Microbubbles

A microbubble is a gas-filled sphere with diameter typically between 1 and 100 micrometers, stabilized by a surrounding shell. They are used as echogenic contrast agents in ultrasound imaging and as carriers for therapeutic agents in various medical applications.

Most microbubbles consist of a gas core—often perfluorocarbons or air—encapsulated by a lipid, protein, polymer, or protein-lipid shell. The mismatch in acoustic impedance between the gas core and surrounding tissue, along with their nonlinear oscillations under ultrasound, makes microbubbles highly reflective and capable of producing harmonic signals that enhance image quality.

Microbubbles are produced by emulsification, sonication, or microfluidic methods. Size can be controlled to yield monodisperse preparations or broader distributions. Shell composition and gas core determine circulation life, stability, and responsiveness to ultrasound. Some designs load drugs or genes onto the shell or into the core for targeted delivery.

In contrast-enhanced ultrasound (CEUS), microbubbles improve visualization of vessels and tissue perfusion. Their nonlinear response generates harmonic signals that can be separated from tissue signals, enabling clearer images.

Beyond imaging, microbubbles can be used to enhance drug or gene delivery (sonoporation), to promote thrombolysis, and, with focused ultrasound, to transiently disrupt the blood-brain barrier for central nervous system therapies. They are a focus of ongoing research in oncology, cardiology, and neurology.

Several microbubble contrast agents are approved for clinical use in many countries. Adverse effects are generally rare but can include hypersensitivity reactions, hypotension, and, with inappropriate ultrasound exposure, tissue injury from cavitation. Patient screening and adherence to recommended ultrasound settings are important.

Limitations include short in vivo lifetimes, sensitivity to pressure, and variability in microbubble stability. Research continues to improve targeting, payload capacity, and safety.