The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield ~ 4 mL, 60 mM 1-¹³C-pyruvic acid in an aqueous solution was quantified in five experiments to P(¹³C) = (38 ± 6) % (19 ± 1) s after dissolution. The mono-exponential time constant of the build-up of the solid-state polarization was quantified to (1032 ± 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized ¹⁵N urea was obtained (P(¹⁵N) = (5.6 ± 0.8) % (30 ± 3) s after dissolution).

The signal of magnetic resonance imaging (MRI) can be enhanced by several orders of magnitude using hyperpolarization. In comparison to a broadly used dynamic nuclear polarization (DNP) technique that is already used in clinical trials, the parahydrogen (pH₂)-based hyperpolarization approaches are less cost-intensive, are scalable, and offer high throughput. However, a pH₂ generator is necessary. Available commercial pH₂ generators are relatively expensive (EUR 10 000–150 000). To facilitate the spread of pH₂-based hyperpolarization studies, here we provide the blueprints and 3D models as open-source for a low-cost (EUR <3000) 50-bar liquid-nitrogen-cooled pH₂ generator.

The hyperpolarization of nuclear spins is a game-changing technology that enables hitherto inaccessible applications for magnetic resonance in chemistry and biomedicine. Despite significant advances and discoveries in the past, however, the quest to establish efficient and effective hyperpolarization methods continues. Here, we describe a new method that combines the advantages of direct parahydrogenation, high polarization (P), fast reaction, and low cost with the broad applicability of polarization transfer via proton exchange. We identified the system propargyl alcohol + pH₂ → allyl alcohol to yield ¹H polarization in excess of P ≈ 13% by using only 50% enriched pH₂ at a pressure of ≈1 bar. The polarization was then successfully relayed via proton exchange from allyl alcohol to various target molecules. The polarizations of water and alcohols (as target molecules) approached P ≈ 1% even at high molar concentrations of 100 mM. Lactate, glucose, and pyruvic acid were also polarized, but to a lesser extent. Several potential improvements of the methodology are discussed. Thus, the parahydrogen-induced hyperpolarization relayed via proton exchange (PHIP-X) is a promising approach to polarize numerous molecules which participate in proton exchange and support new applications for magnetic resonance.

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1- ¹⁵ N-NAM and 1- ¹⁵ N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% ¹⁵ N polarization. We found that the lifetime of hyperpolarized 1- ¹⁵ N-NAM is strongly field- and pH-dependent, with T ₁ being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1- ¹⁵ N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using ¹⁵ N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a ¹⁵ N MRI of 1- ¹⁵ N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.

We describe a new method for pulsed spin order transfer of parahydrogen-induced polarization (PHIP) that enables high polarization in incompletely ² H-labeled molecules by exciting only the desired protons in a frequency-selective manner.