Ultrasound Imaging of Nanodroplet Vaporization for Radiotherapy Monitoring

Comprised in the cure of approximately 50% of all cancer patients, radiation therapy is a fundamental pillar in cancer treatment. Relying on the tissue damaging properties of ionizing radiation, radiation therapy aims to maximally expose tumor tissue with minimal healthy tissue exposure. Thereto, and in accordance with the overall evolution towards customized patient-specific healthcare, recent advances in radiation therapy enable the planning and delivery of complex dose distributions exhibiting high tumor conformity. However, increased tumor conformity requires increased delivery accuracy which needs to be verified to ensure appropriate tumor exposure and minimal healthy tissue irradiation. This implies a growing need for appropriate treatment verification strategies effectively measuring the actual radiation dose imparted on the tumor. The latter is particularly true for proton therapy, as uncertainties on the proton range currently force clinicians to adopt substantial safety margins. Despite this unmistakable need, current dosimetry technology is lagging behind on radiotherapy planning and delivery evolutions. As a consequence, radiotherapy cannot exploit its full capability. Recognizing this missing link, we developed a novel method for in vivo radiotherapy monitoring, consisting in the use of nanometer-sized, injectable droplets which accumulate in tumor tissues and vaporize into microbubble contrast agents upon exposure to ionizing radiation. The vaporization process is monitored by means of ultrasound imaging, as microbubbles are very echogenic. We first explored the conditions under which radiation-induced vaporization could take place and validated the feasibility of the concept both for proton and conventional radiation therapy.  Then, we investigated different ultrasound imaging strategies to detect and localize vaporization events and correlated the latter with the radiation dose distribution and the proton range. Finally, we explored means to bring this technology to the clinic by acoustically modulating the nanodroplet degree of superheat at body temperature.