title: Noninvasive treatment of deep venous thrombosis using pulsed ultrasound cavitation therapy (histotripsy) in a porcine model.
abstract: OBJECTIVE
  This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, high-intensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This is an in vivo feasibility study of histotripsy thrombolysis.
  
  
  METHODS
  Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm-diameter 1-MHz focused transducer was used for therapy. An 8-MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of five cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14 and 19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment.
  
  
  RESULTS
  Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases and in 7 cases improved flow through the vein as measured by color Doppler. Vessel histology found denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed.
  
  
  CONCLUSIONS
  The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. adamdm@umich.edu
authors.forename: Adam D
authors.initials: AD
authors.lastname: Maxwell
authors.forename: Gabe
authors.initials: G
authors.lastname: Owens
authors.forename: Hitinder S
authors.initials: HS
authors.lastname: Gurm
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ives
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Myers
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005268:Femoral Vein / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D057086:High-Intensity Focused Ultrasound Ablation / Q000295:instrumentation; D012039:Regional Blood Flow; D013552:Swine; D014159:Transducers; D018615:Ultrasonography, Doppler, Color; D018084:Ultrasonography, Interventional; D014654:Vascular Patency; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*