Hyperpolarization

Dissolution DNP

Dynamic Nuclear Polarization (DNP) is a well-established technique that transfers the polarization of unpaired electrons to the nuclei under study. Dissolution DNP methods require the sample to be kept cold (e.g., <4 K) while irradiated by microwaves in a strong magnetic field (e.g., 3 T). After irradiation, the sample is rapidly dissolved using a hot, pressurized deuterated NMR solvent and transferred to an NMR tube or an injection syringe for immediate NMR or MRI data acquisition. A free-radical doping agent must be present in the sample at mM concentrations during microwave irradiation to provide the nuclear polarization needed for intermolecular transfer. Acceptable polarization levels are generally achieved with irradiation times ranging from several tens of minutes to several hours.

Low-temperature DNP, a method pioneered by the laboratory of Robert Griffin, differs slightly from dissolution DNP: both hyperpolarization and NMR acquisition take place in the solid state, where the hyperpolarized signal is continually regenerated — allowing data acquisition over hours to many days.

Parahydrogen-Induced Polarization (PHIP)

PHIP is a well-established technique that transfers polarization directly from parahydrogen (para-H₂) to nearby nuclei of interest, or via RF-based magnetization transfer methods. For organic molecules, para-H₂ is either added directly across unsaturated carbon bonds, or mixed with the sample under conditions that allow polarization to transfer from para-H₂ to sites within the molecule. Compared to DNP, PHIP offers two key advantages: a polarized sample can be obtained in seconds to minutes, and no free-radical doping agent is required.

Metabolic Imaging

Perhaps the most exciting consequence of the signal enhancement obtained using DNP and PHIP is the potential for in vivo ¹H, ¹³C, and ¹⁵N monitoring of metabolism. In particular, ¹³C MRI imaging using hyperpolarized ¹³C-enriched organic molecules offers significant advantages over ¹H-based imaging, since background signals are not detected and the large chemical shift range of ¹³C increases molecular selectivity.

There is growing interest in isotopically enriched, hyperpolarized substrates for medical imaging, since they can provide detailed metabolic information (substrate localization and biochemical transformations) as well as physiological information such as intracellular pH. Although the signal enhancement of hyperpolarized spin-1/2 nuclei decays with T₁, research is underway to establish long-lived nuclear states, with the promise that metabolism may be studied over time scales of minutes or even hours instead of seconds.

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