Ultrasound based dosimetry for radiotherapy: In-vitro proof of principle

Abstract

Advances in radiotherapeutic treatments and the ability to detect accidents due to equipment mishandling or malfunctioning require the development of on-line in-vivo dosimetry systems. Here, we propose to use ultrasound contrast agents (UCAs) as a possible candidate for such a system, based on the hypothesis that irradiation of UCAs will modify their viscoelastic and/or their geometric properties and consequently their ultrasonic response. The aim of this study is to provide a proof of principle in-vitro. Solutions of saline with several commercially available lipid-shelled UCAs were investigated and the agents were characterized using a through transmission set-up, before and after irradiation. Although the agents were not yet optimized for radiation sensitivity, Targestar-P showed a noticeable dose dependency of the magnitude of the jump in phase velocity and amplitude of the attenuation at resonance. These results confirm the hypothesis that the ultrasonic readout of UCAs can be correlated with the ionizing radiation dose delivered to the agents. This supports the concept of using ultrasound and UCAs as a potential tool for in-vivo dosimetry.

Effect of a Radiotherapeutic Megavoltage Beam on Ultrasound Contrast Agents

“…6) was distinct for SonoVue, but negligible for Definity. Both the trend observed in the change in attenuation of SonoVue (i.e., decrease 20 Gy, followed by an increase at higher doses) and the fact that the two agents responded differently to radiation agree with a previous study by Verboven et al (2014), who reported that radiation had different influence on the acoustic attenuation of three UCAs (SonoVue, Micromarker and Targestar-P). Furthermore, our results revealed that the changes in the acoustics were in line with the size distribution measurements (Fig.…”

“…Although it was previously hypothesized that the change in attenuation was owing solely to a decrease in concentration (Verboven et al 2014), our results suggest more complex behavior. The size distribution measurements of the SonoVue samples (Fig.…”

“…Experiments characterizing their interaction become crucial as estimating the final influence on microbubble properties is challenging. In previous experiments (Verboven et al 2014), the acoustic attenuation of UCA populations was reported to decrease after irradiation with a megavoltage beam. However, several questions remain.…”

“…Nevertheless, none of these techniques has emerged as a gold standard because of their respective limitations (Mijnheer et al 2013). Ultrasound contrast agents (UCAs) together with ultrasound imaging were proposed as a new method to determine the delivered dose (Verboven et al 2014). The UCAs used for clinical imaging are suspensions of microbubbles coated with a viscoelastic layer that produce strong echoes, compared with tissue, when they are imaged using ultrasound (Frinking et al 2020).…”

“…The UCAs used for clinical imaging are suspensions of microbubbles coated with a viscoelastic layer that produce strong echoes, compared with tissue, when they are imaged using ultrasound (Frinking et al 2020). When a difference in the acoustics of UCA populations was measured after radiotherapeutic irradiation (Verboven et al 2014), it was hypothesized that this difference could be detected by means of an acoustic imaging device and subsequently related to the radiation dose delivered. This novel approach potentially offers a unique solution to measure, in real time and in situ, the absolute spatial dose distribution.…”