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

超极化 MRI：准备长寿命超极化对比年龄的方法

• 批准号: 7532341
• 负责人: Aaron Keith Grant
• 金额: $ 20.55万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7532341
• 关键词: Age; Anatomy; Angiography; Animals; Biochemical; Biocompatible; Blood; Carbon; Cell Nucleus; Characteristics; Chemicals; Class; Classification; Condition; Contrast Media; Development; Diagnostic; Ensure; Family; Gadolinium; Half-Life; Hand; Image; Imaging Techniques; In Vitro; Ionizing radiation; Life; Liquid substance; Literature; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Mechanics; Metabolic; Metabolism; Methods; Molecular; Monitor; Mus; Noise; Nuclear; Oxygen; Perfusion; Phase; Positron-Emission Tomography; Protons; Public Health; Range; Rate; Relative (related person); Relaxation; Research; Research Infrastructure; Resolution; Series; Signal Transduction; Solvents; Specificity; Spectrum Analysis; Surveys; System; Techniques; Temperature; Testing; Time; Tracer; Viscosity; Work; base; cost; experience; in vivo; metabolic abnormality assessment; quantum; research study; spectroscopic imaging; theories; tool; uptake

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.

描述（由申请人提供）：超极化液相对比介质可以提高MRI的灵敏度10,000倍或更多。这些信号增强功能可能会在MRI的许多现有应用（包括血管造影和灌注成像）中产生显着改善。此外，由于可能使内源性物质极化，因此这些技术开始对新应用显示出希望，例如“实时”代谢成像，这些成像不仅可以监测转运和吸收剂，还可以监测代谢转换。超极化所提供的灵敏度的增益在某种程度上被信号增强的寿命相对较短。确实，一旦制备了试剂，其磁化强度以由自旋静态放松时间T1决定的速度不可逆转地衰减。现有代理通常在一分钟或更短的时间内具有放松时间，这意味着超极化磁化的寿命为几分钟。这些短寿命限制了代理商的可用运输，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。最近的工作表明，某些一致的量子机械旋转状态的寿命几乎比常规T1松弛时间长大的数量级。此外，这些长寿命的状态类似于偏二二氢诱导的极化的状态，这是制备超极化培养基的常见方法之一。在我们提出的研究中，我们将研究应用偏高的极化和相关方法来制备长期寿命超极化状态的可能性。对超极化质子的初步实验结果已经证明了寿命比常规T1松弛时间长2.5倍的状态，并且文献中已经记录了8倍增强的示例。我们还开始进行理论工作，以确定这些增强寿命的起源。如果可以在含有核酸核的核酸核13的系统中获得类似的增强，从而从质子分离出长时间松弛时间，则缩放参数表明，可以准备以10分钟或更长时间的寿命制备超极化剂。反过来，这可能使超极化MRI的应用范围更大。我们提出了一系列理论计算和实验研究，这些计算将确定长寿质子系统的有希望的药物。此外，我们还将开发用于准备候选候选状态的方法，这些状态在包含核13等核的系统中。这些药物的寿命将在体外测量并与理论进行比较，并将在动物中进行体内测量。公共卫生相关性：超极化液体对比介质可以相对于常规方法增强磁共振成像（MRI）的灵敏度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，该信号增强的寿命通常为几分钟。在我们提出的工作中，我们将通过使用专门准备的量子力学自旋状态来研究实现更长寿命的方法。理论和实验工作将用于发展能够延长寿命的机制，并将确定和测试候选对比剂。