 MPa was suitable for sustaining the microbubbles without inducing cavitation. The presence of sustained bubbles could be echographycally observed as a beam-shaped brightness change. Moreover, the sustained microbubbles induced cavitation upon additional application of ultrasound pulse at a peak negative pressure of 0.2 MPa. The results obtained suggested that not only the lifetime but also the activity of the microbubbles can be controlled.

Development of Nanodroplets for Histotripsy-Mediated Cell Ablation

“…We hypothesize that PFP-loaded nanodroplets with an average diameter <500 nm can diffuse across tumor’s leaky vasculature and accumulate in the cancer lesion when administered into the systemic circulation. − Applying specific US pulse sequences to the tumor lesion will deliver the acoustic energy necessary to convert the PFP core from the liquid to the gaseous phase in a process known as acoustic droplet vaporization (ADV), ,, which will allow real time US imaging of tumor tissue. Unlike histotripsy that relies on cavitation nuclei derived from rare gas pockets in the tissue and extremely high acoustic pressures to initiate the cavitation process, the gas bubbles formed by ADV can act as cavitation nuclei to generate and maintain the cavitation bubble cloud at a significantly reduced pressure.…”

Intensified and controllable vaporization of phase-changeable nanodroplets induced by simultaneous exposure of laser and ultrasound

“…As this study explored opto-acoustically vaporized NDs with lifetime on the scale of one second, these sustained vaporized NDs can further act as either US contrast agents for imaging purposes or cavitation nucleus for treatment purposes. The feasibility of integrating diagnostic and therapeutic purposes by designing specific US sequences has been verified in an earlier study on acoustically vaporized NDs [23] , and could be adapted to opto-acoustically vaporized NDs with minimal change.…”

Enhancement of High-Intensity Focused Ultrasound Heating by Short-Pulse Generated Cavitation

“…To generate microbubbles containing slightly soluble gas inside a body, the usage of nanoparticles that can be vaporized into microbubbles by HIFU pulses or short bursts has been developed and investigated [23,[37][38][39]. Such phase change nanoparticles enable us to control the region of microbubbles induced by HIFU pulses.…”

“…In the trigger HIFU sequence, the typical acoustic intensity for cavitation generation was higher due to the lack of artificial cavitation nuclei. The duration time of the burst wave for the heat enhancement was shorter because lifetime of cavitation bubbles induced by the trigger pulse is considered to be shorter than that of microbubbles vaporized from nanoparticles with slightly soluble gas [38]. The advantage in the trigger HIFU exposure over the methods using nanoparticles is to have a potentially shorter lead time to be approved as clinical applications.…”