In this work, we present phase subtraction imaging (PSI), a new spatial-temporal beamforming method that enables micrometer level resolution imaging of microvessels inin vivo without labels, which are microbubbles in ultrasound super-resolution imaging. Subtraction of relative phase differences between consecutive frames beamformed with mismatched apodizations is used in PSI to overcome the diffraction limit. Without any microbubble or erythrocyte localization or tracking, PSI provides spatial resolution up to eight times better than color flow imaging using delay and sum (DAS) beamforming. Instead of acquiring data on the same plane for minutes, which is necessary for ultrasound localization microscopy (ULM) to accumulate enough microbubbles tracks, PSI only needs seconds of data acquisition resulting in better temporal resolution than ULM. We have also implemented PSI with CUDA to enable fast label-free super-resolution imaging that could render label-free super-resolution images in less than a minute. We validated this method by imaging both the mouse brain and rabbit kidney using different ultrasound probes with center frequencies ranging from 15 to 50 MHz and different scanning machines including a Verasonics Vantage 256 HF and a Verasonics NXT 256 HF.
Kou et al. (Wed,) studied this question.