Localized singlet-filtered MRS in vivo.

MR is a prominent technology to investigate diseases, with millions of clinical procedures performed every year. Metabolic dysfunction is one common aspect associated with many diseases. Thus, understanding and monitoring metabolic changes is essential to develop cures for many illnesses, including for example cancer and neurodegeneration. MR methodologies are especially suited to study endogenous metabolites and processes within an organism in vivo, which has led to many insights about physiological functions. Advancing metabolic MR techniques is therefore key to further understand physiological processes. Here, we introduce an approach based on nuclear spin singlet states to specifically filter metabolic signals and particularly show that singlet-filtered glutamate can be observed distinctly in the hippocampus of a living mouse in vivo. This development opens opportunities to make use of the singlet spin phenomenon in vivo and besides its use as a filter to provide scope for new contrast agents.

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.

Continuous re-hyperpolarization of nuclear spins using parahydrogen: theory and experiment.

The continuous re-hyperpolarization of nuclear spins in the liquid state by means of parahydrogen (para-H2) and chemical exchange at low magnetic fields was recently discovered and offers intriguing perspectives for many varieties of magnetic resonance. In this contribution, we provide a theoretical assessment of this effect and compare the results to experimental data. A distinct distribution of polarization is found, which shares some features with experimental data and, interestingly, does not directly correspond to the loss of the singlet order of para-H2. We derived expressions for the magnetic field and para-H2-substrate interaction time, for which the polarization transfer is maximal. This work sheds light onto the effect of continuous hyperpolarization and elucidates the underlying mechanism, which may facilitate the development of an optimized catalyst. As an application, continuous hyperpolarization may enable highly sensitive nuclear magnetic resonance at very low magnetic fields, for example, for the cost-efficient screening of drugs.

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.

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy.

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window.

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.