  Ultrasound super-localization microscopy techniques presented in the last few
years enable non-invasive imaging of vascular structures at the capillary level
by tracking the flow of ultrasound contrast agents (gas microbubbles). However,
these techniques are currently limited by low temporal resolution and long
acquisition times. Super-resolution optical fluctuation imaging (SOFI) is a
fluorescence microscopy technique enabling sub-diffraction limit imaging with
high temporal resolution by calculating high order statistics of the
fluctuating optical signal. The aim of this work is to achieve fast acoustic
imaging with enhanced resolution by applying the tools used in SOFI to
contrast-enhance ultrasound (CEUS) plane-wave scans. The proposed method was
tested using numerical simulations and evaluated using two in-vivo rabbit
models: scans of healthy kidneys and VX-2 tumor xenografts. Improved spatial
resolution was observed with a reduction of up to 50% in the full width half
max of the point spread function. In addition, substantial reduction in the
background level was achieved compared to standard mean amplitude persistence
images, revealing small vascular structures within tumors. The scan duration of
the proposed method is less than a second while current superlocalization
techniques require acquisition duration of several minutes. As a result, the
proposed technique may be used to obtain scans with enhanced spatial resolution
and high temporal resolution, facilitating flow-dynamics monitoring. Our method
can also be applied during a breath-hold, reducing the sensitivity to motion
artifacts.
