Isolation of microbubbles beyond Sparrow's resolution limit in super-resolution ultrasonography using phase patterned waves.

. Super-resolution ultrasonography (SR-US) provides detailed microvasculature images, improving diagnostic precision. However, it typically depends on tacking microbubbles (MBs) used as contrast agents at low concentration. This process requires acquiring a large amount of acoustic data, leading to longer acquisition times. In this paper, we describe a method that allows for the use of higher concentrations of MBs, which reduces the acquisition time and enables high-speed SR-US. Our approach involves isolating and detecting individual MBs even when they are located close to each other, making it possible to use higher bubble concentrations efficiently.. In this study, as introduced in previous research, we use phase patterned waves (PPWs) to isolate MBs by adjusting the intensities of each bubble's point spread function (PSF). The PPWs create high and low sound pressure across the lateral plane, optimizing the variation in PSF intensities for MBs positioned side by side. Unlike conventional irradiation method of ultrasound plane waves, PPWs cause significant sound pressure attenuation with increasing axial distance due to destructive interference. This effect allows us to alternate the PSF intensities for MBs aligned along the axial direction. By estimating the positions of MBs in both the lateral and axial directions and combining them into two-dimensional coordinates, we can accurately determine the final positions of the MBs.. We applied PPWs and conventional ultrasound irradiation methods to estimate the positions of two MBs, achieving accuracy within 25% of the wavelength from their actual locations, even when the bubbles were closer than Sparrow's resolution limit. Furthermore, using an overlapped PSF model, we improved the accuracy of the estimated positions to within an average of 15% of the wavelength from their true locations, regardless of the number of overlapping MBs or their relative positions.. Isolating MBs using PPWs is expected to enable high concentrations of MBs in SR-US, paving the way for high-speed SR-US.