title: Sonothrombolysis: an emerging modality for the management of stroke.
abstract: OBJECTIVE
  Ischemic stroke and intracranial hemorrhage remain a persistent scourge in Western civilization. Therefore, novel therapeutic modalities are desperately needed to expand the current limitations of treatment. Sonothrombolysis possesses the potential to fill this void because it has experienced a dramatic evolution from the time of early conceptualization in the 1960s. This process began in the realm of peripheral and cardiovascular disease and has since progressed to encompass intracranial pathologies. Our purpose is to provide a comprehensive review of the historical progression and existing state of knowledge, including underlying mechanisms as well as evidence for clinical application of ultrasound thrombolysis.
  
  
  METHODS
  Using MEDLINE, in addition to cross-referencing existing publications, a meticulous appraisal of the literature was conducted. Additionally, personal communications were used as appropriate.
  
  
  RESULTS
  This appraisal revealed several different technologies close to broad clinical use. However, fundamental questions remain, especially in regard to transcranial high-intensity focused ultrasound. Currently, the evidence supporting low intensity ultrasound's potential in isolation, without tissue plasminogen, remains uncertain; however, possibilities exist in the form of microbubbles to allow for focal augmentation with minimal systemic consequences. Alternatively, the literature clearly demonstrates, the efficacy of high-intensity focused ultrasound for independent thrombolysis.
  
  
  CONCLUSIONS
  Sonothrombolysis exists as a promising modality for the noninvasive or minimally invasive management of stroke, both ischemic and hemorrhagic. Further research facilitating clinical application is warranted.
authors.affiliation: Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Ricky
authors.initials: R
authors.lastname: Medel
authors.forename: R Webster
authors.initials: RW
authors.lastname: Crowley
authors.forename: M Sean
authors.initials: MS
authors.lastname: McKisic
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Dumont
authors.forename: Neal F
authors.initials: NF
authors.lastname: Kassell
mesh_terms: D002986:Clinical Trials as Topic; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D020521:Stroke / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000266:history / Q000379:methods*; D014464:Ultrasonic Therapy / Q000379:methods*