Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Abstract

A phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration.

High-Frequency Acoustic Droplet Vaporization is Initiated by Resonance

“…Experimentally, it has been found that a prominent peak negative pressure (PNP) nucleation threshold exists, above which the nucleation probability increases with the acoustic pressure amplitude and that this threshold, counterintuitively, lowers with an increase in ultrasound frequency and with a decrease in ambient pressure [9,12,[21][22][23][24][25][26][27][28][29][30]. These observations are in line with what is predicted from both classical nucleation theory [31] and superharmonic focusing [23,32], and by the combination of the two [33,34]. Superharmonic focusing results from the focusing of higher harmonics with wavelengths on the order of the droplet diameter that are generated through nonlinear propagation of the transmitted ultrasound wave [32].…”

High-frequency acoustic droplet vaporization is initiated by resonance

“…Experimentally, it has been found that a prominent peak negative pressure (PNP) nucleation threshold exists above which the nucleation probability increases with the acoustic pressure amplitude and that this threshold, counterintuitively, lowers with an increase in ultrasound frequency and with a decrease in ambient pressure [9,12,[21][22][23][24][25][26][27][28][29][30]. These observations are in line with what is predicted from both classical nucleation theory [31] and superhamonic focusing [23,32], and by the combination of the two [33,34]. Superharmonic focusing results from the focusing of higher harmonics with wavelengths on the order of the droplet diameter that are generated through nonlinear propagation of the transmitted ultrasound wave [32].…”

Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets for Contrast-Enhanced Ultrasound Imaging

“…This MPa is well below reported thresholds of 13.7 to 21 MPa for 1.1-MHz ultrasound cavitation in tissue [42], but the mechanical index is above the accepted diagnostic ultrasound imaging threshold of 1.9 [59]. While the cavitation threshold depends on experimental variables such as dissolved gas content, nucleation sites, and water concentration [22], [26], [41], [53], [60], we found the energy levels required for HnD vaporization to be lower than those of cavitation in blank phantoms or OBnD phantoms with nanodroplet nucleation sites. It is important to note this threshold is also dependent on the imaging environment.…”