Methods and systems for using phase change nanodroplets to enhance sonothrombolysis

A method for generation of cavitation internal to a blood clot mass greater than would be achievable with microbubble cavitation agents for a given level of applied ultrasound energy, the method comprising:

• administering metastable liquid perfluorocarbon nanodroplets into a blood vessel that includes or leads to a blood vessel that includes a blood clot, where the metastable liquid perfluorocarbon nanodroplets each have a liquid core comprising a perfluorocarbon material that has a boiling point below 25° C. at atmospheric pressure and the liquid core is encapsulated within a shell, where the metastable liquid perfluorocarbon nanodroplets are in a metastable state and remain stable in liquid form at 25° C. at atmospheric pressure, and where the metastable liquid perfluorocarbon nanodroplets have diameters sufficiently small to penetrate into the blood clot mass, wherein the diameters range from 10 nanometers to 750 nanometers;
• allowing for at least some of the metastable liquid perfluorocarbon nanodroplets to penetrate the blood clot;
• and
• applying ultrasound energy to the blood clot mass, causing the metastable liquid perfluorocarbon nanodroplets within the blood clot, causing the liquid cores of the metastable liquid perfluorocarbon nanodroplets that penetrated the blood clot, to convert from a liquid state to a gaseous state due to the application of the ultrasound energy, resulting in cavitation occurring within the blood clot,
• wherein a metric of cavitation occurring within the blood clot due to the cavitation from the metastable liquid perfluorocarbon nanodroplets that penetrated the blood clot and converted to the gaseous state exceeds the metric of cavitation that would occur within the blood clot due to microbubbles administered externally to the blood clot and to which the ultrasound energy is applied, wherein applying the ultrasound energy includes applying the ultrasound energy intravascularly using an ultrasound transducer, wherein the nanodroplets that penetrate the blood clot spatially control cavitation delivery to reduce heating of tissue surrounding the blood clot, and wherein the cavitation occurring within the blood clot causes lysis of the blood clot.