Novel Ultrasonic Technique for the Treatment of Hemorrhagic Stroke

治疗出血性中风的新型超声波技术

基本信息

批准号：
9791355
负责人：
Aditya S Pandey
金额：
$ 50.87万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/9791355
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 injured innovation minimally invasive mortality novel portability preclinical study pressure prevent safety and feasibility

项目摘要

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.

项目概要脑出血 (ICH) 是最常见的出血性中风类型，有 400 万患者全球年度案例。疏散 ICH 可降低颅内压 (ICP) 以及预防继发性脑损伤。当前消除 ICH 的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，该方法需要数天的时间来疏散 ICH，并存在以下风险：再出血； 2）内镜下超声抽吸也有损伤脑组织的力量作为学习内窥镜技术的需要。显然，临床需求尚未得到满足安全、有效、快速减少ICH体积的微创方法不使用溶栓药物，以最简单的方法应用。我们提出组织解剖学作为一种新型超声技术，可以完全解决这一未满足的问题临床需要。组织解剖学使用微秒持续时间、施加高压超声脉冲从颅骨外部集中到 ICH 内部，产生空化作用，无需液化 ICH 造成脑损伤。液化的 ICH 可以立即通过小口径导管引流。我们使用带有电子焦点控制的组织解剖术来实现快速经颅 ICH 液化（10 分钟内约 40 mL）并通过切除的人头骨引流。我们开发了一个微型水听器集成在导管内，可通过切除的组织精确聚焦超声波人头骨和导管也可用于液化ICH的引流。我们还有证明了猪 ICH 模型的体内可行性和安全性。我们提出三个发展组织解剖学作为一种安全疏散脑出血的新技术的具体目标并改善结果。 1) 设计并构建具有实时性的便携式组织解剖ICH系统时间3D反馈，可以高精度和高效地经颅液化和引流ICH。 2) 验证经颅的靶向精度、治疗位置轮廓和功效人体 ICH 模型和新鲜人体尸体中的组织解剖 ICH 系统。 3）验证安全性以及经颅组织解剖 ICH 系统在已建立的猪体内 ICH 模型中的功效。如果这些目标成功完成，我们将建立便携式组织解剖ICH系统适合临床使用并进行临床试验。