PROTON RELAXATION MECHANISMS IN TISSUES FOR NMR IMAGING

拟议研究的目的是为了更好地了解 确定NMR弛豫特性的基本机制 组织中的质子和疾病中发生的变化。 该项目将 扩大在以前供资期间制定的方法，并继续 测量以检验特定假设。 核磁共振图像中的对比度出现 主要来自组织松弛的不均匀分布 属性，但没有足够的模型存在，以定量说明 松弛率，特别是1/T2，甚至正常组织。 有，为 例如，大分子的性质之间的主要差异， 溶液和有组织的那些。 这些差异包括 交叉弛豫速率、化学交换和其他T2的大小 缩短现象，如扩散效应和 定向水分子的各向异性运动。 我们将量化 个人的相互作用和影响机制的贡献 松弛，并确定那些有助于T1和T2的过程 影响以及那些只影响T2。 各种高分辨率 在200-500 MHz的频谱技术，以及T1和T2测量， 2-500 MHz，将被使用。 我们将测量（a）流体动力学效应，或 水分子内偶极相互作用的影响，使用测量 氘相关时间(b)水和 大分子质子，在氘代样品中使用质子弛豫， 短暂的Overhauser效应（c）限制了组织中的扩散， 使用脉冲梯度对水看到的有效表面积的影响 自旋回波序列（d）可电离质子之间的化学交换率 和水，使用Luz和Meiboom（e）扩散方法， 磁化率的变化，使用各种自旋回波序列， 理论建模和Karlicek和Lowe的方法（f）影响 水的优先取向和各向异性旋转， 使用魔角技术和Goldburg和Lee（g）的方法 顺磁相互作用的研究螯合物和 异源NOEs。 我们将研究一组精选的蛋白质，聚合物 和凝胶，在不同的条件下;在聚集体中，在游离溶液中，或 交联和固定;在不同程度的变性，并在 不同的溶剂和缓冲液，其中表面特性和亲和力 会受到影响。 因此，我们将评估对水松弛的影响 不仅是单个大分子和组分（因此， 组织组成改变的意义），而且 超分子宏观组织，如分子缔合， 细胞器的形成，或在膜中的固定。 测量 将与组织的生物化学测定（蛋白质， 脂质、糖原、水含量）和其他特征测量 的选民。 整个项目应该提供许多新的见解 组织松弛现象，以帮助更好地理解 NMR图像中对比度的来源。

The objective of the proposed studies is to better understand the fundamental mechanisms that determine the NMR relaxation properties of protons in tissues and the changes that occur in disease. The project will extend the methods developed in the previously funded period and pursue measurements to test specific hypotheses. Contrast in NMR images arises primarily from the heterogenous distribution of tissue relaxation properties but no adequate model exists to quantitatively account for the relaxation rates, especially 1/T2, even of normal tissues. There are, for example, major differences between the properties of macromolecules in solution and those of organized tissue. These differences include the magnitudes of cross-relaxation rates, chemical exchange and other T2 shortening phenomena such as diffusion effects and the importance of anisotropic motions of oriented water molecules. We will quantify the contributions of individual interactions and mechanisms that affect relaxation and identify those processes that contribute to T1 and T2 effects as well as those that affect T2 only. A variety of high resolution spectral techniques at 200-500 MHz, as well as T1 and T2 measurements from 2-500 MHz, will be used. We will measure (a) hydrodynamic effects, or the effects on water intramolecular dipolar interactions, using measurements of deuterium correlation times. (b) cross relaxation between water and macromolecular protons, using proton relaxation in deuterated samples and transient Overhauser effects (c) restricted diffusion in tissues, and its influence on the effective surface area seen by water, using pulse gradient spin echo sequences (d) chemical exchange rates between ionizable protons and water, using the method of Luz and Meiboom (e) diffusion amongst variations in magnetic susceptibility, using various spin echo sequences, theoretical modelling and the method of Karlicek and Lowe (f) the influence of water that is preferentially oriented and rotating anisotropically, using magic angle techniques and the method of Goldburg and Lee (g) paramagnetic interactions by studying the effects of chelates and heteronuclear NOEs. We will study a selected group of proteins, polymers and gels, in different conditions; in aggregates, in free solution or cross-linked and immobilized; in different degrees of denaturation, and in different solvents and buffers wherein the surface character and affinity will be affected. We will thereby assess the effects on water relaxation not only of individual macromolecules and constituents (and thus the significance of alterations in tissue composition alone) but also the role of supra-molecular macroscopic organization, such as molecular association, the formation of organelles, or immobilization in membranes. Measurements in tissues will be correlated with biochemical assays of tissues (protein, lipid, glycogen, water content) and other measures of the characteristics of the constituents. The overall project should provide many new insights into tissue relaxation phenomena to aid in the better understanding of the origin of contrast in NMR images.