Super-localization of contrast agents in moving organs, first experiments in a rat kidney

Using individual microbubbles (MBs) to image vasculature with a spatial resolution below the diffraction limit has the potential to greatly improve the in vivo characterization of healthy and diseased tissue. Recent studies have demonstrated a theoretical resolution on the order of microns in stationary tissue using standard imaging arrays. However, the application of this technique to abdominal imaging brings new challenges due to the presence of physiological motion which is far larger than the achievable resolution. In this work, single MBs were localized in vivo in a rat kidney using a dedicated high frame rate (300 Hz) contrast pulse sequence (CPS) with spatial compounding (-5°, 0°, 5°). A stack of 60000 frames was acquired, providing a B-mode image to track tissue motion and a CPS image to track MB position at each time point. Acquisition was accomplished with a standard imaging array (CL15-7, ATL) driven at 6.9 MHz and a programmable ultrasound system (Verasonics). 3.4 million positions were detected and a density map of the MB positions was obtained after compensation for cardiac motion and changes in kidney position. Blood velocity was also estimated by tracking selected MBs over time.