Principles of ULM

Ultrasound localization microscopy (ULM) is a method that uses ultrasound waves to achieve super-resolution imaging of the microcirculation. It relies on the detection of individual scatterers (such as microbubbles or other contrast agents) within a sample. By precisely localizing these scatterers based on their acoustic signals, ULM can create high-resolution images that reveal fine structural details that are typically beyond the resolution limits of conventional ultrasound imaging.

ULM involves several key steps. First, an acquisition step is performed through ultrasound imaging of tissue where microbubbles have been injected, often using ultrafast scanners that capture several hundred to thousands of images per second. Next, the microbubbles are detected in relation to the surrounding tissue, and filters are applied to separate them from the tissue and other microbubbles. Following this, the individual microbubbles are localized; since their punctual signals are not impacted by interference, their positions can be established with micrometric resolution. These micrometric positions are then tracked as the microbubbles flow within the vessels. Finally, the super-resolved tracks are accumulated to form an image of the microvessels at subwavelength resolution.

1) 100s to 100 000s of ultrasound images are acquired and stacked. 2) Slow-time filtering or low concentration allows the separation of particles/microbubbles. 3) Centroids of the hyperbolas or the focal spots created by the microbubble are localized. 4) Localization of microbubbles is assigned to tracks to determine the velocity vector. 5) Resulting tracks through the movie are accumulated in one image. Couture O, Hingot V, Heiles B, Muleki-Seya P, Tanter M. Ultrasound localization microscopy and super-resolution: A state of the art. IEEE transactions on ultrasonics, ferroelectrics, and frequency control. 2018 Jun 26;65(8):1304-20.
ULM of a coronal slice of a preclinical model brain reconstructed with 5 μm pixels after 240 s of acquisition. Couture O, Hingot V, Heiles B, Muleki-Seya P, Tanter M. Ultrasound localization microscopy and super-resolution: A state of the art. IEEE transactions on ultrasonics, ferroelectrics, and frequency control. 2018 Jun 26;65(8):1304-20.

References

Christensen-Jeffries, K., Couture, O., Dayton, P.A., Eldar, Y.C., Hynynen, K., Kiessling, F., et al, 2020. Super-resolution ultrasound imaging. Ultrasound in medicine & biology, 46(4), 865-91.

Couture O., Hingot V., Heiles B., Muleki-Seya P., Tanter M, 2018. Ultrasound localization microscopy and super-resolution: A state of the art. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 65(8):1304-20.