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

磁共振(MR)在许多科学领域中起着举足轻重的作用，为了增强其固有的低信号，人们发展了几种超极化(HP)技术，如溶解动态核极化(DDNP)处于临床前研究状态。它需要低温(~1K)、顺磁剂和微波的配合，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的技术。另一种HP方法是利用对氢的固有自旋顺序(PH2-H2的自旋单重态异构体)，它可以转移到目标分子上。PH2激发极化(PhIP)利用目标分子与PH2的氢化作用，而可逆交换信号放大(SABRE)允许自旋有序转移而不改变目标分子，从而实现连续的HP。由于PH2的生成成本低，对仪器的要求低，并且PH2可以储存数月，PhIP和Sabre是未来临床应用的很有前途的HP方法。项目2P-PhIP旨在开发一种低成本的PhIP和Sabre独立连续流动超极化反应器，用于生物化学和未来体内生物医学的应用。与商用的DDNP相比，该反应堆将能够连续提供高纯度的超极化液体，使磁共振实验能够以更长的采集时间和更大的数量进行。一种将催化剂保留在氟化相(或另一疏水相)中的新型两相PH2诱导高压技术将是最有前途的路线。这种方法将有助于提取未来活体应用所需的高纯度超极化底物。使用这种偏振器也可以实现更传统的(单相)PHIP和SABRE。该独立电抗器可在超低(µT范围)或高磁场(T范围)MR下使用，从而实现了这两种制度的独特功能。高磁场下的MR提供卓越的光谱分辨率，而低磁场下的成像与敏感的植入物(即起搏器)兼容。使用非传统方法对幽门螺杆菌进行调查，将使用现有最灵敏的鱿鱼仪器对幽门螺杆菌本身进行直接观察。随着我们的最终目标是在体内应用，我们还将对生物样本进行概念验证实验，如细胞培养、血液或匀浆脑组织。2P-PhIP项目的结果将是一种基于PH2的多用途独立偏振器，具有高浓度的高度极化底物和高示踪剂吞吐量，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.