Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Ultrasound Med Biol. 2013 Jun;39(6):1047-55. doi: 10.1016/j.ultrasmedbio.2012.12.014. Epub 2013 Feb 27.
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.
先前已将无创组织微爆破疗法用于在绵羊模型中实现精确的胎儿组织消融。为了进一步评估该技术的临床可行性，本研究调查了组织微爆破疗法在剩余妊娠期内的潜在影响及其对胎儿发育的局部影响。在妊娠 95-107 天期间对五只母羊（六只羔羊）进行了治疗，并允许它们完成 150 天的整个妊娠期。使用 1MHz 聚焦换能器以 500Hz 重复率和 10-16MPa 峰值负压用 5μs 脉冲对胎儿的肾脏和肝脏进行治疗；超声成像提供了实时治疗指导。分娩后对羔羊实施安乐死并采集处理后的器官。通过磁共振成像和组织病理学分析检查样本。将这些数据与另外四只接受类似治疗但在手术后立即处死的母羊（四只羔羊）的结果进行了比较。绵羊对治疗耐受良好，急性损伤样本显示出定义明确的消融区域，特征为组织碎裂和出血。所有允许继续妊娠的胎儿均存活并足月分娩。羔羊分娩时健康，无外部损伤迹象。在每个处理过的肾脏中都观察到轻微的凹陷，只有少量纤维组织存在，而在处理过的肝脏中则没有发现明显的病变迹象。在绵羊模型中，组织微爆破介导的胎儿组织消融未引起急性或妊娠相关并发症，支持组织微爆破疗法作为胎儿干预程序中一种工具的潜在安全性和有效性。
