MR and Iontophoretic Diffusion Measurements in Brain

大脑中的 MR 和离子电渗扩散测量

• 批准号: 6867643
• 负责人: JAN HRABE
• 金额: $ 14.8万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867643
• 关键词: Chelonia; anions; bioimaging /biomedical imaging; cell membrane; cell morphology; cell osmotic pressure; cerebellum; cerebral ischemia /hypoxia; diffusion; gel electrophoresis; laboratory rat; magnetic resonance imaging; neocortex; nontherapeutic iontophoresis; technology /technique development

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.

描述（由申请人提供）： 扩散是脑组织细胞外（EC）和细胞内（IC）区室的重要转运机制。这些复杂环境的物理特性可以用两个参数来概括：体积分数决定了扩散分子可进入的大脑体积的比例，而曲折度描述了环境相对于无障碍介质所施加的障碍。扩散加权磁共振 (DW-MR) 可检测 EC 和 IC 信号的复杂混合物。实时离子电渗 (RTI) 方法也可用于测量扩散，但仅限于 EC 空间。这两种方法都已用于研究缺血等病理状况，并且通常发现受损组织中的扩散速度较慢。该机制仍存在争议。 我们将测量小阴离子六氟锑酸盐 (SbF6-) 的扩散，以帮助解释 DW-MR 测量结果。 SbF6- 可以通过 DW-MR 和 RTI 检测到，并且不易穿过细胞膜。在 RTI 方法的帮助下，可以分离 EC 和 IC 隔室的扩散特性。具体目标有以下三个： 目标 1：检验 DW-MR 和 RTI 中测得的 SbF6- 扩散特性相同的假设。对氟敏感的 DW-MR 序列将在 7 特斯拉下进行优化，以可靠地检测作为水替代品的 SbF6- 阴离子。将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。 目标 2：测试正常条件下和模拟缺血细胞体积变化的低渗应激期间乌龟小脑的 EC 和 IC 扩散参数之间是否存在差异。 EC 扩散将通过 DW-MR 测量并与 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 EC 和 IC 扩散特性的分离。 目标 3：测量厚切片体外缺血模型中的 EC 和 IC 扩散。目标 2 中开发的方法将用于确定大鼠新皮质厚片（1000 (m)）中预期扩散减少的特征和来源（EC、IC 或两者）。