biostudies-literatureGorick CMNational Institute of Neurological Disorders and StrokeNIBIB NIH HHSNational Institute for Health Research (NIHR)National Institutes of Health Office of the DirectorNINDS NIH HHSNCI NIH HHSNational Institutes of HealthNational Institute of Biomedical Imaging and BioengineeringNIH HHS114583https://www.ebi.ac.uk/biostudies/studies/S-EPMC9712235biostudies-literatureUnknown191The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases.Advanced drug delivery reviewsApplications of focused ultrasound-mediated blood-brain barrier opening.PMC9712235R01EB030744R01 EB030409DP5 OD031846CL-2018-02-002R21 NS118278T32 CA009109R01 NS111102R01EB030409DP5OD031846R01 EB030744R21NS118278R01NS111102Breza VRSheybani NDHoch MRCheng VWTGorick CMFisher DGTran NMNowak KMDebski ACSchwartz MRPrice RJDemir ZEFfalseApplications of focused ultrasound-mediated blood-brain barrier opening.The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases.2022-01-01T00:00:00Z2022 Dec2025-04-04T09:50:13.081Z2025-02-19T01:17:39.589ZS-EPMC97122353627263510.1016/j.addr.2022.114583