title: Therapeutic ultrasound to noninvasively create intracardiac communications in an intact animal model.
abstract: OBJECTIVE
  To determine if pulsed cavitational ultrasound therapy (histotripsy) can accurately and safely generate ventricular septal defects (VSDs) through the intact chest of a neonatal animal, with the eventual goal of developing a noninvasive technique of creating intra-cardiac communications in patients with congenital heart disease.
  
  
  BACKGROUND
  Histotripsy is an innovative ultrasonic technique that generates demarcated, mechanical tissue fractionation utilizing high intensity ultrasound pulses. Previous work has shown that histotripsy can create atrial septal defects in a beating heart in an open-chest canine model.
  
  
  METHODS
  Nine neonatal pigs were treated with transcutaneous histotripsy targeting the ventricular septum. Ultrasound pulses of 5-μsec duration at a peak negative pressure of 13 MPa and a pulse repetition frequency of 1 kHz were generated by a 1 MHz focused transducer. The procedure was guided by real-time ultrasound imaging.
  
  
  RESULTS
  VSDs were created in all pigs with diameters ranging from 2 to 6.5 mm. Six pigs were euthanized within 2 hrs of treatment, while three were recovered and maintained for 2-3 days to evaluate lesion maturation and clinical side effects. There were only transient clinical effects and pathology revealed mild collateral damage around the VSD with no significant damage to other cardiac or extra-cardiac structures.
  
  
  CONCLUSIONS
  Histotripsy can accurately and safely generate VSDs through the intact chest in a neonatal animal model. These results suggest that with further advances, histotripsy can be a useful, noninvasive technique to create intracardiac communications, which currently require invasive catheter-based or surgical procedures, to clinically stabilize newborn infants with complex congenital heart disease.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, University of Michigan, Ann Arbor, Michigan, USA. gabeo@med.umich.edu
authors.forename: Gabe E
authors.initials: GE
authors.lastname: Owens
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Miller
authors.forename: Greg
authors.initials: G
authors.lastname: Ensing
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ives
authors.forename: David
authors.initials: D
authors.lastname: Gordon
authors.forename: Achi
authors.initials: A
authors.lastname: Ludomirsky
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D018618:Echocardiography, Doppler, Color; D004867:Equipment Design; D006345:Heart Septal Defects, Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D045423:Microbubbles; D013552:Swine; D013997:Time Factors; D014159:Transducers; D014464:Ultrasonic Therapy / Q000009:adverse effects* / Q000295:instrumentation; D018084:Ultrasonography, Interventional