Improved Ultrasound Localization Microscopy Based on Microbubble Uncoupling via Transmit Excitation

Jihun Kim, Mathew R. Lowerison, Nathiya V.Chandra Sekaran, Zhengchang Kou, Zhijie Dong, Michael L. Oelze, Daniel A. Llano, Pengfei Song

Research output: Contribution to journalArticlepeer-review


Ultrasound localization microscopy (ULM) demonstrates great potential for visualization of tissue microvasculature at depth with high spatial resolution. The success of ULM heavily depends on robust localization of isolated microbubbles (MBs), which can be challenging in vivo especially within larger vessels where MBs can overlap and cluster close together. While MB dilution alleviates the issue of MB overlap to a certain extent, it drastically increases the data acquisition time needed for MBs to populate the microvasculature, which is already on the order of several minutes using recommended MB concentrations. Inspired by optical super-resolution imaging based on stimulated emission depletion (STED), here we propose a novel ULM imaging sequence based on MB uncoupling via transmit excitation (MUTE). MUTE 'silences' MB signals by creating acoustic nulls to facilitate MB separation, which leads to robust localization of MBs especially under high concentrations. The efficiency of localization accomplished via the proposed technique was first evaluated in simulation studies with conventional ULM as a benchmark. Then, an in-vivo study based on the chorioallantoic membrane (CAM) of chicken embryos showed that MUTE could reduce the data acquisition time by half, thanks to the enhanced MB separation and localization. Finally, the performance of MUTE was validated in an in vivo mouse brain study. These results demonstrate the high MB localization efficacy of MUTE-ULM, which contributes to a reduced data acquisition time and improved temporal resolution for ULM.

Original languageEnglish (US)
Pages (from-to)1041-1052
Number of pages12
JournalIEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Issue number3
StatePublished - Mar 1 2022


  • MB uncoupling
  • Microbubble (MB) separation
  • null excitation
  • super-resolution imaging
  • ultrasound localization microscopy (ULM)

ASJC Scopus subject areas

  • Instrumentation
  • Acoustics and Ultrasonics
  • Electrical and Electronic Engineering


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