Improved Ultrasound Localization Microscopy Based on Microbubble Uncoupling via Transmit Excitation

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 superresolution 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.

3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents

“…Super-resolution image quality is strongly dependent upon acquisition time and MB concentration, and hence is challenging to improve. Strategies such as MB uncoupling, MB separation, or improved beamforming have been trialed with success [34][35][36] but are still restricted by the limitations of using MBs. By increasing the frequency at which PCCAs are activated in the microcirculation, the acquisition time could be reduced.…”

Contrast-free Super-resolution Doppler (CS Doppler) based on Deep Generative Neural Networks

“…This is a fundamental limitation of the proposed CS Doppler technique because it relies on paired ULM images for training. To address this issue, accelerated ULM imaging techniques such as CTSP [26], MUTE [28], and deep learning-based techniques [29][30][31][32] may be considered for fast imaging with less tissue motions. Nevertheless, based on the robust generalizability of the proposed method, one can also use transfer learning techniques [57] to adapt CS Doppler to different applications where only a small amount of application-specific ULM images is needed to fine-tune the network.…”

“…Early studies conducted by Viessmann et al [1], Desailly et al [2][3], and O'Reilly et al [4] showed that one can break the resolution limit of acoustic waves by localizing microbubbles in the blood stream. The seminal papers by Errico et al [5] and Christensen-Jeffries et al [6] catalyzed the growth of the field, leading to many subsequent reports with successful in vivo applications [7][8][9][10][11][12][13][14][15][16] and technical advancements of super-resolution ultrasound imaging [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”

Microvascular Imaging with Super-Resolution Ultrasound

“…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.…”

“…The precision of this localization is a critical step in obtaining super-resolu-tion [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.…”