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 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.
Highlights
SUPER resolution ultrasound localization microscopy (ULM) is an acoustic analog to optical super-resolution microscopy such as the photoactivated localization microscopy (PALM) [1] or stochastic optical reconstruction microscopy (STORM) [2]
Inspired by the optical super-resolution technique stimulated emission depletion (STED), in this paper, we propose to implement a similar principle of contrast signal suppression in ultrasound imaging to promote MB separation and enhance ULM imaging performance
We introduce a method named microbubble uncoupling via transmit excitation (MUTE) that uses the principles of acoustic null generation and subtraction imaging to realize STED in ultrasound
Summary
SUPER resolution ultrasound localization microscopy (ULM) is an acoustic analog to optical super-resolution microscopy such as the photoactivated localization microscopy (PALM) [1] or stochastic optical reconstruction microscopy (STORM) [2]. It was recently introduced for microvasculature imaging beyond the inherent acoustic spatial resolution limit while conserving the imaging depth of conventional ultrasound. Practical implementation of ULM is currently limited by its Achilles’ heel – slow temporal resolution, which is largely attributed to the long data acquisition time that is required to capture adequate, spatially separated MB signals for localization and tracking. As such, developing a method that is highly efficient at localizing MBs under high concentration is essential to accelerate ULM
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