Percutaneous Ultrasound-Guided Injection of the Trachea in Fetal Sheep: A Novel Technique to Target the Fetal Airways

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Abstract
Objective: To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep. Methods: Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.5–0.8 term, n = 18) fetal sheep using ultrasound guidance. Results: Injection of the trachea in the fetal thorax was successful in 16 out of 18 fetuses and achieved at the first attempt in 9 fetuses within 12 min [mean 7 min and 31 s ± (SD) 3 min and 4 s]. Survival was 100%. Injecting the trachea in the neck was less successful. Conclusions: The fetal trachea of the sheep can be safely accessed by percutaneous ultrasound-guided injection to deliver vectors directly to the fetal airways for gene therapy. It may also enable tracheal occlusion for the antenatal treatment of congenital diaphragmatic hernia without the need for endoscopy or open surgery.