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的 刺激大脑深处的特定目标。FUS已经用于在 个脑袋CT扫描目前用于计算相位畸变校正。焦斑被校准 通过成像5°C的温度上升。正常情况下，CT扫描和组织加热均不可接受 志愿者除此之外，具有相似CT扫描的头骨在超声衰减方面差异很大。是 必须准确地预测和测量焦点和其他地方的功率，这既是为了安全， 以及该技术的实验再现性。这项工作的目的是发展这些 基于核磁共振成像的急需工具。 我们小组研究了大脑中FUS的各个方面。我们在绘制 用于FUS神经调节的参数空间，在使用温度和MR测量大脑中的FUS束中 声辐射力成像，并在确定大型FUS阵列的波束聚焦权重， 通过颅骨聚焦超声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，可重复和准确的研究工具，对正常志愿者来说是安全的。 有了这些校准和定位工具，我们可以回答什么是物理 超声波刺激大脑的效果。我们在老鼠身上的研究表明 折射率或粒子位移，而在视网膜上工作的指向辐射力。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 人类的神经调节我们建议在猪模型中回答这个问题， 在头骨厚度上与人类非常接近。不像我们的啮齿动物研究， 通过前肢的EMG电极进行监测，我们将采用更灵敏的功能磁共振成像， 测量大脑的反应，特别是视觉皮层，同时对深层结构进行超声处理， 外侧膝状体核（LGN） 在这个项目结束时，我们将开发出使FUS成为一个安全和 研究正常志愿者的可重复神经科学研究工具。我们将能够集中FUS 基于MRI的阵列，并准确预测目标处的超声强度和温度， 在整个大脑中。我们还将更好地了解FUS的生物物理基础 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.