Three-Dimensional Ultrasound Localization Microscopy with Bipartite Graph-Based Microbubble Pairing and Kalman-Filtering-Based Tracking on a 256-Channel Verasonics Ultrasound System with a 32 × 32 Matrix Array

Purpose: Three-dimensional (3D) ultrasound localization microscopy (ULM) using a 2-D matrix probe and microbubbles (MBs) has recently been proposed to visualize microvasculature in three spatial dimensions beyond the ultrasound diffraction limit. However, 3D ULM has several limitations, including: (1) high system complexity, (2) complex MB flow dynamics in 3D, and (3) extremely long acquisition time that had to be addressed. Method: To reduce the system complexity while maintaining high image quality, we used a sub-aperture process to reduce received channel counts. To address the second issue, a 3D bipartite graph-based method with Kalman filtering-based tracking was used in this study for MB tracking. An MB separation approach was incorporated to separate high concentration MB data into multiple, sparser MB datasets, allowing better MB localization and tracking for a limited acquisition time. Results: The proposed method was first validated in a flow channel phantom, showing improved spatial resolutions compared with the contrasted enhanced power Doppler image. Then the proposed method was evaluated with an in vivo chicken embryo brain dataset. Results showed that the reconstructed 3D super-resolution image achieved a spatial resolution of around 52 μm (smaller than the wavelength of around 200 μm). Conclusion: A lower system complexity of 3D ULM has been proposed. In addition, our proposed 3D ULM provided the capability of 3D motion compensation and MB tracking. Microvessels that cannot be resolved clearly using localization only, can be well identified with the proposed method.