Magnetic Resonance Imaging of Cortical Neuronal Activity

描述(申请人提供)：自诞生以来，使用血氧水平依赖(BOLD)对比的功能磁共振成像(FMRI)在基础和临床神经科学中的应用出现了爆炸性增长，并继续成为神经成像的主导方法。然而，BOLD成像也受到来自各种大小血管系统的血流动力学调节的分散的空间定位和时间延迟的影响，并且在某种程度上仍然是对神经元功能的定性评估。在大胆的对比中，不断努力提高空间局部化和时间分辨率。近年来，基于神经电活动的完全独立的对照已经被提出和发展，并在体外和体内的应用中显示出初步的前景。在这个方案中，我们将结合近年来血液动力学和神经电成像的进展，开发一种直接的MRI方法，重点是显著提高神经电信号的灵敏度。具体地说，提出了三个相辅相成的目标，共同强调实现更高的灵敏度，但也分别侧重于创新的成像硬件、成像软件和驱动神经元振荡，以实现离子神经电活动的直接MRI。首先，我们将开发一种新的多模并行接收线圈，以实现高灵敏度、高分辨率、扩散对比成像，以改善与皮质神经元活动的空间对应；其次，我们将开发螺旋回声体积成像(EVI)技术，以进一步提高成像灵敏度；第三，我们将利用同步梯度振荡和高频驱动视觉刺激，开发离子神经电活动的直接MRI方法，并结合先前目标的进展，通过在神经元激活区域内进行时间锁定的时间平均，进一步获得亟需的信噪比。我们预计，我们的集成方法将允许尽可能高的灵敏度来测量离子神经电信号，表征它们的空间和时间相关性，并显著朝着直接和灵敏的fMRI方法发展，以成像活体中的皮质神经电活动。 公共卫生相关性：该项目基于一种综合方法，使用血流动力学和神经电学对比成像皮质神经元活动。我们提出了三个具体目标来实现这一中心目标，所有目标都集中在极大地提高灵敏度，但也分别侧重于新的成像硬件、软件和创新的神经元激活范例。这三个目标的进展将使具有直接空间和时间特异性的离子神经电流的时间锁定检测成为可能。我们预计，我们的集成方法将使我们能够为建立敏感、非侵入性的、更重要的直接神经成像方法奠定坚实的技术基础。

DESCRIPTION (provided by applicant): Since its inception, functional MRI (fMRI) using blood oxygenation level dependent (BOLD) contrast has seen an explosive growth in its applications in basic and clinical neurosciences, and continues to be the dominant method in neuroimaging. However, BOLD imaging also suffers from dispersed spatial localizations and temporal delays due to hemodynamic modulations from vasculature of all sizes, and remains a somewhat qualitative assessment of neuronal functions. Continued effort has been made to improve the spatial localization and the temporal resolution within the BOLD contrast. In more recent years, completely independent contrasts based on neuroelectric activities have been proposed and developed, and have shown initial promises in applications in vitro and in vivo. In this proposal, we will integrate the advances of hemodynamic and neuroelectric imaging in the recent years, and develop a direct MRI approach with a central focus on drastically improving the sensitivity of the neuroelectric signal. Specifically, three complementing aims, with a common emphasis on achieving a much greater sensitivity, but also with individual focuses on innovative imaging hardware, imaging software and driven neuronal oscillations, are proposed to achieve a direct MRI of ionic neuroelectric activity. First, we will develop a new multi-mode parallel receive coil to achieve high-sensitivity, high-resolution, diffusion contrast imaging for improved spatial correspondence with cortical neuronal activities; Second, we will develop a spiral echo volume imaging (EVI) technique to further improve the imaging sensitivity; Third, we will develop direct MRI methodology of ionic neuroelectric activities using synchronized gradient oscillation and high-frequency driven visual stimulation, and in conjunction with advances in the previous aims, to further gain the much needed signal- to-noise ratio (SNR) by time-locked temporal averaging within the neuronally activated regions. We anticipate that our integrated approach will allow the highest sensitivity possible to measure ionic neuroelectric signals, characterize their spatial and temporal dependences, and move significantly toward a direct and sensitive fMRI methodology for imaging cortical neuroelectric activities in vivo. PUBLIC HEALTH RELEVANCE: This project is based on an integrated approach to image cortical neuronal activities using hemodynamic and neuroelectric contrasts. We propose three specific aims to achieve this central objective, all with a central focus for a greatly improved sensitivity, but also with respective focuses on new imaging hardware, software and innovative neuronal activation paradigms. The advances from these three aims will enable time-locked detection of ionic neuroelectric currents with direct spatial and temporal specificity. We anticipate that our integrated approach will allow us to establish a solid technical foundation toward a sensitive, non-invasive, and more importantly, direct neuroimaging methodology.