TY - JOUR
T1 - Acoustic Modulation Enables Proton Detection with Nanodroplets at Body Temperature
AU - Heymans, Sophie V.
AU - Collado-Lara, Gonzalo
AU - Rovituso, Marta
AU - Vos, Hendrik J.
AU - D'hooge, Jan
AU - De Jong, Nico
AU - Van Den Abeele, Koen
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - acoustic droplet vaporization
KW - acoustic modulation
KW - Acoustics
KW - In vivo
KW - Liquids
KW - Nanodroplets
KW - proton range verification
KW - proton therapy
KW - Protons
KW - Temperature sensors
KW - Transducers
KW - Ultrasonic imaging
KW - ultrasound contrast agents
UR - http://www.scopus.com/inward/record.url?scp=85127800524&partnerID=8YFLogxK
U2 - 10.1109/TUFFC.2022.3164805
DO - 10.1109/TUFFC.2022.3164805
M3 - Article
AN - SCOPUS:85127800524
SN - 0885-3010
VL - 69
SP - 2028
EP - 2038
JO - IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
JF - IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
IS - 6
ER -