Fast and selective super-resolution ultrasound in vivo with sono-switchable nanodroplets

TL;DR

This paper introduces AWSALM and fast-AWSALM, novel ultrasound super-resolution techniques using sono-switchable nanodroplets, enabling rapid, selective, and high-resolution imaging of microvasculature in vivo within seconds.

Contribution

It presents the first in vivo demonstration of ultrasound super-resolution imaging with contrast on demand and vascular selectivity using sono-switchable nanodroplets.

Findings

Achieved super-localization of rabbit renal vasculature in under 6 seconds.

Demonstrated 4-fold improvement in spatial resolution.

Enabled visualization of specific vascular branches and microvasculature.

Abstract

Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization Microscopy (ULM) provides very high spatiotemporal resolution but the use of microbubbles requires low contrast agent concentrations, a long acquisition time, and gives little control over the spatial and temporal distribution of the bubbles. The present study is the first to demonstrate Acoustic Wave Sparsely-Activated Localization Microscopy (AWSALM) and fast-AWSALM for in vivo super-resolution ultrasound imaging, offering contrast on demand and vascular selectivity. Three different formulations of sono-switchable contrast agents were tested. We demonstrate their use with ultrasound mechanical indices well within recommended safety limits to enable fast on-demand sparse switching at very high agent concentrations. We produce super-localization maps of the rabbit renal vasculature with acquisition times between 5.5 s and 0.25 s, and an 4-fold improvement in spatial resolution. We present the unique selectivity of AWSALM in visualizing specific vascular branches and downstream microvasculature, and we show super-localized kidney structures in systole and diastole with fast-AWSALM. In conclusion we demonstrate the feasibility of fast and selective measurement of microvascular dynamics in vivo with subwavelength resolution using ultrasound and sono-switchable nanodroplets.