Ultrasound-assisted investigation of photon triggered vaporization of poly(vinylalcohol) phase-change nanodroplets: A preliminary concept study with dosimetry perspective

Yosra Toumia*, Roberto Miceli, Fabio Domenici, Sophie V. Heymans, Bram Carlier, Madalina Cociorb, Letizia Oddo, Piero Rossi, Rolando Maria D'Angellilo, Edmond Sterpin, Emiliano D'Agostino, Koen Van Den Abeele, Jan D'hooge, Gaio Paradossi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


Purpose: We investigate the vaporization of phase-change ultrasound contrast agents using photon radiation for dosimetry perspectives in radiotherapy. Methods: We studied superheated perfluorobutane nanodroplets with a crosslinked poly(vinylalcohol) shell. The nanodroplets' physico-chemical properties, and their acoustic transition have been assessed firstly. Then, poly(vinylalcohol)-perfluorobutane nanodroplets were dispersed in poly(acrylamide) hydrogel phantoms and exposed to a photon beam. We addressed the effect of several parameters influencing the nanodroplets radiation sensitivity (energy/delivered dose/dose rate/temperature). The nanodroplets-vaporization post-photon exposure was evaluated using ultrasound imaging at a low mechanical index. Results: Poly(vinylalcohol)-perfluorobutane nanodroplets show a good colloidal stability over four weeks and remain highly stable at temperatures up to 78 °C. Nanodroplets acoustically-triggered phase transition leads to microbubbles with diameters <10 μm and an activation threshold of mechanical index = 0.4, at 7.5 MHz. A small number of vaporization events occur post-photon exposure (6MV/15MV), at doses between 2 and 10 Gy, leading to ultrasound contrast increase up to 60% at RT. The nanodroplets become efficiently sensitive to photons when heated to a temperature of 65 °C (while remaining below the superheat limit temperature) during irradiation. Conclusions: Nanodroplets’ core is linked to the degree of superheat in the metastable state and plays a critical role in determining nanodroplet’ stability and sensitivity to ionizing radiation, requiring higher or lower linear energy transfer vaporization thresholds. While poly(vinylalcohol)-perfluorobutane nanodroplets could be slightly activated by photons at ambient conditions, a good balance between the degree of superheat and stability will aim at optimizing the design of nanodroplets to reach high sensitivity to photons at physiological conditions.

Original languageEnglish
Pages (from-to)232-242
Number of pages11
JournalPhysica Medica
Early online date20 Aug 2021
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
This work was funded by the European Union's Horizon 2020 research and innovation program under grant agreement n?766456 ("AMPHORA"). The authors acknowledge the financial support from INFN Istituto Nazionale di Fisica Nucleare (Rome, Italy), SR3T project.

Publisher Copyright:
© 2021 Associazione Italiana di Fisica Medica


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