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将MRI的灵敏度提高10，000倍或更多。这些信号增强可以在MRI的许多现有应用中产生显著的改进，包括血管造影和灌注成像。此外，由于可以检测内源性物质，这些技术开始显示出新的应用前景，如“实时”代谢成像，不仅监测药物的运输和摄取，还监测代谢转化。由超极化提供的灵敏度的增益在某种程度上被信号增强的相对短的寿命所抵消。事实上，一旦制备了试剂，其磁化强度就会以自旋-晶格弛豫时间T1所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。这些短的寿命限制了试剂的可用运输、摄取和代谢的时间窗。这反过来又可能限制超极化MRI的可行应用范围。最近的工作表明，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，这些长寿命的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见方法之一。在我们的研究中，我们将探讨应用仲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了寿命比传统T1弛豫时间长2.5倍的状态，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，以确定这些增强寿命的起源。如果类似的增强可以在包含原子核的系统中获得，例如当与质子分离时具有长弛豫时间的碳-13，那么缩放参数表明，有可能制备寿命为10分钟或更长的超极化剂。这反过来又可以使超极化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，将确定有前途的代理长寿命的质子系统。此外，我们还将开发在含有碳-13等原子核的系统中制备候选长寿命态的方法。将在体外测量这些药剂的寿命并与理论进行比较，并在动物中进行体内测量。公共卫生相关性：超极化液体造影剂可使磁共振成像（MRI）的灵敏度相对于常规方法提高10，000倍。超极化的许多潜在应用受到信号增强的短寿命的限制，其通常为几分钟的量级。在我们提出的工作中，我们将研究通过使用特别制备的量子力学自旋态来实现更长寿命的方法。理论和实验工作将被用来开发一个理解的机制，使寿命延长，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.