Functional Brain Imaging with Oscillating Gradient DW-MRI

描述(申请人提供)：这份R21申请旨在开发和评估一种新的磁共振成像(MRI)技术，该技术具有相当大的潜力来检测和映射大脑中的神经活动，其时间分辨率远远高于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。这项拟议的技术建立在成熟研究人员的挑衅性声明基础上，即对组织水的扩散特性敏感的MRI方法(扩散加权MRI，DW-MRI)可以检测到伴随神经放电的水移动和轴突肿胀，这些现象并不出人意料，光学成像也报告了这些现象，并且在空间和时间上立即发生在神经电活动的近端。然而，这些改变的起源和稳健性仍然存在争议和未经证实，显然使用传统的DW-MRI很难检测到。我们开创了一种新的扩散成像方法，它可以选择性地敏化特定维度的神经结构，并且应该对神经细胞和水隔间的尺寸变化更加敏感。因此，我们建议探索将其用作检测和绘制大脑活动图的一种方法。基于脉冲梯度自旋回波(PGSE)方法的常规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，这导致了对细胞尺寸变化的高敏感性。在这里，我们建议确定OGSE成像是否可以可靠地检测到由神经活动引起的即刻扩散变化。我们将应用优化的OGSE、传统的BOLD和PGSE方法，在给药(PCP)之前和之后对大鼠的体内大脑进行成像，已知PCP可以在大脑激活中引起强劲的、缓慢变化的变化，无论是否使用阻断这种作用的试剂(BINA)进行预处理。这些缓慢变化的激活将允许对组织内微结构变化的定量估计。我们还将在事件相关设计的前爪刺激期间、在正常呼吸期间或在呼吸Carbogen时以高时间分辨率记录BOLD、OGSE和PGSE图像。通过比较这些不同图像序列的时间进程，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数据是否揭示了组织微结构(神经元肿胀)的变化，这些变化发生得更快，比其他方法更接近潜在的电事件。这些研究的潜在结果将是一种以高时间和空间分辨率绘制神经激活图的方法，可以用于不同的人类和动物对大脑功能组织的研究。 公共卫生相关性：在神经科学研究和临床神经学和精神病学实践中，成像方法都有广泛的应用，这些方法可以检测和绘制大脑活动图，以描绘和了解大脑的功能组织。功能磁共振成像是目前可用于获得高空间分辨率的大脑激活信息的最强大的单一方法，但不幸的是，它依赖于具有非常慢的时间特征的血流变化，因此以潜在的电活动的速度获得的关于神经事件的时间的信息非常少。建议开发的MRI方法原则上可以克服这一缺点，并允许以高空间和时间分辨率记录大脑活动。这项工作还将证实或驳斥其他人关于MRI以高时间分辨率评估神经活动的能力的说法。

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. PUBLIC HEALTH RELEVANCE: There are widespread applications, in both neuroscience research and clinical neurological and psychiatric practice, for imaging methods that can detect and map brain activity to delineate and understand the functional organization of the brain. Functional MRI is currently the single most powerful method available for obtaining information on brain activation with high spatial resolution, but unfortunately it relies on blood flow changes that have very slow temporal characteristics, so that very little information is obtainable about the timing of neural events at the speed of the underlying electrical activity. The MRI method proposed for development may in principle overcome this shortcoming and allows recordings of brain activity with both high spatial and temporal resolution. The work would also substantiate or refute claims by others about the ability of MRI to assess neural activity with high temporal resolution.