Multi-functional biomedical ultrasound: Imaging, manipulation, neuromodulation and therapy

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As a safe, low-cost, portable and fast imaging modality, ultrasound has been widely used in various clinical fields. Ultrasound imaging is used in every branch of medicine and can be used to visualize almost every organ. Recently, numerous new ultrasound technologies, such as microbubble-based nonlinear contrast imaging, ultrasound molecular imaging, ultrasound-assisted targeted drug delivery, ultrasonic neuro-modulation and theranostics-based integrative application, have been developed for early-stage diagnosis and treatment, based on the multi-disciplinary developments in physics, engineering, and biomedicine. The nature of biomedical ultrasound technology is also changing, from being an imaging technology into a multi-functional tool that allows both precise diagnosis and treatment. This review offers a critical analysis of the state-of-the-art biomedical ultrasound technology and its application in clinical diagnosis and drug delivery. In this paper, we first introduce some basic physical characteristics of biomedical ultrasound technology, including its wave and mechanical properties, the history of the development of ultrasound contrast agent microbubbles, and the biomedical effects of ultrasound, such as cavitation and heat deposition. Then, we review the recent progress and our research on the preparation and acoustic characterization of microbubbles, nonlinear ultrasound contrast imaging and ultrasound molecular imaging, and ultrasound-assisted drug delivery and treatment based on the large surface of a drug-loaded microbubble and on the surface modification-enabled elastic shell. In addition, we discuss the integrative applications of ultrasound diagnostics and therapeutics in clinical medicine. Moreover, we review the advances in ultrasound-based deep brain stimulation, which indicates that ultrasound technology might be used as a potential noninvasive tool in neuroscience and in the treatment of brain disorders. Finally, we review the challenges associated with the development of biomedical ultrasound technology, which include acoustic power thresholds in drug delivery and deep brain stimulation for the safety and precision control of acoustic fields in inhomogeneous media. In conclusion, besides assessing the conventional tissue anatomy and hemodynamics, we argue that biomedical ultrasound techniques can provide information on tissue elasticity, metabolic function, distribution of temperature, and even biochemical processes. Owing to its advantages such as acoustic radiation force, the use of ultrasound might open a new era in neuro-modulation in the neurosciences, in addition to its traditional areas of use such as imaging and thermal therapy.