title: Emerging Applications of Therapeutic Ultrasound in Neuro-oncology: Moving Beyond Tumor Ablation.
abstract: : Transcranial focused ultrasound (FUS) can noninvasively transmit acoustic energy with a high degree of accuracy and safety to targets and regions within the brain. Technological advances, including phased-array transducers and real-time temperature monitoring with magnetic resonance thermometry, have created new opportunities for FUS research and clinical translation. Neuro-oncology, in particular, has become a major area of interest because FUS offers a multifaceted approach to the treatment of brain tumors. FUS has the potential to generate cytotoxicity within tumor tissue, both directly via thermal ablation and indirectly through radiosensitization and sonodynamic therapy; to enhance the delivery of therapeutic agents to brain tumors by transiently opening the blood-brain barrier or improving distribution through the brain extracellular space; and to modulate the tumor microenvironment to generate an immune response. In this review, we describe each of these applications for FUS, the proposed mechanisms of action, and the preclinical and clinical studies that have set the foundation for using FUS in neuro-oncology.
  
  
  BACKGROUND
  BBB, blood-brain barrierCED, convection-enhanced delivery5-Ala, 5-aminolevulinic acidFUS, focused ultrasoundGBM, glioblastoma multiformeHSP, heat shock proteinMRgFUS, magnetic resonance-guided focused ultrasoundpFUS, pulsed focused ultrasound.
authors.affiliation: *Department of Neurosurgery,‡Marlene and Stewart Greenebaum Cancer Center,¶Center for Biomedical Engineering and Technology,‖Department of Surgery,#Center for Vascular and Inflammatory Diseases, and**Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland;§Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland.
authors.forename: David S
authors.initials: DS
authors.lastname: Hersh
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kim
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Winkles
authors.forename: Howard M
authors.initials: HM
authors.lastname: Eisenberg
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Woodworth
authors.forename: Victor
authors.initials: V
authors.lastname: Frenkel
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000628:therapy*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000628:therapy*; D005910:Glioma / Q000628:therapy; D006801:Humans; D056747:Immunomodulation; D008279:Magnetic Resonance Imaging; D011836:Radiation Tolerance; D059708:Ultrasonic Surgical Procedures / Q000379:methods*; D014464:Ultrasonic Therapy / Q000379:methods