Super-Resolution Ultrasound Localization Microscopy Based on a High Frame-rate Clinical Ultrasound Scanner: An In-human Feasibility Study

Non-invasive detection of microvascular alterations in deep tissues in vivo provides critical information for clinical diagnosis and evaluation of a broad-spectrum of pathologies. Recently, the emergence of super-resolution ultrasound localization microscopy (ULM) offers new possibilities for clinical imaging of microvasculature at capillary level. Currently, the clinical utility of ULM on clinical ultrasound scanners is hindered by the technical limitations, such as long data acquisition time, and compromised tracking performance associated with low imaging frame-rate. Here we present an in-human ULM on a high frame-rate (HFR) clinical ultrasound scanner to achieve super-resolution microvessel imaging using a short acquisition time (<10s). Ultrasound MB data were acquired from different human tissues, (liver, kidney, pancreatic, and breast tumor) using an HFR clinical scanner. By leveraging the HFR and advanced processing techniques including sub-pixel motion registration, MB signal separation, and Kalman filter-based tracking, MBs can be robustly localized and tracked for successful ULM under the circumstances of relatively high MB concentration and limited data acquisition time in humans. Subtle morphological and hemodynamic information were demonstrated on data acquired with single breath-hold and free-hand scanning. Compared with contrast-enhanced power Doppler generated based on the same MB dataset, ULM showed a 5.7-fold resolution improvement in a vessel, and provided a wide-range flow speed measurement that is Doppler angle-independent. This study demonstrated the feasibility of ultrafast in-human ULM in various human tissues based on a clinical scanner that supports HFR imaging, and showed a great potential for the implementation of super-resolution ultrasound microvessel imaging in a myriad of clinical applications involving microvascular abnormalities and pathologies.