Selective occlusion of placental vessels using non-invasive focused ultrasound delivered by a toroidal transducer: Preclinical application in a pregnant monkey model for the treatment of twin-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) arises in 15% of monochorionic twin pregnancies due to unbalanced vascular anastomoses and remains a major cause of perinatal morbidity and mortality. Current treatment with laser fetoscopy is invasive, limited to superficial vessels, and technically challenging with anterior placentas. This study evaluated the feasibility, safety, and efficacy of non-invasive vascular occlusion using a hand-held high-intensity focused ultrasound (HIFU) device in a pregnant primate model. Seven pregnant monkeys with singleton fetuses were treated under general anesthesia using a toroidal HIFU transducer. Targeted placental vessels were exposed to acoustic power of 95-110 W with sonication durations of 20-30 s. Lesion formation and vessel occlusion were monitored by B-mode and Doppler ultrasound. Cesarean section immediately after treatment enabled macroscopic and histological assessment. Doppler ultrasound confirmed complete occlusion of all targeted vessels (20 sonications). Macroscopic lesions measured 8.8 ± 2.6 mm on the longest axis and 6.6 ± 1.7 mm on the shortest axis, closely correlating with ultrasound-based measurements (rank correlation coefficient 0.96, p < 0.001). Histology confirmed necrosis confined to placental tissue without damage to adjacent structures. Maternal vital parameters remained stable, and no fetal or organ complications were observed. This preclinical study demonstrates that HIFU enables selective, non-invasive placental vessel occlusion with high precision and safety. The approach holds promise as an alternative or adjunct to fetoscopic laser therapy, particularly for anterior placentas or deep anastomoses inaccessible to conventional techniques.