Song-I Han

A new model for Overhauser enhanced nuclear magnetic resonance using nitroxide radicals

Nitroxide free radicals are the most commonly used source for dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) experiments and are also exclusively employed as spin labels for electron spin resonance (ESR) spectroscopy of diamagnetic molecules and materials. Nitroxide free radicals have been shown to have strong dipolar coupling to (1)H in water, and thus result in large DNP enhancement of (1)H NMR signal via the well known Overhauser effect. The fundamental parameter in a DNP experiment is the coupling factor, since it ultimately determines the maximum NMR signal enhancements which can be achieved. Despite their widespread use, measurements of the coupling factor of nitroxide free radicals have been inconsistent, and current models have failed to successfully explain our experimental data. We found that the inconsistency in determining the coupling factor arises from not taking into account the characteristics of the ESR transitions, which are split into three (or two) lines due to the hyperfine coupling of the electron to the (14)N nuclei (or (15)N) of the nitric oxide radical. Both intermolecular Heisenberg spin exchange interactions as well as intramolecular nitrogen nuclear spin relaxation mix the three (or two) ESR transitions. However, neither effect has been taken into account in any experimental studies on utilizing or quantifying the Overhauser driven DNP effects. The expected effect of Heisenberg spin exchange on Overhauser enhancements has already been theoretically predicted and observed by Bates and Drozdoski [J. Chem. Phys. 67, 4038 (1977)]. Here, we present a new model for quantifying Overhauser enhancements through nitroxide free radicals that includes both effects on mixing the ESR hyperfine states. This model predicts the maximum saturation factor to be considerably higher by the effect of nitrogen nuclear spin relaxation. Because intramolecular nitrogen spin relaxation is independent of the nitroxide concentration, this effect is still significant at low radical concentrations where electron spin exchange is negligible. This implies that the only correct way to determine the coupling factor of nitroxide free radicals is to measure the maximum enhancement at different concentrations and extrapolate the results to infinite concentration. We verify our model with a series of DNP experimental studies on (1)H NMR signal enhancement of water by means of (14)N as well as (15)N isotope enriched nitroxide radicals.

Amplification of xenon NMR and MRI by remote detection

A technique is proposed in which an NMR spectrum or MRI is encoded and stored as spin polarization and is then moved to a different physical location to be detected. Remote detection allows the separate optimization of the encoding and detection steps, permitting the independent choice of experimental conditions and excitation and detection methodologies. In the initial experimental demonstration of this technique, we show that taking dilute 129Xe from a porous sample placed inside a large encoding coil and concentrating it into a smaller detection coil can amplify NMR signal. In general, the study of NMR active molecules at low concentration that have low physical filling factor is facilitated by remote detection. In the second experimental demonstration, MRI information encoded in a very low-field magnet (4–7 mT) is transferred to a high-field magnet (4.2 T) to be detected under optimized conditions. Furthermore, remote detection allows the utilization of ultrasensitive optical or superconducting quantum interference device detection techniques, which broadens the horizon of NMR experimentation.

Hyperpolarized water as an authentic magnetic resonance imaging contrast agent

Pure water in a highly 1H spin-polarized state is proposed as a contrast-agent-free contrast agent to visualize its macroscopic evolution in aqueous media by MRI. Remotely enhanced liquids for image contrast (RELIC) utilizes a 1H signal of water that is enhanced outside the sample in continuous-flow mode and immediately delivered to the sample to obtain maximum contrast between entering and bulk fluids. Hyperpolarization suggests an ideal contrast mechanism to highlight the ubiquitous and specific function of water in physiology, biology, and materials because the physiological, chemical, and macroscopic function of water is not altered by the degree of magnetization. We present an approach that is capable of instantaneously enhancing the 1H MRI signal by up to 2 orders of magnitude through the Overhauser effect under ambient conditions at 0.35 tesla by using highly spin-polarized unpaired electrons that are covalently immobilized onto a porous, water-saturated gel matrix. The continuous polarization of radical-free flowing water allowed us to distinctively visualize vortices in model reactors and dispersion patterns through porous media. A 1H signal enhancement of water by a factor of −10 and −100 provides for an observation time of >4 and 7 s, respectively, upon its injection into fluids with a T1 relaxation time of >1.5 s. The implications for chemical engineering or biomedical applications of using hyperpolarized solvents or physiological fluids to visualize mass transport and perfusion with high and authentic MRI contrast originating from water itself, and not from foreign contrast agents, are immediate.

In situ observation of diffusion and reaction dynamics in gel microreactors by chemically resolved NMR microscopy

The enzymatically catalyzed esterification reaction of propionic acid+1-butanol ⇆ propionic-acid-butyl-ester+water inside an immobilizing hydrogel environment has been investigated by means of spectroscopically resolved nuclear magnetic resonance (NMR) imaging. The alginate hydrogel was in the shape of a 3–4 mm diameter bead, with both the gel-forming water and the solvent (cyclohexane) being fully deuterated to simplify the identification of small amounts of reactants. In the absence of enzymes, the self-diffusion process of the separate reactants (propionic acid and butanol) proved to be severely slowed down compared to pure Fickian self-diffusion, and the concentration buildup inside the gel bead was shown to depend strongly on the properties of the reactants. Two-dimensional, non-chemically resolved images revealed that the diffusion process is not radially symmetric as expected, thus complicating the modelling of the diffusion and reaction kinetics. The reaction itself has been observed with chemical resolution in a time series of up to 40 h, clearly demonstrating the reduction of 1-butanol and production of water inside the gel bead.

Two-dimensional representation of position, velocity and acceleration by PFG-NMR

A novel view on the presentation of pulsed field-gradient nuclear magnetic resonance experiments to encode position and translational displacements is given. A conventional diffusion or flow experiment employing two magnetic field gradients of effective areak1, andk2 separated by a time interval Δ can formally be expressed as a means to probek space in a two-dimensional way. While for most applications, a full coverage of the [k1,k2] space is not necessary, an experiment withk1 = −k2 can be regarded as a sampling of the secondary diagonal in [k1,k2] space. Likewise, the main diagonal is represented by the conditionk1 =k2 and encodes position. Thus, the [r1,r2] space conjugate to [k1,k2], which is obtained by Fourier transformation, can be transferred into a position/displacement correlation plot simply by rotation of the coordinate system by an angle of 45°. While displacementR =r2 −r1 corresponds to an average velocity⊻ =R/Δ, an extension towards higher-order derivations such as acceleration is straightforward by modification of the pulse sequence. We discuss this new concept in a general way, treating both the magnetic field and the particle position by Taylor expansions with respect to space and time, respectively, and present examples for fluid flowing through capillary systems in the light of the suggested interpretation.

Spectrally resolved velocity exchange spectroscopy of two-phase flow.

The Velocity EXchange SpectroscopY (VEXSY) technique, which provides a means to correlate macroscopic molecular displacements measured during two intervals separated by a variable mixing period, has been applied for the first time to a system of two-phase flow. The chemical shift difference between water and methyl protons has been exploited to simultaneously determine the probability of displacements, or propagator, of both components in a water/silicone oil mixture flowing through a glass bead pack. The joint two-time probability densities as well as the conditional probabilities of velocities show a clearly distinct dispersion behaviour of both fluids which is a consequence of the different wetting properties of the fluids with respect to the glass surface of the bead pack.

ANALYSIS OF SLOW MOTION BY MULTIDIMENSIONAL NMR

Slow translational motion is conventionally probed by magnetic gradient fields which are manipulated in time so that different moments of the gradient modulation function are either adjusted to zero or stepped through a range of values for subsequent Fourier transformation to obtain the displacement propagators, and probability densities of motional parameters like position, velocity and acceleration. It is shown, that this formalism is not restricted to time-dependent linear fields to probe translational motion, but can be applied to time-dependent offset fields in general with arbitrary parameter dependences including angular dependences to probe rotational motion. Three cases are considered in particular: a linear space dependence, a quadratic space dependence, and an angular dependence of the offset field following the second Legendre polynomial. Experimental examples concern position exchange NMR of laminar flow through a narrowing pipe and velocity exchange NMR for a hollow fiber filtration module with pulsed linear fields, laminar flow through a pipe in a time-invariant parabolic field profile, and 13C solid-state exchange of dimethyl sulfone in a homogeneous polarization field.

Catching a Falling Drop by NMR: Correlation of Position and Velocity

The spin density profile and the statistical probability density of displacements of a drop free falling through a vertical-bore magnet was measured in all three spatial directions, both separated and in a correlated way employing NMR imaging methods and in particular pulsed field gradient (PFG) NMR techniques. The falling motion was monitored by double encoding of vertical position at successive times separated by Δ within a single two-dimensional (2D) PFG NMR experiment i.e. position exchange spectroscopy (POXSY). 2D images along the cross-section of the drop, mapping the z- velocity component in each pixel, verifies the constant z-velocity throughout the total drop volume. 2D images encoded with transverse velocities contain structures characteristic of velocity distributions which can be attributed either to vortex-motions inside the drop or coherent oscillations of the whole drop. The fact that the net transverse velocity over the cross-section is zero proves that no net motions of the drop itself contribute to the results. The essential challenge has been to implement one- and multi-dimensional NMR imaging techniques within the residence time of the falling drop inside the resonator of about 10 ms. The solution was to accumulate information from many drops by triggering every single acquisition to another falling drop. The regularity and uniformity of the dripping process was clearly demonstrated, which was the absolute requirement for signal accumulation as well as for multidimensional NMR experiments. Given that the experimentally determined velocity profile of the drop by NMR imaging methods was reproducible and reliable, the basis for mapping motion of and inside a drop in a direct, three-dimensional and non-invasive way by NMR flow imaging methods is given.

Spatio-Temporal Correlations in Gravity-Driven and Pressure-Driven Fluid Transport Processes

NMR pulsed-field gradient velocity encoding techniques and NMR imaging have been combined for the investigation of flow behaviour for two fluid systems of greatly differing geometry, the free falling planar liquid film and counterflow in a matrix of porous cylindrical membranes, respectively. Both systems have in common that material transport is predominantly influenced by the dynamics near the interfaces. At the liquid/gas interface of the falling film, the occurrence of waves above a critical threshold volume flow rate was demonstrated; transport within the wavy film was investigated in terms of spatially dependent velocity profiles which allow the computation of the velocity field at arbitrary positions within the film. In flow through thin porous capillaries, the efficiency of trans-membrane fluid exchange was determined by multi-encoding techniques which allow both a statistical description of the velocity distribution and the quantification of exchange processes in comparison to purely diffusion-governed transport.