Breaking free from vascular confinement: status and prospects for submicron ultrasound contrast agents

The development of encapsulated microbubbles (~1-6 μm) has expanded the utility of ultrasound from soft tissue anatomical imaging to not only functional intravascular imaging, but therapeutic interventions, with compelling studies of elicited biological effects. The large diameter of these bubbles has confined their utility to the vasculature, but converging interdisciplinary research pathways are giving rise to new submicron ultrasound contrast agents capable of extending their effects beyond the vascular compartment. This article reviews the status and prospects of exogenous agents including nanobubbles, echogenic liposomes, gas vesicles, cavitation seeds, and nanodroplets, and assesses outstanding criticisms preventing their advance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies.