High Intensity Ultrasonic Device for Mitigating Neonatal Perioperative Bleeding

描述（由申请人提供）：先天性心脏病（CHD）范围从良性病变到危及生命的结构异常。良性病变无需干预即可解决，严重的结构性病变则需要复杂的小儿心脏手术。儿童主动脉弓重建是一项复杂的修复手术，其中围手术期出血是一个重要且常见的并发症。中度至重度先天性心脏病（CHD）发生率约为千分之六。据报道，需要复杂儿科手术的严重结构性病变约占活产婴儿的1/ 1000；这些儿童中有太多因围手术期出血和缺乏更有效的止血方法而死亡。严重先天性心脏病患儿的主动脉弓重建通常需要横断大血管，显著增大，然后使用非常小口径的缝合线进行缝合修复，缝合线放置得非常近，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，以及在心肺旁路术中需要的抗凝治疗方案，围手术期出血是一个重要且常见的并发症。有一个关键的，尚未满足的临床需要，有效的方法来影响围手术期止血的这类患者。高强度聚焦超声（HIFU）是治疗围手术期出血的新方法。已定性证明HIFU能有效地诱导止血。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，从而降低与手术相关的围产期发病率和死亡率。本提案的目的是建立可行性和所需参数，使HIFU可以安全有效地用于减轻围手术期出血（目标1），开发临床手持式HIFU系统治疗围手术期出血（目标2），并进行体外和离体实验，为动物模型的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，以开发一种减轻手术重建新生儿大血管围手术期出血的设备。该I期申请建议进行必要的安全性和有效性研究，以开发特定适应症的设备。该项目的第二阶段将在急性和存活动物模型中评估该装置。我们预计第二阶段将需要大约100万美元来生产一个可供临床评估的设备。

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.