High resolution electrical brain mapping by real-time and portable 4D Acoustoelectric Imaging

 描述（由申请人提供）：我们的愿景是开发第一个基于破坏性声电（AE）技术的非侵入性、实时和便携式脑电标测系统。我们的目标是克服功能性脑成像和脑电图（EEG）的局限性，因为当电信号通过大脑和头骨时，它们的分辨率很差，而且不准确。声电脑成像（ABI）采用脉冲超声（US）瞬时调制局部组织电阻率。当US与神经电流相互作用时，在US频率下产生电压调制（“AE信号”），并由远端电极检测。该AE信号与局部电流密度成比例，并且在空间上局限于US焦点。通过在大脑中快速扫描聚焦的US束并检测调制信号，4D ABI可以实现通过成人颅骨的电流密度的准确，实时，体积图像，分辨率接近1 mm 3。在经颅ABI可以安全有效地用作功能性人脑成像的工具之前，必须克服几个主要障碍。最大的挑战是通过颅骨检测微弱的AE相互作用信号，同时保持头部和大脑的安全US暴露。因此，我们提出了几种策略，以显着提高检测的AE信号的因子为10或更多，而不影响患者的安全。通过精心的团队规划过程，我们将设计和开发第一个ABI平台，用于在逼真的头部模型中进行评估和优化，然后在活体大鼠和猪脑中进行性能测试。为了解决这些和其他挑战，我们建议：1）开发第一种能够经颅ABI的US传输系统; 2）设计方法以显著改善通过骨骼的AE信号的检测并定义安全超声传输的参数; 3）应用ABI来映射大鼠大脑中的脑电和脑电振荡，并使用标准电生理学进行验证;（4）与金标准EEG相比，在猪脑中应用并优化ABI（静息态振荡、诱发电位和诱发癫痫发作）。这些目标将技术、创新、建模和翻译交织在一起，以克服开发人类经颅ABI的主要障碍。他们将被嵌入到一个互动的规划过程中，汇集了广泛的想法，具有挑战性的问题，以及医学成像，超声技术，神经工程，神经外科，神经电生理学，数学，心理学和急诊医学的多学科专业知识。规划过程不仅将实施面对面的会议和现场访问，还将使用社交媒体（ABI.curiosityforall.org）和电话会议工具，以最大限度地提高互动，促进战略规划，解决安全问题，并克服头骨带来的大脑大挑战。该项目还与多个机构和行业的思想领袖建立了新的合作关系，以考虑在不同环境中实施护理点ABI的计划。一个为人类设计的安全、便携和实时的平台可以改变我们对正常大脑功能的理解，并改善对各种神经、精神和行为障碍的管理（诊断、分期、监测、治疗）。癫痫、抑郁症、强迫症）。

 DESCRIPTION (provided by applicant): Our vision is to develop the first noninvasive, real-time and portable electrical brain mapping system based on disruptive acoustoelectric (AE) technology. Our goal is to overcome limitations with functional brain imaging and electroencephalography (EEG), which suffers from poor resolution and inaccuracies due to the blurring of electrical signals as they pass through the brain and skull. Acoustoelectric Brain Imaging (ABI) implements pulsed ultrasound (US) to transiently modulate local tissue resistivity. As the US interacts with neural currents, a voltage modulation ("AE signal") is generated at the US frequency and detected by a distant electrode. This AE signal is proportional to the local current density and spatially confined to the US focus. By rapidly scanning a focused US beam in the brain and detecting the modulation signals, 4D ABI could achieve accurate, real-time, volumetric images of current densities through the adult human skull with a resolution near 1 mm3. Before transcranial ABI can be safely and effectively employed as a tool for functional human brain imaging, several major obstacles must be overcome. The greatest challenge is detecting the weak AE interaction signal through the skull, while maintaining safe US exposure to the head and brain. We, therefore, propose several strategies to dramatically enhance detection of the AE signal by a factor of 10 or more without compromising patient safety. Through a careful team-oriented planning process, we will design and develop the first ABI platform for evaluation and optimization in a realistic head phantom and, later, performance testing in living rat and pig brains. To address these and other challenges, we propose to 1) Develop the first-of-its-kind US delivery system capable of transcranial ABI; 2) Devise methods to dramatically improve detection of the AE signal through bone and define parameters for safe ultrasound delivery; 3) Apply ABI to map  and  oscillations in rat brain with validation usin standard electrophysiology; and 4) Apply and optimize ABI in pig brain (resting-state oscillations, evoked potentials, and induced seizures) compared with gold standard EEG. These aims interweave technology, innovation, modeling, and translation to overcome major obstacles in developing transcranial ABI for humans. They will be embedded in an interactive planning process that brings together wide-ranging ideas, challenging questions, and multidisciplinary expertise in medical imaging, ultrasound technology, neuroengineering, neurosurgery, neuroelectrophysiology, mathematics, psychology, and emergency medicine. The planning process will not only implement face-to-face meetings and site visits, but also social media (ABI.curiosityforall.org) and teleconferencing tools to maximize interaction, facilitate strategic planning, address safety issues, and overcome the Grand Brain Challenge posed by the skull. The project also establishes new collaborations with thought leaders at multiple institutions and industry to consider plans for point-of-care ABI in diverse settings. A safe, portable, and real-time platform designed for humans could transform our understanding of normal brain function and improve management (diagnose, stage, monitor, treat) of a wide variety of neurologic, psychiatric and behavioral disorders (e.g., epilepsy, depression, OCD).