Hyperpolarized MRI: Methods for Preparing Long-lived Hyperpolarized Contrast Age

描述（申请人提供）：超极化液相造影剂可以将MRI的灵敏度提高10,000倍或更多。这些信号增强可能会显着改善 MRI 的许多现有应用，包括血管造影和灌注成像。此外，由于可以极化内源性物质，这些技术开始显示出新应用的前景，例如“实时”代谢成像，不仅可以监测药物的运输和摄取，还可以监测代谢转化。超极化带来的灵敏度增益在一定程度上被信号增强的相对较短的寿命所抵消。事实上，一旦制备了一种试剂，它的磁化强度就会以自旋晶格弛豫时间 T1 决定的速率不可逆地衰减。现有试剂通常具有大约一分钟或更短的弛豫时间，这意味着超极化磁化具有几分钟的有用寿命。这些较短的寿命限制了药物的运输、摄取和代谢的时间窗口。反过来，这可能会限制超极化 MRI 的可行应用范围。最近的研究表明，某些相干量子力学自旋态的寿命比传统的 T1 弛豫时间长近一个数量级。此外，这些长寿命状态类似于仲氢诱导极化中使用的状态，仲氢诱导极化是制备超极化介质的常用方法之一。在我们提出的研究中，我们将研究应用仲氢诱导极化和相关方法来制备长寿命超极化态的可能性。超极化质子的初步实验结果已经证明其状态寿命比传统 T1 弛豫时间长 2.5 倍，并且文献中已经记录了 8 倍增强的例子。我们还开始了理论工作，以确定这些寿命延长的起源。如果在含有碳-13等原子核的系统中获得类似的增强效果，当与质子分离时，这些原子核具有较长的弛豫时间，那么尺度论证表明，有可能制备出寿命为10分钟或更长的超极化剂。反过来，这可能使超极化 MRI 具有更广泛的应用范围。我们提出了一系列理论计算和实验研究，将确定长寿命质子系统的有前途的试剂。此外，我们将开发在含有碳13等原子核的系统中准备候选长寿命态的方法。这些药物的寿命将在体外进行测量并与理论进行比较，体内测量将在动物身上进行。公共健康相关性：超极化液体造影剂可以将磁共振成像 (MRI) 的灵敏度提高 10,000 倍（相对于传统方法）。超极化的许多潜在应用都受到信号增强寿命短的限制，信号增强寿命通常约为几分钟。在我们提出的工作中，我们将研究通过使用专门制备的量子力学自旋态来实现更长寿命的方法。将利用理论和实验工作来了解延长寿命的机制，并将识别和测试候选造影剂。

DESCRIPTION (provided by applicant): Hyperpolarized liquid-phase contrast media can enhance the sensitivity of MRI by a factor of 10,000 or more. These signal enhancements may yield significant improvements in many existing applications of MRI, including angiography and perfusion imaging. In addition, because it is possible to polarize endogenous substances, these techniques are beginning to show promise for new applications such as `real-time' metabolic imaging that monitors not just transport and uptake of agents, but metabolic transformations as well. The gains in sensitivity afforded by hyperpolarization are offset to some degree by the relatively short lifetime of the signal enhancement. Indeed, once an agent has been prepared, its magnetization decays away irreversibly at a rate dictated by the spin-lattice relaxation time T1. Existing agents generally have relaxation times on the order of a minute or less, implying that the hyperpolarized magnetization has a useful lifetime of a few minutes. These short lifetimes limit the time window that is available transport, uptake, and metabolism of the agents. This, in turn, may limit the range of feasible applications for hyperpolarized MRI. Recent work has shown that certain coherent quantum-mechanical spin states can have lifetimes nearly an order of magnitude longer than the conventional T1 relaxation time. Moreover, these long-lived states are analogous to states employed in parahydrogen-induced polarization, one of the common methods for preparing hyperpolarized media. In our proposed research, we will investigate the possibility of applying parahydrogen-induced polarization and related methods to prepare long-lived hyperpolarized states. Preliminary experimental results on hyperpolarized protons have already demonstrated states with lifetimes 2.5 times longer than the conventional T1 relaxation time, and examples of 8-fold enhancements have been documented in the literature. We have also begun theoretical work to determine the origin of these enhanced lifetimes. If similar enhancements can be obtained in systems containing nuclei such as Carbon-13 that have long relaxation times when isolated from protons, then scaling arguments suggest that it may be possible to prepare hyperpolarized agents with lifetimes of 10 minutes or more. This, in turn, may enable a much wider range of applications for hyperpolarized MRI. We propose a series of theoretical calculations and experimental studies that will identify promising agents for long-lived proton systems. In addition, we will develop methods for preparing candidate long-lived states in systems containing nuclei such as Carbon-13. The lifetimes of these agents will be measured in vitro and compared with theory, and in vivo measurements will be performed in animals. PUBLIC HEALTH RELEVANCE: Hyperpolarized liquid contrast media can enhance the sensitivity of magnetic resonance imaging (MRI) by a factor of 10,000 relative to conventional methods. Many potential applications of hyperpolarization are limited by the short lifetime of the signal enhancement, which is generally on the order of a few minutes. In our proposed work, we will investigate methods for achieving longer lifetimes through the use of specially prepared quantum-mechanical spin states. Theoretical and experimental work will be used to develop an understanding the mechanisms that enable prolonged lifetimes, and candidate contrast agents will be identified and tested.