Noninvasive ultrasound neuromodulation for functional brain mapping

用于功能性大脑绘图的无创超声神经调节

• 批准号: 8519579
• 负责人: Sumon k Pal
• 金额: $ 35.2万
• 依托单位: THYNC, INC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8519579
• 关键词: Acoustics; Address; Biological Assay; Brain; Brain Mapping; Brain Part; Brain imaging; Brain region; Characteristics; Computer software; Data; Development; Diagnosis; Diagnostic; Disease; Electrodes; Electroencephalography; Electromagnetics; Electrophysiology (science); Epilepsy; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Human; Image; Individual; Kinetics; Macaca; Medicine; Mental Depression; Methods; Modeling; Nerve; Parkinson Disease; Peripheral Nerve Stimulation; Phase; Physiologic pulse; Primates; Resolution; Scanning; Series; Signal Transduction; Small Business Innovation Research Grant; Source; Stimulus; System; Techniques; Technology; Testing; Transducers; Translating; Ultrasonic Therapy; Ultrasonography; absorption; cranium; data acquisition; imaging modality; improved; millimeter; nervous system disorder; neuroimaging; neuroregulation; novel; phantom model; programs; research study; response; screening; tool

DESCRIPTION (provided by applicant): Brain mapping tools are essential for both our understanding the brain as well as diagnosing dysfunction. A method to noninvasively and precisely stimulate any three-dimensional locus within the human brain would be transformative, both clinically and scientifically. If compatible with modern functional brain imaging methods, such an improved stimulation tool could support unprecedented studies exploring human brain function and connectivity. Clinically, it could support novel screening/diagnostic strategies and improved treatments for diseases such as depression, Parkinson's, and epilepsy which are becoming more frequently treated using invasive stimulation methods (for example with deep-brain stimulating electrodes; DBS). Pulsed ultrasound (US) energy can be used to modulate brain circuit activity and has the characteristics required to achieve targeted stimulation with millimeter spatial resolution anywhere in the brain. Our goal is to translate ultrasound neuromodulation to humans and develop technologies to combine ultrasound-induced neuromodulation with current neuroimaging and electrophysiology methods. The methods we propose to develop will establish a new paradigm in diagnostic medicine and be broadly applicable to neurological disorders as well as increase our ability to understand integrative functions of the brain. Specific Aim 1. Development of a hardware and software platform for identifying optimal pulsed UNMOD waveforms. Milestone: Hardware and software platform that integrates US stimulation with electrophysiological and fMRI data acquisition to establish a systematic approach for assaying the optimal ultrasound neuromodulation (UNMOD) stimulus parameter space. Specific Aim 2. Development of focusing and scanning strategies for deep neurostimulation through the skull using ultrasound. Milestone: Neuromodulation strategies using multiple sources of ultrasound that offer an improvement in spatial resolution of activation, decrease undesirable thermal effects, and increase in activation efficiency. Specific Aim3. Testing focal neurostimulation strategies in the primate brain. We will use this model to test approaches developed in Specific Aims 1 and 2. Milestone: Proof of concept in primates and the selection of optimal focusing and scanning strategies to be tested in humans. Specific Aim 4. Simultaneous ultrasound nerve stimulation, fMRI imaging and EEG recordings in humans. Milestone: Successful integration of UNMOD, fMRI imaging and EEG recordings in humans. At the successful conclusion of this Phase I SBIR we will have developed a number of key technology pieces for translating functional brain mapping with noninvasive ultrasound neuromodulation in humans. These include the ability to stimulate targeted brain regions through the skull, a proof of concept in primates, and successful integration of UNMOT, fMRI and EEG in humans. We will be poised in Phase II to use this technique to compare the functional brain maps of healthy individuals with ones suffering from neurological disorders.

描述（由申请人提供）：大脑绘图工具对于我们了解大脑以及诊断功能障碍至关重要。一种无创且精确地刺激人脑内任何三维位点的方法无论在临床上还是在科学上都将是变革性的。如果与现代功能性大脑成像方法兼容，这种改进的刺激工具可以支持探索人类大脑功能和连接性的前所未有的研究。在临床上，它可以支持新的筛查/诊断策略并改进抑郁症、帕金森病和癫痫等疾病的治疗方法，这些疾病越来越频繁地使用侵入性刺激方法（例如深部脑刺激电极；DBS）进行治疗。脉冲超声 (US) 能量可用于调节大脑回路活动，并具有在大脑任何位置以毫米空间分辨率实现目标刺激所需的特性。我们的目标是将超声神经调节应用于人类，并开发将超声诱导的神经调节与当前的神经成像和电生理学方法相结合的技术。我们建议开发的方法将建立诊断医学的新范例，广泛适用于神经系统疾病，并提高我们理解大脑整合功能的能力。具体目标 1. 开发用于识别最佳脉冲 UNMOD 波形的硬件和软件平台。里程碑：硬件和软件平台将超声刺激与电生理学和功能磁共振成像数据采集相结合，建立一种系统方法来分析最佳超声神经调节 (UNMOD) 刺激参数空间。具体目标 2. 开发使用超声波通过颅骨进行深层神经刺激的聚焦和扫描策略。里程碑：使用多个超声源的神经调节策略可提高激活的空间分辨率， 减少不良热效应并提高活化效率。具体目标3。测试灵长类动物大脑中的局灶性神经刺激策略。我们将使用该模型来测试特定目标 1 和 2 中开发的方法。里程碑：在灵长类动物中进行概念验证，并选择要在人类中进行测试的最佳聚焦和扫描策略。具体目标 4. 对人体进行同步超声神经刺激、功能磁共振成像和脑电图记录。里程碑：UNMOD、功能磁共振成像和脑电图记录在人体中的成功整合。在第一阶段 SBIR 成功结束时，我们将开发出许多关键技术，用于通过无创超声神经调节来转化人类的功能性大脑图谱。其中包括通过头骨刺激目标大脑区域的能力、灵长类动物的概念证明，以及 UNMOT、功能磁共振成像和脑电图在人类身上的成功整合。我们将在第二阶段准备使用这项技术来比较健康人和患有神经系统疾病的人的功能性大脑图。