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- $\mu \text{m}$ 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- $\mu \text{m}$ diameter microtube at 68.5 mm in depth and at 2.5 MHz. Microbubble contrast agents were diluted to a concentration of $1.6\times 10^{6}$ 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 $\mu \text{m}$ , was reduced to as low as 50 $\mu \text{m}$ 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- $\mu \text{m}$ error for the uncorrected emission, to a 284- $\mu \text{m}$ 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.