MR and Iontophoretic Diffusion Measurements in Brain

描述(由申请人提供)： 扩散是脑组织细胞外(EC)和细胞内(IC)的重要转运机制。这些复杂环境的物理性质可以用两个参数来概括：体积分数决定了扩散分子可获得的大脑体积的比例，曲折度描述了环境相对于无障碍介质施加的障碍。扩散加权磁共振(DW-MR)检测EC和IC信号的复杂混合。实时离子导入(RTI)方法也可用于测量扩散，但仅限于EC空间。这两种方法都被用于研究缺血等病理情况，通常发现受损组织中的扩散速度较慢。有关机制仍存在争议。 我们将测量一个小阴离子，六氟锑酸(SbF6-)的扩散，以帮助解释DW-MR测量。SbF6-可被DW-MR和RTI检测到，并且不容易穿过细胞膜。在RTI方法的帮助下，可以分离EC和IC隔室的扩散特性。具体目标有三个： 目的1：验证DW-MR和RTI测量的SbF6-扩散性质相同的假设。氟敏感的DW-MR序列将在7特斯拉进行优化，以可靠地检测充当水替代品的SbF6-阴离子。使用这两种方法在稀释的琼脂糖凝胶中测量扩散，以确定它们的对应程度。 目的：检测正常状态下和低渗应激模拟缺血时细胞体积变化时，海龟小脑EC和IC的弥散参数是否存在差异。用DW-MR测量EC的扩散，并与RTI进行比较。然后，DW-MR测量将持续几个小时，促进细胞外SbF6-逐渐进入细胞。这将允许分离EC和IC扩散属性。 目的3：在体外大鼠脑缺血模型中测定EC和IC的扩散。目标2中开发的方法将用于确定大鼠新皮质厚(1000米)切片中预期扩散减少的特征和来源(EC、IC或两者)。

DESCRIPTION (provided by applicant): Diffusion is an important transport mechanism in both the extracellular (EC) and intracellular (IC) compartments of brain tissue. The physical properties of these complex environments can be summarized by two parameters: the volume fraction determines the proportion of the brain volume accessible to diffusing molecules and the tortuosity describes the hindrance imposed by the environment relative to an obstacle free medium. Diffusion-weighted magnetic resonance (DW-MR) detects a complicated mixture of the EC and IC signals. The Real-Time Iontophoresis (RTI) method also can be used to measure diffusion but only in the EC space. Both methods have been used to study pathological conditions such as ischemia, and generally found slower diffusion in the compromised tissue. The mechanisms are still debated. We will measure diffusion of a small anion, hexafluoroantimonate (SbF6-), to aid in the interpretation of the DW-MR measurements. SbF6- can be detected by both DW-MR and RTI, and does not easily cross cellular membranes. With help from the RTI method, it will be possible to separate the diffusion properties of the EC and IC compartments. There are three specific aims: Aim 1: Test the hypothesis that the measured diffusion properties of SbF6- are the same in DW-MR and RTI. A fluorine-sensitive DW-MR sequence will be optimized at 7 Tesla to reliably detect the SbF6- anion acting as a water substitute. The diffusion will be measured in a diluted agarose gel using both methods to establish the degree of their correspondence. Aim 2: Test whether differences exist between the EC and IC diffusion parameters in the turtle cerebellum under normal conditions and during hypoosmotic stress mimicking cell volume changes in ischemia. The EC diffusion will be measured by DW-MR and compared with RTI. The DW-MR measurement will then continue for several hours, facilitating gradual entry of extracellular SbF6- into cells. This will allow separation of the EC and IC diffusion properties. Aim 3: Measure EC and IC diffusion in a thick-slice in vitro model of ischemia. The method developed in Aim 2 will be applied to determine the characteristics and origins (EC, IC, or both) of the expected diffusion decrease in the thick (1000 (m) slices of rat neocortex.