In Vivo Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles

TLDR

The structure of microvasculature cannot be resolved using standard clinical ultrasound imaging frequencies due to the fundamental diffraction limit of US waves. The study aims to use a clinical ultrasound system to localize microbubble signals for sub‑diffraction imaging of mouse ear microvasculature and compare the results to optical microscopy, with the goal of enabling future noninvasive imaging of pathological changes. The authors employed a standard clinical ultrasound system to localize isolated microbubble signals in vivo and tracked individual bubbles to generate super‑resolved velocity maps of the ear microvasculature. The technique achieved lateral and axial resolution down to 19 μm, produced velocity maps that differentiate opposing flow directions and speed distributions in adjacent vessels, and enabled noninvasive super‑resolved imaging of microvasculature at centimeter depths.

Abstract

The structure of microvasculature cannot be resolved using standard clinical ultrasound (US) imaging frequencies due to the fundamental diffraction limit of US waves. In this work, we use a standard clinical US system to perform in vivo sub-diffraction imaging on a CD1, female mouse aged eight weeks by localizing isolated US signals from microbubbles flowing within the ear microvasculature, and compare our results to optical microscopy. Furthermore, we develop a new technique to map blood velocity at super-resolution by tracking individual bubbles through the vasculature. Resolution is improved from a measured lateral and axial resolution of 112 μm and 94 μm respectively in original US data, to super-resolved images of microvasculature where vessel features as fine as 19 μm are clearly visualized. Velocity maps clearly distinguish opposing flow direction and separated speed distributions in adjacent vessels, thereby enabling further differentiation between vessels otherwise not spatially separated in the image. This technique overcomes the diffraction limit to provide a noninvasive means of imaging the microvasculature at super-resolution, to depths of many centimeters. In the future, this method could noninvasively image pathological or therapeutic changes in the microvasculature at centimeter depths in vivo.