Bursting microbubbles: How nanobubble contrast agents can enable the future of medical ultrasound molecular imaging and image-guided therapy

The field of medical ultrasound has undergone a significant evolution since the development of microbubbles as contrast agents. However, because of their size, microbubbles remain in the vasculature and therefore have limited clinical applications. Building a better—and smaller—bubble can expand the applications of contrast-enhanced ultrasound by allowing bubbles to extravasate from blood vessels—creating new opportunities. In this review, we summarize recent research on the formulation and use of nanobubbles (NBs) as imaging agents and as therapeutic vehicles. We discuss the ongoing debates in the field and reluctance to accepting NBs as an acoustically active construct and a potentially impactful clinical tool that can help shape the future of medical ultrasound. We hope that the overview of key experimental and theoretical findings in the NB field presented in this article provides a fundamental framework that will help clarify NB–ultrasound interactions and inspire engagement in the field.