Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR

Abstract

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 ...

Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1‐13C]pyruvate and 13C‐urea

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Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

“…Hyperpolarization of 13 C nuclei can increase their sensitivity to detection in a magnetic resonance experiment by more than 10 000‐fold 35. This enormous increase in sensitivity has enabled real‐time imaging of tissue metabolism in vivo following intravenous injection of hyperpolarized 13 C‐labelled substrates,36 including in humans 37, 38.…”

Unprecedented Carbon Signal Enhancement in Liquid‐State NMR Spectroscopy

“…Any increase by technical means will significantly extend the possibility range of NMR application.”1 This quotation from Richard Ernst's Nobel prize lecture sets the stage for numerous studies and approaches to improve the signal‐to‐noise‐ratio (S/N) in NMR. In recent years, many different methods, including PHIP,2 SABRE,2 hyperpolarized noble gases,3 MAS DNP,4 nitrogen vacancies in diamonds,5 dissolution DNP,6 and DNP in the solid‐state,7 have been developed, and a summary of these can be found in a recent review article in Angewandte Chemie 8…”