Ultrasound Localization Microscopy Imaging by Monodisperse Microbubble Uncoupling: First Experimental Study

Ultrasound Localization Microscopy allows the characterization of micro-vascular structures by precisely localizing and tracking microbubbles (MBs) injected in the circulation. ULM-generated images possess a sub-millimetric resolution, overcoming the ultrasound’s resolution limit set by diffraction. However, ULM requires low MBs concentrations to ensure isolated MBs signals. While low concentrations ensure MBs’ localization precision, they lead to long acquisition times to fully cover the vascular structures in the region of interest. These prolonged acquisition times are not practical in the clinical setting. Here, towards the increase of MBs concentrations, we demonstrate the feasibility of uncoupling two monodisperse MB populations. The uncoupling is performed by means of a signal processing pipeline, which deploys the strong non-linear response of MBs having resonance frequency tuned with the transmission frequency. Density and flow direction maps are produced after data acquisition in a 3D-printed phantom and demonstrate the capability of uncoupling the two selected MB populations. The ability to discriminate different MBs populations mitigates ULM’s low concentration requirement, allowing higher MBs concentrations, ultimately alleviating the need of long acquisition times for microvascular imaging.