Uncoupling a bi-disperse microbubble population for decreased ULM acquisition times: A proof-of-concept study

Ultrasound Localization Microscopy (ULM) enables to accurately characterize micro-vascular structures by means of ultrasound imaging. In ULM, the backscattering signals of injected microbubbles (MBs) are utilized to sub-wavelength localize and track MBs flowing in the circulatory system. To ensure precise MB localizations, ULM is constrained to low MB concentrations, leading to prolonged acquisition times. Owing to patient comfort, motion, and computational cost to elaborate data, the constraint on low MB concentrations is a bottleneck for ULM clinical translation. To mitigate the need of low MB concentration, we propose to uncouple a bi-disperse MB population. The bi-disperse population is composed of two monodisperse MB populations having diameter (and resonance frequency) of 2.5 μm (3 MHz) and 3.8 μm (5.5 MHz), respectively. The different diameter determines a different resonance response. Experiments are performed injecting the populations singularly and simultaneously in a 3-D printed phantom. Uncoupling is performed by means of a signal processing pipeline, which exploits the strong nonlinear response of MBs having resonance frequency tuned with the transmission frequency. After uncoupling, super-resolved density and velocity flow maps are generated for each MB population. The results demonstrate the capability of uncoupling the selected pair of MB populations, thus potentially permitting increased MB concentrations.