title: Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.
abstract: OBJECTIVE
  Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model.
  
  
  METHODS
  The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury.
  
  
  RESULTS
  Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs.
  
  
  CONCLUSIONS
  Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures.
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. yohankim@umich.edu
authors: Y
authors: Y
authors: Kim
authors: S K
authors: SK
authors: Gelehrter
authors: C G
authors: CG
authors: Fifer
authors: J C
authors: JC
authors: Lu
authors: G E
authors: GE
authors: Owens
authors: D R
authors: DR
authors: Berman
authors: J
authors: J
authors: Williams
authors: J E
authors: JE
authors: Wilkinson
authors: K A
authors: KA
authors: Ives
authors: Z
authors: Z
authors: Xu
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D005333:Fetus / Q000473:pathology / Q000601:surgery; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D007668:Kidney / Q000473:pathology / Q000601:surgery; D008099:Liver / Q000473:pathology / Q000601:surgery; D008168:Lung / Q000473:pathology / Q000601:surgery; D034561:Sheep, Domestic