4D Transcranial Acoustoelectric Imaging for High Resolution Functional Mapping of Neuronal Currents

摘要 该项目的总体目标是优化、验证和实施一种革命性的安全模式 通过颅骨对人脑深处的神经电流进行非侵入性功能成像， 前所未有的时空分辨率。经颅声电脑成像（tABI）是一种 利用超声波（US）脉冲与生理电流瞬时相互作用的破坏性技术， 产生由一个或多个传感器检测到的射频（RF）特征（例如，表面电极）。通过 快速扫描US波束并同时检测这些RF调制，4D高分辨率电流 生成密度图。这种方法克服了脑电图（EEG）的局限性， 由于电信号通过时的模糊， 与功能磁共振成像（fMRI）和正电子发射断层成像（PET）测量缓慢的“内在”信号不同，tABI直接快速映射 在mm和ms尺度下的限定脑体积内的时变电流。作为一种颠覆性的、可扩展的 作为一种非侵入性的人脑成像方式，tABI具有以下优点：1）高空间分辨率 由美国焦点确定（例如，0.3 2）局部场电位的实时体积成像，以及 诱发活动; 3）来自深部脑结构的神经电流的4D成像，而不假设 电导率分布;以及4）神经电流（tABI）与脑结构、运动（脉搏）的共配准 超声（echo US）和脑血流（Doppler）。我们的工程师，物理学家， 神经科学家、心理学家和成像学家将克服检测弱相互作用的主要挑战 以安全的超声强度通过颅骨发出信号。为了证明tABI是一种安全可靠的电治疗方式， 在健康志愿者的mm和ms尺度的脑成像中，我们建议1）优化，校准， 使用已建立的人头部和体内猪模型验证tABI; 2）开发并验证第一个tABI 用于人类受试者中的功能性脑成像的平台; 2a）评估用于标测患者的手术外tABI 难治性癫痫转诊手术;和2b）评估tABI，用于标测 健康志愿者如果成功，该项目将提供一种安全，革命性和移动的技术， 非侵入性人脑成像，旨在改变我们对大脑功能的理解， 诊断、分期、监测和治疗各种神经系统疾病（例如，癫痫，帕金森氏症），精神病（例如， 抑郁症）和行为（例如，强迫症）障碍。

ABSTRACT The overarching goal of this project is to optimize, validate and implement a revolutionary and safe modality for noninvasive functional imaging of neural currents deep in the human brain through the skull at unprecedented spatial and temporal resolution. Transcranial Acoustoelectric Brain Imaging (tABI) is a disruptive technology that exploits pulses of ultrasound (US) to transiently interact with physiologic current, producing a radiofrequency (RF) signature detected by one or more sensors (e.g., surface electrodes). By rapidly sweeping the US beam and simultaneously detecting these RF modulations, 4D high resolution current density maps are generated. This approach overcomes limitations with electroencephalography (EEG), which suffers from poor spatial resolution and inaccuracies due to blurring of electrical signals as they pass through the brain and skull, and, unlike fMRI and PET that measure slow “intrinsic” signals, tABI directly maps fast time-varying current within a defined brain volume at the mm and ms scales. As a disruptive and scalable modality for noninvasive human brain imaging, tABI offers the following benefits: 1) High spatial resolution determined by the US focus (e.g., 0.3 – 3 mm); 2) Real-time, volumetric imaging of local field potentials and evoked activity; 3) 4D imaging of neural currents from deep brain structures without assuming the conductivity distribution; and 4) Co-registration of neural currents (tABI) with brain structure, motion (pulse echo US) and cerebral blood flow (Doppler). Our multidisciplinary team of engineers, physicists, neuroscientists, psychologists, and imagers will overcome the primary challenge of detecting weak interaction signals through skull at safe US intensities. To demonstrate tABI as a safe and reliable modality for electrical brain imaging at the mm and ms scales in healthy volunteers, we propose to 1) Optimize, calibrate, and validate tABI using established human head and in vivo swine models; 2) Develop and validate the first tABI platform for functional brain imaging in human subjects; 2a) Assess extraoperative tABI for mapping patients with intractable epilepsy referred for surgery; and 2b) Assess tABI for mapping somatotopic organization in healthy volunteers. If successful, this project will deliver a safe, revolutionary and mobile technology for noninvasive human brain imaging with the goal of transforming our understanding of brain function and help diagnose, stage, monitor and treat a wide variety of neurologic (e.g., epilepsy, Parkinson’s), psychiatric (e.g., depression) and behavioral (e.g., OCD) disorders.