MULIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

描述(摘自申请者的摘要)：心肌缺血是 发达国家严重疾病和过早死亡的最常见原因 世界。许多研究表明，细胞内钠离子(NaI+)的变化 在缺血后细胞功能障碍和损伤中起关键作用。的主要目标是 这项研究是为了验证多量子滤光器(MQF)23Na 磁共振波谱和成像可以定量地确定 缺血发作后急性心脏损伤的范围和位置。 MQF~(23)Na核磁共振被认为是一种主要观察NaI+的方法。这个 MQF 23Na磁共振(MR)技术的压倒性优势是 它们允许非侵入性测量，并可应用于人类。尽管有些人 细胞外Na+对MQF 23Na信号有贡献，申请人的数据来自 其他小组的研究表明，这种信号在缺血和其他情况下不会改变 生理操作。因此，MQF磁共振技术可以提供一种 检测NaI+变化的完全非侵入性方法。申请人的 第一个目标是开发和验证MQF 23Na磁共振波谱(MRS) 用23Na位移试剂定量测定[NaI+]的变化， TmDOPTP5-。全脑缺血再灌流过程中MQF~(23)Na-MRS的变化 将与磷能量代谢和心脏功能相关 隔离灌流的兔心。第二个目标是开发和验证 定量MQF~(23)Na磁共振成像(MRI)标测[NaI+]和 将MRI结果与功能性测量的组织活性相关联 表现和三苯基四氮唑(TTC)的MRI染色 局部缺血和再灌流期间的心脏灌流。MQF的功效 监测缺血性损害的23Na MRI也将与弥散相比较 局部缺血时心脏灌注的1H加权成像 使用和不使用保护心脏的阿米洛利类似物进行再灌注。第三个目标 是开发一种表面线圈MAF 23Na磁共振技术来获得定量地图 的变化，并应用这项技术来评估组织的活性 紧闭胸口的兔心。最后，对心脏定量的可行性进行了探讨 将演示MQF 23Na在人体4T时的磁共振成像。 MQF-23Na磁共振评价和成像缺血后心肌的研究进展 损伤和恢复可能被证明有助于识别存活的组织和 评估旨在保存的治疗干预措施的效果 细胞生存能力。

DESCRIPTION (Adapted from applicant's abstract): Myocardial ischemia is one of the most common causes of serious illness and early death in the developed world. Many studies have shown that alterations in intracellular sodium (Nai+) play a key role in cell dysfunction and damage after ischemia. The main goal of this research is to test the hypothesis that multiple-quantum-filter (MQF) 23Na magnetic resonance spectroscopy and imaging can quantitatively determine the extent and location of acute cardiac injury after an ischemic episode. MQF 23Na NMR has been suggested as a method to mainly observe Nai+. The overwhelming advantage of MQF 23Na magnetic resonance (MR) techniques is that they allow non-invasive measurement and can be applied to humans. Although some extracellular Na+ contributes to the MQF 23Na signal, the applicant's data from other groups, show that this signal does not change during ischemia and other physiological manipulations. Therefore, MQF MR techniques can provide a completely noninvasive method of detecting changes in Nai+. The applicant's first aim is to develop and validate MQF 23Na MR spectroscopy (MRS) for quantitation of changes in [Nai+] with the help of a 23Na shift reagent, TmDOPTP5-. The changes in MQF 23Na MRS during global ischemia and reperfusion will be correlated with phosphorus energy metabolism and cardiac performance in the isolated perfused rabbit heart. The second aim is to develop and validate quantitative MQF 23Na MR imaging (MRI) for mapping changes in [Nai+] and correlate the MRI results with tissue viability as measured by functional performance and triphenyltetrazolium chloride (TTC) MRI staining in the perfused heart during regional ischemia and reperfusion. The efficacy of MQF 23Na MRI to monitor ischemic damage will also be compared with diffusion weighted 1H imaging in the perfused heart during regional ischemia and reperfusion with and without a cardioprotective amiloride analog. The third aim is to develop a surface coil MAF 23Na MRI technique to obtain quantitative maps of changes in Nai+ and apply this technique to assess tissue viability in closed chest rabbit hearts. Finally, the feasibility of quantitative cardiac MQF 23Na MRI in humans at 4T will be demonstrated. The development of MQF 23Na MRI to assess and image post-ischemic myocardial injury and recovery may prove useful for identifying viable tissue and assessing the efficacy of therapeutic interventions aimed at preserving cellular viability.