title: Microbubble mediated thrombus dissolution with diagnostic ultrasound for the treatment of chronic venous thrombi.
abstract: BACKGROUND
  Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo.
  
  
  RESULTS
  A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2) respectively in Group A; compared to 0.24 and 0.21 cm(2) in Group B (p  = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment.
  
  
  CONCLUSIONS
  Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.
authors.affiliation: Joint Division of Pediatric Cardiology, University of Nebraska College of Medicine/Creighton University, Children's Hospital and Medical Center, Omaha, Nebraska, USA.
authors.forename: Shelby
authors.initials: S
authors.lastname: Kutty
authors.forename: Juefei
authors.initials: J
authors.lastname: Wu
authors.forename: James M
authors.initials: JM
authors.lastname: Hammel
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: Shunji
authors.initials: S
authors.lastname: Gao
authors.forename: Lucas K
authors.initials: LK
authors.lastname: Drvol
authors.forename: John
authors.initials: J
authors.lastname: Lof
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Radio
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Therrien
authors.forename: David A
authors.initials: DA
authors.lastname: Danford
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Porter
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000000981:diagnostic imaging; D017115:Catheter Ablation; D062905:Central Venous Catheters; D002908:Chronic Disease; D004562:Electrocardiography; D005240:Feasibility Studies; D005471:Fluoroscopy; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D045423:Microbubbles; D011877:Radionuclide Imaging; D034421:Sus scrofa; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*