title: Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study.
abstract: We investigated the efficacy, maternofetal responses, and safety of using high-intensity focused ultrasound (HIFU) for noninvasive occlusion of placental vasculature compared to sham treatment in anesthetized pregnant sheep. This technique for noninvasive occlusion of placental vasculature may be translatable to the treatment of conditions arising from abnormal placental vasculature, such as twin-twin transfusion syndrome (TTTS). Eleven pregnant sheep were instrumented with maternal and fetal arterial catheters and time-transit flow probes to monitor cardiovascular, acid-base, and metabolic status, and then exposed to HIFU (n = 5) or sham (n = 6) ablation of placental vasculature through the exposed uterine surface. Placental vascular flow was occluded in 28 of 30 targets, and histological examination confirmed occlusion in 24 of 30 targets. In both HIFU and sham exposures, uterine contact reduced maternal uterine artery flow, but delivery of oxygen and glucose to the fetal brain remained normal. HIFU can consistently occlude in vivo placental vessels and ablate blood flow in a pregnant sheep model. Cardiovascular and metabolic fetal responses suggest that the technique is safe in the short term and potentially translatable to human pregnancy.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Shaw
authors.affiliation: Joint Department of Physics, Institute of Cancer Research, Sutton, London SM2 5NG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Civale
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Kimberley J
authors.initials: KJ
authors.lastname: Botting
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Joint Department of Physics, Institute of Cancer Research, Sutton, London SM2 5NG, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Ter Haar
authors.affiliation: Joint Department of Physics, Institute of Cancer Research, Sutton, London SM2 5NG, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Rivens
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK. Department of Obstetrics and Gynaecology, University Hospitals Leuven, 3000 Leuven, Belgium. christoph.lees@imperial.nhs.uk.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Lees
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D005330:Fetofetal Transfusion / Q000601:surgery*; D005333:Fetus / Q000378:metabolism / Q000601:surgery*; D005947:Glucose / Q000378:metabolism; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep
chemical_list: D005947:Glucose; D010100:Oxygen