YTTRIUM HYPERPOLARIZATION

钇超极化

• 批准号: 8363914
• 负责人: Zoltan Kovacs
• 金额: $ 1.61万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363914
• 关键词: Anterior; Arteries; Back; Caliber; Cardiac; Cell Nucleus; Characteristics; Chelating Agents; Chemical Shift Imaging; Chemicals; Communities; Engineering; Environment; Frequencies; Funding; Glucose; Grant; Heart; Human; Image; Imaging Techniques; Ions; Ischemia; Left; Location; Measures; Metabolism; Methods; Modeling; Morphologic artifacts; Myocardial Infarction; Myocardium; National Center for Research Resources; Nature; Nuclear; Pathway interactions; Perfusion; Phase; Physiologic pulse; Principal Investigator; Protons; Rattus; Relaxation; Research; Research Infrastructure; Resources; Sampling; Scheme; Simulate; Slice; Solutions; Source; Spectrum Analysis; Techniques; Time; United States National Institutes of Health; Yttrium; base; cost; fly; heart imaging; in vivo; interest; research study; yttria

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Yttrium-89 does not find widespread use in the NMR community due to its low gyromagnetic ratio (approximately 5% of 1H) and, consequently, its low sensitivity. In spite of this limitation, 89Y does bring characteristics that would make it an excellent imaging agent. To begin with, the chemical shift dispersion can be greater than 100 ppm, implying that chelates sensitive to the local environment such as pH or [glucose] could be detected using chemical shift imaging (CSI). Secondly, 89Y has intrinsically long relaxation times - T1's of up to 8 minutes or more and T2's in the range of 60  100 ms have been measured. Long spin-lattice relaxation times dramatically expand the window over which hyperpolarized 89Y compounds can be delivered and consequently imaged, and also make 89Y an ideal choice for use in fly-back imaging techniques where the magnetization is restored along the Z-axis between acquisitions for resampling. Long spin-spin relaxation times make 89Y highly suitable for fast imaging schemes, such as the turbo spin echo, where numerous phase encodes can be conducted without significant loss of coherent transverse magnetization. Third, metabolically sensitive chelating agents specifically engineered for Gd3+, a powerful T1 relaxation agent, are likewise applicable to yttrium as the Y3+ ion is isoelectronic with Gd3+. Lastly, the 89Y nucleus is found in 100% abundance in nature. Even the inherently low sensitivity of 89Y can be overcome by the use of hyperpolarization via the dynamic nuclear polarization (DNP) method. Using a shallow 10 degree hard excitation pulse and 8 mM concentration of hyperpolarized Y(DOTA), initial spectroscopy results show that a 55:1 SNR and an enhancement of 1500 (with respect to 90 degree pulse acquired on a 3M thermal sample of YCl3) is possible via the DNP technique. These preliminary results indicate the successful application of hyperpolarized 89Y to imaging experiments to be very favorable. The hyperpolarized 89Y experiments of interest are those involving ex-vivo cardiac imaging of rat hearts. Regional ischemia can be induced in rat heart models to simulate the situation following a human myocardial infarction. By snaring the left anterior descending artery, the delivery of perfusate and hyperpolarized 89Y will be inhibited via this pathway, inducing temporary ischemia in the corresponding region of the myocardium. Upon imaging a cross section of the myocardium, bright regions will indicate the presence of hyperpolarized 89Y while dark regions will signify the locations of ischemia. To remove the possibility of motional artifacts while imaging, the heart can be arrested by mixing into the perfusate a 25 mM solution of KCl. In order to successfully image hyperpolarized 89Y in rat hearts, an appropriate rf probe and suitable imaging pulse sequences must be engineered. To accommodate a perfused rat heart hung in a perfusion column, a vertically oriented rf coil of approximately 20 mm in diameter must be built. Along with resonating at the desired 89Y frequency (19.6 MHz), this probe should be tunable to the proton frequency as well (400 MHz) to have the ability to collect proton scout images of the desired imaging plane. For the purposes of imaging hyperpolarized 89Y based upon chemical shift dispersion (as mentioned previously), 89Y CSI techniques would need to be developed. In order to preserve the hyperpolarized magnetization between acquisition pulses, fly-back sequences can be implemented. To rapidly collect multiple slices in various imaging planes, a fast imaging sequence can potentially be combined with a fly-back technique.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 钇-89由于其低旋磁比（约为1H的5%）和低灵敏度而没有在NMR界得到广泛应用。 尽管有这个限制，89 Y确实带来了使其成为优秀成像剂的特性。 开始时，化学位移分散度可以大于100 ppm，这意味着可以使用化学位移成像（CSI）检测对局部环境（如pH或[葡萄糖]）敏感的螯合物。 其次，89 Y具有固有的长弛豫时间- T1高达8分钟或更长，T2在60  测量了100 ms。 长的自旋-晶格弛豫时间极大地扩展了超极化89 Y化合物可以被递送并因此成像的窗口，并且还使89 Y成为用于回扫成像技术的理想选择，其中磁化在用于再激发的采集之间沿着Z轴恢复。 长的自旋-自旋弛豫时间使89 Y非常适合快速成像方案，例如涡轮自旋回波，其中可以进行许多相位编码而不会显著损失相干横向磁化。 第三，专门针对Gd 3+设计的代谢敏感性螯合剂，一种强大的T1弛豫剂，同样适用于钇，因为Y 3+离子与Gd 3+是等电子的。 最后，89 Y核在自然界中的丰度为100%。 即使89 Y固有的低灵敏度也可以通过动态核极化（DNP）方法使用超极化来克服。 使用浅的10度硬激发脉冲和8 mM浓度的超极化Y（DOTA），初始光谱结果显示，通过DNP技术，55：1的SNR和1500的增强（相对于在YCl 3的3 M热样品上获得的90度脉冲）是可能的。 这些初步结果表明，超极化89 Y在成像实验中的成功应用是非常有利的。 感兴趣的超极化89 Y实验是涉及大鼠心脏的离体心脏成像的那些实验。 可以在大鼠心脏模型中诱导局部缺血以模拟人类心肌梗死后的情况。 通过圈套左前降支动脉，灌注液和超极化89 Y的输送将通过该途径被抑制，从而在心肌的相应区域中诱导暂时性缺血。 在对心肌的横截面成像时，亮区域将指示超极化89 Y的存在，而暗区域将表示缺血的位置。 为了消除成像时运动伪影的可能性，可以通过将25 mM KCl溶液混合到灌注液中来停止心脏。 为了成功地在大鼠心脏中成像超极化89 Y，必须设计合适的RF探头和合适的成像脉冲序列。 为了容纳一个灌注大鼠心脏挂在灌注柱，一个垂直定向的射频线圈直径约20毫米必须建立。 沿着在期望的89 Y频率（19.6 MHz）处谐振，该探头也应当可调谐到质子频率（400 MHz），以具有收集期望的成像平面的质子侦察图像的能力。 为了基于化学位移色散（如前所述）对超极化89 Y进行成像，需要开发89 Y CSI技术。为了保持采集脉冲之间的超极化磁化，可以实现回扫序列。 为了快速收集各种成像平面中的多个切片，快速成像序列可以潜在地与回扫技术相结合。