Author:

Keywords:

Science & Technology, Technology, Life Sciences & Biomedicine, Acoustics, Obstetrics & Gynecology, Radiology, Nuclear Medicine & Medical Imaging, congenital diaphragmatic hernia, fetal, sheep, tracheal occlusion, ultrasound, CONGENITAL DIAPHRAGMATIC-HERNIA, MEDIATED GENE-TRANSFER, IN-UTERO, LUNG, BALLOON, SURFACTANT, EPITHELIA, FETOSCOPY, PREGNANCY, DIAMETER, Animals, Balloon Occlusion, Chi-Square Distribution, Female, Fetal Diseases, Genetic Therapy, Injections, Pregnancy, Sheep, Domestic, Trachea, Ultrasonography, Interventional, Ultrasonography, Prenatal, 1114 Paediatrics and Reproductive Medicine, Obstetrics & Reproductive Medicine, 3202 Clinical sciences, 3215 Reproductive medicine

Abstract:

OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate.