PROTON RELAXATION MECHANISMS IN TISSUES FOR NMR IMAGING

拟议研究的目的是为了更好地了解 决定核磁共振弛豫性质的基本机理 组织中的质子和疾病中发生的变化。该项目将 扩展在上一次资助期间开发的方法，并追求 用于检验特定假设的测量。核磁共振图像出现对比度 主要来自于组织松弛的不均匀分布 属性，但不存在足够的模型来定量解释 松弛速率，特别是1/T2，即使是正常组织。有，对于 例如，大分子的性质之间的主要差异 溶液和有组织组织的溶液。这些差异包括 交叉松弛速率、化学交换和其他T2的大小 缩短现象，如扩散效应和重要性 定向水分子的各向异性运动。我们将量化 个人互动的贡献和影响的机制 松弛并确定对T1和T2有贡献的过程 以及那些只影响T2的影响。各种高分辨率 200-500 MHz的频谱技术，以及来自 2-500 MHz，将使用。我们将测量(A)水动力效应，或 水分子内偶极相互作用的影响，使用测量 重氢关联时间。(B)水和水之间的交叉松弛 大分子质子，使用氢化样品中的质子弛豫和 瞬时Overhauser效应(C)限制组织内扩散，及其 脉冲梯度对水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Meiom(E)扩散方法 磁化率的变化，使用各种自旋回波序列， Karlicek和Lowe(F)影响的理论模型和方法 优先定向和各向异性旋转的水， 利用幻角技巧和Goldburg和Lee(G)的方法 通过研究螯合物和顺磁相互作用的影响 异核NO。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，在自由溶液中 交联和固定化；在不同程度的变性，以及在 不同的溶剂和缓冲剂，其中表面特性和亲和力 都会受到影响。因此，我们将评估对水松弛的影响 不仅是单个大分子和成分(因此 仅组织成分改变的意义)，但也包括 超分子宏观组织，如分子缔合， 细胞器的形成，或膜上的固定化。测量结果 将与组织的生化分析(蛋白质， 脂肪、糖原、水分等指标的特征 选民名单中。整个项目应该会提供许多新的见解 组织松弛现象有助于更好地了解 核磁共振图像的对比度来源。

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.