Fig. 2.

Thermal and Mechanical Focused Ultrasound Mechanisms of Action include Blood–Brain Barrier Opening, Sonodynamic Therapy, Radiation Sensitization, Histotripsy, and Liquid Biopsy. A Various thermal and mechanical focused ultrasound mechanisms of action related to power. B Blood–Brain Barrier Opening for Drug Delivery. In the precise location of the focused ultrasound beam, intravenously injected intravenous microbubbles expand and contract causing: 1. Opening of the tight junctions; 2. An increase in the number of transcytotic vesicles; and 3. Decreasing efflux pumps, which contribute to enhanced therapeutic delivery of chemotherapies, antibodies, or cargo-loaded viral particles across the BBB. C Sonodynamic Therapy. An intravenously injected sonosensitizer (5-ALA) crosses the blood–brain barrier, accumulates in tumor cells, and converts to protoporphyrin IX (PpIX). Focused ultrasound activates the PpIX, which generates reactive oxygen species (ROS). ROS causes apoptosis and tumor cell death. D Radiation Sensitization. In the presence of microbubbles, the focused ultrasound beam causes oscillations of injected intravenous microbubbles, which mechanically damages the endothelium (black arrows) and releases ceramide. Along with radiation therapy, ceramide induces endothelial and tumor cell death