Diffusion Imaging in Gray Matter

描述（由申请人提供）：扩散张量成像（DTI）由于其对神经组织中扩散各向异性（DA）的微观变化的敏感性，在基础神经科学研究和临床应用中引起了极大的兴趣，作为一种方法，它提供了对神经组织结构状态的非侵入性评估的潜力。然而，标准的DTI方法，包括其利用单对脉冲场梯度（sPFG）的高角分辨率（HARDI）扩展，是基于在成像分辨率尺度上表现出宏观DA的体素组成的存在。这种情况通常发生在含有白质纤维束的体素中，因此WM中的DTI已成为DTI研究和应用的主要焦点。然而，在灰质（GM）中并非如此，灰质在微观上是异质的，但在体素的空间尺度上缺乏结构相干性，无法表现出宏观的DA。这严重限制了我们利用MRI对扩散的敏感性来研究GM微结构的能力，这是一个具有重要临床意义的组织。最近，一套新的基于双脉冲场梯度（dPFG）对的磁共振方法已经从理论上进行了研究，并在简单的实验中得到了验证，以显示对宏观均匀体素的微观DA的敏感性。这些研究主要应用于具有微观孔隙的材料，反映了这些方法发展的重点是多孔材料。然而，虽然我们假设这些方法在转基因研究中具有很大的潜力，但这种组织的巨大复杂性使得dPFG方法在转基因中的研究几乎不可能进行分析。因此，本提案的目标是利用我们最近开发的扩散模拟平台（DiffSim），结合我们最近开发的dPFG理论框架，研究dPFG方法检测和量化灰质结构参数和变化的能力，并开发用于临床应用这些方法的实验技术。

DESCRIPTION (provided by applicant): Diffusion tensor imaging (DTI), with its sensitivity to microscopic variations in diffusion anisotropy (DA) in neural tissues, has generated great interest in both basic neuroscience research and clinical applications as a method that offers the potential for the non-invasive assessment of the status of neural tissue architecture. However, the standard DTI methodology, including its high angular resolution (HARDI) extensions, which utilizes a single pair of pulsed field gradients (sPFG), are predicated on the existence of voxel compositions that exhibit a macroscopic DA on the scale of the imaging resolution. This is often the case with voxels containing bundles of white matter (WM) fibers and thus DTI in WM has become a major focus of DTI research and applications. However, this is not the case in gray matter (GM) which is microscopically heterogeneous but lacks the structural coherence on the spatial scale of voxels to exhibit macroscopic DA. This has severely limited our ability to utilize the sensitivity of MRI to diffusion in the investigation of GM microstructure, which is a tissue of significant clinical interest. Recently, a novel set of MR methods based upon the double pulsed field gradient (dPFG) pairs have been investigated theoretically and verified in simple experiments to exhibit sensitivity to microscopic DA in voxels that are macroscopically homogeneous. These studies have primarily been applied to materials with microscopic pores, reflecting the focus on porous materials from which these methods developed. However, while we hypothesize that these methods have great potential for the study of GM, the great complexity of this tissue makes investigation of dPFG methods in GM nearly impossible to do analytically. Thus the goal of this proposal is to utilize our recently developed diffusion simulation platform (DiffSim), in conjunction with our recently developed theoretical framework for dPFG, to investigate the ability of dPFG methods to detect and quantitate gray matter architectural parameters and changes, and develop experimental techniques for applying these methods clinically. PUBLIC HEALTH RELEVANCE: While diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that offers the potential for the non-invasive assessment of neural tissue structure, its usage is predicated on the existence of neuronal fibers with macroscopic organization on the scale of imaging resolution; thus its application has been almost exclusively to white matter (WM) structure and disease, to the exclusion of gray matter (GM), which is macroscopically incoherent, despite being microscopically coherent. Recently, however, a new class of diffusion sensitive MRI methods, called double pulsed field gradient (dPFG) MRI, has demonstrated a unique sensitivity to microscopically coherent tissues and thus may have an enormous impact on a wide range of clinical and basic research applications related to GM. Our goal is to use our sophisticated diffusion MRI simulation platform DiffSim to augment our theoretical studies of dPFG in GM to develop practical implementations in humans and thus provide the basis for clinical techniques that provide consistent and meaningful measurements of GM architecture and physiology.