Field Cycling Method Research Articles

Nuclear spin polarization of lactic acid via exchange of parahydrogen-polarized protons

Hyperpolarization has become a powerful tool to enhance the sensitivity of magnetic resonance. A universal tool to hyperpolarize small molecules in solution, however, has not yet emerged. Transferring hyperpolarized, labile protons between molecules is a promising approach towards this end. Therefore, hydrogenative parahydrogen-induced polarization (PHIP) was recently proposed as a source to polarize exchanging protons (PHIP-X). Here, we identified four key components that govern PHIP-X: adding the spin order, polarizing the labile proton, proton exchange, and polarization of the target nucleus. We investigated the last two steps experimentally and using simulations. We found optimal exchange rates and field cycling methods to polarize the target molecules. We also investigated the influence of spin relaxation of exchanging protons on the target polarization. It was found experimentally that transferring the polarization from protons directly bound to the target X-nucleus (here 13C) of lactate and methanol using a pulse sequence was more efficient than applying a corresponding sequence to the labile proton. Furthermore, varying the concentrations of the transfer and target molecules yielded a distinct maximum 13C polarization. We believe this work will further help to understand and optimize PHIP-X towards a broadly applicable hyperpolarization method.

Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization

Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective method for hyperpolarization of 13C metabolites (e.g. acetate, pyruvate) for metabolic MRI. The timing and efficiency of typical spin order transfer methods including magnetic field cycling and tailored RF pulse sequences crucially depends on the heteronuclear J coupling network between nascent parahydrogen protons and 13C, post-parahydrogenation of the target compound. In this work, heteronuclear nJHC (1 < n ≤ 5) couplings of acetate and pyruvate esters pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC-based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond JHC ≲ 0.5 Hz were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT-simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for 13C hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type spin order transfer methods for PHIP-SAH were assessed, and the influence of direct nascent parahydrogen proton to 13C coupling when compared with indirect homonuclear TOCSY-type transfer through intermediate (non-nascent parahydrogen) protons was studied by the density matrix approach.

Dynamic Nuclear Polarization Fast Field Cycling Method for the Selective Study of Molecular Dynamics in Block Copolymers.

Dynamic nuclear polarization (DNP) is one of the most useful methods to increase sensitivity in NMR spectroscopy. It is based on the transfer of magnetization from an electron to the nuclear spin system. Based on previous work that demonstrated the feasibility of integrating DNP with fast field cycling (FFC) relaxometry and the possibility to distinguish between different mechanisms, such as the Overhauser effect (OE) and the solid effect (SE), the first FFC study of the differential relaxation properties of a copolymer is presented. For this purpose, concentrated solutions of the polystyrene-block-polybutadiene-block-polystyrene (SBS) triblock copolymer and the corresponding homopolymers were investigated. T1 -T2 relaxation data are discussed in terms of molecular mobility and the presence of radicals. The DNP selective data indicate a dominant SE contribution to the enhancement of the NMR signal for both blocks of the triblock copolymer and for the homopolymer solutions. The enhancement factors are different for both polymer types and in the copolymer, which is explained by the individual 1 H T1 relaxation times and different electron-nucleus coupling strength. The T1 relaxation dispersion measurements of the SE enhanced signal were performed, which led to improved signal-to-noise ratios that allowed the site-specific separation of relaxation times and their dependence on the Larmor frequency with a higher accuracy.

Dry-cured ham tissue characterization by fast field cycling NMR relaxometry and quantitative magnetization transfer.

Fast field cycling (FFC) and quantitative magnetization transfer (qMT) NMR methods are two powerful tools in NMR analysis of biological tissues. The qMT method is well established in biomedical NMR applications, while the FFC method is often used in investigations of molecular dynamics on which longitudinal NMR relaxation times of the investigated material critically depend. Despite their proven analytical potential, these two methods were rarely used in NMR studies of food, especially when combined together. In our study, we demonstrate the feasibility of a combined FFC/qMT-NMR approach for the fast and nondestructive characterization of dry-curing ham tissues differing by protein content. The characterization is based on quantifying the pure quadrupolar peak area (area under the quadrupolar contribution of dispersion curve obtained by FFC-NMR) and the restricted magnetization pool size (obtained by qMT-NMR). Both quantities correlate well with concentration of partially immobilized, nitrogen-containing and proton magnetization exchanging muscle proteins. Therefore, these two quantities could serve as potential markers for dry-curing process monitoring. Copyright © 2016 John Wiley & Sons, Ltd.

A fast field-cycling device for high-resolution NMR: Design and application to spin relaxation and hyperpolarization experiments

A device for performing fast magnetic field-cycling NMR experiments is described. A key feature of this setup is that it combines fast switching of the external magnetic field and high-resolution NMR detection. The field-cycling method is based on precise mechanical positioning of the NMR probe with the mounted sample in the inhomogeneous fringe field of the spectrometer magnet. The device enables field variation over several decades (from 100μT up to 7T) within less than 0.3s; progress in NMR probe design provides NMR linewidths of about 10−3ppm. The experimental method is very versatile and enables site-specific studies of spin relaxation (NMRD, LLSs) and spin hyperpolarization (DNP, CIDNP, and SABRE) at variable magnetic field and at variable temperature. Experimental examples of such studies are demonstrated; advantages of the experimental method are described and existing challenges in the field are outlined.

1H relaxation enhancement induced by nanoparticles in solutions: influence of magnetic properties and diffusion.

Magnetic nanoparticles that induce nuclear relaxation are the most promising materials to enhance the sensitivity in Magnetic Resonance Imaging. In order to provide a comprehensive understanding of the magnetic field dependence of the relaxation enhancement in solutions, Nuclear Magnetic Resonance (1)H spin-lattice relaxation for decalin and toluene solutions of various Fe2O3 nanoparticles was investigated. The relaxation experiments were performed in a frequency range of 10 kHz-20 MHz by applying Field Cycling method, and in the temperature range of 257-298 K, using nanoparticles differing in size and shape: spherical--5 nm diameter, cubic--6.5 nm diameter, and cubic--9 nm diameter. The relaxation dispersion data were interpreted in terms of a theory of nuclear relaxation induced by magnetic crystals in solution. The approach was tested with respect to its applicability depending on the magnetic characteristics of the nanocrystals and the time-scale of translational diffusion of the solvent. The role of Curie relaxation and the contributions to the overall (1)H spin-lattice relaxation associated with the electronic spin-lattice and spin-spin relaxation was thoroughly discussed. It was demonstrated that the approach leads to consistent results providing information on the magnetic (electronic) properties of the nanocrystals, i.e., effective electron spin and relaxation times. In addition, features of the (1)H spin-lattice relaxation resulting from the electronic properties of the crystals and the solvent diffusion were explained.

Paramagnetic Ions Affect Relaxation Rate Dispersion of Blood: Implications for Magnetic Resonance Relaxation Dispersion Imaging

The proton relaxation rate dispersion of paramagnetic ions in blood samples was studied in the frequency interval from 10 kHz to 10 MHz. With the Field cycling method we applied, the samples were first magnetized by a relatively high magnetic field (0.5 T). By electronic means this field was rapidly (1 ms) reduced to a lower value in the interval 0.1 mT - 0.5 T, where the excited proton spin may relax during a time interval of about 3·T1max. Then the magnetic field is again quickly raised up to the higher level for the detection of the NMR-signal. The relaxation characteristics were analyzed by applying a model with three compartments of water proton-spin exchange. For each compartment we estimated a correlation frequency by fitting the dispersion curves to a sum of Lorentz distributions. We found that low concentrations of paramagnetic ions have a large influence on the relaxation rate dispersion in the low frequency region 100 mT) and low (<10 mT) relaxation fields. Such sequences of images could be used to study the oxygen status and metabolism of the brain as well as the generation and distribution of reactive oxygen species (ROS). This technique called “Magnetic resonance Relaxation Dispersion Imaging” (MARDI) would be particularly suitable to analyze various neurological diseases such as stroke, MS, Alzheimer´s disease as well as brain tumor progression. It might also be suitable for imaging of tumour oxygenation and in vivo ROS distributions in radiation therapy, which could be used in dose planning and for analyzing and optimizing the effect of various radiation therapy regimes.

Nuclear magnetic relaxation in water revisited

In this study, we revisited nuclear magnetic relaxation of (1)H in water at very low Larmor frequencies that has been studied intensively in earlier years. We make use of the recently developed superconducting quantum interference device based ultra-low field NMR technique, which enables much easier access to the longitudinal spin-lattice relaxation time T(1) and the transversal spin-spin relaxation time T(2) below several kHz than traditional field cycling methods. Our data reproduce and complement the earlier results, in that they corroborate the finding of an exchange process with a correlation time of about 0.34 ms at room temperature which can be attributed to the migration of hydronium and hydroxyl ions in neutral water via hydrogen bridges. The corresponding relaxation process is driven by the interaction of the protons with (17)O and contributes to the T(1) and the T(2) relaxation rate by about 0.12 s(-1). In addition, we found evidence of a very slow exchange process at about 100 Hz that has hitherto not been reported.

31P NMR Studies of Active Site and Activator Site Ligands Binding to PTEN

PTEN, a tumor suppressor mutated in a large variety of human tumor cells, antagonizes the PI3K signaling pathway by dephosphorylating the PI(3,4,5)P3 at the 3 position of the inositol ring. PI(4,5)P2, the product of PI(3,4,5)P3 hydrolysis, has been shown to activate PTEN, possibly by binding to the N terminus of the protein. However, the mechanism for this activation is still in dispute. 31P NMR, both fixed field and field cycling methods, was used to study the binding of PTEN to different diC8PI derivatives. There were distinct differences in motional parameters for active site ligands (e.g., D-diCnPI species) versus those for activator molecules (D-diCnPI(4,5)P2). Molecules binding in the active site exhibited a significant increase in linewidth consistent with intermediate exchange that was not observed for activator molecules. Spin-labeled protein was also used to interrogate active and activator sites. Modeling studies of the catalytic domain of PTEN indentified a hydrophobic pocket formed by the loop containing Arg47 that appeared to play an important role in substrate and substrate analog binding. Mutations of this residue (R47G, R47K, R47L and R47W) exhibited dramatically decreased activity. 31P NMR analyses of these mutants and short-chain PI ligand binding together with kinetics are used to propose a model for the two sites on PTEN.

High Resolution Field Cycling for Analysis of Lipid Dynamics in Membranes

Phospholipid dynamics often play a role in binding of peripheral membrane proteins. Whether there are discrete phospholipid binding sites on the proteins is often difficult to assess unless binding is quite tight. Yet for many proteins that bind reversibly to membranes, weaker interactions with specific phospholipids can have important functional consequences. For example, phosphatidylinositol‐specific phospholipase C (PI‐PLC) enzymes can be activated by nonsubstrate phospholipids with the extent of activation tuned by the lipid composition. Activity of the Bacillus thuringiensis PI‐PLC is significantly enhanced by a small amount of phosphatidylcholine (PC) in the target membrane. Whether (and where) there is a discrete site for an activator PC molecule or whether lipid mixtures alter bilayer properties is hard to distinguish. High resolution 31P and 13C NMR relaxation studies from 0.005 to 11.7 T can be used to explore interactions of such a peripheral membrane protein with mixed phospholipid vesicles as well as with small molecules. If spin‐labeled proteins are used, estimates of site‐off rates and phospholipid binding site location can be made. With this novel approach for PI‐PLC, we see that (i) discrete complexes for each type of phospholipid on the enzyme with lifetimes around a microsecond must exist; (ii) the discrete site for a substrate analog is spatially different from that for activator PC; and (iii) modeling coupled with the NMR results suggests a PC site, near a series of tyrosine residues, that would aid in anchoring the protein to membranes. The high resolution field cycling method illustrated here may be extended to a wide range of proteins that reversibly bind to membranes to explore differential interactions with phospholipid components as well as other intermolecular interactions.

Delta relaxation enhanced MR: Improving activation‐specificity of molecular probes through R1 dispersion imaging

MR molecular imaging enables high-resolution, in vivo study of molecular processes frequently utilizing gadolinium-based probes that specifically bind to a particular biological molecule or tissue. While some MR probes are inactive when unbound and produce enhancement only after binding, the majority are less specific and cause enhancement in either state. Accumulation processes are then required to increase probe concentration in regions of the target molecule/tissue. Herein, a method is described for creating specificity for traditionally nonspecific probes. This method utilizes MR field-cycling methods to produce MRI contrast related to the dependence of R(1) upon magnetic field. It is shown that the partial derivative of R(1) with respect to magnetic field strength, R(1)', can be used as an unambiguous measure of probe binding. T(1)-weighted images and R(1)' images were produced for samples of albumin and buffer both enhanced with the albumin-binding agent Vasovist. For T(1) images, samples with low concentrations of Vasovist in an albumin solution could not be differentiated from samples with higher concentrations of Vasovist in buffer. Conversely, the R(1)' images showed high specificity to albumin. Albumin samples with a 10-microM concentration of Vasovist were enhanced over buffer samples containing up to 16 times more Vasovist.

Field cycling methods as a tool for dynamics investigations in solid state systems: Recent theoretical progress

In this paper physical mechanisms and theoretical treatments of polarization transfer and field-dependent relaxation in solid state systems, containing mutually coupled spins of spin quantum numbers I = 1 2 (spins 1 2 ) and S⩾1 (quadrupolar spins), are presented. First, theoretical descriptions of these effects are given in detail for an illustrative, simple system. Next, it is shown how to generalize the theories to much more complex spin systems. The polarization transfer and relaxation effects are illustrated by several examples. Typical misunderstandings regarding their physical origins are clarified. This paper reviews recent theoretical descriptions of the polarization transfer and relaxation phenomena. Its goal is to popularize the proper theoretical treatments with the intention to establish them as standard tools for analyzing field cycling data.

NMR study of novel heavy fermion superconductor [formula omitted

Si 29 NMR experiments were performed to study microscopically the normal and superconducting states in Si 29 enriched CePt 3 Si . A Si 29 Knight shift parallel to the c-axis did not decrease below the T c . The 1 / T 1 result taken with a field cycling method showed no distinct coherence peak just below T c and a steep decrease below T c on cooling. The estimated value of the superconducting energy gap was about 2 Δ = 3.6 k B T c . These results may be an evidence for triplet pairing superconductivity.

Dynamics of the 1st order phase transition between the nuclear ordered phases of solid 3He

Dynamics of the 1st order phase transition between the U2D2 and the high field phases (HFP) was studied by field-cycling method between these phases by using ultra low temperature magnetic resonance imaging (ULT-MRI). Single Crystal of U2D2 3He was produced at the bottom of compressional cell in superfluid 3He-B at about 0.5 mK. Domain distribution in the U2D2 crystal was examined by ULT-MRI. We have measured the NMR signal intensity to extract the time-evolution of the HFP, after the static magnetic field was swept quickly through the critical field B C1 and was stayed at B= B C1+Δ B. The volume concentration of the U2D2 decreased exponentially in time during the early stage of the phase transition. The rate constant depended positively on Δ B. After the phase transition to the HFP was completed, the static field decreased through B C1 and was fixed at B= B C1−Δ B. The observed rate constant was similar to the value in the opposite direction with identical Δ B. This exponential evolution and Δ B dependence of its rate suggest that the early stage of the phase transition is controlled by the nucleation process.

Dynamics of the 1st order phase transition between U2D2 and high field phases of 3He

Dynamics of the 1st order phase transition between the U2D2 and the high field phases (HFP) of nuclear ordered solid 3He was studied by field-cycling method between the two phases. Single crystals of U2D2 3He were grown at the bottom of the compressional cell in superfluid 3He-B at about 0.5 mK. The domain distribution in the U2D2 crystal was determined by ULT-MRI (Ultra Low Temperature − Magnetic Resonance Imaging)1. We have measured evolution of the HFP after the static magnetic field was suddenly changed to B = BC1 + ΔB through the lower critical field BC1. The HFP developed exponentially in time and showed two stage evolution with a fast stage rate and a slow stage rule. We observed that the fast stage rate increased with ΔB. Similar behavior was observed in the reversed phase transition. MRI measurements indicate that this phase transition occurs, at least for small ΔB, by the heterogeneous nucleation mechanism, where new seeds appear at the liquid-crystal interface.

SQUID‐detected MRI at 132 μT with T1‐weighted contrast established at 10 μT–300 mT

T(1)-weighted contrast MRI with prepolarization was detected with a superconducting quantum interference device (SQUID). A spin evolution period in a variable field between prepolarization and detection enabled the measurement of T(1) in fields between 1.7 microT and 300 mT; T(1) dispersion curves of agarose gel samples over five decades in frequency were obtained. SQUID detection at 5.6 kHz drastically reduces the field homogeneity requirements compared to conventional field-cycling methods using Faraday coil detection. This allows T(1) dispersion measurements to be easily combined with MRI, so that T(1) in a wide range of fields can be used for tissue contrast. Images of gel phantoms with T(1)-weighted contrast at four different fields between 10 microT and 300 mT demonstrated dramatic contrast enhancement in low fields. A modified inversion recovery technique further enhanced the contrast by selectively suppressing the signal contribution for a specific value of the low-field T(1).

Field-cycling method with central transition readout for pure quadrupole resonance detection in dilute systems

We present a modification of a field-cycling method which uses the NMR signal of the central transition at high field to indirectly detect zero-field quadrupole transitions. The quadrupole transitions at zero-field are detected as changes in the overall intensity of the central transition signal after the field cycle, and the method is relatively immune to lineshape distortions of the central transition caused by receiver dead time, frequency response of the probe, longer pulse lengths, etc. Cross-polarization with protons is used to enhance the central-transition signal and to increase the recycling rate of the experiment. The technique is especially useful when mixtures of several species are present. In a frozen solution of phenylboronic acid, 11B quadrupole signals of the tetrahedral species at 600 kHz and planar-trigonal species at 1450 kHz are clearly resolved. The field-cycling approach allows high-sensitivity detection of low-frequency quadrupole transitions; the experiment is sensitive enough to study boronic-acid protease inhibitors bound to proteins and may possibly be extended to lower sensitivity nuclei. The experiments are performed using a low-temperature field-cycling apparatus, operated at 10–30 K, capable of pneumatically moving the sample from the high field of a commercial 500 MHz magnet to the area above the top of the magnet where the low field is controlled by a pair of Helmholz coils.

Molecular dynamics of n-dodecylammonium chloride in aqueous solutions investigated by 2H NMR and 1H NMR relaxometry

Molecular dynamics in n-dodecylammonium chloride/water solutions for concentrations of 34 and 45 wt% was studied by 2H NMR and by 1H NMR dispersion of spin–lattice relaxation in the 2 kHz–90 MHz frequency range. The system exhibits a number of lyotropic liquid crystalline phases, which differ in symmetry and involve motions characterized by a wide frequency scale. The analysis of 2H NMR lineshapes of selectively deuterated DDACl molecules gave us an evidence for local trans–gauche conformational changes in the chains, whereas the dispersion of spin–lattice relaxation times T 1 explored by fast field cycling method revealed fast local motions, translational diffusion and collective molecular dynamics of the chains. In particular, we have found that the order director fluctuation mechanism in smectic and nematic phases dominates spin–lattice relaxation below 1 MHz and that local motions and translational diffusion are responsible for the spin–lattice relaxation in the higher Larmor frequency range.

Magnetic field compensation for field-cycling NMR Relaxometry in the ULF band

In setting up field-cycling experiments aimed to study physical phenomena in the low-field region, magnetic field contributions from external sources (earth’s field, environment, other magnets, etc.) become important. Indeed, a compensation of these contributions has successfully been used for the application of field-cycling methods to nuclear magnetic relaxation and double resonance experiments. This feature becomes relevant in samples where local fields are stronly averaged due to motional narrowing, on the ground that relaxation experiments can therefore be extended to lower fields. Compensation of external contributions is also crucial for the study of kinky processes related to internal local fields. In this article we outline NMR field-cycling experiments aimed to detect and quantify the external net magnetic field sensed by the spin-system. Both parallel and normal components with respect to the high-field Zeeman axis can be determined separately by using different experimental protocols.

Dynamics of water and oil at the solid–liquid interface in macroporous media and reservoir rocks

Nuclear magnetic relaxation dispersion experiments at different temperatures, using the magnetic field-cycling method, are reported. These experiments allow the obtaining of original information about water or oil molecular dynamics at solid–liquid interface in porous media, such as grain packing or reservoir rocks. These results on molecular dynamics at the pore surface are of real interest for oil-recovery. The water surface diffusion coefficients are compared to the volume self-diffusion coefficients of water in pores, measured by PGSE method, the latter values being more than an order of magnitude higher than the surface ones. Nous avons obtenu des informations originales sur la dynamique de l’eau et de l’huile aux interfaces solide–liquide de milieux poreux plus ou moins complexes, comme les empilements granulaires et les roches réservoirs. Ces informations proviennent d’expériences de relaxation magnétique nucléaire du proton en champ magnétique cyclé à différentes températures. Ces résultats sur la dynamique des molécules à la surface des pores présentent un réel intérêt dans le domaine de la récupération du pétrole. Des mesures de diffusion par la méthode des gradients de champ pulsés permettent une comparaison entre les coefficients de diffusion en surface et en volume, ces derniers étant de plus d’un ordre de grandeur supérieurs à ceux en surface.