SABRE polarized low field rare-spin spectroscopy

Abstract

High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR instruments operating at low magnetic fields are emerging as a compact, inexpensive, and highly accessible alternative but suffer from low thermal polarization at a low field strength and consequently a low signal. However, certain hyperpolarization techniques create high polarization levels on target molecules independent of magnetic fields, giving low-field NMR a significant sensitivity boost. In this study, SABRE (Signal Amplification By Reversible Exchange) was combined with high homogeneity electromagnets operating at mT fields, enabling high resolution 1H, 13C, 15N, and 19F spectra to be detected with a single scan at magnetic fields between 1 mT and 10 mT. Chemical specificity is attained at mT magnetic fields with complex, highly resolved spectra. Most spectra are in the strong coupling regime where J-couplings are on the order of chemical shift differences. The spectra and the hyperpolarization spin dynamics are simulated with SPINACH. The simulations start from the parahydrogen singlet in the bound complex and include both chemical exchange and spin evolution at these mT fields. The simulations qualitatively match the experimental spectra and are used to identify the spin order terms formed during mT SABRE. The combination of low field NMR instruments with SABRE polarization results in sensitive measurements, even for rare spins with low gyromagnetic ratios at low magnetic fields.

Spin dynamics of [1,2-13C2]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields

“…The code for simulation of field-cycled SABRE experiments was developed based on previous work and is provided as supplement. 43 Specifically, we added the capabilities for shuttling and field sweeps. The parameters of the simulation were optimized to mirror the parameters and the design of the experimental field sweeps.…”

Recent advances in the application of parahydrogen in catalysis and biochemistry

“…100 Bernarding et al 75,101,102 described the hyperpolarization of 19 F containing substrates, which has a high application potential as contrast agent in MRI, as there is practically no 19 F background in living tissue. Glöggler et al 103,104 reported a pulsed transfer experiment, which can nearly completely transfer the hyperpolarization from the protons to the 13 C. Theis et al 105 discussed SABRE hyperpolarization for sensitivity enhancement of rare X-nuclei. Ivanov et al 106 proposed the INEPT-SABRE sequence for polarization transfer in SABRE experiments and developed a number of versatile tools based on utilizing level-anti-crossing (LAC) in the rotating frame for transferring spin hyperpolarization.…”

Comprehensive Literature Review of Hyperpolarized Carbon-13 MRI: The Road to Clinical Application

“…Multiple methods to achieve hyperpolarization have been explored including brute force polarization, parahydrogen-induced polarization (PHIP)-based methods [ 81 , 82 , 83 ], and dynamic nuclear polarization (DNP). Currently, the only polarization process approved to be used for clinical studies of carbon-13 is DNP [ 11 ].…”

“…PHIP has the advantage of being cheap and easy to use and allows for very rapid polarization. Several proposals to alter the PHIP process have been suggested, such as signal amplification by reversible exchange (SABRE [ 82 ]), synthesis amid the magnet bore allows dramatically enhanced nuclear alignment (SAMBADENA [ 83 ]), and PHIP by means of side arm hydrogenation (PHIP-SAH [ 86 ]). Until recently, the requirements of unsaturated precursor molecules, toxic solutions, and catalyzers have been a significant limitation for in vivo applications.…”