Abstract
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.
Highlights
Proton therapy is emerging as an advanced radiation therapy modality for tumors in critical locations (Grau et al 2020)
Nanodroplet and phantom synthesis Nanodroplets with a perfluorobutane core and a crosslinked polymeric shell made of polyvinyl alcohol (PVA) were prepared according to the protocol described by Heymans et al (2021)
It was previously reported for the droplets used in these experiments that at moderate degrees of superheat, vaporization is induced by high-linear energy transfer (LET) secondary particles only (Carlier et al 2020; Heymans et al 2021), which can be produced by nuclear reactions up until the proton energy drops below the Coulomb barrier
Summary
Proton therapy is emerging as an advanced radiation therapy modality for tumors in critical locations (Grau et al 2020). Because protons deposit most of their dose in a narrow (few millimeters wide) peak at the end of their range, called the Bragg peak, followed by a sharp distal dose fall-off, the spatial dose distribution can be better conformed to the tumor volume than in Gonzalo Collado-Lara and Sophie V. Conventional radiotherapy, thereby improving healthy tissue sparing (Parodi and Polf 2018). The physical benefits of protons cannot be fully exploited because deviations from the planned dose distribution may arise from different sources of range uncertainty, including treatment planning, setup errors and patient and organ motion (Paganetti 2012; Knopf and Lomax 2013). Substantial safety margins are included in the treatment plan (Paganetti 2012; Polf and Parodi 2015), reducing the potential improvement compared with conventional radiotherapy. The benefits of proton therapy could be maximized if deviations during the treatment were detected and Ultrasound in Medicine & Biology
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