Metabolic and Molecular MRI using Hyperpolarized Tracers

点击翻译按钮获取中文摘要

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.