Controllable Nucleation of Cavitation from Plasmonic Gold Nanoparticles for Enhancing High Intensity Focused Ultrasound Applications.

James R Mclaughlan

doi:10.3791/58045

Abstract

In this study, plasmonic gold nanoparticles were simultaneously exposed to pulsed near-infrared laser light and high intensity focused ultrasound (HIFU) for the controllable nucleation of cavitation in tissue-mimicking gel phantoms. This in vitro protocol was developed to demonstrate the feasibility of this approach, for both enhancement of imaging and therapeutic applications for cancer. The same apparatus can be used for both imaging and therapeutic applications by varying the exposure duration of the HIFU system. For short duration exposures (10 µs), broadband acoustic emissions were generated through the controlled nucleation of inertial cavitation around the gold nanoparticles. These emissions provide direct localization of nanoparticles. For future applications, these particles may be functionalized with molecular-targeting antibodies (e.g. anti-HER2 for breast cancer) and can provide precise localization of cancerous regions, complementing routine diagnostic ultrasound imaging. For continuous wave (CW) exposures, the cavitation activity was used to increase the localized heating from the HIFU exposures resulting in larger thermal damage in the gel phantoms. The acoustic emissions generated from inertial cavitation activity during these CW exposures was monitored using a passive cavitation detection (PCD) system to provide feedback of cavitation activity. Increased localized heating was only achieved through the unique combination of nanoparticles, laser light and HIFU. Further validation of this technique in pre-clinical models of cancer is necessary.

Highlights

High intensity focused ultrasound (HIFU), or focused ultrasound surgery (FUS), is a non-ionizing and non-invasive technique that is used for the thermal ablation of subcutaneous tissue[1]
The method employed in this study has previously shown that by simultaneously exposing the plasmonic nanoparticles to both laser illumination and HIFU, the laser fluence and acoustic pressures needed to nucleate these small vapor bubbles is dramatically reduced, and the signal-to-noise ratio for imaging is increased[23]
It is important to ensure that the ratio of ammonium persulfate (APS) and TEMED is such that the process does not catalyze too quickly

Summary

Introduction

High intensity focused ultrasound (HIFU), or focused ultrasound surgery (FUS), is a non-ionizing and non-invasive technique that is used for the thermal ablation of subcutaneous tissue[1]. In order to control cavitation activity during HIFU exposures, the introduction of external nuclei has been investigated These can take the form of microbubbles[13], phase-shift nanoemulsions[14] or plasmonic nanoparticles[15]. The method employed in this study has previously shown that by simultaneously exposing the plasmonic nanoparticles to both laser illumination and HIFU, the laser fluence and acoustic pressures needed to nucleate these small vapor bubbles is dramatically reduced, and the signal-to-noise ratio for imaging is increased[23]. A method is described here for combining plasmonic nanoparticles with both laser and HIFU exposures for a highly controllable technique for the nucleation and activity of vapor bubbles

Tissue Mimicking Phantom Manufacture

Calibration of HIFU Transducers Free Field Acoustic Pressure

Cavitation Threshold Detection from Pulsed HIFU Exposures

Thermal Denaturation from Continuous Wave HIFU Exposures

Representative Results

Discussion