Minimally Invasive Ultrasonic Brain-Machine Interface

摘要 脑机接口(BMI)是推动Brain Initiative发展的关键应用之一 大规模记录神经活动的创新技术，不仅使BMI受益，而且使许多其他神经科学受益 学习。目前最先进的神经记录和BMI技术是侵入性的，会对生命造成局部损害 脑组织，限制了它们在人类神经科学研究和BMI中的应用。另一方面，非侵入性技术 通常提供相对较低的空间分辨率和灵敏度。微创的BMI将弥合 这些极端，为神经科学研究和神经假体开辟了一条新的途径。最近，功能超声(FUS) 成像被引入为大规模记录神经活动的一项突破性技术-提供高度的 活动相关血流变化的灵敏成像，时空分辨率为~100微米和100毫秒 几厘米深。重要的是，FUS可以从大脑和保护硬脑膜组织以外的地方记录，极大地扩大了它的 在神经科学应用和BMI方面的潜在用途。虽然FUS是一种血液动力学技术，但它的卓越 时空表现和单次试验的敏感性提供了与潜在神经元的更紧密的联系 与其他血流动力学方法(如功能磁共振成像)相比，可以获得更多的信号。 在这个项目中，我们将推动FUS作为一种大规模记录神经活动的技术的边界，通过开发 一种基于FUS的微创BMI。这项建议是基于合作调查人员获得的初步数据 显示非人灵长类动物(NHP)顶叶后皮质的超快FUS成像提供了足够的 从单次试验FUS记录中预测计划移动的信息。这些引人注目的发现表明，它可能 可以使用FUS作为微创BMI的基础，该BMI被植入颅骨并且不会穿透 硬脑膜或脑组织。 要将这种潜力变成现实，需要在FUS神经成像技术方面取得几项根本性的进步，这将 极大地增强了这种大规模神经成像技术在神经科学应用中的实用性。这些进展 包括(1)最大化从FUS提取的速度、数据处理和信息内容，以使高- 性能，实时急性BMI；(2)开发一种外科可植入的FUS技术，用于慢性、纵向 微创记录特定大脑区域的神经活动；以及(3)将FUS技术从2D扩展到 到3D，以促进需要对大脑体积进行实时成像的应用程序。这项提议是由两个关键因素促成的 合作伙伴的创新：坦特发明了FUS，安徒生的合作团队发现了FUS， Shapiro和Tanter认为FUS信号包含可用于BMI的信息。此外，几项新的创新是 通过拟议的工作，包括实时获取和处理FUS数据的技术，介绍了FUS的进展 用于慢性植入的硬件和手术技术，以及实现宽视野和稀疏实时3D的进展 成像。如果成功，该项目将显著提高FUS的能力，使其成为一项广泛适用的快速、 灵敏、大规模的神经成像，实现微创的BMI。

Abstract Brain-machine interfaces (BMIs) are one of the key motivating applications for the BRAIN Initiative’s drive to develop innovative technologies for large-scale recording of neural activity, benefiting not only BMI, but many other neuroscience studies. The most advanced techniques for neural recording and BMIs are currently invasive, causing local damage to living brain tissue, limiting their applications in human neuroscience research and BMI. On the other hand, noninvasive techniques typically offer relatively low spatial resolution and sensitivity. A minimally invasive BMI would bridge the gap between these extremes, opening a new avenue for neuroscience research and neuroprosthetics. Recently, functional ultrasound (fUS) imaging was introduced as a breakthrough technology for large-scale recording of neural activity – providing highly sensitive imaging of activity-dependent changes in blood flow with a spatiotemporal resolution of ~100 µm and 100 ms at several-cm depth. Importantly, fUS can record from outside the brain and protective dura mater tissue, vastly expanding its potential use in neuroscience applications and BMIs alike. While fUS is a hemodynamic technique, its excellent spatiotemporal performance and single-trial sensitivity offer a substantially closer connection to the underlying neuronal signals than achievable with other hemodynamic methods such as fMRI. In this project, we will push the boundaries of fUS as a technology for large-scale recording of neural activity by developing a fUS-based minimally invasive BMI. This proposal is based on preliminary data acquired by the collaborating investigators showing that ultrafast fUS imaging of the posterior parietal cortex in non-human primates (NHP) provides sufficient information to predict planned movements from single trial fUS recordings. These remarkable findings suggest that it may be possible to use fUS as the basis for a minimally invasive BMI that is implanted in the skull and does not penetrate the dura or brain tissue. Turning this potential into reality requires several fundamental advances in fUS neural imaging technology, which will greatly enhance the utility of this large-scale neural imaging technique across neuroscience applications. These advances include (1) maximizing the speed, data processing and information content extracted from fUS to enable a high- performance, real-time acute BMI; (2) developing a surgically implantable fUS technology for chronic, longitudinal minimally invasive recording of neural activity from a specific brain region; and (3) extending the fUS technology from 2D to 3D to facilitate applications requiring real-time imaging of large brain volumes. This proposal is enabled by two key innovations made by the co-PIs: the invention of fUS by Tanter, and the discovery by the collaborative team of Andersen, Shapiro and Tanter that fUS signals contain information that can be used for BMI. In addition, several new innovations are introduced through the proposed work including techniques to acquire and process fUS data in real time, advances in fUS hardware and surgical techniques for chronic implantation, and advances to enable wide-field and sparse real-time 3D imaging. If successful, this project will significantly advance the capabilities of fUS as a widely useful technology for rapid, sensitive, large-scale neural imaging and enable minimally invasive BMI.