High Intensity Ultrasonic Device for Mitigating Neonatal Perioperative Bleeding

描述（由申请人提供）：先天性心脏病（CHD）的范围从良性病变到危及生命的结构异常。虽然良性病变可能无需干预即可消退，但严重的结构性病变需要复杂的儿科心脏手术。儿童主动脉弓重建术是一项复杂的手术，围手术期出血是一个重要而常见的并发症。中度至重度先天性心脏病（CHD）发生在约6/1，000活产婴儿中。据报道，需要复杂儿科手术的严重结构性病变约占活产的1/1，000;这些儿童中有太多人死于围手术期出血和缺乏更有效的止血方法。在患有严重先天性心脏病的儿童中进行主动脉弓重建通常需要横断大血管，显著增强，然后使用非常小口径的缝线进行缝合修复，这些缝线非常靠近，以确保修复的完整性。然而，由于修复的复杂性，新生儿弓的解剖结构，以及在心肺转流过程中所需的抗凝方案，围手术期出血是一个显着的，重要的和常见的并发症。对于此类患者的有效围手术期止血方法，存在关键的未满足的临床需求。高强度聚焦超声（HIFU）为治疗围手术期出血提供了一种新的方法。已定性证明HIFU可有效诱导止血。我们的总体研究目标是减轻手术重建大血管围手术期出血的影响，从而降低围产期发病率和死亡率与外科手术。本提案的目的是确定可行性和所需参数，以便HIFU可以安全有效地用于减轻围手术期出血（目标1），开发用于治疗围手术期出血的临床手持式HIFU系统（目标2），并在动物模型中进行体外和离体实验，为II期研究做准备（目标3）。此次合作汇集了BioDesign Research & Development的声学和仪器专业知识、华盛顿大学的声学生物效应专业知识以及西雅图儿童医院的儿科外科医生，以开发一种用于减轻手术重建新生儿大血管围手术期出血的设备。本次I期申请拟进行必要的安全性和有效性研究，以开发适应症特定器械。本项目的第二阶段将在急性和存活动物模型中评价该器械。我们的项目第二阶段将需要大约100万美元来生产一个准备用于临床评估的设备。

DESCRIPTION (provided by applicant): Congenital heart disease (CHD) ranges from benign lesions to life-threatening structural abnormalities. While benign lesions may resolve without intervention, severe structural lesions require complex pediatric cardiac surgery. The reconstruction of the aortic arch in children is a complex repair in which perioperative bleeding i a significant, important and frequent complication. Moderate to severe Congenital Heart Disease (CHD) occurs in about 6/1,000 live births. Severe structural lesions that require complex pediatric surgeries have been reported as about 1/1,000 of live births; too many of these children die as a result of perioperative bleeding and the lack of more effective methods to stop bleeding. The reconstruction of the aortic arch in children with severe congenital heart disease often requires transection of the great vessels, significant augmentation, and then suture repair using very small caliber sutures placed extremely close together to ensure repair integrity. However, due to the complex nature of the repair, the anatomy of the neonatal arch, and the anti-coagulation regimen that is required during the cardio-pulmonary bypass, perioperative bleeding is a significant, important and frequent complication. There is a critical, unmet clinical need for an effective method to effect perioperative hemostasis in such patients. High Intensity Focused Ultrasound (HIFU) provides a novel approach for treating perioperative bleeding. HIFU has been demonstrated qualitatively to effectively induce hemostasis. Our overarching research objective is to mitigate the effects of perioperative bleeding in surgically reconstructed great vessels, thus reducing the perinatal morbidity and mortality associated with surgical procedures. The objectives of this proposal is to establish the feasibility and required parameters such that HIFU can be used safely and effectively to mitigate perioperative bleeding (Aim 1), develop a clinical hand-held HIFU system for treating perioperative bleeding (Aim 2), and conduct in vitro and ex vivo experiments in preparations for Phase II studies in an animal model (Aim 3). This collaboration brings together acoustics and instrumentation expertise at BioDesign Research & Development, acoustic bioeffects expertise at the University of Washington, and pediatric surgeons at Seattle's Children's Hospital to develop a device for mitigating perioperative bleeding of surgically reconstructed neonatal great vessels. This Phase I application proposed to conduct the necessary safety and efficacy studies to develop an indication specific device. Phase II of this project will be to evaluate the device in acute and survival animal models. We project Phase II would require approximately 1 million dollars to produce a device ready for clinical evaluation.