Roberto Melzi

Boosting Dissolution Dynamic Nuclear Polarization by Cross Polarization

The efficiency of dissolution dynamic nuclear polarization can be boosted by Hartmann-Hahn cross polarization at temperatures near 1.2 K. This enables high throughput of hyperpolarized solutions with substantial gains in buildup times and polarization levels. During dissolution and transport, the (13)C nuclear spin polarization P((13)C) merely decreases from 45 to 40%.

Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization

Significance Hyperpolarization by dissolution dynamic nuclear polarization can dramatically enhance signal intensities in MRI and NMR, notably for metabolic tracers for imaging and diagnosis. It is applicable to a variety of substrates for in vivo imaging and chemistry but requires the use of contaminants (glassing agents and free radicals) that may interact with cells and proteins and can have potential side effects. These contaminants can sometimes be eliminated by precipitation followed by filtration or solvent extraction, but these methods are substrate-specific, are usually time-consuming, and typically result in signal loss. Here, production of pure hyperpolarized liquids free of contaminants is shown by a simple wetting–polarization–filtration sequence for a solid silica matrix containing homogeneously distributed persistent radicals. Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion.

Hyperpolarization of deuterated metabolites via remote cross-polarization and dissolution dynamic nuclear polarization.

In deuterated molecules such as [1-(13)C]pyruvate-d3, the nuclear spin polarization of (13)C nuclei can be enhanced by combining Hartmann-Hahn cross-polarization (CP) at low temperatures (1.2 K) with dissolution dynamic nuclear polarization (D-DNP). The polarization is transferred from remote solvent protons to the (13)C spins of interest. This allows one not only to slightly reduce build-up times but also to increase polarization levels and extend the lifetimes T1((13)C) of the enhanced (13)C polarization during and after transfer from the polarizer to the NMR or MRI system. This extends time scales over which metabolic processes and chemical reactions can be monitored.

Dissolution dynamic nuclear polarization of deuterated molecules enhanced by cross-polarization

We present novel means to hyperpolarize deuterium nuclei in 13CD2 groups at cryogenic temperatures. The method is based on cross-polarization from 1H to 13C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by 13C NMR in solution. These long-lived states result from a sextet-triplet imbalance (STI) that involves the two equivalent deuterons with spin I = 1. An STI has similar properties as a triplet-singlet imbalance that can occur in systems with two equivalent I = 12 spins. Although the lifetimes TSTI are shorter than T1(Cz), they can exceed the life-time T1(Dz) of deuterium Zeeman magnetization by a factor of more than 20.

Hyperpolarization of nitrogen-15 nuclei by cross polarization and dissolution dynamic nuclear polarization

Dynamic Nuclear Polarization (DNP) is often achieved by the direct transfer of polarization from electrons to nuclei such as 13C, induced by microwave saturation of the wings of narrow EPR lines of radicals like trityl. In the indirect approach on the other hand, DNP is used to transfer the polarization from the electrons of radicals such as nitroxides that have broad EPR lines to nuclear spins I = 1H, followed by cross-polarization (CP) from I = 1H to S = 13C or other nuclei with low gyromagnetic ratios. This approach is particularly attractive for S = 15N, since direct DNP yields modest polarizations P(15N) < 4% with build-up times that can be as long as τDNP(15N) > 2 h. In this paper, we show that CP from 1H to 15N at 1.2 K can yield P(15N) = 25% with τCP-DNP(15N) = 10-15 min. After rapid dissolution and transfer to a solution-state NMR spectrometer, a polarization P(15N) = 20% was observed at 300 K. The longitudinal relaxation times in solution can be as long as T1(15N) > 800 s in favorable cases.

Cross polarization from H-1 to quadrupolar Li-6 nuclei for dissolution DNP

Cross polarization from protons to quadrupolar (6)Li nuclei is combined with dynamic nuclear polarization of protons at 1.2 K and 6.7 T using TEMPOL as a polarizing agent followed by rapid dissolution. Compared to direct (6)Li DNP without cross-polarization, a higher nuclear spin polarization P((6)Li) can be obtained in a shorter time. A double resonance (1)H-(6)Li probe was designed that is equipped for Longitudinally Detected Electron Spin Resonance.