Improved Ultrasound Localization Microscopy based on Microbubble Uncoupling via Transmit Excitation (MUTE)

Abstract

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 the 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 microbubble 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.

Microvascular Imaging with Super-Resolution Ultrasound

“…The precision of this localization is a critical step in obtaining super-resolution 5 . Instead of merely superposing each of the microbubble localizations, as done in super-resolution microscopy, the movements of the microbubbles as they follow the bloodstream between frames are used to create trajectories that can reveal microbubble velocity and direction 6 7 8 9 10 . Lastly, another essential difference between super-resolved microscopy and ultrasound is motion.…”

“…Die Präzision dieser Lokalisierung ist ein entscheidender Schritt zur Erzielung der Superresolution 5 . Anstatt wie bei der Superresolution-Mikroskopie jede einzelne Lokalisierung der Mikrobläschen zu überlagern, werden die Bewegungen der Mikrobläschen, während sie zwischen den Bildern dem Blutstrom folgen, verwendet, um Trajektorien zu erstellen, die die Geschwindigkeit und Richtung der Mikrobläschen aufzeigen können 6 7 8 9 10 . Schließlich ist die Bewegung ein weiterer wesentlicher Unterschied zwischen der Superresolution-Mikroskopie und dem -Ultraschall.…”