In vivo ultrasound localization microscopy for high-density microbubbles.

Ultrasound Localization Microscopy (ULM) surpasses the constraints imposed by acoustic diffraction, achieving sub-wavelength resolution visualization of microvasculature through the precise localization of minute microbubbles (MBs). Nonetheless, the analysis of densely populated regions with overlapping MB point spread responses introduces significant localization errors, limiting the use of technique to low-concentration conditions. This raises a trade-off issue between localization efficiency and MB density. In this work, we present a new deep learning framework that combines Transformer and U-Net architectures, termed ULM-TransUNet. As a non-linear model, it is able to learn the complex data patterns of overlapping MBs in dense conditions for accurate localization. To evaluate the performance of ULM-TransUNet, a series of numerical simulations and in vivo experiments are carried out. Numerical simulation results indicate that ULM-TransUNet achieves high-quality ULM imaging, with improvements of 21.93 % in detection rate, 17.36 % in detection precision, and 20.53 % in detection sensitivity, compared to previous state-of-the-art deep learning (DL) method (e.g., ULM-UNet). For the in vivo experiments, ULM-TransUNet achieves the highest spatial resolution (9.4 μm) and rapid inference speed (26.04 ms/frame). Furthermore, it consistently detects more small vessels and resolves closely spaced vessels more effectively. The outcomes of this work imply that ULM-TransUNet can potentially enhance the microvascular imaging performance on high-density MB conditions.