Developmental impact and lesion maturation of histotripsy-mediated non-invasive tissue ablation in a fetal sheep model

Non-invasive histotripsy therapy has previously been used to achieve precise fetal tissue ablation in a sheep model. To further assess the clinical viability of the technique, this study investigated potential effects of histotripsy therapy during the remaining gestation and its local impact on fetal development. Five ewes (six lambs) at 95-107 d of gestation were treated and allowed to complete the full gestation period of 150 d. A 1-MHz focused transducer was used to treat the fetal kidney and liver with 5-μs pulses at 500-Hz repetition rates and 10- to 16-MPa peak negative pressures; ultrasound imaging provided real-time treatment guidance. The lambs were euthanized after delivery and treated organs were harvested. Samples were examined by magnetic resonance imaging and histopathologic analysis. These data were compared with results from four other ewes (four lambs) that underwent similar treatments but were sacrificed immediately after the procedure. The sheep tolerated the treatment well, and acute lesion samples displayed well-defined ablated regions characterized by the presence of fractionated tissue and hemorrhage. All fetuses that were allowed to continue gestation survived and were delivered at full term. The lambs were healthy on delivery, with no signs of external injury. A minor indentation was observed in each of the treated kidneys with minimal presence of fibrous tissue, while no discernible signs of lesions were detected in treated livers. In a sheep model, histotripsy-mediated fetal tissue ablation caused no acute or pregnancy-related complications, supporting the potential safety and effectiveness of histotripsy therapy as a tool in fetal intervention procedures.