Spatiotemporal Distribution of Nanodroplet Vaporization in a Proton Beam Using Real-Time Ultrasound Imaging for Range Verification

Gonzalo Collado-Lara*, Sophie V. Heymans, Marta Rovituso, Bram Carlier, Yosra Toumia, Martin Verweij, Hendrik J. Vos, Nico de Jong, Verya Daeichin, More Authors

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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The potential of proton therapy to improve the conformity of the delivered dose to the tumor volume is currently limited by range uncertainties. Injectable superheated nanodroplets have recently been proposed for ultrasound-based in vivo range verification, as these vaporize into echogenic microbubbles on proton irradiation. In previous studies, offline ultrasound images of phantoms with dispersed nanodroplets were acquired after irradiation, relating the induced vaporization profiles to the proton range. However, the aforementioned method did not enable the counting of individual vaporization events, and offline imaging cannot provide real-time feedback. In this study, we overcame these limitations using high-frame-rate ultrasound imaging with a linear array during proton irradiation of phantoms with dispersed perfluorobutane nanodroplets at 37°C and 50°C. Differential image analysis of subsequent frames allowed us to count individual vaporization events and to localize them with a resolution beyond the ultrasound diffraction limit, enabling spatial and temporal quantification of the interaction between ionizing radiation and nanodroplets. Vaporization maps were found to accurately correlate with the stopping distribution of protons (at 50°C) or secondary particles (at both temperatures). Furthermore, a linear relationship between the vaporization count and the number of incoming protons was observed. These results indicate the potential of real-time high-frame-rate contrast-enhanced ultrasound imaging for proton range verification and dosimetry.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalUltrasound in Medicine and Biology
Issue number1
Publication statusPublished - 2021


  • Dosimetry
  • Nanodroplets
  • Proton therapy
  • Range verification
  • Ultrasound


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