MULIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

描述（改编自申请人摘要）：心肌缺血是 在发达国家中， 世界许多研究表明，细胞内钠（Nai+） 在缺血后细胞功能障碍和损伤中起关键作用。的主要目标 本研究旨在验证多量子滤波器（MQF）23 Na 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程度和位置。 MQF 23 Na NMR已被建议作为主要观察Nai+的方法。的 MQF 23 Na磁共振（MR）技术的压倒性优势在于， 它们允许非侵入性测量并且可以应用于人类。尽管一些 细胞外Na+有助于MQF 23 Na信号，申请人的数据来自 其他组显示该信号在缺血期间不改变， 生理操作。因此，MQF MR技术可以提供 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 23 Na MR光谱（MRS）， 在23 Na位移试剂的帮助下定量[Nai+]的变化， TmDOPTP 5-。全脑缺血再灌注时MQF ~（23）Na磁共振波谱的变化 将与磷能量代谢和心脏性能相关， 离体灌流兔心脏。第二个目标是开发和验证 定量MQF 23 Na MR成像（MRI），用于绘制[Nai+]和 将MRI结果与通过功能测定的组织活力相关联 性能和氯化三苯基四唑（TTC）MRI染色， 在局部缺血和再灌注期间灌注心脏。MQF的功效 监测缺血性损伤的23 Na MRI也将与弥散进行比较 在局部缺血期间灌注心脏中的加权1H成像， 用和不用心脏保护性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 23 Na MRI技术，以获得定量图 的变化，并应用该技术评估组织活力， 闭胸兔心。最后，对定量心脏 将证明在4 T下人体中的MQF 23 Na MRI。 MQF 23 Na MRI评价和成像缺血后心肌的研究进展 损伤和恢复可以证明对于鉴定存活组织是有用的， 评估旨在保护人类健康的治疗干预措施的有效性， 细胞活力

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.