IEEE Trans Ultrason Ferroelectr Freq Control. 2022 Mar;69(3):1041-1052. doi: 10.1109/TUFFC.2022.3143864. Epub 2022 Mar 2.
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.
超声定位显微镜（ULM）具有在深度上以高空间分辨率可视化组织微血管的巨大潜力。ULM 的成功在很大程度上取决于对分离微泡（MB）的稳健定位，这在体内尤其具有挑战性，尤其是在较大的血管中，MB 可能重叠并紧密聚集在一起。虽然 MB 稀释在一定程度上缓解了 MB 重叠的问题，但它大大增加了 MB 填充微血管所需的数据采集时间，使用推荐的 MB 浓度，这已经需要几分钟的时间。受基于受激发射损耗（STED）的光学超分辨率成像的启发，我们在这里提出了一种基于通过发射激发使 MB 解耦的新型 ULM 成像序列（MUTE）。MUTE 通过创建声空来“静默”MB 信号，以促进 MB 分离，从而实现 MB 的稳健定位，特别是在高浓度下。通过与传统 ULM 作为基准的模拟研究，首先评估了所提出技术的定位效率。然后，基于鸡胚的脉络膜-尿囊膜（CAM）的体内研究表明，由于增强的 MB 分离和定位，MUTE 可以将数据采集时间缩短一半。最后，在体内小鼠大脑研究中验证了 MUTE 的性能。这些结果证明了 MUTE-ULM 对 MB 的高定位效果，有助于减少 ULM 的数据采集时间和提高时间分辨率。
