Discrimination of PHIP Signals Through their Evolution in Multipulse Sequences.

The antiphase character of the PHIP associated signals after a hydrogenation reaction is particularly sensitive to line broadening introduced by magnetic field inhomogeneities and interferences by the presence of resonance lines steaming from a large amount of thermally polarized spins. These obstacles impose a limitation in the detection of reaction products as well as in the experimental setups. A simple way to overcome these impediments consists of acquiring the signal with a train of refocusing pulses instead of a single r.f. pulse. We present here a number of examples where this multipulse acquisition, denominated PhD-PHIP, displays its potentiality in improving the information related to hyperpolarized spins performed in a sample, where the former parahydrogen nuclei are part of a complex J-coupling network.

Radiofrequency encoded Only Parahydrogen SpectroscopY.

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.

Diffusion measurements with continuous hydrogenation in PHIP.

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.

Quasiequilibrium states in thermotropic liquid crystals studied by multiple-quantum NMR.

Previous work showed that by means of the Jeener-Broekaert (JB) experiment, two quasiequilibrium states can be selectively prepared in the proton spin system of thermotropic nematic liquid crystals (LCs) in a strong magnetic field. The similarity of the experimental results obtained in a variety of LC in a broad Larmor frequency range, with crystal hydrates, supports the assumption that also in LC the two spin reservoirs, into which the Zeeman order is transferred, originate in the dipolar energy and that they are associated with a separation in energy scales: A constant of motion related to the stronger dipolar interactions (S), and a second one (W) corresponding to the secular part of the weaker dipolar interactions with regard to the Zeeman and the strong dipolar part. We study the nature of these quasi-invariants in nematic 5CB (4(')-pentyl-4-biphenyl-carbonitrile) and measure their relaxation times by encoding the multiple-quantum coherences of the states following the JB pulse pair on two orthogonal bases, Z and X. The experiments were also performed in powder adamantane at 301 K which is used as a reference compound having only one dipolar quasi-invariant. We show that the evolution of the quantum states during the buildup of the quasiequilibrium state in 5CB prepared under the S condition is similar to the case of powder adamantane and that their quasiequilibrium density operators have the same tensor structure. In contrast, the second constant of motion, whose explicit operator form is not known, involves a richer composition of multiple-quantum coherences of even order on the X basis, in consistency with the truncation inherent in its definition. We exploited the exclusive presence of coherences of +/-4,+/-6,+/-8, besides 0 and +/-2 under the W condition to measure the spin-lattice relaxation time T(W) accurately, so avoiding experimental difficulties that usually impair dipolar order relaxation measurement such as Zeeman contamination at high fields and also superposition of the different quasi-invariants. This procedure opens the possibility of measuring the spin-lattice relaxation of a quasi-invariant independent of the Zeeman and S reservoirs, so incorporating a new relaxation parameter useful for studying the complex molecular dynamics in mesophases. In fact, we report the first measurement of T(W) in a LC at high magnetic fields. Comparison of the obtained value with the one corresponding to a lower field (16 MHz) points out that the relaxation of the W-order strongly depends on the intensity of the external magnetic field, similarly to the case of the S reservoir, indicating that the relaxation of the W-quasi-invariant is also governed by the cooperative molecular motions.

NMR dipolar constants of motion in liquid crystals: Jeener-Broekaert, double quantum coherence experiments and numerical calculation on a 10-spin cluster.

Two proton quasi-equilibrium states were previously observed in nematic liquid crystals, namely the S and W quasi-invariants. Even though the experimental evidence suggested that they originate in a partition of the spin dipolar energy into a strong and a weak part, respectively, from a theoretical viewpoint, the existence of an appropriate energy scale which allows such energy separation remains to be confirmed and a representation of the quasi-invariants is still to be given. We compare the dipolar NMR signals yielded both by the Jeener-Broekaert (JB) experiment as a function of the preparation time and the free evolution of the double quantum coherence (DQC) spectra excited from the S state, with numerical calculations carried out from first principles under different models for the dipolar quasi-invariants, in a 10-spin cluster which represents the 5CB (4(')-pentyl-4-biphenyl-carbonitrile) molecule. The calculated signals qualitatively agree with the experiments and the DQC spectra as a function of the single-quantum detection time are sensible enough to the different models to allow both to probe the physical nature of the initial dipolar-ordered state and to assign a subset of dipolar interactions to each constant of motion, which are compatible with the experiments. As a criterion for selecting a suitable quasi-equilibrium model of the 5CB molecule, we impose on the time evolution operator consistency with the occurrence of two dipolar quasi-invariants, that is, the calculated spectra must be unaffected by truncation of non-secular terms of the weaker dipolar energy. We find that defining the S quasi-invariant as the subset of the dipolar interactions of each proton with its two nearest neighbours yields a realistic characterization of the dipolar constants of motion in 5CB. We conclude that the proton-spin system of the 5CB molecule admits a partition of the dipolar energy into a bilinear strong and a multiple-spin weak contributions therefore providing two orthogonal constants of motion, which can be prepared and observed by means of the JB experiment. This feature, which implies the existence of two timescales of very different nature in the proton-spin dynamics, is ultimately dictated by the topology of the spin distribution in the dipole network and can be expected in other liquid crystals. Knowledge of the nature of the dipolar quasi-invariants will be useful in studies of dipolar-order relaxation, decoherence and multiple quantum NMR experiments where the initial state is a dipolar-ordered one.

Combination of OPSY and PhD-PHIP results in enhanced sensitivity in PHIP.

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.

Optimized phases for the acquisition of J-spectra in coupled spin systems for thermally and PHIP polarized molecules.

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.

Influence of the incorporation of fibers in biscuit dough on proton mobility characterized by time domain NMR.

The effect of fiber addition on the distribution and mobility of protons in biscuits is studied by using low resolution time domain nuclear magnetic resonance (TD-NMR). The proportion of flour is reduced in order to incorporate inulin and oat fiber. NMR temperature dependent experiments are carried out in order to gain insight on the processes occurring in biscuit baking. Proton populations were identified measuring spin-spin relaxation times (T2). The major change in the relaxation profiles upon incorporation of fibers corresponds to mobile water molecules, which appear to be related to dough spreading behavior and biscuit quality. Biscuit samples baked in a commercial oven were studied by two dimensional spin-lattice/spin-spin (T1-T2) relaxation maps. The T1/T2 ratio is used as an indicator of the population mobility, where changes in the mobility of water in contact with flour components as starch, proteins and pentosans are observed.

Parahydrogen discriminated PHIP at low magnetic fields.

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.

Imaging of a mixture of hyperpolarized 3He and 129Xe.

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.

Experimental NMR spin-lattice relaxometry study in the liquid crystalline nematic phase of propylcyano-phenylcyclohexane.

The NMR spin-lattice proton relaxation dispersion T1(nu(L)) of the liquid crystal propylcyano-phenylcyclohexane is studied over several decades of Larmor frequencies and at different temperatures in the nematic mesophase. The results show that the order fluctuation of the local nematic director contribution to T1(nu(L)) undergoes a transition between two power regimes: from T1(nu(L)) protional to nu(1/2)L to nu(alpha)L (alpha approximately 1/3) on going from low to high Larmor frequencies.

NMR proton spin dynamics in thermotropic liquid crystals subject to multipulse excitation.

Previous experiments of NMR spin-lattice relaxation times as a function of the Larmor frequency, as measured with the field-cycling technique (FC), were shown to be very useful to disentangle the various molecular motions, both local and collective, that dominate the relaxation in different time scales in liquid crystals. However, there are many examples where the known theoretical models that represent the molecular relaxation mechanisms cannot be fitted to the experimental trend in the region of low fields, making it difficult to obtain reliable values for the spectral densities involved, especially for the cooperative motions which dominate at low frequencies. In some cases, these anomalies are loosely ascribed to "local-field" effects but, to our knowledge, there is not a detailed explanation about the origin of these problems nor the range of frequencies where they should be expected. With the aim of isolating the dipolar effects from the influence of molecular dynamics, and taking into account the previous results in solids, in this work we investigate the response of the proton spin system of thermotropic liquid crystals 4-pentyl-4'-cyanobiphenyl (5CB) and 4-octyl-4'-cyanobiphenyl (8CB) in nematic and smectic A phases, due to the NMR multipulse sequence 90( composite function )y-(tau-thetax-tau)N. The nuclear magnetization presents an early transient period characterized by strong oscillations, after which a quasistationary state is attained. Subsequently, this state relaxes towards internal equilibrium over a time much longer than the transverse relaxation time T2. As occurs in solids, the decay time of the quasistationary state T2e presents a minimum when the pulse width thetax and the offset of the radiofrequency are set to satisfy resonance conditions (spin-lock). When measured as a function of the pulse spacing tau in "on-resonance" experiments, T2e shows the behavior expected for cross relaxation between the effective Zeeman and dipolar reservoirs, in accordance with the thermodynamic theory previously developed for solids. Particularly, for values of tau comparable with T2, the relaxation rate follows a power law T2e proportional to tau(-2), in all the observed cases, for the resonance conditions thetax=pi/3 and equivalent frequency omegae=pi/3tau. When tau is similar to or greater than typical dipolar periods, the relaxation rate becomes constant and for tau much shorter than T2, the thermodynamic reservoirs get decoupled. These experiments confirm that the thermodynamic picture is valid also in liquid crystals and the cross relaxation between the reservoirs can be detected without interference with spin-lattice relaxation effects. Accordingly, this technique can be used to estimate the frequency range, where cross-relaxation effects can be expected when Zeeman and dipolar reservoirs are put in thermal contact with each other and with the lattice, as in FC experiments. In particular, the present results allow us to associate the anomalies observed in low-field spin-lattice relaxation with nonadiabatic energy exchange between the reservoirs.

High resolution para-hydrogen induced polarization in inhomogeneous magnetic fields.

The application of parahydrogen for the generation of hyperpolarization has increased continuously during the last years. When the chemical reaction is carried out at the same field as the NMR experiment (PASADENA protocol) an antiphase signal is obtained, with a separation of the resonance lines of a few Hz. This imposes a stringent limit to the homogeneity of the magnetic field in order to avoid signal cancellation. In this work we detect the signal arising from hyperpolarized Hexene by means of a CPMG pulse train. After Fourier transformation the obtained J-spectra not only presents an enhanced spectral resolution but also avoids partial peak cancellation.

Resolution enhancement in MRI of laser polarized 3He by control of diffusion.

Diffusion of atoms or molecules in presence of magnetic field gradients not only attenuates the NMR signal but also leads to distortions close to restricting boundaries. This phenomenon is most evident in imaging with laser polarized (LP) noble gases. Diffusion of gases can be manipulated, however, by admixing inert gases of different molecular weight. In this work we analyze the effect of mixing LP-(3)He with SF(6) on the image quality of a phantom consisting of an arrangement of capillaries with different diameters. Admixing buffer gases of higher molecular weight changes the contrast and offers a means to record images with high spatial and time resolution. Additionally we demonstrate how distortions due to edge enhancement can be reduced even for long timed MRI-sequences.

Diffusion in binary gas mixtures studied by NMR of hyperpolarized gases and molecular dynamics simulations.

The dependence of the individual mean square displacement of rare gases in binary mixtures is studied by a combined experimental and theoretical approach. We show that the diffusion constant can be varied in a considerable range by changing the molar fractions of the mixtures. On the experimental side, NMR diffusion measurements are done on hyperpolarized 3He and 129Xe, mixed with several inert buffer gases, in the presence of a magnetic field gradient. The results are compared to diffusion coefficients obtained from atomistic molecular dynamics simulations based on Lennard-Jones type potentials of the corresponding gas mixtures, and to appropriate analytical expressions, yielding very good mutual agreement. This study is the first quantitative validation of the effects of the mutual interactions between gas particles on the individual diffusion properties. It is shown that the dependency of gas phase diffusion properties on the local chemical environment may not be neglected, e.g. in diffusion-controlled chemical reactions.

On the role of collective and local molecular fluctuations in the relaxation of proton intrapair dipolar order in nematic 5CB.

We investigate the role that local motions and slow cooperative fluctuations have on the relaxation of the intrapair dipolar order in the nematic 5CB. With this purpose we present a theoretical and experimental systematic study which allow us to quantify the contribution from each type of molecular fluctuation to the intrapair dipolar order relaxation time, T(1D). The experimental work includes measurements of Zeeman and intrapair dipolar order relaxation times (T(1Z) and T(1D)) as a function of temperature at conventional NMR frequencies, in three complementary samples: normal and chain deuterated 4-n-pentyl-4(')-cyanobiphenyl (5CB and 5CB(d11)) and a mixture of normal 5CB and fully deuterated 4-n-pentyl-4'-cyanobiphenyl (5CB(d19)), 50% in weight. Additionally we perform T(1Z) field-cycling Larmor frequency-dependent measurements to obtain the spectral density of the cooperative fluctuations. The obtained results are as follows. (a) The cooperative molecular fluctuations have a strong relative weight in the relaxation of the intrapair dipolar order state, even at Larmor frequencies in the range of conventional NMR. (b) Alkyl chain rotations are an important relaxation mechanism of the intrapair dipolar order at megahertz frequencies. (c) Intermolecular fluctuations mediated by translational self-diffusion of the molecules is not an efficient mechanism of relaxation of the intrapair dipolar order.

Pseudonematic order fluctuations of the director in the smectic phase of thermotropic liquid crystals.

The NMR spin-lattice proton relaxation dispersion in the smectic mesophase of two liquid crystals, 4cyano-4'-8-alkylbiphenyl and 4,4'-bis-heptyloxyazoxybenzene, are studied over several decades of Larmor frequencies. The results show that the order fluctuation of the local smectic director contribution to T1(nu(L)) undergoes a transition between two power regimes: from T1(nu(L)) proportional, variantnu(1)(L) to nu(1/2)(L) on going from low to high Larmor frequencies. We explain this behavior by assuming, in the smectic mesophases, short coherence length nematiclike cooperative molecular reorientations.