Nonlinear vibro-thermal-acoustical damage imaging in composites by selective activation of defects using time-reversal elastic waves

The ability of proton therapy to better conform the radiation dose to the tumor is currently hindered by uncertainties on the proton range, forcing clinicians to adopt substantial safety margins and suboptimal planning strategies. To allow proton therapy to reach its full potential, in vivo range verification methods are actively sought. Recently, we showed that injectable nanodroplets can vaporize into microbubbles when exposed to proton radiation. The generated ultrasound contrast could be related to the proton range with sub-millimeter reproducibility, thereby opening the door for ultrasound-based proton range verification. Moreover, the vaporization was proportional to the proton fluence, indicating that in vivo dosimetry might also be within reach. In this proposal, we address two important challenges related to (i) the indirect nanodroplet radiation response at physiological temperature and (ii) the acoustic detection and localization of radiation-induced vaporization events in flow conditions. We suggest to use an external acoustic field to lower the nanodroplet vaporization threshold and allow direct vaporization by protons at 37°C, and to develop advanced online ultrasound imaging methods to detect and localize those vaporization events. These developments will enable to experimentally assess the performance of nanodroplets and ultrasound imaging for real-time proton range verification and dosimetry using clinical settings and nearly physiological conditions.