Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study.
Authors: Shaw CJ, Civale J, Botting KJ, Niu Y, Ter Haar G, Rivens I, Giussani DA, Lees CC
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.
Introduction
Purpose
Thermal ablation
Study Objective
To evaluate the feasibility, efficacy, and maternal–fetal safety of ultrasound-guided high-intensity focused ultrasound (HIFU) for noninvasive occlusion of placental vasculature as a potential treatment for twin–twin transfusion syndrome (TTTS).
Animal model / Human subject
Sheep; pregnant; n=11
Disease model
Healthy
MRI or image guidance method
ultrasound imaging
Targeted brain region(s)
Targeted Placental Blood Vessels (Placentomes) In Pregnant Sheep.
Outcomes and Safety
Summary of Outcomes
HIFU successfully occluded 28/30 (93.3%) targeted placental vessels, with histological confirmation of vascular occlusion. Maternal and fetal cardiovascular and metabolic parameters remained stable, supporting the feasibility and short-term safety of noninvasive placental vascular ablation.
Duration of biological effect
Acute (up to 30-minute recovery period). Vascular occlusion persisted throughout the experimental observation period and was confirmed by postmortem histology performed within 4 hours after treatment.
Safety-related matter
No maternal, uterine, fetal, or adjacent tissue injury was observed. One case of vessel hemorrhage occurred due to equipment malfunction (repeated exposure at the same location), while maternal and fetal physiological responses were comparable to sham treatment, indicating favorable short-term safety.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Sonic Concepts H148MR transducer
FUS Frequency
1.66 MHz
FUS Intensity
4000 to 5700 W/cm2
Duration of a single FUS session
5 s
Focal Characteristics
focal diameter 1.2 mm, focal length 8.9 mm
Treatment frequency
single session
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