High Angular Resolution Diffusion Imaging with MRI

描述(由申请人提供)： 磁共振弥散加权成像(DW-MRI)测量的脑内弥散各向异性(DA)与局部脑白质(WM)结构有关，因此可以作为与退行性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先兆，当与功能磁共振(FMRI)研究结合使用时，这些方法具有了解大脑连通性的潜力。目前测量DA的标准方法是扩散张量成像(DTI)，其中沿多个方向的磁场变化编码了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)有关，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的复杂性不一定与标准模型很好地拟合，需要高角度分辨率的扩散(HARD)测量来更好地描述LTD。这带来了两个重要的问题：成像时间的增加，使得临床应用更加困难，以及没有通用的分析方案来表征各向异性。最终，对LTD和DA的评估需要开发更准确的组织扩散物理模型，其中包括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调查我们最近提出的针对这两个问题的解决方案。我们推广了目前用于DTI的分析，以纳入更一般的物理模型，用于扩散。这种方法被称为球谐分解(SHD)，已被用于临床应用的快速数值实现。第一个具体目标是将我们的SHD方法扩展到一种更普遍的适用于我们已经开发的多个b值的方法，称为球面波分解(SWD)。其次，我们描述了一种基于最近引入的超回波(HE)概念的新的DW-MRI方法，该方法有可能显著提高标准临床应用的单位时间的扩散灵敏度，从而便于在最小时间损失的情况下扩展到硬测量，但大大提高了DA灵敏度。虽然与传统的DW-MRI采集方法相比，HyperECHO DW-MRI具有明显的理论优势，但它在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来解决，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，通过实验建立DW MRI对复杂组织结构的敏感性。受我们最近显示酒精中毒患者WM DA变化的工作的启发，我们的建议侧重于提高DW-MRI对DA的敏感性，我们的最终长期目标是在临床环境中使用这些方法，特别是在我们正在进行的阿尔茨海默氏症、艾滋病，特别是酒精中毒等退行性脑白质疾病的评估中。

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.