High Angular Resolution Diffusion Imaging with MRI

描述（由申请人提供）： 通过扩散加权MRI（DW-MRI）测量的脑中的扩散各向异性（DA）已知与局部白色物质（WM）结构相关，因此可用作与退行性WM疾病相关的变化的指标。DA的估计也是所有纤维束映射方法的必要前提，当与功能性MRI（fMRI）研究结合使用时，这些方法具有了解大脑连接的潜力。目前用于测量DA的标准方法是扩散张量成像（DTI），其中磁场沿沿着多个方向的变化编码微观水运动的复杂模式。作为扩散编码方向的函数的信号变化与局部组织扩散（LTD）相关，根据该局部组织扩散（LTD），基于仅需要几个编码方向的组织扩散的简化模型来估计DA。然而，最近的研究表明，LTD的复杂性不一定是很好地符合标准模型和高角分辨率扩散（HARD）的测量需要更好地表征LTD。这带来了两个重要的问题：增加成像时间，使临床应用更加困难，并没有一般的分析方案来表征各向异性。最终，LTD和DA的评估需要开发更准确的组织扩散物理模型，其中包含边界和限制以及越来越敏感的测量方法。这项工作的主要目标是进一步研究我们最近提出的解决这两个问题的方法。我们已经推广了目前用于DTI的分析，以纳入更一般的物理模型，用于扩散。这种方法，称为球谐分解（SHD），已被用于快速数值实现有效的临床应用。第一个具体目标是将我们的SHD方法扩展到我们开发的更普遍适用于多个b值的方法，称为球面波分解（SWD）。其次，我们已经描述了一种新的DW-MRI方法的基础上，最近推出的概念hyperechoes（HE），有可能显着增加标准的临床应用的每单位时间的扩散灵敏度，从而促进扩展到硬测量与最小的时间惩罚，但大大增加DA灵敏度。虽然超回声DW-MRI与传统DW-MRI采集方法相比具有明显的理论优势，但在其实施过程中容易遇到独特的技术困难，这将作为我们的第二个具体目标加以解决，使其成为临床可行的方法。这两个目标都将用于开发我们的第三个特定目标，即通过使用HE-HARD的变体结合SWD，通过实验确定DW MRI对复杂组织结构的灵敏度。我们最近的工作表明，在酒精中毒患者的WM DA的变化的动机，我们的建议集中在增加DW-MRI DA的敏感性，我们的最终长期目标是利用这些方法在临床环境中，特别是在我们正在进行的评估退化白色物质疾病，如阿尔茨海默氏症，艾滋病，特别是酒精中毒。

DESCRIPTION (provided by applicant): The diffusion anisotropy (DA) in the brain measured by diffusion weighted MRI (DW-MRI) is known to be related to the local white matter (WM) structure and therefore can be used as an indicator for changes associated with degenerative WM diseases. The estimation of DA is also a necessary precursor to all fiber tract mapping methods, which hold the potential for understanding brain connectivity when used in conjunction with functional MRI (fMRI) studies. The current standard method for measuring DA is diffusion tensor imaging (DTI) in which magnetic field variations along multiple directions encode complex patterns of microscopic water motion. Signal variations as a function of the diffusion encoding direction are related to the local tissue diffusion (LTD) from which DA is estimated based upon a simplified model for tissue diffusion that require only a few encoding directions. However, recent studies have shown that the complexity of LTD is not necessarily well fit by the standard model and high angular resolution diffusion (HARD) measurements are needed to better characterize LTD. This poses two significant problems: An increase in imaging time, making clinical applications more difficult, and no general analysis scheme by which to characterize anisotropy. Ultimately, the assessment of LTD and DA requires the development of more accurate physical models for tissue diffusion that incorporate boundaries and restrictions and increasingly sensitive methods of measurement. The primary goal of this work is to further investigate our recently proposed solutions to these two problems. We have generalized the analysis currently used for DTI to incorporate more a general physical model, for diffusion. This method, called the spherical harmonic decomposition (SHD), has been employed in a rapid numerical implementation efficient for clinical applications. The first specific aim is to extend our SHD approach to an even more general applicable to multiple b-values that we have developed, called the spherical wave decomposition (SWD). Secondly, we have described a novel DW-MRI method based on the recently introduced concept of hyperechoes (HE) that has the potential to dramatically increased the diffusion sensitivity per unit time of standard clinical applications, thereby facilitating the extension to HARD measurements with minimal time penalty but greatly increased DA sensitivity. While hyperecho DW-MRI has a clear theoretical advantage over traditional DW-MRI acquisition methods, it is prone to unique technical difficulties in its implementation that will be addressed as our second specific aim to make it a clinically viable methodology. Both these two aims will be used in the development of our third specific aim, which is to establish experimentally, through the use of variations of HE-HARD, in conjunction with SWD, the sensitivity of DW MRI to the structure of complex tissues. Motivated by our recent work showing changes in WM DA in alcoholic patients, our proposal focuses on increasing the sensitivity of DW-MRI to DA, our ultimate long term goal is to utilize these methods in a clinical environment, specifically in our ongoing assessment of degenerate white matter diseases such as Alzheimer's, AIDS, and, in particular, alcoholism.