Search

The site-specific signal enhancement provided by parahydrogen induced polarization (PHIP) may be combined with magnetic resonance imaging (MRI) to study chemical and biomolecular processes. However, imaging of hydrogen nuclei ( 1 H) is hampered by background signals arising from the presence of thermally polarized nuclei. Additionally, fast imaging sequences are commonly based on multiple radio-frequency pulses, where the signals resulting from PHIP oscillate due to the evolution with a J-coupling Hamiltonian. In this article, an innovative imaging scheme for single-scan MRI is presented that effectively detects hyperpolarized components while simultaneously canceling out thermal contributions. This method is based on the quenching of inherent oscillations of PHIP-originated signals due to J-couplings during the multipulse sequence and the suppression of thermal signals by spin dynamics and a tailored restructuring of the k-space. A series of numerical simulations on specific two- and three-spin systems serve to support the feasibility of the approach. Furthermore, this theoretical study demonstrates the potential of combining hyperpolarization and long-lived states (PHIP and LLS) in the selected molecules, which could be seen as a preliminary step towards the development of fast imaging techniques, for example in the field of biomolecular research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L. Buljubasich reports financial support was provided by National University of Cordoba Secretariat of Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nuclear spin hyperpolarization techniques, such as dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP), have revolutionized nuclear magnetic resonance and magnetic resonance imaging. In these methods, a readily available source of high spin order, either electron spins in DNP or singlet states in hydrogen for PHIP, is brought into close proximity with nuclear spin targets, enabling efficient transfer of spin order under external quantum control. Despite vast disparities in energy scales and interaction mechanisms between electron spins in DNP and nuclear singlet states in PHIP, a pseudo-spin formalism allows us to establish an intriguing equivalence. As a result, the important low-field polarization transfer regime of PHIP can be mapped onto an analogous system equivalent to pulsed-DNP. This establishes a correspondence between key polarization transfer sequences in PHIP and DNP, facilitating the transfer of sequence development concepts. This promises fresh insights and significant cross-pollination between DNP and PHIP polarization sequence developers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laurynas Dagys, Tim R. Eichhorn, Stefan Knecht, Christoph Müller, Alon Salhov, and Ilai Schwartz are employees of NVision Imaging Technologies GmbH (NVision). Martin B. Plenio and Ilai Schwartz are co-founders and shareholders of NVision. NVision is commercializing products in the field of magnetic resonance hyperpolarization. A patent application relating to the subject matter of this work has been filed under International Filing Number: PCT/IB2021/000202., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The use of parahydrogen - the isomer of molecular hydrogen with zero nuclear spin - is important for promising and actively developing methods for spin hyperpolarization of nuclei called parahydrogen induced polarization (PHIP). However, the dissolved parahydrogen in PHIP experiments quickly loses its spin order, resulting in the formation of orthohydrogen and reduction of the overall nuclear polarization of the substrate. This process is due to the difference of chemical shifts of hydride protons, as well as spin-spin couplings between nuclei, in the intermediate catalytic complexes, and it has not been rigorously explained so far. We proposed a new experimental technique based on magnetic field cycling for measuring the rate of molecular hydrogen para-ortho conversion in solution and applied it for non-hydrogenative PHIP Signal Amplification By Reversible Exchange (SABRE) experiments. The para-ortho conversion rate was measured over a wide range of magnetic field from 0.5 mT to 9.4 T. It was found that the conversion rate strongly depends on the magnetic field in which the reaction occurs, as well as on the concentrations of reactants. The rate decreases with increasing the concentration of pyridine ligand and increases with increasing the concentration of iridium catalyst. The model, which takes into account the reversible exchange of molecular hydrogen with the catalyst, nuclear spin-spin interaction of hydride protons with nuclei of ligands within catalytic complex and nuclear Zeeman interactions, qualitatively describes the experimental data. Two types of complexes with different spin system symmetry contribute to the molecular hydrogen conversion. In asymmetric complexes possessing hydride protons with different chemical shifts due to the presence of chlorine anion ligand the para-ortho conversion rate increases with magnetic field, while for symmetric complexes this mechanism is not operable. In the magnetic field where level anti-crossing occurs the resonant feature for the rate of para-ortho conversion is found. The results of this work can be utilized for finding the optimal conditions for obtaining the maximum hyperpolarization in the experiments employing parahydrogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A new pulse sequence aimed to filter out NMR signals coming from thermally polarized protons in PHIP experiments based on the OPSY pulse sequence (Only Parahydrogen SpectroscopY) is presented. In analogy to OPSY, which removes thermal polarization by using a pair of magnetic field gradient pulses with an intensity ratio 1:2 and equal duration, the same effect can be achieved using inhomogeneous radiofrequency fields. The spatial dependence of the radiofrequency field is used to control the Hamiltonian, which results in an effective suppression of thermal contributions in the NMR signal, while PHIP originated signals remain unmodified. A theoretical model for the radiofrequency encoded only parahydrogen (REOPSY) sequence is presented along with an experimental implementation on a birdcage coil in a 7 T magnetic field. The control level achieved by this strategy allows the inclusion of a long train of refocusing pulses. Therefore, the new sequence can be combined with the parahydrogen discriminated PHIP (PhD-PHIP) pulse sequence as a detection block to improve sensitivity and resolution in a single-scan experiment. Experiments with REOPSY and REOPSY+PhD-PHIP are presented in thermally and hyperpolarized samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In a RASER (Radio-frequency Amplification by Stimulated Emission of Radiation), the fast relaxing electromagnetic modes of an LC resonator are enslaved by the slow nuclear spin motion, whose coherence decays with the transverse relaxation rate γ m =1/T 2 ∗ , a second adiabatic elimination process applies and the spectral properties of the RASER can be predicted. The resulting model is similar to the model of two non-linear coupled oscillators and predicts the observed RASER phenomena, including frequency combs and mode collapse. If the second adiabatic elimination is not applicable, mode collapse is completely absent and successive period doubling processes and chaos occur at very high population inversions. We compare these theoretical predictions with experimental results from a PHIP (Para-Hydrogen Induced Polarization) pumped m , a second adiabatic elimination process applies and the spectral properties of the RASER can be predicted. The resulting model is similar to the model of two non-linear coupled oscillators and predicts the observed RASER phenomena, including frequency combs and mode collapse. If the second adiabatic elimination is not applicable, mode collapse is completely absent and successive period doubling processes and chaos occur at very high population inversions. We compare these theoretical predictions with experimental results from a PHIP (Para-Hydrogen Induced Polarization) pumped 1 H RASER. Moreover, in SABRE (Signal Amplification By Reversible Exchange) pumped 1 H experiments, RASER revivals are observed long after the parahydrogen pumping source has been switched off. All these findings shed light onto the links between NMR spectroscopy, RASER physics, synergetics and chaos theory. Several new applications are envisioned in the fields of quantum sensor technology, structure investigation or magnetic resonance imaging (MRI)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several important NMR procedures involve the conversion of nuclear singlet order into heteronuclear magnetisation, including some experiments involving long-lived spin states and parahydrogen-induced hyperpolarisation. However most existing sequences suffer from a limited range of validity or a lack of robustness against experimental imperfections. We present a new radio-frequency scheme for the transformation of the singlet order of a chemically-equivalent homonuclear spin pair into the magnetisation of a heteronuclear coupling partner. The proposed radio-frequency (RF) scheme is called gS2hM (generalized singlet-to-heteronuclear magnetisation) and has good compensation for common experimental errors such as RF and static field inhomogeneities. The sequence retains its robustness for homonuclear spin pairs in the intermediate coupling regime, characterised by the in-pair coupling being of the same order of magnitude as the difference between the out-of-pair couplings. This is a substantial improvement to the validity range of existing sequences. Analytical solutions for the pulse sequence parameters are provided. Experimental results are shown for two test cases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Nuclear spin hyperpolarization derived from parahydrogen can enable nuclear magnetic resonance spectroscopy and imaging with sensitivity enhancements exceeding four orders of magnitude. The NMR signal enhancement is proportional to 4x p -1, where x p is the parahydrogen mole fraction. For convenience, many labs elect to carry out the ortho-para conversion at 77 K where 50% enrichment is obtained. In theory, enrichment to 100% yields an automatic three-fold increase in the NMR signal enhancement. Herein, construction and testing of a simple and inexpensive continuous-flow converter for high para-enrichment is described. During operation, the converter is immersed in liquid helium contained in a transport dewar of the type commonly found in NMR labs for filling superconducting magnets. A maximum enrichment of 97.3±1.9% at 30 K was observed at 4.5 bar and 300 mL/min flow rate. The theoretically predicted 2.9-fold increase in the signal enhancement factor was confirmed in the heterogeneous hydrogenation of propene to propane over a PdIn/SBA-15 catalyst. The relatively low-cost to construct and operate this system could make high parahydrogen enrichment, and the associated increase in the parahydrogen-derived NMR signals, more widely accessible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

DOSY is a powerful spectroscopic NMR technique that resolves components in mixtures through the evaluation of different diffusion coefficients. The application of DOSY to dilute mixtures is hampered by the low signal to noise ratios (SNR), leading to long acquisition times. The use of PHIP may resolve this issue as long as reproducible signals are obtained in order to perform 2D experiments. Here we show that the use of hollow membranes and adequate gas flow produce constant polarization for a time-span that enables the acquisition of 2D experiments. A pressure gradient is evidenced by the presence of convection, which is accounted for by using a DPGSE sequence. The influence of J-coupling evolution during the sequence is studied both numerically and experimentally, to determine the optimum echo-time. The applicability of the method for samples with poor SNR is explored by setting the reaction rate to achieve a low intensity of polarized signals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Despite the large degree of polarization in PHIP experiments compared to the Boltzmann factor, the presence of a large amount of non-reacted molecules with thermal polarization is an important obstacle when dealing with very diluted samples. The feasibility of enhancing both sensitivity and resolution in a single experiment by combining two well established pulse sequences, OPSY and PHD-PHIP is presented. OPSY is used as a block for filtering the signals originated from thermally polarized protons. PhD-PHIP, on the other hand, is used as an acquisition block, increasing the resolution and further improving the sensitivity by preventing signal canceling in the presence of magnetic field inhomogeneities. Experiments in a complex sample with very low hyperpolarization levels are presented showing the excellent performance of the method., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The hyperpolarization of nuclear spins using parahydrogen is an interesting effect that allows to increase the magnetic resonance signal by several orders of magnitude. Known as ParaHydrogen And Synthesis Allow Dramatically Enhanced Nuclear Alignment (PASADENA) and ParaHydrogen Induced Polarization (PHIP), the method was successfully used for in vitro analysis and in vivo imaging. In this contribution, we investigated four known and four new variants of Only Parahydrogen SpectroscopY (OPSY) sequences (Aguilar et al., 2007) with respect to the selective preparation of hyperpolarized NMR signal and background suppression. Depending on the method chosen, either anti-phase, in-phase or a mixture of both signals are obtained: anti-phase signals are beneficial to identify hyperpolarized signals and the structure or J-coupling constants; in-phase signals are useful for imaging applications or when the lines are broad. This comprehensive overview of sequences new and old facilitates selecting the right sequence for the task at hand., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We demonstrate that the relative phases in the refocusing pulses of multipulse sequences can compensate for pulse errors and off-resonant effects, which are commonly encountered in J-spectroscopy when CPMG is used for acquisition. The use of supercycles has been considered many times in the past, but always from the view point of time-domain NMR, that is, in an effort to lengthen the decay of the magnetization. Here we use simple spin-coupled systems, in which the quantum evolution of the system can be simulated and contrasted to experimental results. In order to explore fine details, we resort to partial J-spectroscopy, that is, to the acquisition of J-spectra of a defined multiplet, which is acquired with a suitable digital filter. We unambiguously show that when finite radiofrequency pulses are considered, the off-resonance effects on nearby multiplets affects the dynamics of the spins within the spectral window under acquisition. Moreover, the most robust phase cycling scheme for our setup consists of a 4-pulse cycle, with phases yyyy‾ or xxxx‾ for an excitation pulse with phase x. We show simulated and experimental results in both thermally polarized and PHIP hyperpolarized systems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Signal Amplification by Reversible Exchange (SABRE) is an attractive nuclear spin hyperpolarization technique capable of huge sensitivity enhancement in nuclear magnetic resonance (NMR) detection. The resonance condition of SABRE hyperpolarization depends on coherent spin mixing, which can be achieved naturally at a low magnetic field. The optimum transfer field to spin-1/2 heteronuclei is technically demanding, as it requires field strengths weaker than the earth's magnetic field for efficient spin mixing. In this paper, we illustrate an approach to achieve strong 15 N SABRE hyperpolarization at high magnetic field by a radio frequency (RF) driven coherent transfer mechanism based on alternate pulsing and delay to achieve polarization transfer. The presented scheme is found to be highly robust and much faster than existing related methods, producing ∼3 orders of magnitude 15 N signal enhancement within 2 s of RF pulsing., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

We have demonstrated two radiofrequency pulse methods which convert the nuclear singlet order of proton spin pairs into the magnetisation of nearby 13 C nuclei. These irradiation schemes work well in the near-equivalence regime of the three-spin system, which applies when the difference in the two 1 H- 13 C couplings is much smaller than the 1 H- 1 H coupling. We use pulse sequences to generate thermally polarized singlet states in a reproducible manner, and study the singlet-to-magnetisation transfer step. Preliminary results demonstrate a parahydrogen-enhanced 13 C polarization level of at least 9%, providing a signal enhancement factor of more than 9000, using 50% enriched parahydrogen., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A new methodology for producing hyperpolarized 13 C nuclei in small organic systems via parahydrogen induced polarization (PHIP) is proposed: ADAPT (Alternating Delays Achieve Polarization Transfer). The theoretical foundation of the process is investigated in some detail and experimental examples demonstrating the viability of the approach are provided as well. The number of adjustable parameters is fewer than most of other conversion schemes. The achieved theoretical heteronuclear polarization is close to unity for any examined magnetic equivalence regime. The duration of the pulse sequence, which was successfully implemented, can be shorter than other established methods reducing possible relaxation losses. The conversion scheme is robust to B 1 inhomogeneities, but more sensitive to off-resonance RF irradiation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hyperpolarization is a powerful tool to overcome the low sensitivity of nuclear magnetic resonance (NMR). However, applications are limited due to the short lifetime of this non equilibrium spin state caused by relaxation processes. This issue can be addressed by storing hyperpolarization in slowly decaying singlet spin states which was so far mostly demonstrated for non-proton spin pairs, e.g. (13)C-(13)C. Protons hyperpolarized by parahydrogen induced polarization (PHIP) in symmetrical molecules, are very well suited for this strategy because they naturally exhibit a long-lived singlet state. The conversion of the NMR silent singlet spin state to observable magnetization can be achieved by making use of singlet-triplet level anticrossings. In this study, a low-power radiofrequency pulse sequence is used for this purpose, which allows multiple successive singlet-triplet conversions. The generated magnetization is used to record proton images in a clinical magnetic resonance imaging (MRI) system, after 3min waiting time. Our results may open unprecedented opportunities to use the standard MRI nucleus (1)H for e.g. metabolic imaging in the future., (Copyright © 2016. Published by Elsevier Inc.)

Parahydrogen induced polarization (PHIP) is a powerful hyperpolarization technique. However, as the signal created has an anti-phase characteristic, it is subject to signal cancellation when the experiment is carried out in inhomogeneous magnetic fields or in low fields that lack the necessary spectral resolution. The use of benchtop spectrometers and time domain (TD) analyzers has continuously grown in the last years and many applications are found in the food industry, for non-invasive compound detection or as a test bench for new contrast agents among others. In this type of NMR devices the combination of low and inhomogeneous magnetic fields renders the application of PHIP quite challenging. We have recently shown that the acquisition of J-spectra in high magnetic fields not only removes the anti-phase peak cancellation but also produces a separation of thermal from hyperpolarized signals, providing Parahydrogen Discriminated (PhD-PHIP) spectra. In this work we extend the use of PhD-PHIP to low and inhomogeneous fields. In this case the strong coupling found for the protons of the sample renders spin-echo spectra that have a great complexity, however, a central region in the spectrum with only hyperpolarized signal is clearly identified. This experimental approach is ideal for monitoring real time chemical reaction of pure PHIP signals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Modern NMR spectroscopy has reached an unprecedented level of sophistication in the determination of biomolecular structure and dynamics at atomic resolution in liquids. However, the sensitivity of this technique is still too low to solve a variety of cutting-edge biological problems in solution, especially those that involve viscous samples, very large biomolecules or aggregation-prone systems that need to be kept at low concentration. Despite the challenges, a variety of efforts have been carried out over the years to increase sensitivity of NMR spectroscopy in liquids. This review discusses basic concepts, recent developments and future opportunities in this exciting area of research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The first instance of para-hydrogen induced polarization (PHIP) in an NMR experiment was serendipitously observed in the 1980s while investigating a hydrogenation reaction (Seldler et al., 1983; Bowers and Weitekamp, 1986, 1987; Eisenschmid et al., 1987) [1-4]. Remarkably a theoretical investigation of the applicability of para-hydrogen as a hyperpolarization agent was being performed in the 1980's thereby quickly providing a theoretical basis for the PHIP-effect (Bowers and Weitekamp, 1986) [2]. The discovery of signal amplification by a non-hydrogenating interaction with para-hydrogen has recently extended the interest to exploit the PHIP effect, as it enables investigation of compounds without structural alteration while retaining the advantages of spectroscopy with hyperpolarized compounds [5]. In this article we will place more emphasis of the future applications of the method while only briefly discussing the efforts that have been made in the understanding of the phenomenon and the development of the method so far., (Copyright © 2013 Elsevier Inc. All rights reserved.)