Non-invasive high-intensity focused ultrasound treatment of the placenta: a preliminary in-vivo study using a simian model.
OBJECTIVE
To demonstrate the feasibility and efficacy of high-intensity focused ultrasound (HIFU) for the non-invasive creation of placental lesions in a simian model.


METHODS
Eight pregnant monkeys were exposed to HIFU treatment after anesthesia, using a toroidal HIFU 2.5-MHz transducer with an integrated ultrasound imaging probe. Lesions on the placental tissue were created non-invasively by placing the HIFU probe on the skin surface. Fetal and maternal parameters, such as maternal heart rate, fetal heart rate and subcutaneous and intra-amniotic fluid temperature, were recorded during HIFU exposure. Cesarean section was performed immediately after the procedure to extract the placenta and examine the fetus and the maternal abdominal cavity. Placental HIFU lesions were assessed by ultrasound, gross pathology and histology.


RESULTS
The mean gestational age of the monkeys was 72 ± 4 days. In total, 13 HIFU procedures were performed. The acoustic power and exposure time were increased progressively. This gradual increase in total energy delivered was used to determine a set of parameters to create reproducible lesions in the placenta without complications. Five placental lesions were observed with average diameters of 6.4 ± 0.5 mm and 7.8 ± 0.7 mm and an average depth of 3.8 ± 1.5 mm. Ultrasound examination of the placentae revealed hyperechoic regions that correlated well with macroscopic analysis of the HIFU lesions. Necrosis of placental tissue exposed to HIFU was confirmed with macroscopic and microscopic analysis. There was no significant variation in maternal and fetal parameters during HIFU exposure.


CONCLUSIONS
This study demonstrates the feasibility of HIFU applied non-invasively to the placental unit in an in-vivo pregnant monkey model. The technique is safe in the immediate short term and is potentially translatable to human pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Inserm, U1032, Laboratory of Therapeutic Applications of Ultrasound, Lyon, France.|Université de Lyon, Lyon, France.|Department of Obstetrics and Gynecology, Croix Rousse University Hospital, Lyon, France.
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J
Caloone
Department of Obstetrics and Gynecology, Croix Rousse University Hospital, Lyon, France.|Stem Cell and Brain Research Institute, Institut National de la Sante et de la Recherche Médicale U846, Bron, France.
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Huissoud
Inserm, U1032, Laboratory of Therapeutic Applications of Ultrasound, Lyon, France.|Université de Lyon, Lyon, France.
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A
Kocot
Inserm, U1032, Laboratory of Therapeutic Applications of Ultrasound, Lyon, France.|Université de Lyon, Lyon, France.
J
J
Vincenot
Stem Cell and Brain Research Institute, Institut National de la Sante et de la Recherche Médicale U846, Bron, France.
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C
Dehay
Stem Cell and Brain Research Institute, Institut National de la Sante et de la Recherche Médicale U846, Bron, France.
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P
Giroud
Stem Cell and Brain Research Institute, Institut National de la Sante et de la Recherche Médicale U846, Bron, France.
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Misery
Université de Lyon, Lyon, France.|Department of Pathology, Croix Rousse University Hospital, Lyon, France.
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F
Allias
Department of Obstetrics and Gynecology, Croix Rousse University Hospital, Lyon, France.
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RC
Rudigoz
Inserm, U1032, Laboratory of Therapeutic Applications of Ultrasound, Lyon, France.|Université de Lyon, Lyon, France.
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Melodelima
D000818:Animals; D000074059:Extracorporeal Shockwave Therapy / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005865:Gestational Age; D000882:Haplorhini; D023421:Models, Animal; D010922:Placenta Diseases / Q000209:etiology / Q000628:therapy*; D011247:Pregnancy; D016896:Treatment Outcome; D016216:Ultrasonography, Prenatal / Q000379:methods*
HIFU; extracorporeal; high-intensity focused ultrasound; monkey; placental unit; twin-to-twin transfusion syndrome