Functional Brain Imaging with Oscillating Gradient DW-MRI

描述（由申请人提供）：本R21申请旨在开发和评估一种新型磁共振成像（MRI）技术，该技术具有相当大的潜力，可以检测和绘制大脑中的神经活动，其时间分辨率远高于BOLD（血氧水平依赖）成像或依赖于检测血流动力学变化的类似方法。提出的技术建立在已有研究人员提出的具有挑衅性的主张之上，即对组织水的扩散特性敏感的MRI方法（弥散加权MRI， DW-MRI）可以检测伴随神经放电的水转移和轴突肿胀，这些现象并不意外，光学成像也报道过，并且在空间和时间上与神经电活动密切相关。然而，这些变化的起源和稳健性仍然存在争议和未经证实，显然不容易用传统的DW-MRI检测到。我们开创了一种新的扩散成像方法，可以选择性地对特定维度的神经结构敏感，并且对神经细胞和水室的尺寸变化更加敏感。因此，我们建议探索将其作为一种检测和绘制大脑活动的方法。基于脉冲梯度自旋回波（PGSE）方法的传统DW-MRI方法反映了多种结构特征的综合效应，包括相对较大的空间尺度，大于神经细胞直径的结构特征，包括神经细胞膜。我们已经开发了一种替代技术，振荡梯度自旋回波（OGSE），它能够在更小的空间尺度上检测扩散的限制，从而对细胞尺寸变化的影响具有高灵敏度。在这里，我们提出建立OGSE成像是否可以可靠地检测神经活动引起的即时扩散变化。我们将应用优化的OGSE，传统的BOLD和PGSE方法，在给药前和给药后对大鼠大脑进行成像，已知药物（PCP）会引起强大的，缓慢变化的大脑激活变化，有/没有阻断作用的药物（BINA）预处理。这些缓慢变化的激活将允许对组织内微观结构变化的定量估计的推导。我们还将记录在事件相关设计中前爪刺激、正常呼吸或呼吸碳时的高时间分辨率BOLD、OGSE和PGSE图像。通过比较这些不同图像序列的时间过程，我们将能够验证与激活相关的扩散变化是否可检测到，它们是否比血管变化发生得更快，以及高频OGSE数据是否显示组织微观结构（神经元肿胀）的变化比其他方法发生得更快，更接近潜在的电事件。这些研究的潜在结果将是一种具有高时间和空间分辨率的神经激活映射方法，可用于各种人类和动物大脑功能组织的研究。

DESCRIPTION (provided by applicant): This R21 application aims to develop and evaluate a novel magnetic resonance imaging (MRI) technique that has considerable potential for detection and mapping of neural activity in the brain with temporal resolution much greater than BOLD (blood oxygen level dependent) imaging or similar approaches that rely on detecting hemodynamic changes. The proposed technique builds on provocative claims by established investigators that MRI methods that are sensitive to the diffusion properties of tissue water (diffusion-weighted MRI, DW-MRI) can detect water shifts and axonal swelling that accompany neural firing, phenomena that are not unexpected and have also been reported by optical imaging, and which occur immediately proximal in space and time to neural electrical activity. However, the origins and robustness of these changes remain controversial and unsubstantiated, and clearly are not easy to detect using conventional DW-MRI. We have pioneered a novel diffusion imaging method that can be selectively sensitized to neural structures of a specific dimension, and which should be much more sensitive to changes in the dimensions of neural cells and water compartments. We therefore propose to explore its use as a method of detecting and mapping brain activity. Conventional DW-MRI methods based on the Pulsed Gradient Spin Echo (PGSE) method reflect the integrated effects of a variety of structural features, including those of relatively large spatial scale, greater than a nerve cell diameter, including nerve cell membranes. We have developed an alternative technique, oscillating gradient spin-echo (OGSE), which is capable of detecting restrictions to diffusion over much smaller spatial scales, which results in a high sensitivity specifically to the effects of changes in cell dimensions. Here we propose to establish whether OGSE imaging can reliably detect immediate diffusion changes induced by neural activity. We will apply optimized OGSE, conventional BOLD and PGSE methods, to image rat brain in vivo before and after administration of a pharmacological agent (PCP) known to elicit robust, slowly varying changes in brain activation, with/or without pre-treatment with an agent that blocks the effect (BINA). These slow-varying activations will allow derivation of quantitative estimates of microstructural changes within the tissue. We will also record BOLD, OGSE and PGSE images at high temporal resolution during forepaw stimulation administered in an event-related design, during normal breathing or while breathing carbogen. By comparing the time courses of these various image series we will be able to verify whether diffusion changes related to activation are detectable, whether they occur faster than vascular changes, and whether the OGSE data at high frequency reveal changes in tissue microstructure (neuronal swelling) that occurs faster and more proximal to the underlying electrical events than other methods. The potential outcome of these studies would be a method for mapping neural activation with high temporal and spatial resolution that could be used in diverse human and animal studies of the functional organization of the brain.