Novel Ultrasonic Technique for the Treatment of Hemorrhagic Stroke

项目摘要 脑出血(ICH)是最常见的出血性卒中类型，有400万 全球每年的病例。清除脑出血导致颅内压降低(ICP) 以及预防继发性脑损伤。当前消除非物质文化遗产的战略需要 侵入性开颅手术和穿越正常大脑的需要。微创方法 包括：1)颅针/tPA方法，需要数天的ICH疏散和风险 再次出血；2)内窥镜超声抽吸对脑组织也有损伤作用。 因为需要学习内窥镜技术。有一种明显的未得到满足的临床需求 安全、有效、快速缩小脑出血量的微创方法 无需使用溶栓药物，并以最简单的方法应用。我们 提出组织摩擦学作为一种新的超声技术，可以完全解决这一未满足的问题 临床需要。组织摩擦检查使用微秒持续时间，施加高压超声脉冲 从头骨外向脑出血内部集中，产生空化以液化脑出血，而不需要 导致脑部损伤。液化的脑出血可通过小口径导管立即排出。我们 使用电子聚焦引导的组织摩擦术实现了经颅脑出血的快速液化 (10分钟内约40毫升)，并通过切除的人头骨进行引流。我们已经研制出一种微型模型 集成在导管内的水听器，通过切除精确聚焦超声波 人的头骨和导管也可用于液化脑出血的引流。我们还有 在猪脑出血模型上证明了该方法的可行性和安全性。我们提出三个建议 旨在发展组织摩擦学作为一种安全疏散脑出血的新技术 以及改善结果。1)设计和构建了一种便携式组织学脑出血系统，该系统具有真实的 时间3D反馈，可高精度、高效率地经颅液化引流脑出血。 2)验证经颅手术的靶向精度、治疗部位分布和疗效 人脑出血模体和新鲜身体的组织学脑出血系统。3)验证安全性 以及经颅组织摩擦脑出血系统在已建立的活体猪脑出血模型中的有效性。 如果这些目标成功实现，我们将建立一个可移植的组织学非物质文化遗产系统 适合临床使用，并正在进行临床试验。

Project Summary Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke with 4 million annual cases worldwide. Evacuation of the ICH leads to reduction in intracranial pressure (ICP) as well as prevention of secondary cerebral injuries. Current strategy for removing ICH requires an invasive craniotomy and the need for traversing normal brain. Minimally invasive methods include: 1) craniopuncture/tPA method which requires days for evacuation of ICH and risk of rehemorrhage; 2) endoscopic ultrasonic aspiration has the force to injure cerebral tissue as well as the need for learning endoscopic techniques. There is a clear unmet clinical need for a minimally invasive method that can safely, effectively, and rapidly reduce the ICH volume without using thrombolytic drugs and be applied with the simplest methodology. We propose histotripsy as a novel ultrasonic technique that can fully address this unmet clinical need. Histotripsy uses microsecond duration, high-pressure ultrasound pulses applied from outside the skull and focused inside the ICH to produce cavitation to liquefy the ICH without causing brain injury. The liquefied ICH can be immediately drained via a small bore catheter. We have used histotripsy with electronic focal steering to achieve rapid transcranial ICH liquefaction (~40 mL in 10 min) and drainage through excised human skulls. We have developed a miniature hydrophone integrated within the catheter to precisely focus the ultrasound through excised human skulls and the catheter can also be used for drainage of the liquefied ICH. We have also demonstrated the in vivo feasibility and safety in a porcine ICH model. We propose three specific aims toward developing Histotripsy as a novel technique for safely evacuating ICH and improving outcomes. 1) Design and construct a portable histotripsy ICH system with real- time 3D feedback that can transcranially liquefy and drain ICH with high precision and efficacy. 2) Validate the targeting precision, treatment location profile, and efficacy of the transcranial histotripsy ICH system in human ICH phantom and fresh human cadaver. 3) Validate the safety and efficacy of the transcranial histotripsy ICH system in an established in vivo porcine ICH model. If these aims are successfully completed, we will establish a portable histotripsy ICH system suitable for clinical use and proceed towards a clinical trial.