MR STUDY OF BRAIN INTERSTITIAL WATER MOTION

描述(改编自申请人的摘要)：脑水运动， 可以通过磁共振技术检测到，取决于许多因素，一些 具有正常生理学特征和其他病理学特征。结果, 弥散加权成像被广泛用于评价一些 CNS州。保持水的运动本身对 大脑功能正常，或者至少是一个很好的生理标志 州政府。尼尔/阿克曼实验室的研究项目侧重于 阐明决定水运动的因素。这项提案将重点放在 关于进一步了解胞外水分对总量的贡献 (细胞内加细胞外)水ADC。间质流体中的运动具有 间隔性脑脊液(CSF)大量流动的贡献 边界和布朗运动。实验的设计是为了确定 这三个因素对ADC的相对贡献。间隙水 ADC将通过测量大范围内的运动来间接测量 细胞外标志物。最近的结果表明，化合物的ADC限制了 到细胞外空间的距离大致相等，尽管标记了 相对分子质量(MW)的差异。这表明大量脑脊液流动是一种 主导因素。这一想法将在两个大的细胞外 标记物(相对分子质量为0.9和4kD的聚乙二醇组)和一个非常小的标记物 (钠，相对分子质量=23)。最后，脑脊液流量将被药物改变为 直接评估其对细胞外水ADC的影响。

DESCRIPTION (Adapted from applicant's abstract): Brain water motion, which can be detected by MR techniques, varies depending on many factors, some characteristic of normal physiology and others of pathology. As a result, diffusion weighted imaging is used widely for the evaluation of a number of CNS states. Maintenance of water motion is either itself important for normal brain function or is at least an excellent marker of physiologic state. The Neil/Ackerman laboratory's research program focuses on elucidating the factors which determine water motion. This proposal focuses on learning more about the contribution of extracellular water to the total (intra- plus extracellular) water ADC. Motion in the interstitial fluid has contributions from bulk cerebrospinal fluid (CSF) flow, compartmental boundaries, and Brownian motion. Experiments were designed to determine the relative contribution of these three factors to ADC. The interstitial water ADC will be measured indirectly by measuring the motion of a broad range of extracellular markers. Recent results show that ADCs of compounds confined to the extracellular space are approximately equal despite marked differences in molecular weight (MW). This suggests that bulk CSF flow is a dominating factor. This idea will be tested with both large extracellular markers (polyethyleneglycols of MW=0.9 and 4 kD) and one very small marker (sodium, MW=23). Finally, CSF flow will be pharmacologically altered to directly assess its effect on extracellular water ADC.