Non-invasive fetal therapy using histotripsy: Feasibility study in the sheep model

Pulsed cavitational ultrasound, or histotripsy, has been shown to be an effective technique to mechanically fractionate tissue through controlled cavitation. In this study, we investigate the feasibility of using histotripsy as a therapeutic tool to non-invasively fractionate and remove fetal tissue. Pregnant ewes at 102–129 days into gestation were exposed to histotripsy by a focused 1 MHz transducer coupled to the maternal abdominal wall. The fetal heart, kidney and liver were exposed to short ultrasound pulses (≪10 µs) at a 1 kHz pulse repetition rate and 10–16 MPa peak negative pressure. The entire procedure was guided and monitored by real-time ultrasound imaging. A total of 11 experiments were performed and preliminary results show that with suitable acoustic windows, histotripsy was able to generate a cavitation bubble cloud at the targeted fetal tissue and create mechanical tissue fractionation and removal. Morphological and histological assessment of the treated tissue confirmed that lesion locations corresponded to regions where the cavitation bubble cloud was observed. These results suggest that histotripsy has potential to become a non-invasive clinical tool for early fetal intervention on congenital anomalies such as prenatal treatment for hypoplastic left heart syndrome.