Stand-alone two-phase parahydrogen induced hyperpolarizer for ultra-low and high field MR (2P-PHIP)

磁共振（MR）在许多科学领域发挥着举足轻重的作用，为了增强其固有的低信号，一些超极化（HP）技术被开发出来，例如溶解动态核极化（dDNP）技术正处于临床前研究阶段。它需要低温（~ 1k），顺磁剂和微波一起用于HP，并在合适的载体中快速溶解。这使得dDNP在技术上具有挑战性，本质上是一种一次性技术。另一种HP方法是利用对氢（pH2 - H2的自旋单重异构体）的本征自旋顺序，它可以转移到目标分子上。pH2诱导极化（PHIP）利用目标分子与pH2的氢化作用，而可逆交换（SABRE）的信号放大允许自旋顺序转移而无需修饰目标分子，从而实现连续的HP。由于pH2生成成本低，仪器需求低，并且pH2可以存储数月，因此PHIP和SABRE是未来临床应用中有前途的HP方法。2P-PHIP项目旨在开发一种具有成本效益的PHIP和基于sabre的独立连续流超极化反应器，用于生物化学和未来的体内生物医学应用。与市售的dDNP相比，该反应器将能够连续提供高纯度的超极化液体，从而使MR实验具有更长的采集时间和更大的数量。一种新的两相pH2诱导HP技术，催化剂保留在氟化相（或另一种疏水相）中，将是最有前途的途径。这种方法将有助于提取高纯度的超极化底物，以满足未来体内应用的需要。更传统的（单相）PHIP和SABRE实现也可以使用该偏振器。独立电抗器可用于超低（μ t范围）或高磁场（t范围）MR，从而实现两种状态的独特功能。高磁场下的磁共振成像提供卓越的光谱分辨率，而低磁场下的成像与敏感植入物（即起搏器）兼容。使用非传统方法对HP进行调查，直接观察HP本身将使用最灵敏的SQUID仪器进行。由于我们的最终目标是在体内应用，因此也将进行生物样品（如细胞培养，血液或均质脑组织）的概念验证实验。2P-PHIP项目的成果将是一个多用途的独立的基于ph2的偏振器，具有高浓度的高度极化底物和高示踪通量，可用于体内应用。

Magnetic resonance (MR) plays a pivotal role in many fields of science, and to enhance its intrinsically low signal several hyperpolarization (HP) techniques were developed For instance, dissolution dynamic nuclear polarization (dDNP) is in a state of preclinical research. It requires low temperatures (~1 K), paramagnetic agents together with microwaves for HP, and the rapid dissolution in a suitable carrier. This makes dDNP technically challenging and essentially a one-shot technique.An alternative HP method is the exploitation of the intrinsic spin order of para hydrogen (pH2 – the spin singlet isomer of H2), which can be transferred to target molecules. pH2 induced polarization (PHIP) makes use of the hydrogenation of target molecules with pH2, whereas signal amplification by reversible exchange (SABRE) allows spin order transfer without the modification of target molecules and enables continuous HP. As pH2 generation is low cost, low instrumentation demands and pH2 can be stored for months, PHIP and SABRE are promising methods of HP for future clinical applications.The project 2P-PHIP aims to the development of a cost-efficient PHIP and SABRE-based stand-alone continuous flow hyperpolarization reactor for biochemistry and future in vivo biomedical applications. In contrast to commercially available dDNP, the reactor will be able to continuously deliver high purity hyperpolarized liquids enabling MR experiments with longer acquisition times and larger quantities. A novel two-phase pH2 induced HP technique with the catalyst retained in a fluorinated phase (or another hydrophobic phase) will be pursued as the most promising route. This approach will facilitate the extraction of hyperpolarized substrates with high purity needed for future in vivo applications. More traditional (single-phase) PHIP and SABRE implementations will also be possible with this polarizer. The stand-alone reactor can be used at ultra-low (µT-range) or high magnetic field (T-range) MR enabling unique features of both regimes. MR at high magnetic fields provide superior spectral resolution, whereas imaging at low magnetic fields is compatible with sensitive implants (i.e. pacemakers). The investigation of HP using non-traditional methods, the direct observation of the HP itself will be carried out using the most sensitive SQUID instrumentation available. As we ultimately aim to in vivo applications, proof-of-concept experiments on biological samples, such as cell cultures, blood or homogenized brain tissue will also be undertaken.The outcome of the 2P-PHIP project will be a multipurpose stand-alone pH2-based polarizer featuring high concentrations of highly polarized substrates with high tracer throughput for in vivo applications.