SABRE Hyperpolarization with up to 200 bar Parahydrogen in Standard and Quickly Removable Solvents

Parahydrogen (p-H2)-based techniques are known to drastically enhance NMR signals but are usually limited by p-H2 supply. This work reports p-H2-based SABRE hyperpolarization at p-H2 pressures of hundreds of bar, far beyond the typical ten bar currently reported in the literature. A recently designed high-pressure setup was utilized to compress p-H2 gas up to 200 bar. The measurements were conducted using a sapphire high-pressure NMR tube and a 43 MHz benchtop NMR spectrometer. In standard methanol solutions, it could be shown that the signal intensities increased with pressure until they eventually reached a plateau. A polarization of about 2%, equal to a molar polarization of 1.2 mmol L−1, could be achieved for the sample with the highest substrate concentration. While the signal plateaued, the H2 solubility increased linearly with pressure from 1 to 200 bar, indicating that p-H2 availability is not the limiting factor in signal enhancement beyond a certain pressure, depending on sample composition. Furthermore, the possibility of using liquefied ethane and compressed CO2 as removable solvents for hyperpolarization was demonstrated. The use of high pressures together with quickly removable organic/non-organic solvents represents an important breakthrough in the field of hyperpolarization, advancing SABRE as a promising tool for materials science, biophysics, and molecular imaging

RASER MRI: Magnetic resonance images formed spontaneously exploiting cooperative nonlinear interaction

The spatial resolution of magnetic resonance imaging (MRI) is fundamentally limited by the width of Lorentzian point spread functions (PSF) associated with the exponential decay rate of transverse magnetization (1/T2*). Here we show a different contrast mechanism in MRI by establishing RASER (Radio-frequency Amplification by Stimulated Emission of Radiation) in imaged media. RASER imaging bursts emerge out of noise and without applying (Radio Frequency) RF pulses when placing spins with sufficient population inversion in a weak magnetic field gradient. A small difference in initial population inversion density creates a stronger image contrast than conventional MRI. This contrast is based on the cooperative nonlinear interaction between all slices. On the other hand, the cooperative nonlinear interaction gives rise to imaging artifacts, such as amplitude distortions and side lobes outside of the imaging domain. Both the contrast and the artifacts are demonstrated experimentally and predicted by simulations based on a proposed theory. This theory of RASER MRI is strongly connected to many other distinct fields related to synergetics and non-linear dynamics

Exploring synchrony and chaos of parahydrogen-pumped two-compartment radio-frequency amplification by stimulated emission of radiation

A nuclear-spin-based RASER (radio-frequency amplification by stimulated emission of radiation) is an ideal experimental system to explore nonlinear interaction phenomena of nuclear spins coupled via virtual photons to a resonator. This is due to the RASER being stable for several hours, allowing for extended observation of these phenomena. Nonlinear phenomena in multimode RASERs range from mode oscillations in synchrony, frequency shifts, frequency combs, period doublings, and even chaos. These phenomena are observed in a parahydrogen-pumped two-compartment proton RASER. In two independently pumped compartments, the separation in frequency space between the two RASER modes is precisely controlled with a magnetic field gradient. By controlling the mode separation, we can select the type of nonlinear phenomena observed. A key finding is that the ranges of mode separation where chaos and synchrony occur are very close together. The experimental results are supported by numerical simulations, based on two-mode RASER equations

RASER MRI: Magnetic resonance images formed spontaneously exploiting cooperative nonlinear interaction

The spatial resolution of magnetic resonance imaging (MRI) is limited by the width of Lorentzian point spread functions associated with the transverse relaxation rate 1/T2*. Here, we show a different contrast mechanism in MRI by establishing RASER (radio-frequency amplification by stimulated emission of radiation) in imaged media. RASER imaging bursts emerge out of noise and without applying radio-frequency pulses when placing spins with sufficient population inversion in a weak magnetic field gradient. Small local differences in initial population inversion density can create stronger image contrast than conventional MRI. This different contrast mechanism is based on the cooperative nonlinear interaction between all slices. On the other hand, the cooperative nonlinear interaction gives rise to imaging artifacts, such as amplitude distortions and side lobes outside of the imaging domain. Contrast mechanism and artifacts are explored experimentally and predicted by simulations on the basis of a proposed RASER MRI theory

Hyperpolarization with parahydrogen in NMR

Parahydrogen based hyperpolarization can drastically boost NMR signals and merges many disciplines from science and technology. Especially, the relatively new SABRE approach is promising as it enables easy, affordable and repetitive hyperpolarization of suitable target molecules. Despite many successful efforts towards broad applicability, especially in the context of biocompatibility have already been taken, it is still a growing topic with vast untapped potential. To advance and broaden this field, four hitherto not accomplished steps were chosen for this work: Heterogeneous catalysts allow for convenient recovery from reaction mixtures and reuse compared to the often toxic homogeneous catalysts. For this purpose, homogeneous PHIP catalysts were anchored on Al2O3 using a heteropolyacid as a linker. This modular system, known for efficient and enantioselective hydrogenations at negligible leaching, is evaluated for its potential in parahydrogen experiments. The activation, experimental procedures and operating conditions for the immobilized catalysts were optimized in a model system and extended to various exemplary substrates and catalysts. Additionally, a suitable choice of the nature and particle size of the support material turned out to be essential. Only PHIP mechanisms based on p-H2 addition and replacement in target substrates were observed so far. Thus, experiments with alternate immobilization approaches with a focus on heterogeneous SABRE and water based systems were part of a sidetrack.Moving towards biomedical applications, water and L-histidine were hyperpolarized with parahydrogen for the first time. The impact of various experimental conditions on the water polarization was studied using a water soluble SABRE catalyst. A special focus is laid on the polarization transfer field, crucial for the polarization of both water and histidine. Based on these results, the underlying spin order transfer mechanisms are elaborated. In addition, a setup for hyperpolarization during continuous flow was introduced. A membrane reactor at its core brought the parahydrogen into solution. Important experimental parameters such as pressure and flow rate of this system are evaluated in proof of principle experiments under continuous flow SABRE over several hours. Finally, a parahydrogen fueled RASER has been discovered by us. Based on the protons of organic molecules and continuously fed by SABRE pumping, this system emits coherent radiation similar to LASERs and MASERs. Its initial nonlinear dynamics is studied by simulations and experiments with various substrates. The impact of heteronuclei such as 13C and 15N on proton RASERs is elaborated. The first self oscillating system based heteronuclear two-spin order is presented, which as a result self-compensates distant dipolar fields. Most excitingly, its multi mode operation, based on spin eigenstates of RASER active molecules, envisions precise chemical structure elucidation and therefore applications not only in the fundamental physics, but in various fields of science and technology

Approaching the Ultimate Limit in Measurement Precision with RASER NMR

Radio-frequency Amplification by Stimulated Emission of Radiation (RASER) is a promising tool to study nonlinear phenomena or measure NMR parameters with unprecedented precision. Magnetic fields, J-couplings, and chemical shifts can be recorded over long periods of time without the need for radiofrequency excitation and signal averaging. One key feature of RASER NMR spectroscopy is the improvement in precision, which grows with the measurement time, unlike conventional NMR spectroscopy, where the precision increases with. However, when detecting NMR signals over minutes to hours, using available NMR magnets (ppb homogeneity), the achieved frequency resolution will eventually be limited by magnetic field fluctuations. Here, we demonstrate that full compensation is possible even for open low-field electromagnets, where magnetic field fluctuations are intrinsically present (in the ppm regime). A prerequisite for compensation is that the spectrum contains at least one isolated RASER line to be used as a reference, and the sample experiences exclusively common magnetic field fluctuations, that is, ones that are equal over the entire sample volume. We discuss the current limits of precision for RASER NMR measurements for two different cases: The single-compartment RASER involving J-coupled modes, and the two-compartment RASER involving chemically shifted species. In the first case, the limit of measurable difference approaches the Cramér-Rao lower bound (CRLB), achieving a measurement precision Hz. In the second case, the measured chemical shift separation is plagued by independently fluctuating distant dipolar fields (DDF). The measured independent field fluctuation between the two chambers is in the order of tens of mHz. In both cases, new limits of precision are achieved, which paves the way for sub-mHz detection of NMR parameters, rotational rates, and non-linear phenomena such as chaos and synchrony

From LASER physics to the para-hydrogen pumped RASER

The properties of the LASER with respect to self-organization are compared with the key features of the p-H2 pumped RASER. According to LASER theory the equations of motion for the LASER can be derived from the enslaving principle, i.e. the slowest-changing order parameter (the light field in the resonator) enslaves the rapidly relaxing atomic degrees of freedom. Likewise, it is shown here that the equations of motion for the p-H2 pumped RASER result from a set of order parameters, where the transverse magnetization of the RASER-active spin states enslaves the electromagnetic modes. The consequences are striking for nuclear magnetic resonance (NMR) spectroscopy, since long-lasting multi-mode RASER oscillations enable unprecedented spectroscopic resolution down to the micro-Hertz regime. Based on the theory for multi-mode RASER operation we analyze the conditions that reveal either the collapse of the entire NMR spectrum, the occurrence of self-organized frequency-combs, or RASER spectra which reflect the J-coupled network of the molecule. Certain RASER experiments involving the protons of 15N pyridine or 3-picoline molecules pumped with p-H2 via SABRE (Signal Amplification By Reversible Exchange) show either a single RASER oscillation in the time domain, giant RASER pulses or a complex RASER beat pattern. The corresponding 1H spectra consist of one narrow line, equidistant narrow lines (frequency-comb), or highly resolved lines reporting NMR properties, respectively. Numerous applications in the areas of material sciences, fundamental physics and medicine involving high precision sensors for magnetic fields, rotational motions or molecular structures become feasible