Extracorporeal high intensity focused ultrasound treatment of the placental unit: In vivo study using a monkey model of pregnancy

Abstract

The last 20 years have seen the development of fetal surgery, particularly for the treatment of twin-to-twin transfusion syndrome (TTTS). Although fetoscopy increases survival rate, it is also invasive and responsible for fetal and maternal complications affecting the neonatal outcome. A completely non-invasive treatment that could occlude deep anastomoses would prevent the risks of invasive fetoscopy while offering the potential for more effective therapy. We previously developed a toroidal HIFU transducer that enables the destruction of large tissue volumes. The effectiveness of this HIFU device applied to the perfused placental unit must now be studied in a preclinical animal study under conditions similar to those in humans before starting a clinical trial. We report here the first use of a completely non-invasive treatment of the placenta in pregnant animals. A toroidal HIFU transducer working at 2.5 MHz and composed of 32 ring-shaped emitters was used. In vivo experiments were performed in eight pregnant monkeys. Lesions on placental tissues were performed non-invasively by placing the HIFU probe on the skin. Fetal and maternal parameters, such as maternal heart rate, fetal heart rate, and subcutaneous and intra-amniotic fluid temperature, were recorded. A C-section was performed immediately after insonification to extract the placenta, inspect the fetus and inspect the maternal abdominal cavity. Placental HIFU lesions were studied using ultrasound images, gross pathology and histology. Thirteen HIFU exposures were performed on placentas. The parameters used in this study were acoustic powers of 65, 80, 110 and 120 W applied for 30, 15, 20 and 20 seconds, respectively. This gradual increase in the total energy delivered was used to determine a set of parameters to create reproducible lesions in the placentas without any complications. The dimensions of the placental lesions were an average diameter of 6.4 ± 0.5 mm and 7.8 ± 0.7 mm and an average depth of 3.8 ± 1.5 mm. Ultrasound images revealed a hyperechoic region that was correlated with the macroscopic analyses of the HIFU lesions. Necrosis of placental tissues exposed to HIFU was confirmed with histology. No significant variation in maternal and fetal parameters was observed during HIFU exposure. This study demonstrates in a monkey model of pregnancy the feasibility of HIFU treatment applied to the placenta for potential application to treat twin-to-twin transfusion syndrome.