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

 描述(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、实时和便携式脑电地形图系统。我们的目标是克服功能性脑成像和脑电(EEG)的局限性，EEG由于电信号通过大脑和头骨时模糊而导致分辨率低和不准确。声电脑成像(ABI)采用脉冲超声(US)来瞬时调制局部组织的电阻率。当美国与神经电流相互作用时，电压调制(“声发射信号”)在美国频率上产生，并被远处的电极探测到。这种声发射信号与局部电流密度成正比，并且在空间上局限于US焦点。通过快速扫描大脑中聚焦的超声光束并检测调制信号，4D ABI可以获得分辨率接近1mm3的准确、实时的成人头骨电流密度的体积图像。在经颅ABI被安全有效地用作人脑功能成像工具之前，必须克服几个主要障碍。最大的挑战是通过头骨检测微弱的声发射相互作用信号，同时保持美国人对头部和大脑的安全暴露。因此，我们提出了几种策略，在不损害患者安全的情况下，将AE信号的检测能力显著提高10倍或更多。通过仔细的面向团队的规划过程，我们将设计和开发第一个ABI平台，用于在现实的头部模型中进行评估和优化，然后在活的老鼠和猪的大脑中进行性能测试。为了应对这些和其他挑战，我们建议1)开发首个能够经颅ABI的美国递送系统；2)设计方法，大幅改进通过骨骼的AE信号的检测，并定义安全超声递送的参数；3)应用ABI绘制大鼠大脑中和振荡的图谱，并使用标准电生理学进行验证；以及4)应用并优化猪脑的ABI(静息状态振荡、诱发电位和诱发癫痫)，并与金标准脑电进行比较。这些目标交织着技术、创新、建模和翻译，以克服为人类开发经颅ABI的主要障碍。他们将被嵌入到一个互动的规划过程中，该过程汇集了医学成像、超声波技术、神经工程、神经外科、神经电生理学、数学、心理学和急救医学方面的广泛想法、具有挑战性的问题和多学科的专业知识。规划过程不仅将实施面对面的会议和现场访问，还将实施社交媒体(ABI.curiosityforall.org)和电话会议工具，以最大限度地互动，促进战略规划，解决安全问题，并克服头骨带来的巨大大脑挑战。该项目还与多个机构和行业的思想领袖建立了新的合作，以考虑在不同环境中的护理点ABI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，并改进对各种神经、精神和行为障碍(如癫痫、抑郁症、强迫症)的管理(诊断、分期、监测和治疗)。

 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).