Super-Resolution Imaging Through the Human Skull.

High-resolution transcranial ultrasound imaging in humans has been a persistent challenge for ultrasound due to the imaging degradation effects from aberration and reverberation. These mechanisms depend strongly on skull morphology and have high variability across individuals. Here, we demonstrate the feasibility of human transcranial super-resolution imaging using a geometrical focusing approach to efficiently concentrate energy at the region of interest, and a phase correction focusing approach that takes the skull morphology into account. It is shown that using the proposed focused super-resolution method, we can image a 208- [Formula: see text] microtube behind a human skull phantom in both an out-of-plane and an in-plane configuration. Individual phase correction profiles for the temporal region of the human skull were calculated and subsequently applied to transmit-receive a custom focused super-resolution imaging sequence through a human skull phantom, targeting the 208- [Formula: see text] diameter microtube at 68.5 mm in depth and at 2.5 MHz. Microbubble contrast agents were diluted to a concentration of 1.6×106 bubbles/mL and perfused through the microtube. It is shown that by correcting for the skull aberration, the RF signal amplitude from the tube improved by a factor of 1.6 in the out-of-plane focused emission case. The lateral registration error of the tube's position, which in the uncorrected case was 990 [Formula: see text], was reduced to as low as 50 [Formula: see text] in the corrected case as measured in the B-mode images. Sensitivity in microbubble detection for the phase-corrected case increased by a factor of 1.48 in the out-of-plane imaging case, while, in the in-plane target case, it improved by a factor of 1.31 while achieving an axial registration correction from an initial 1885- [Formula: see text] error for the uncorrected emission, to a 284- [Formula: see text] error for the corrected counterpart. These findings suggest that super-resolution imaging may be used far more generally as a clinical imaging modality in the brain.

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 full-wave 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 15 dB 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 versus 257 bubble events).