title: Noninvasive creation of an atrial septal defect by histotripsy in a canine model.
abstract: BACKGROUND
  The primary objective of this study was to develop an image-guided, noninvasive procedure to create or enlarge an atrial septal defect for the treatment of neonates with hypoplastic left heart syndrome and an intact or restrictive atrial septum. Histotripsy is an innovative ultrasonic technique that produces nonthermal, mechanical tissue fractionation through the use of high-intensity ultrasound pulses. This article reports the pilot in vivo study to create an atrial septal defect through the use of extracardiac application of histotripsy in an open-chest canine model.
  
  
  RESULTS
  In 10 canines, the atrial septum was exposed to histotripsy by an ultrasound transducer positioned outside the heart. Ultrasound pulses of 6-microsecond duration at a peak negative pressure of 15 MPa and a pulse repetition frequency of 3.3 kHz were generated by a 1-MHz focused transducer. The procedure was guided and monitored by real-time ultrasound imaging. In 9 of 10 canines, an atrial septal defect was produced, and shunting across the atrial septum was visualized. Pathology of the hearts showed atrial septal defects with minimal damage to surrounding tissue. No damage was found on the epicardial surface of the heart or other structures.
  
  
  CONCLUSIONS
  Under real-time ultrasound guidance, atrial septal defects were successfully created with extracardiac histotripsy in a live canine model. Although further studies in an intact animal model are needed, these results provide promise of histotripsy becoming a valuable clinical tool.
authors.affiliation: Departments of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. zhenx@umich.edu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Gabe
authors.initials: G
authors.lastname: Owens
authors.forename: David
authors.initials: D
authors.lastname: Gordon
authors.forename: Charles
authors.initials: C
authors.lastname: Cain
authors.forename: Achi
authors.initials: A
authors.lastname: Ludomirsky
mesh_terms: D000818:Animals; D054087:Atrial Septum / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D004617:Embolism / Q000453:epidemiology; D006344:Heart Septal Defects, Atrial / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000000981:diagnostic imaging; D007231:Infant, Newborn; D010865:Pilot Projects; D012307:Risk Factors; D014465:Ultrasonics / Q000009:adverse effects*; D018615:Ultrasonography, Doppler, Color