Adaptive multifocus beamforming for contrast-enhanced-super-resolution ultrasound imaging in deep tissue.

Contrast-enhanced-super-resolution ultrasound imaging, also referred to as ultrasound localization microscopy, can resolve vessels that are smaller than the diffraction limit and has recently been able to generate super resolved vascular images of shallow in vivo structures in small animals. To fully translate this technology to the clinic, it is advantageous to be able to detect microbubbles at deeper locations in tissue while maintaining a short acquisition time. Current implementations of this imaging method rely on plane wave imaging. This method has the advantage of maximizing the frame rate, which is important due to the large amount of frames required for super resolution processing. However, the wide planar beam used to illuminate the field of view produces poor contrast and low sensitivity bubble detection. Here, we propose an "adaptive multifocus" sequence, a new ultrasound imaging sequence that combines the high frame rate feature of a plane wave with the increased bubble detection sensitivity of a focused beam. This sequence simultaneously sonicates two or more foci with a single emission, hence retaining a high frame rate, yet achieving improved sensitivity to microbubbles. In the limit of one target, the beam reduces to a conventional focused transmission; and for an infinite number of targets, it converges to plane wave imaging. Numerical simulations, using the Fullwave code, are performed to compare the point spread function of the proposed sequence to that generated by the plane wave emission. Our numerical results predict an improvement of up to 15dB in the signal to noise ratio. Ex vivo experiments of a tissue-embedded microtube phantom are used to generate super resolved images and to compare the adaptive beamforming approach to plane wave imaging. These experimental results show that the adaptive multifocus sequence successfully detects 744 microbubble events at 60 mm, when they are undetectable by the plane wave sequence under the same imaging conditions. At a shallower depth of 44 mm, the proposed adaptive multifocus method detects 6.9 times more bubbles than plane wave imaging (1763 vs. 257 bubble events).