Acoustic Droplet Vaporization and Bubble-Enhanced Heating
High Intensity Focused Ultrasound (HIFU) is a noninvasive medical procedure for the treatment of solid tumors. It is well documented that bubbles at ultrasound focus concentrate acoustic energy and yield higher thermal doses, which could lead to a more efficient HIFU protocol. However, bubbles are not readily available in tissue and thus must be formed. This is possible using ultrasound pulses; however, it is well documented that the pressure required for bubble formation in tissue can exceed 10 MPa. The introduction of nuclei (i.e. encapsulated microbubbles) into solid tumors can reduce the pressure threshold significantly, thus making bubble-enhanced heating and lesion formation more feasible. It is well documented that particles smaller than 500 nm can extravasate through leaky tumor vasculature and accumulate in solid tumors. We have developed a submicron phase-shift nanoemulsion that can be vaporized using microsecond acoustic pulses with a high degree of spatial and temporal control (500mv_6cycles_10msBurstPeriod). These nanoemulsions can be used to nucleate bubbles in tumors and reduce the acoustic power and sonication time required for ultrasound-mediated thermal ablation.
The objectives of this research project are 1) to develop and characterize submicron particles that can accumulate in solid tumors via enhanced permeability and retention effect, and elucidate the relationship between the energy radiated by acoustically-driven bubbles and the location and magnitude of heat deposition.
In completed studies, perfluorocarbon based phase-shift nanoemulsion (PSNE) has been developed, which can be vaporized Thermocouples were used to measure temperature elevations enhanced by PSNE-nucleated gas bubbles in tissue-mimicking gel. The results indicate that PSNE competent as a nucleation agent for bubble-enhanced HIFU therapy. By varying related parameters, such as bubble concentration and acoustic pressure, it is possible to mediate the contributions of different bubble activities in the heating such as scattering and inertial cavitation, and thus have an optimized size and symmetry of the lesion. The current study is focused on evaluating the effects of different parameters and using the feedback from backscattering signal to adjust these parameters and optimize lesion.