Transient acoustic vaporization signatures unique to low boiling point phase change contrast agents enable super-resolution ultrasound imaging without spatiotemporal filtering

The unique activation signal of phase-change contrast agents (PCCAs or droplets) can be separated from the tissue signal and localized to generate super-resolution (SR) ultrasound (US) images. Lipid-shelled, perfluorocarbon PCCAs can be stochastically vaporized (activated) by a plane wave US transmission thereby enabling them to be used as separable targets for ultrasound localization microscopy. The unique signature of droplet vaporization imaging and the transient inherent nature of this signature increases signal contrast and therefore localization confidence, while the poor resolution of the low-frequency vaporization signal is overcome by the super-resolution result. Furthermore, our proposed PCCA SR technique does not require the use of user-dependent and flow-dependent spatio-temporal filtering via singular-value decomposition. Rather, matched filters selected by Fourier-domain analysis are able to identify and localize PCCA activations. Droplet SR was demonstrated in a crossed-microtube water phantom by localizing the activation signals of octafluoropropane nanodroplets (OFP, C(3)F(8), −37 °C boiling point) to resolve 100 µm diameter fluorinated ethylene propylene tubes, which are ordinarily 35% smaller than the native diffraction-limited resolution of the imaging system utilized.