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

描述（由申请人提供）：超极化液相造影剂可以将MRI的灵敏度提高1万倍或更多。这些信号增强可能会显著改善MRI的许多现有应用，包括血管造影和灌注成像。此外，由于可以使内源性物质极化，这些技术开始显示出新的应用前景，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相对较短的信号增强寿命所抵消。事实上，一旦制备了一种试剂，它的磁化强度就会以由自旋晶格弛豫时间T1决定的速率不可逆地衰减。现有的介质通常具有一分钟或更短的松弛时间，这意味着超极化磁化的有效寿命为几分钟。这些短暂的生命期限制了药物的运输、吸收和代谢的时间窗口。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可以比传统的T1弛豫时间长近一个数量级。此外，这些长寿命态类似于制备超极化介质的常见方法之一——对氢诱导极化中的态。在我们提出的研究中，我们将探讨应用副氢诱导极化和相关方法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寿命是传统T1弛豫时间的2.5倍，并且文献中已经记录了8倍增强的例子。我们也开始了理论研究，以确定这些延长寿命的起源。如果类似的增强可以在含有碳-13等原子核的系统中获得，这些原子核在与质子分离时具有很长的弛豫时间，那么缩放论点表明，有可能制备寿命为10分钟或更长时间的超极化试剂。反过来，这可能使超极化MRI的应用范围更广。我们提出了一系列的理论计算和实验研究，将确定长寿命质子系统的有希望的剂。此外，我们将开发在含有碳-13等原子核的系统中制备候选长寿命态的方法。这些药物的寿命将在体外测量并与理论进行比较，而在体内的测量将在动物身上进行。公共卫生相关性：相对于传统方法，超偏振液体造影剂可将磁共振成像（MRI）的灵敏度提高10,000倍。超极化的许多潜在应用受到信号增强寿命短的限制，通常在几分钟左右。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的寿命的方法。理论和实验工作将用于了解延长使用寿命的机制，候选造影剂将被确定和测试。

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.