Toward biocompatible nuclear hyperpolarization using signal amplification by reversible exchange: quantitative in situ spectroscopy and high-field imaging.

Signal amplification by reversible exchange (SABRE) of a substrate and parahydrogen at a catalytic center promises to overcome the inherent insensitivity of magnetic resonance. In order to apply the new approach to biomedical applications, there is a need to develop experimental equipment, in situ quantification methods, and a biocompatible solvent. We present results detailing a low-field SABRE polarizer which provides well-controlled experimental conditions, defined spins manipulations, and which allows in situ detection of thermally polarized and hyperpolarized samples. We introduce a method for absolute quantification of hyperpolarization yield in situ by means of a thermally polarized reference. A maximum signal-to-noise ratio of ∼10(3) for 148 µmol of substance, a signal enhancement of 10(6) with respect to polarization transfer field of SABRE, or an absolute (1)H-polarization level of ≈10(-2) is achieved. In an important step toward biomedical application, we demonstrate (1)H in situ NMR as well as (1)H and (13)C high-field MRI using hyperpolarized pyridine (d3) and (13)C nicotinamide in pure and 11% ethanol in aqueous solution. Further increase of hyperpolarization yield, implications of in situ detection, and in vivo application are discussed.

A hyperpolarized equilibrium for magnetic resonance.

Nuclear magnetic resonance spectroscopy and imaging (MRI) play an indispensable role in science and healthcare but use only a tiny fraction of their potential. No more than ≈10 p.p.m. of all ¹H nuclei are effectively detected in a 3-Tesla clinical MRI system. Thus, a vast array of new applications lays dormant, awaiting improved sensitivity. Here we demonstrate the continuous polarization of small molecules in solution to a level that cannot be achieved in a viable magnet. The magnetization does not decay and is effectively reinitialized within seconds after being measured. This effect depends on the long-lived, entangled spin-order of parahydrogen and an exchange reaction in a low magnetic field of 10⁻³ Tesla. We demonstrate the potential of this method by fast MRI and envision the catalysis of new applications such as cancer screening or indeed low-field MRI for routine use and remote application.

A battery-driven, low-field NMR unit for thermally and hyperpolarized samples.

OBJECT: The design of a multinuclear low-field NMR unit with variable field strength <6 mT providing accurate spin manipulations and sufficient sensitivity for direct detection of samples in thermal equilibrium to aid parahydrogen-based hyperpolarization experiments. MATERIALS AND METHODS: An optimized, resistive magnet connected to a battery or wall-power driven current source was constructed to provide a magnetic field <6 mT. A digital device connected to a saddle-shaped transmit- and solenoid receive-coil enabled MR signal excitation and detection with up to 10(6) samples/s, controlled by a flexible pulse-programming software. RESULTS: The magnetization of thermally polarized samples at 1.8 and 5.7 mT is detected in a single acquisition with a SNR ≈10(1) and ≈10(2) and a line width of 42 and 32 Hz, respectively. Nuclear spins are manipulated to an uncertainty of ±1° by means of pulses, which can be arranged in an arbitrary combination. As a demonstration, standard experiments for the measurement of relaxation parameters of thermally polarized samples were implemented. The detection of much stronger hyperpolarized signal was exemplified employing parahydrogen. CONCLUSION: Direct detection of thermal and hyperpolarized (1)H-MR signal in a single acquisition and accurate spin manipulations at 1.8 and 5.5 mT were successfully demonstrated.