Acoustic Modulation Enables Proton Detection with Nanodroplets at Body Temperature

Heymans, Sophie V.; Collado Lara, G.; Rovituso, M.; Vos, H.J.; D'hooge, Jan; de Jong, N.; Van Den Abeele, Koen

doi:10.1109/TUFFC.2022.3164805

Acoustic Modulation Enables Proton Detection with Nanodroplets at Body Temperature

Title

Acoustic Modulation Enables Proton Detection with Nanodroplets at Body Temperature

Author

Heymans, Sophie V. (Katholieke Universiteit Leuven; Erasmus MC)
Collado Lara, G. (Erasmus MC)
Rovituso, M. (HollandPTC)
Vos, H.J. (TU Delft ImPhys/Medical Imaging; Erasmus MC)
D'hooge, Jan (Katholieke Universiteit Leuven)
de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus MC)
Van Den Abeele, Koen (Katholieke Universiteit Leuven)

Date

2022

Abstract

Superheated nanodroplet (ND) vaporization by proton radiation was recently demonstrated, opening the door to ultrasound-based in vivo proton range verification. However, at body temperature and physiological pressures, perfluorobutane nanodroplets (PFB-NDs), which offer a good compromise between stability and radiation sensitivity, are not directly sensitive to primary protons. Instead, they are vaporized by infrequent secondary particles, which limits the precision for range verification. The radiation-induced vaporization threshold (i.e., sensitization threshold) can be reduced by lowering the pressure in the droplet such that ND vaporization by primary protons can occur. Here, we propose to use an acoustic field to modulate the pressure, intermittently lowering the proton sensitization threshold of PFB-NDs during the rarefactional phase of the ultrasound wave. Simultaneous proton irradiation and sonication with a 1.1 MHz focused transducer, using increasing peak negative pressures (PNPs), were applied on a dilution of PFB-NDs flowing in a tube, while vaporization was acoustically monitored with a linear array. Sensitization to primary protons was achieved at temperatures between 29 °C and 40 °C using acoustic PNPs of relatively low amplitude (from 800 to 200 kPa, respectively), while sonication alone did not lead to ND vaporization at those PNPs. Sensitization was also measured at the clinically relevant body temperature (i.e., 37 °C) using a PNP of 400 kPa. These findings confirm that acoustic modulation lowers the sensitization threshold of superheated NDs, enabling a direct proton response at body temperature.

Subject

acoustic droplet vaporization
acoustic modulation
Acoustics
In vivo
Liquids
Nanodroplets
proton range verification
proton therapy
Protons
Temperature sensors
Transducers
Ultrasonic imaging
ultrasound contrast agents