NONDIAMAGNETIC AGENTS IN IN VIVO 23 NA AND 1H20 MR

拟议的工作将继续探索和展示以下范围 非抗磁剂在这两个方面的应用 最强的组织核磁共振信号：1H2O和23Na-AQ。形容词 非抗磁性在这里用来表示任何磁性行为(例如 顺磁、超顺磁、铁磁等)展览地点： 除了简单的抗磁性。第一个一般的具体项目 提出了(1H2O)类。其中一些想法的起源 来源于23Na-AQ的早期工作。然而，现在的优先事项必须是 给予前者，而不是后者的类似研究。 这将证明，人们可以使1H2O磁共振图像的对比度 试剂(CR)直接分配体积，以及细胞膜水 渗透系数图，细胞质；体积图像，和 细胞外体积图。后两者代表编辑 基态的定量(自旋密度)1H2O图像 生物学的区隔，这可以从根本上改变 病理学，如水肿病和肿瘤。制造这些东西的预付款 发展可能是弛豫成像和核磁共振相结合的新技术 成像(CRI)是本实验室最近推出的。CRI技术 在本提案中进行了解释，并且完全是通用的，适用于 纵向、横向或旋转框架核磁共振弛豫。它可以是 用于研究任何CR，无论是使用超细还是散装 磁化率机制(或两者都有)。纵向松弛 在本方案中，强调超细CRS。这个项目有 最近搬到了一所新的机构，而且水平大大提高了 努力。因此，除了老鼠实验之外，对犬类的研究 (Beagle)和灵长类()模型被提出。这些涉及到 程序化的，步骤四的CRS输注被批准用于人类，并且相当 前无古人的水平。研究大型动物的能力提供了 有机会解决规模扩大的重要问题 药代动力学和可获得的图像分辨率。图像的类型 将检查上面列出的任何组织是否存在于任何选定的 视野包括各种肌肉群、肝脏、肿瘤模型 植入大鼠大腿肌肉、脑内，并植入肿瘤模型 在老鼠的大脑里。后两者需要直接脑室注射 注射CR，因为它不能通过血脑屏障 正常组织，这种方法将只适用于大鼠和狗。 肿瘤模型允许评估更大的组织异质性， 以及其研究的基本依据日益受到人们的欢迎 动态CR增强方法，包括静脉推注。这 工作涉及物理、物理化学、生物物理学和 生理学，并在许多研究中产生了影响 病理情况，包括神经和心血管疾病 精神错乱。

The work proposed will continue to explore and demonstrate the range of applications of the effects of non-diamagnetic agents on the two strongest tissue NMR signals: those of 1H2O and 23Na-aq. The adjective non-diamagnetic is used here to indicate any magnetic behavior (ex. paramagnetic, super-paramagnetic, ferromagnetic, etc.) exhibited in addition to simple diamagnetism. Specific projects in the first general category (1H2O) are proposed. The genesis of some of these ideas derived from early work with 23Na-aq. However, now priority must be given to the former, over analogous studies of the latter. It will be demonstrated that one can make 1H2O MR images of contrast reagent (CR) distribution volumes directly, as well as cytolemmal water permeability coefficient maps, cytoplasmic; volume images, and extracellular volume maps. The latter two represent the editing of quantitative (spin density) 1H2O images for the fundamental compartmentalization of biology, which can be radically altered in pathologies such as edemas and tumors. The advance making these development possible is the new technique of combined relaxography and imaging (CRI) recently introduced by this laboratory. The CRI technique is explained in this proposal, and is totally general and applicable to longitudinal, transverse, or rotating-frame NMR relaxation. It can be used to study any CR, whether employing the hyperfine or the bulk magnetic susceptibility mechanisms (or both). Longitudinal relaxation and hyperfine CRs are emphasized in this proposal. This program has recently moved to a new institution and a significantly higher level of effort. Thus, in addition to rat experiments, studies of canine (beagle) and primate (baboon) models are proposed. These involve the programmed, stepped IV infusions of CRs approved for humans, and a quite precedented levels. The ability to study the larger animals provides the opportunity to address important issues of the scaling of the pharmacokinetics and attainable image resolution. The types of images itemized above will be examined for any tissue present in any selected field-of-view, including various muscle groups, the liver, a tumor model implanted in rat thigh muscle, the brain, and a tumor model implanted in the rat brain. The latter two require direct intracerebroventricular injection of the CR since it does not cross the blood-brain-barrier in normal tissue and this approach will be applied only to rats and dogs. The tumor models allow assessment of much greater tissue heterogeneity, and the fundamental bases of their study by the increasingly popular dynamic CR-enhanced method, which involves bolus IV injections. This work involves aspects of physics, physical chemistry, biophysics, and physiology and has ramifications in the study of a number of pathological conditions including neurological and cardiovascular disorders.