A method for obtaining strongly polarized nuclear spins in solution has been developed. The method uses low temperature, high magnetic field, and dynamic nuclear polarization (DNP) to strongly polarize nuclear spins in the solid state. The solid sample is subsequently dissolved rapidly in a suitable solvent to create a solution of molecules with hyperpolarized nuclear spins. The polarization is performed in a DNP polarizer, consisting of a superconducting magnet (3.35 T) and a liquid-helium cooled sample space. The sample is irradiated with microwaves at Ϸ94 GHz. Subsequent to polarization, the sample is dissolved by an injection system inside the DNP magnet. The dissolution process effectively preserves the nuclear polarization. The resulting hyperpolarized liquid sample can be transferred to a high-resolution NMR spectrometer, where an enhanced NMR signal can be acquired, or it may be used as an agent for in vivo imaging or spectroscopy. In this article we describe the use of the method on aqueous solutions of [ 13 C]urea. Polarizations of 37% for 13 C and 7.8% for 15 N, respectively, were obtained after the dissolution. These polarizations correspond to an enhancement of 44,400 for 13 C and 23,500 for 15 N, respectively, compared with thermal equilibrium at 9.4 T and room temperature. The method can be used generally for signal enhancement and reduction of measurement time in liquid-state NMR and opens up for a variety of in vitro and in vivo applications of DNP-enhanced NMR. T wo major applications exist for NMR: spectroscopy and imaging. NMR spectroscopy has gained acceptance as one of the major analytical techniques due to the detailed information that can be obtained about molecular structure, dynamics, and intra-and intermolecular interactions. MRI is a noninvasive technique with superior soft-tissue contrast and broad diagnostic value. The technique has gained wide clinical acceptance and is of great importance in diagnostic medicine.However, despite significant technological advancements (increasing field strength and cooling of electronics), the application of NMR is limited by an intrinsically low sensitivity as compared with other analytical methods. Fundamentally, the low sensitivity originates from the low magnetic energy of nuclear spins compared with the thermal energy at room temperature. At a magnetic field strength of 1.5 T and room temperature, the 1 H spins are polarized to only 5 ppm, and an improvement of 200,000 is thus theoretically possible. The two most sensitive nuclei are 1 H and 19 F, which have large magnetic moments and 100% abundance. But, even at the largest field strength available today (21 T), these nuclei are polarized to only 70 and 67 ppm, respectively. For other nuclei bearing lower magnetic moments (1͞4 for 13 C and 1͞10 for 15 N compared with 1 H), the theoretical enhancement factor is proportionally greater. The weak nuclear polarization is generally compensated by a high concentration (i.e., a large number of nuclear spins). However, the sensitivity of several other ...

The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...

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