MR-guided Focused Ultrasound Neuromodulation of Deep Brain Structures

磁共振引导聚焦超声神经调节脑深部结构

基本信息

批准号：
9228441
负责人：
Kim Butts-Pauly
金额：
$ 39.25万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-26 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9228441
关键词：
Ablation Acoustics Behavior Brain Calibration Data Development Diagnostic Imaging Electrodes Environment Equipment Family suidae Focused Ultrasound Forelimb Functional Magnetic Resonance Imaging Future Goals Hand Heating Human Image Lateral Geniculate Body Lead Magnetic Resonance Imaging Maps Measures Mechanics Methods Modeling Monitor Mus Neurosciences Neurosciences Research Phase Population Procedures Process Protocols documentation Radiation Reproducibility Research Resources Retina Rodent Safety Signal Transduction Sonication Spottings Structure Techniques Technology Temperature Therapeutic Thermometry Thick Time Tissues Transducers Ultrasonography Variant Visual Cortex Weight Work X-Ray Computed Tomography abstracting attenuation base behavioral study bone cognitive neuroscience cranium experience frontier imaging modality in vivo in vivo Model indexing innovation neuroregulation particle pressure programs research study response simulation tool volunteer

项目摘要

Project Abstract Completely noninvasive neuromodulation using focused ultrasound (FUS) offers the promise of precisely stimulating speciﬁc targets deep in the brain. FUS is already used to deliver precise ablations deep in the brain. A CT scan is currently used to calculate the phase aberration corrections. The focal spot is calibrated by imaging a 5°C temperature rise. Both the CT scan and tissue heating are unacceptable in normal volunteers. Beyond that, skulls with similar CT scans vary widely in their ultrasound attenuation. It is imperative to accurately predict and measure the power at the focal spot and elsewhere, both for safety, and for the experimental reproducibility of the technique. The purpose of this work is to develop these critically needed tools based on MRI. Our group has studied all aspects of FUS in the brain. We have extensive experience in mapping the parameter space for FUS neuromodulation, in measuring the FUS beam in brain using temperature and MR acoustic radiation force imaging, and in determining the beam focusing weights for large FUS arrays for focusing FUS through the skull. Our goal is to direct this expertise into turning FUS neuromodulation into a widely available, repeatable, and accurate research tool that would be safe for normal volunteers. With these calibration and targeting tools in hand, we can answer the important question of what physical effect the ultrasound is creating that stimulates the brain. Our work in the mouse points to the cavitation index or particle displacement, while work in the retina points to radiation force. This is the central question in FUS neuromodulation. We need to know what physical effect to create in the brain to produce neuromodulation in humans. We propose to answer this question in the porcine model, which is physiologically very close to humans in terms of skull thickness. Unlike our rodent studies, where behavior was monitored by means of EMG electrodes in the forelimbs, we will employ more sensitive fMRI to measure the response in the brain, speciﬁcally the visual cortex, while sonicating a deep structure, speciﬁcally the lateral geniculate nucleus (LGN). At the end of this project, we will have developed all of the technologies required to make FUS a safe and repeatable neuroscience research tool for studying normal volunteers. We will be able to focus the FUS array based on MRI, and accurately predict ultrasound intensities and temperatures at the target and throughout the brain. We will also have a much better understanding of the biophysical basis of FUS neuromodulation, which will allow us to optimize the FUS stimulation protocol.

项目摘要使用聚焦超声 (FUS) 的完全无创神经调节有望实现精确的神经调节 FUS 已用于刺激大脑深处的特定目标，以实现对大脑深处的精确消融。目前使用 CT 扫描来计算相位像差校正。正常情况下，CT 扫描和组织加热均无法接受 5°C 的温升。除此之外，具有相似 CT 扫描的头骨的超声波衰减也有很大差异。为了安全起见，必须准确预测和测量焦点和其他地方的功率，以及该技术的实验再现性。这项工作的目的是开发这些技术。迫切需要基于 MRI 的工具。我们的团队研究了大脑中 FUS 的各个方面，我们在绘制 FUS 图谱方面拥有丰富的经验。 FUS 神经调节的参数空间，使用温度和 MR 测量大脑中的 FUS 光束声辐射力成像，以及确定大型 FUS 阵列的波束聚焦权重通过头骨聚焦 FUS 我们的目标是将这种专业知识转化为 FUS 神经调节。广泛可用、可重复且准确的研究工具，对普通志愿者来说是安全的。有了这些校准和瞄准工具，我们就可以回答以下重要问题：物理性质是什么？我们在小鼠身上的研究表明了超声波产生的刺激大脑的效应。指数或粒子位移，而视网膜中的工作则指向辐射力，这是核心问题。在 FUS 神经调节中，我们需要知道要在大脑中产生什么物理效应。我们建议在猪模型中回答这个问题。与我们的啮齿动物研究不同，其行为在生理上非常接近人类。通过前肢的肌电图电极进行监测，我们将采用更灵敏的功能磁共振成像来测量大脑的反应，特别是视觉皮层，同时对深层结构进行声波处理，特别是外侧膝状核（LGN）。在该项目结束时，我们将开发出使 FUS 成为安全且可靠的设备所需的所有技术。用于研究正常志愿者的可重复的神经科学研究工具我们将能够集中 FUS。基于MRI的阵列，准确预测目标处的超声强度和温度我们还将更好地了解 FUS 的生物物理学基础。神经调节，这将使我们能够优化 FUS 刺激方案。