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 ofULMon clinical ultrasound scanners is hindered by the technical limitations, such as long data acquisition time, high microbubble (MB) concentration, and compromised tracking performance associated with low imaging frame-rate. Here we present a robust in-humanULMon a high frame-rate (HFR) clinical ultrasound scanner to achieve super-resolution microvessel imaging using a short acquisition time (<10 s). UltrasoundMBdata were acquired from different human tissues, including a healthy liver and a diseased liver with acute-on-chronic liver failure, a kidney, a pancreatic tumor, and a breast mass using an HFR clinical scanner. By leveraging the HFR and advanced processing techniques including sub-pixel motion registration,MBsignal separation, and Kalman filter-based tracking, MBs can be robustly localized and tracked forULMunder the circumstances of relatively highMBconcentration associated with standard clinicalMBadministration and limited data acquisition time in humans. Subtle morphological and hemodynamic information in microvasculature were shown based on data acquired with single breath-hold and free-hand scanning. Compared with contrast-enhanced power Doppler generated based on the sameMBdataset,ULMshowed a 5.7-fold resolution improvement in a vessel based on a linear transducer, and provided a wide-range blood flow speed measurement that is Doppler angle-independent. Microvasculatures with complex hemodynamics can be well-differentiated at super-resolution in both normal and pathological tissues. This preliminary study implemented the ultrafast in-humanULMin various human tissues based on a clinical scanner that supports HFR imaging, indicating the potentials of the technique for various clinical applications. However, rigorous validation of the technique in imaging human microvasculature (especially for those tiny vessel structure), preferably with a gold standard, is still required.