MULTIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

钠梯度对许多细胞功能至关重要， 对疾病敏感;因此， 方法区分Na+在不同的组织隔室。 已经提出了至少两种磁共振（MR）方法， 区分细胞内和细胞外Na+，使用阴离子 移位试剂（SR）和多量子（MQ）过滤技术。每个 这种方法具有缺点，特别是对于体内应用。的 SR的主要缺点是可能的毒性，而MQ过滤器 不能准确地过滤细胞内信号和细胞外信号。然而，在这方面， MQ技术确实区分了各向同性和瞬时绑定 的Na+状态，并可以应用于人体研究非侵入性。的 这项研究的长期目标是表征和评估 使用MQ过滤的23 Na光谱学和成像来检测 完整动物和灌注心脏的生理异常， 该技术可应用于临床。这其中的核心假设是 MQ过滤的细胞内Na+（Na+i）信号比MQ过滤的细胞内Na+（Na+i）信号更强。 比单量子（SQ）对生理扰动敏感 信号强度 我们最近在生物医学领域引入了一种新的SR TmDOTP 5， 动物活体实验社区。该试剂提供了 在完整动物中测试MQ过滤器性能的绝佳方法 和灌注器官实验。我们对该试剂的初步数据 显示在死亡时，MQ过滤来自大鼠肝脏的Na+1信号 比SQ信号的增加快3-4倍。这并不 结果从Na+的弛豫时间的变化，而是由于 可以通过MQ过滤器并因此建议 Na+i结合的显著变化，这是其他方法检测不到的。 技术.本提案中概述的实验旨在 解决以下问题：1）细胞中是否存在更微妙的变化 生理学将产生MQ过滤Na+i的相同增加， 信号？2)这种MQ过滤信号的增加是否是肝脏特有的， 还是在其他器官也会发生3)这种效应是可逆的吗 它是否是比SQ Na+i信号更敏感的细胞损伤指标 强度？此外，我们还将研究缺血的影响， 豚鼠心脏灌流中的不同药理学操作 以了解MQ过滤的23 Na光谱中这些变化的机制。 最后，为了使MQ技术在临床上有用，MQ过滤23 Na 成像技术将开发和测试，这将使用加权 信号平均和相干回波相加以增强信号到 噪声比

A sodium gradient is critically important to many cell functions and is sensitive to disease; consequently there is a continuing interesting methods which differentiate between Na+ in various tissue compartments. At least two magnetic resonance (MR) methods have been proposed to differentiate between intra- and extracellular Na+, the use of anionic shift reagents (SR) and multiple quantum (MQ) filter techniques. Each approach has disadvantages, especially for in vivo applications. The primary disadvantage of SRs concerns possible toxicity while MQ filters do not accurately filter intra- versus extracellular signals. However, MQ techniques do discriminate between isotropic and transiently bound states of Na+, and can be applied to human studies noninvasively. The long term objective of this research is to characterize and evaluate the use of MQ filtered 23Na spectroscopy and imaging for detecting physiological abnormalities in intact animals and perfused heart so that the technique may be applied clinically. The central hypothesis in this project is that the MQ filtered intracellular Na+ (Na+i) signal is more sensitive to physiological perturbations than the single quantum (SQ) signal intensity. We have recently introduced a new SR, TmDOTP5, to the biomedical community for in vivo animal experiments. This reagent provides an excellent way of testing the performance of MQ filters in intact animal and perfused organ experiments. Our preliminary data with this reagent shows that upon death, the MQ filtered Na+i signal from the rat liver increases 3-4 times faster than the increase in SQ signal. This does not result from changes in the relaxation times of Na+ but is rather due to the amount of Na+i that can pass through a MQ filter and thus suggest significant changes in binding of Na+i which are not detectable by other techniques. The experiments outlined in this proposal are designed to address the following questions; 1) Are there more subtle changes in cell physiology that will produce this same increase in the MQ filtered Na+i signal? 2) Is this increase in MQ filtered signal specific to the liver, or does it occur in other organs as well? 3) Is this effect reversible and is it a more sensitive indicator of cell damage than SQ Na+i signal intensity? In addition, we will study the effects of ischemia and different pharmacological manipulations in the perfused guinea pig heart to understand the mechanism of these changes in MQ filtered 23Na spectra. Finally, for MQ techniques to be useful clinically, a MQ filtered 23Na imaging technique will be developed and tested which will use weighted signal averaging and coherent echo addition to enhance the signal-to noise ratio.