Novel Ultrasonic Technique for the Treatment of Hemorrhagic Stroke

治疗出血性中风的新型超声波技术

• 批准号: 10214710
• 负责人: Aditya S Pandey
• 金额: $ 51.37万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214710
• 关键词: 3-Dimensional; 3D ultrasound; Acoustics; Address; Aftercare; Anatomy; Autopsy; Axon; Blood Vessels; Blood coagulation; Brain; Brain Injuries; Brain hemorrhage; Brain scan; Cadaver; Catheters; Cerebral hemisphere hemorrhage; Cerebral perfusion pressure; Cerebrum; Clinical; Clinical Treatment; Clinical Trials; Coagulation Process; Craniotomy; Devices; Diagnostic radiologic examination; Drainage procedure; Edema; Elements; Ensure; Family suidae; Feedback; Fibrinolytic Agents; Focused Ultrasound; Future; Goals; Grant; Hematoma; Hemoglobin; Hemorrhage; Histologic; Histopathology; Hour; Human; Injury; Intracranial Pressure; Iron; Lead; Learning; Length; Location; Magnetic Resonance Imaging; Maps; Mechanics; Medical; Methodology; Methods; Modeling; Nervous System Trauma; Neurons; Neurosurgeon; Operative Surgical Procedures; Outcome; Patients; Physiologic pulse; Positioning Attribute; Precision therapeutics; Randomized Clinical Trials; Risk; Rupture; Safety; Secondary Prevention; Secondary to; Stroke; Surface; Survival Rate; Survivors; System; Techniques; Time; Tissues; Training; Trephine hole; Ultrasonics; Ultrasonography; Ventriculostomy; X-Ray Computed Tomography; base; blood product; clinical translation; cranium; design and construction; frontal lobe; improved; improved outcome; in vivo; innovation; minimally invasive; mortality; novel; portability; preclinical study; pressure; prevent; safety and feasibility

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.

项目摘要 脑出血（ICH）是最常见的出血性卒中类型， 全球每年的病例。ICH的排空导致颅内压（ICP）降低 以及预防继发性脑损伤。目前的ICH删除策略需要 侵入性开颅手术和穿越正常大脑的需要微创方法 包括：1）颅骨穿刺/tPA方法，需要数天时间来清除ICH， 内镜超声抽吸术对脑组织也有损伤作用 因为需要学习内窥镜技术。有一个明确的未满足的临床需求， 微创方法，可安全、有效、快速地减少ICH体积 不使用溶栓药物，并以最简单的方法应用。我们 我提出组织摧毁术作为一种新的超声技术，可以完全解决这一未满足的 临床需要组织破坏术使用微秒持续时间，施加高压超声脉冲 并聚焦在脑出血内以产生空化作用， 导致脑损伤液化的ICH可以通过小口径导管立即排出。我们 我使用组织粉碎术和电子聚焦转向来实现快速经颅ICH液化 （10分钟内约40 mL）并通过切除的人颅骨引流。我们开发了一种微型 水听器集成在导管内，通过切除的 人头骨和导管也可用于排出液化的ICH。我们还 证明了在猪ICH模型中的体内可行性和安全性。我们提出了三 具体目标是将组织破坏术开发为安全清除ICH的新技术 并改善结果。1)设计并构建了一个便携式ICH组织破坏系统， 实时3D反馈，可以高精度和高效率地经颅穿刺和引流ICH。 2)验证了经颅穿刺的靶向精度、治疗位置概况和疗效。 脑出血模型和新鲜人尸脑出血组织破坏系统。3)保证安全 和经颅组织摧毁术ICH系统在建立的体内猪ICH模型中的功效。 如果这些目标得以成功实现，我们将建立一个便携式脑出血组织破坏系统 适合临床使用并进行临床试验。