MULTIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

钠梯度对许多细胞功能至关重要，而且 对疾病敏感的；因此有一种持续的有趣 区分不同组织间Na+的方法。 已经提出了至少两种磁共振(MR)方法来 区分细胞内和细胞外的Na+，阴离子的使用 移位试剂(SR)和多量子(MQ)过滤技术。每个人 这种方法有缺点，特别是在活体应用方面。这个 SRS的主要缺点是可能的毒性，而MQ过滤器 不要准确地过滤细胞内信号和细胞外信号。然而， MQ技术确实区分了各向同性和瞬变约束 Na+的状态，并可非侵入性地应用于人类研究。这个 这项研究的长期目标是描述和评估 MQ滤波~(23)Na光谱和成像在检测中的应用 完整动物和灌流心脏的生理异常 该技术可应用于临床。这其中的中心假设是 项目是MQ滤波后的细胞内Na+(Na+i)信号更多 对生理扰动的敏感度比单量子(SQ) 信号强度。 我们最近推出了一种新的SR，TmDOTP5，用于生物医学 活体动物实验社区。这种试剂提供了一种 在完整动物身上测试MQ过滤器性能的极佳方法 和灌流的器官实验。我们用这种试剂得到的初步数据 显示在死亡后，MQ过滤了大鼠肝脏的Na+i信号 比SQ信号的增加快3-4倍。这不是 是由于Na+的驰豫时间的变化，而不是由于 可以通过MQ过滤器的Na+i量因此建议 Na+i结合的显著变化，而其他 技巧。本提案中概述的实验旨在 回答以下问题：1)单元格是否有更细微的变化 会在MQ过滤的Na+i中产生同样的增加的生理因素 信号？2)MQ滤波信号的这种增加是肝脏特有的， 或者它也发生在其他器官中？这种影响可逆吗？ 它是不是比SQ Na+i信号更敏感的细胞损伤指标 紧张吗？此外，我们还将研究缺血和缺氧的影响。 不同药物在豚鼠心脏灌流中的作用 为了了解MQ中这些变化的机制，我们对23Na光谱进行了过滤。 最后，为了让MQ技术在临床上有用，MQ过滤了23Na 将开发和测试成像技术，它将使用加权 信号平均和相干回波相加以增强信噪比 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.