Metabolic and Molecular MRI using Hyperpolarized Tracers

在临床检查中，磁共振（MR）仅使用理论可用信号的百万分之三（极化≈3∙10-6）。尽管磁共振的潜力没有得到充分利用，但它对现代诊断至关重要。本应用程序的目标是使用新的（目标1）和已建立的（目标2）超极化方法来访问这种潜力。因此，可能会出现全新的或显著改进的诊断方法。直到最近，我们才提出了一种新方法，该方法可以在磁共振扫描期间将磁共振信号增加几个数量级（即100,000倍，对应于bbb100 T的磁场）。这种磁共振扫描不需要强大的磁铁，这是传统MR高成本的原因。我们将研究这种方法在潜在的生物医学应用方面的应用。其结果可能是使用低成本、低场的移动MR扫描仪对体内肿瘤进行快速、高分辨率成像，而不需要专用的基础设施。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对MR信号进行一次强增强。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。超极化代谢示踪剂、功能性示踪剂和靶向示踪剂都是可用的，并将应用于宿主研究所可用的实验模型：作为tca循环的一部分，生物分子1-13C， 2,3- 2h2琥珀酸盐的信号将被提高几个数量级，并提供给细胞培养和动物模型。一方面，这可能允许无创地、实时地、在体内跟踪新陈代谢。另一方面，我们将评估这种分子作为对比剂的潜力，以检测例如血脑屏障的小破坏。2. 胆盐在几秒钟内就会被健康的肝脏过滤掉。由于信号低，试图用19f标记的胆汁盐和MRI测量该参数失败。我们将把信号增强几个数量级，以便在活体动物模型中获得肝功能。3. libs抗体在几秒钟内就能与易损斑块结合。它成功地与铁标签和MRI一起用于斑块成像。我们将用一个具有强增强信号的超极化分子代替铁标签。这可能使体内斑块的高分辨率、无背景成像成为可能。

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.