Three-dimensional super resolution ultrasound imaging with a multi-frequency hemispherical phased array.

High resolution imaging of the microvasculature plays an important role in both diagnostic and therapeutic applications in the brain. However, ultrasound pulse-echo sonography imaging the brain vasculatures has been limited to narrow acoustic windows and low frequencies due to the distortion of the skull bone, which sacrifices axial resolution since it is pulse length dependent. To overcome the detect limit, a large aperture 256-module sparse hemispherical transmit/receive array was used to visualize the acoustic emissions of ultrasound-vaporized lipid-coated decafluorobutane nanodroplets flowing through tube phantoms and within rabbit cerebral vasculature in vivo via passive acoustic mapping and super resolution techniques. Nanodroplets were vaporized with 55 kHz burst-mode ultrasound (burst length = 145 μs, burst repetition frequency = 9-45 Hz, peak negative acoustic pressure = 0.10-0.22 MPa), which propagates through overlying tissues well without suffering from severe distortions. The resulting emissions were received at a higher frequency (612 or 1224 kHz subarray) to improve the resulting spatial resolution during passive beamforming. Normal resolution three-dimensional images were formed using a delay, sum, and integrate beamforming algorithm, and super-resolved images were extracted via Gaussian fitting of the estimated point-spread-function to the normal resolution data. With super resolution techniques, the mean lateral (axial) full-width-at-half-maximum image intensity was 16 ± 3 (32 ± 6) μm, and 7 ± 1 (15 ± 2) μm corresponding to ∼1/67 of the normal resolution at 612 and 1224 kHz, respectively. The mean positional uncertainties were ∼1/350 (lateral) and ∼1/180 (axial) of the receive wavelength in water. In addition, a temporal correlation between nanodroplet vaporization and the transmit waveform shape was observed, which may provide the opportunity to enhance the signal-to-noise ratio in future studies. Here, we demonstrate the feasibility of vaporizing nanodroplets via low frequency ultrasound and simultaneously performing spatial mapping via passive beamforming at higher frequencies to improve the resulting spatial resolution of super resolution imaging techniques. This method may enable complete four-dimensional vascular mapping in organs where a hemispherical array could be positioned to surround the target, such as the brain, breast, or testicles.