Abstract 2192: Transcutaneous Creation of Ventricular Septal Defects Using Histotripsy in a Neonatal Animal Model
Introduction: Histotripsy is an innovative ultrasonic technique that produces mechanical tissue fractionation using high intensity ultrasound pulses. We have previously demonstrated that this therapy can precisely create atrial septal defects in an open-chest canine model. This study investigates the feasibility of histotripsy to transcutaneously create intra-cardiac communications in an intact neonatal animal model. The overall goal is develop a non-invasive procedure to create intra-cardiac communications in congenital heart diseases requiring such procedures such as Hypoplastic Left Heart Syndrome with a restrictive or intact atrial septum.
Methods: Six 3– 4 kg neonatal piglets were anesthetized and seated in a water bath. Transcutaneous treatments were delivered by a spherically focused 1MHz transducer positioned in the water outside the piglet’s chest wall from a right parasternal transducer position. Histotripsy treatment was applied using 5-cycle ultrasound pulses at 1 kHz pulse repetition frequency with 12–18 MPa peak negative pressure. Treatments were guided and monitored with an imaging transducer inserted in the center hole of the therapy transducer.
Results: Despite lung and bone in the therapeautic field, histotripsy pulses through the piglet’s chest wall generated a hyperechoic targeted bubble cloud of cavitation on the ventricular septum in all six animals. After 1–12 minutes of treatment, a VSD was created in 4 separate piglets and confirmed by 2-dimensional imaging and color flow Doppler. Gross morphology and histology on all hearts showed demarcated damage to the target location on the ventricular septum with complete perforations found in the four hearts where a VSD was identified by Doppler. Complications included variable degrees of cyanosis, pulmonary hemorrhage, and arrhythmia, likely from targeting of the ventricular septum.
Conclusions: Ventricular septal defects can be created transcutaneously in a neonatal animal model using histotripsy under real-time ultrasound guidance. With future advances and targeting of the atrial septum, histotripsy may become a useful non-invasive tool to aid in the treatment of congenital heart disease.