Volumetric Passive Ultrasound Localization Microscopy of Radiation-Induced Nanodroplet Vaporization with a Large Aperture Matrix Array

Superheated nanodroplets (NDs) are proposed for in vivo radiation dose sensing applications, based on their ability to vaporize into echogenic microbubbles when exposed to ionizing radiation. Combined with Ultrasound Localization Microscopy (ULM), the ultrafast detection of radiation-induced ND vaporization
produces super-resolved vaporization maps that match the radiation field with sub-millimeter accuracy. However, in the presence of flow, discriminating between microbubbles moving in the field of view and radiation-induced vaporization events is not trivial. As an alternative, sparse acoustic signatures emitted by vaporizing NDs can be super-localized by passive ULM, i.e. P-ULM. In this work, we extend our previous 2D implementation of P-ULM to 3D, using a large aperture matrix array probe.We exposed perfluorobutane NDs to a proton beam and recorded their vaporization signatures during irradiation. The events were extracted from the radiofrequency channel data using a spatiotemporal filtering approach and super-localized by fitting the time differences of arrival between channels to a one-way time of flight model. The vaporization maps were overlaid on the proton beam distribution and estimated the proton range and beam dispersion within 0.98 ± 0.04mmand 0.03±0.02mmof the reference range measurement (depth-dose distribution in water measured with a diode), respectively. These results pave the way for volumetric dose mapping using radiosensitive nanodroplets and passive imaging.