MR-guided Focused Ultrasound Neuromodulation of Deep Brain Structures

项目摘要 使用聚焦超声(FUS)的完全非侵入性神经调节提供了精确 刺激特定的fic靶点在大脑深处。FUS已经被用来在深部提供精确的消融 大脑。目前使用CT扫描来计算相位像差校正。对焦斑进行了标定 通过成像5摄氏度的温度升高。CT扫描和组织加热在正常情况下都是不可接受的 志愿者。除此之外，具有相似CT扫描的头骨在超声衰减方面存在很大差异。它是 为了安全，必须准确预测和测量焦点和其他地方的威力， 以及该技术在实验上的重复性。这项工作的目的是开发这些 基于核磁共振的迫切需要的工具。 我们小组研究了大脑中FUS的各个方面。我们有丰富的地图绘制经验。 利用温度和磁共振测量脑内FUS波束时FUS神经调节的参数空间 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。我们的目标是将这一专业知识转化为FUS神经调节 广泛可用的、可重复的、准确的研究工具，对正常志愿者来说是安全的。 有了这些校准和目标工具，我们可以回答什么是物理上的重要问题 超声波正在产生刺激大脑的效果。我们在老鼠身上所做的工作指向空化 指数或粒子位移，而视网膜中的功则指向辐射力。这是中心问题 在FUS神经调节中。我们需要知道在大脑中产生什么样的物理效应才能产生 人类的神经调节。我们建议在猪模型中回答这个问题，即 就头骨厚度而言，它在生理上与人类非常接近。不像我们的啮齿动物研究，在那里行为 通过前肢的肌电电极进行监测，我们将采用更灵敏的功能磁共振成像来 测量大脑的反应，特别是视觉皮质的反应，同时对深层结构进行超声波检测，fi fi主要分布于外侧膝状核。 在这个项目结束时，我们将开发所有必要的技术，使FUS成为一个安全和 可重复使用的神经科学研究工具，用于研究正常志愿者。我们将能够将FUS的注意力集中在 基于MRI的阵列，并准确预测目标处的超声强度和温度 贯穿整个大脑。我们还将对FUS的生物物理基础有更好的了解 神经调节，这将使我们能够优化FUS刺激方案。

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.