Metabolic and Molecular MRI using Hyperpolarized Tracers

使用超极化示踪剂的代谢和分子 MRI

• 批准号: 246504068
• 负责人: Professor Dr. Jan-Bernd Hövener
• 金额: --
• 依托单位: Molecular Imaging North Competence Center (MOIN CC)
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/246504068?language=en
• 关键词: Metabolic; Molecular; MRI; using; Hyperpolarized

In a clinical examination, Magnetic Resonance (MR) uses only about 3 parts of a million of the theoretically available signal (the polarization is ≈ 3 ∙ 10-6). Despite the poor use of its potential, MR is vital to modern diagnostics. The goal of this application is to access this potential using new (Goal 1) and established (Goal 2) hyperpolarization methods. As a result, entirely new or dramatically improved diagnostic methods may become available. Goal 1: New Hyperpolarization Methods Only recently, we presented a new method, which allows the increase the MR signal during an MR scan by several orders of magnitude (i.e. 100.000 fold, corresponding to a magnetic field of >100 T). This MR scan requires no strong magnets, which are responsible for the high cost of conventional MR. We will investigate this method with respect to a potential biomedical application. A result may be fast and high-resolution imaging of tumors in vivo with low-cost, low-field mobile MR scanners, which require no dedicated infrastructure. Goal 2: Application of Established Hyperpolarization Methods Conventional hyperpolarization methods allow to strongly enhance MR signal once and for a limited time only. In contrast to the new technique being investigated in Goal 1, the methods to generate a transient and single-use signal enhancement were already established by the applicant. Hyperpolarized metabolic, functional and targeted tracers are available and will be applied to experimental models available at the host institute: 1. The signal of biomolecule 1-13C, 2,3-2H2 succinate, part of the TCA-cycle, will be enhanced by several orders of magnitude and supplied to cell cultures and animal models. On the one hand, this may allow to follow metabolism non invasively, in real time and in vivo. On the other hand, we will evaluate the potential of this molecule as a contrast agent to detect e.g. small breaches of the blood-brain barrier. 2. Bile-salts are being filtered by the healthy liver within few seconds. Attempts to measure this parameter with 19F-labeled bile salts and MRI failed because of low signal. We will enhance the signal by several orders of magnitude, to access liver function in an animal model in vivo. 3. The LIBS-antibody binds to vulnerable plaque within seconds. It was successfully used with iron-label and MRI to image plaques. We will replace the iron label by a hyperpolarized molecule with strongly enhanced signal. This may allow high-resolution, background-free imaging of plaques in vivo.

在临床检查中，磁共振 (MR) 仅使用理论上可用信号的约百万分之三（极化为 ≈ 3 ∙ 10-6）。尽管 MR 的潜力未被充分利用，但它对于现代诊断至关重要。该应用的目标是使用新的（目标 1）和已建立的（目标 2）超极化方法来发挥这种潜力。因此，可能会出现全新的或显着改进的诊断方法。目标 1：新的超极化方法 最近，我们提出了一种新方法，它允许在 MR 扫描期间将 MR 信号增加几个数量级（即 100.000 倍，对应于 >100 T 的磁场）。这种 MR 扫描不需要强磁体，而强磁体是传统 MR 成本较高的原因。我们将研究这种方法的潜在生物医学应用。其结果可能是使用低成本、低场移动磁共振扫描仪对体内肿瘤进行快速、高分辨率成像，而无需专用基础设施。目标 2：已建立的超极化方法的应用传统的超极化方法只能在有限的时间内强烈增强 MR 信号。与目标1中正在研究的新技术相反，申请人已经建立了产生瞬态和一次性信号增强的方法。超极化代谢、功能和靶向示踪剂可供使用，并将应用于主办机构提供的实验模型： 1. TCA 循环一部分的生物分子 1-13C、2,3-2H2 琥珀酸的信号将增强几个数量级，并提供给细胞培养物和动物模型。一方面，这可以允许在体内非侵入性地实时跟踪新陈代谢。另一方面，我们将评估该分子作为造影剂的潜力，以检测例如血脑屏障的微小突破。 2. 胆汁盐在几秒钟内被健康的肝脏过滤。由于信号低，尝试用 19F 标记的胆盐和 MRI 测量该参数失败。我们将把信号增强几个数量级，以了解动物模型体内的肝功能。 3. LIBS 抗体在几秒钟内与易损斑块结合。它成功地与铁标记和 MRI 一起使用来对斑块进行成像。我们将用信号强烈增强的超极化分子取代铁标记。这可以实现体内斑块的高分辨率、无背景成像。