YTTRIUM HYPERPOLARIZATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 由于Y-89的旋磁比较低(约为1H的5%)，因此其灵敏度较低，因此在核磁共振领域没有得到广泛使用。尽管存在这一限制，89Y确实带来了使其成为一种优秀显像剂的特性。首先，化学位移分散可以大于100ppm，这意味着可以使用化学位移成像(CSI)检测到对局部环境(如pH或[葡萄糖])敏感的螯合物。其次，89Y具有很长的弛豫时间--测量了S的T1‘在8分钟或更长时间，T2’S在60~100毫秒的范围内。长的自旋-晶格弛豫时间极大地扩大了超极化89Y化合物的传输窗口并因此成像，也使89Y成为反激式成像技术的理想选择，在这种技术中，磁化强度在两次采集之间恢复以进行重新采样。长的自旋-自旋弛豫时间使89Y非常适合快速成像方案，例如涡轮自旋回波，在这种方案中，可以进行大量的相位编码，而不会显著损失相干横向磁化。第三，专门为Gd3+设计的代谢灵敏的螯合剂，一种强大的T1弛豫剂，同样适用于Y，因为Y3+离子与Gd3+是等电子的。最后，在自然界中发现了丰度为100%的89Y核。 即使89Y本身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)，初始光谱结果表明，通过DNP技术可以获得55：1的信噪比和1500的增强(相对于在3M热样YCl3上获得的90度脉冲)。这些初步结果表明，超极化89Y在成像实验中的成功应用是非常有利的。 超极化的89Y实验是那些涉及大鼠心脏的体外心脏成像的实验。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。夹住左前降支后，89Y的灌流和超极化通过这一途径被抑制，在相应的心肌区域引起一过性缺血。在对心肌横切面进行成像时，亮区表示超极化89Y的存在，而暗区表示缺血的位置。为了在成像时消除运动伪影的可能性，可以通过将25 mm的氯化钾溶液混合到灌流液中来停止心脏跳动。 为了成功地对大鼠心脏超极化的89Y进行成像，必须设计合适的射频探头和合适的成像脉冲序列。为了容纳悬挂在灌流柱中的灌流的大鼠心脏，必须建立一个直径约20 mm的垂直取向的射频线圈。除了以所需的89Y频率(19.6 MHz)共振外，该探头还应可调至质子频率(400 MHz)，以便能够收集所需成像面的质子侦察图像。为了对基于化学位移色散的89Y超极化成像(如前所述)，需要开发89Y CSI技术。为了保持采集脉冲之间的超极化磁化，可以实现反激式序列。为了快速收集不同成像平面上的多个切片，可以潜在地将快速成像序列与回扫技术相结合。

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.