Friday, June 24, 2011

DNP by Thermal Mixing under Optimized Conditions Yields >60‚000-fold Enhancement of 89Y NMR Signal

Lumata, L., et al., DNP by Thermal Mixing under Optimized Conditions Yields >60‚000-fold Enhancement of 89Y NMR Signal. J. Am. Chem. Soc., 2011. 133(22): p. 8673-8680


Hyperpolarized 89Y complexes are attractive NMR spectroscopy and MR imaging probes due to the exceptionally long spin–lattice relaxation time (T1 ~ 10 min) of the 89Y nucleus. However, in vivo imaging of 89Y has not yet been realized because of the low NMR signal enhancement levels previously achieved for this ultra low-gamma nucleus. Here, we report liquid-state 89Y NMR signal enhancements over 60 000 times the thermal signal at 298 K in a 9.4 T magnet, achieved after the dynamic nuclear polarization (DNP) of Y(III) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) samples at 3.35 T and 1.4 K. The 89Y DNP was shown to proceed by thermal mixing and the liquid state 89Y NMR signal enhancement was maximized by (i) establishing the optimal microwave irradiation frequency, (ii) optimizing the glassing matrix, (iii) choosing a radical with negligible inhomogeneous line broadening contribution to the ESR linewidth, and (iv) addition of an electron T1e relaxation agent. The highest enhancements were achieved using a trityl OX063 radical combined with a gadolinium relaxation agent in water-glycerol matrix. Co-polarization of 89YDOTA and sodium [1-13C]pyruvate showed that both 89Y and 13C nuclear species acquired the same spin temperature, consistent with thermal mixing theory of DNP. This methodology may be applicable for the optimization of DNP of other low-gamma nuclei.



Dissolution DNP NMR with solvent mixtures: Substrate concentration and radical extraction

Harris, T., C. Bretschneider, and L. Frydman, Dissolution DNP NMR with solvent mixtures: Substrate concentration and radical extraction. J. Magn. Reson., 2011. 211(1): p. 96-100


Dynamic nuclear polarization (DNP) followed by sudden sample dissolution, is a topic of active investigation owing to the method's unique prospects for the delivery of NMR spectra and images with unprecedented sensitivity. This experiment achieves hyperpolarization by the combined effects of electron-nuclear irradiation and cryogenic operation; the exploitation of these states occurs following a sudden melting and flushing of the resulting pellet from its original environment into a conventional, liquid-state setting. This melting and flushing usually demands using the equivalent of a few milliliters of hot solvent, a procedure which although well suited for in vivo studies leads to an excessive sample volume when considering typical analytical settings. The present study explores a way of reducing the ensuing dilution of the hyperpolarized analytes, by employing a combination of immiscible liquids for performing the melting and flushing. It is shown that suitable combinations of immiscible solvents - both in terms of their heat capacities and densities - allow one to melt the targeted cryogenic pellet and dissolve the hyperpolarized analytes in a fraction of the solvent hitherto required. By tailoring the resulting volume to the needs of a conventional 5 mm NMR probe, a substantial sensitivity enhancement can be added to the hyperpolarization process. An extra benefit may arise from using radicals that preferentially dissolve in the immiscible organic phase, by way of a lengthening of the relaxation time of the investigated analytes. Examples of these principles are given, and further potential extensions of this approach are discussed.

Wednesday, June 22, 2011

Low-temperature dynamic nuclear polarization at 9.4 T with a 30 mW microwave source

Thurber, K.R., W.-M. Yau, and R. Tycko, Low-temperature dynamic nuclear polarization at 9.4 T with a 30 mW microwave source. J. Magn. Reson., 2010. 204(2): p. 303-313


Dynamic nuclear polarization (DNP) can provide large signal enhancements in nuclear magnetic resonance (NMR) by transfer of polarization from electron spins to nuclear spins. We discuss several aspects of DNP experiments at 9.4 T (400 MHz resonant frequency for 1H, 264 GHz for electron spins in organic radicals) in the 7-80 K temperature range, using a 30 mW, frequency-tunable microwave source and a quasi-optical microwave bridge for polarization control and low-loss microwave transmission. In experiments on frozen glycerol/water doped with nitroxide radicals, DNP signal enhancements up to a factor of 80 are observed (relative to 1H NMR signals with thermal equilibrium spin polarization). The largest sensitivity enhancements are observed with a new triradical dopant, DOTOPA-TEMPO. Field modulation with a 10 G root-mean-squared amplitude during DNP increases the nuclear spin polarizations by up to 135%. Dependencies of 1H NMR signal amplitudes, nuclear spin relaxation times, and DNP build-up times on the dopant and its concentration, temperature, microwave power, and modulation frequency are reported and discussed. The benefits of low-temperature DNP can be dramatic: the 1H spin polarization is increased approximately 1000-fold at 7 K with DNP, relative to thermal polarization at 80 K.

Tuesday, June 21, 2011

Simulating spin dynamics in NMR with a new computer program intended for education: Insensitive

This article is not directly related to Dynamic Nuclear Polarization, however, it describes a simulation program for NMR spectroscopy that can even be used on an iPhone.

Boldt, K., Simulating spin dynamics in NMR with a new computer program intended for education: Insensitive. Concepts in Magnetic Resonance Part A, 2011. 38A(2): p. 17-24


Abstract The NMR experiment is usually described by a choice of three models that operate on different levels of abstraction: the vector model, the product operator formalism and the density matrix approach. The transition between these models poses a didactic challenge for teacher and student alike. A new computer program is presented, which simulates a spin system on the textbook level and compares the three approaches, with the possibility to manipulate the system at every step. It closes a gap between NMR education and professional simulation tools. Some algorithms are explained, which are used in the simulation to extract information from the density matrix. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38A: 17–24, 2011.



Water 1H relaxation dispersion analysis on a nitroxide radical provides information on the maximal signal enhancement in Overhauser dynamic nuclear polarization experiments

Bennati, M., et al., Water 1H relaxation dispersion analysis on a nitroxide radical provides information on the maximal signal enhancement in Overhauser dynamic nuclear polarization experiments. Phys. Chem. Chem. Phys., 2010. 12(22): p. 5902-5910


Water 1H relaxation rate measurements of 15N-2H-TEMPONE solutions at temperatures ranging from 298 to 328 K have been performed as a function of magnetic field from 0.00023 to 9.4 T, corresponding to 1H Larmor frequencies of 0.01 to 400 MHz. The relaxation profiles were analyzed according to the full theory for dipolar and contact relaxation, and used to estimate the coupling factor responsible for observed solution DNP effects. The experimental DNP enhancement at 1H Larmor frequency of 15 MHz obtained by saturating one of the lines of the 15N doublet is only ca. 20% lower than the limiting value predicted from the relaxation data, indicating that the experimental DNP setup is nearly optimal, the residual discrepancy arising from incomplete saturation of the other line.



Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast

Lingwood, M.D., et al., Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast. J. Magn. Reson., 2010. 205(2): p. 247-254


We describe and demonstrate a system to generate hyperpolarized water in the 0.35 T fringe field of a clinical 1.5 T whole-body magnetic resonance imaging (MRI) magnet. Once generated, the hyperpolarized water is quickly and continuously transferred from the 0.35 T fringe to the 1.5 T center field of the same magnet for image acquisition using standard MRI equipment. The hyperpolarization is based on Overhauser dynamic nuclear polarization (DNP), which effectively and quickly transfers the higher spin polarization of free radicals to nuclear spins at ambient temperatures. We visualize the dispersion of hyperpolarized water as it flows through water-saturated systems by utilizing an observed -15-fold DNP signal enhancement with respect to the unenhanced 1H MRI signal of water at 1.5 T. The experimental DNP apparatus presented here is readily portable and can be brought to and used with any conventional unshielded MRI system. A new method of immobilizing radicals to gel beads via polyelectrolyte linker arms is described, which led to superior flow Overhauser DNP performance compared to previously presented gels. We discuss the general applicability of Overhauser DNP of water and aqueous solutions in the fringe field of commercially available magnets with central fields up to 4.7 T.

Wednesday, June 1, 2011

2H-decoupling-accelerated 1H spin diffusion in dynamic nuclear polarization with photoexcited triplet electrons

Negoro, M., et al., [sup 2]H-decoupling-accelerated [sup 1]H spin diffusion in dynamic nuclear polarization with photoexcited triplet electrons. J. Chem. Phys., 2010. 133(15): p. 154504-6


In dynamic nuclear polarization (DNP) experiments applied to organic solids for creating nonequilibrium, high 1H spin polarization, an efficient buildup of 1H polarization is attained by partially deuterating the material of interest with an appropriate 1H concentration. In such a dilute 1H spin system, it is shown that the 1H spin diffusion rate and thereby the buildup efficiency of 1H polarization can further be enhanced by continually applying radiofrequency irradiation for deuterium decoupling during the DNP process. As experimentally confirmed in this work, the electron spin polarization of the photoexcited triplet state is mainly transferred only to those 1H spins, which are in the vicinity of the electron spins, and 1H spin diffusion transports the localized 1H polarization over the whole sample volume. The 1H spin diffusion coefficients are estimated from DNP repetition interval dependence of the initial buildup rate of 1H polarization, and the result indicates that the spin diffusion coefficient is enhanced by a factor of 2 compared to that without 2H decoupling.

Quantum mechanical theory of dynamic nuclear polarization in solid dielectrics

Hu, K.-N., et al., Quantum mechanical theory of dynamic nuclear polarization in solid dielectrics. J. Chem. Phys., 2011. 134(12): p. 125105-19


Microwave driven dynamic nuclear polarization (DNP) is a process in which the large polarization present in an electron spin reservoir is transferred to nuclei, thereby enhancing NMR signal intensities. In solid dielectrics there are three mechanisms that mediate this transfer—the solid effect (SE), the cross effect (CE), and thermal mixing (TM). Historically these mechanisms have been discussed theoretically using thermodynamic parameters and average spin interactions. However, the SE and the CE can also be modeled quantum mechanically with a system consisting of a small number of spins and the results provide a foundation for the calculations involving TM. In the case of the SE, a single electron–nuclear spin pair is sufficient to explain the polarization mechanism, while the CE requires participation of two electrons and a nuclear spin, and can be used to understand the improved DNP enhancements observed using biradical polarizing agents. Calculations establish the relations among the electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) frequencies and the microwave irradiation frequency that must be satisfied for polarization transfer via the SE or the CE. In particular, if δ, Δ < ω0I, where δ and Δ are the homogeneous linewidth and inhomogeneous breadth of the EPR spectrum, respectively, we verify that the SE occurs when ωM = ω0S ± ω0I, where ωM, ω0S and ω0I are, respectively, the microwave, and the EPR and NMR frequencies. Alternatively, when Δ > ω0I > δ, the CE dominates the polarization transfer. This two-electron process is optimized when ω0S1−ω0S2 = ω0I and ωM ∼ ω0S1 or ω0S2, where ω0S1 and ω0S2 are the EPR Larmor frequencies of the two electrons. Using these matching conditions, we calculate the evolution of the density operator from electron Zeeman order to nuclear Zeeman order for both the SE and the CE. The results provide insights into the influence of the microwave irradiation field, the external magnetic field, and the electron−electron and electron−nuclear interactions on DNP enhancements.

Saturation factor of nitroxide radicals in liquid DNP by pulsed ELDOR experiments

Turke, M.-T. and M. Bennati, Saturation factor of nitroxide radicals in liquid DNP by pulsed ELDOR experiments. Phys. Chem. Chem. Phys., 2011. 13(9): p. 3630-3633


We propose the use of the pulse electron double resonance (ELDOR) method to determine the effective saturation factor of nitroxide radicals for dynamic nuclear polarization (DNP) experiments in liquids. The obtained values for the nitroxide radical TEMPONE-D,15N at different concentrations are rationalized in terms of spin relaxation and are shown to fulfil the Overhauser theory.



Dynamics and state of lipid bilayer-internal water unraveled with solution state 1H dynamic nuclear polarization

Kausik, R. and S. Han, Dynamics and state of lipid bilayer-internal water unraveled with solution state 1H dynamic nuclear polarization. Phys. Chem. Chem. Phys., 2011. 13(17): p. 7732-7746


The dynamics and state of lipid bilayer-internal hydration water of unilamellar lipid vesicles dispersed in solutions is characterized. This study was enabled by a recently developed technique based on Overhauser dynamic nuclear polarization (DNP)-driven amplification of 1H nuclear magnetic resonance (NMR) signal of hydration water. This technique can, in the full presence of bulk water, selectively quantify the translational dynamics of hydration water within [similar]10 A around spin labels that are specifically introduced to the local volume of interest within the lipid bilayer. With this approach, the local apparent diffusion coefficients of internal water at different depths of the lipid bilayer were determined. The modulation of these values as a response to external stimuli, such as the addition of sodium chloride or ethanol and the lipid phase transitions, that alter the fluctuations of bilayer interfaces together with the activation energy values of water diffusivity shows that water is not individually and homogeneously solvating lipid's hydrocarbon tails in the lipid bilayer. We provide experimental evidence that instead, water and the lipid membrane comprise a heterogeneous system whose constituents include transient hydrophobic water pores or water structures traversing the lipid bilayer. We show how these transient pore structures, as key vehicles for passive water transport can better reconcile our experimental data with existing literature data on lipid bilayer hydration and dynamics.



Microwave field distribution in a magic angle spinning dynamic nuclear polarization NMR probe

Nanni, E.A., et al., Microwave field distribution in a magic angle spinning dynamic nuclear polarization NMR probe. J. Magn. Reson., 2011. 210(1): p. 16-23

http://dx.doi.org/10.1016/j.jmr.2011.02.001

We present a calculation of the microwave field distribution in a magic angle spinning (MAS) probe utilized in dynamic nuclear polarization (DNP) experiments. The microwave magnetic field (B1S) profile was obtained from simulations performed with the High Frequency Structure Simulator (HFSS) software suite, using a model that includes the launching antenna, the outer Kel-F stator housing coated with Ag, the RF coil, and the 4 mm diameter sapphire rotor containing the sample. The predicted average B1S field is 13 microT/W^1/2, where S denotes the electron spin. For a routinely achievable input power of 5 W the corresponding value is 0.84 MHz. The calculations provide insights into the coupling of the microwave power to the sample, including reflections from the RF coil and diffraction of the power transmitted through the coil. The variation of enhancement with rotor wall thickness was also successfully simulated. A second, simplified calculation was performed using a single pass model based on Gaussian beam propagation and Fresnel diffraction. This model provided additional physical insight and was in good agreement with the full HFSS simulation. These calculations indicate approaches to increasing the coupling of the microwave power to the sample, including the use of a converging lens and fine adjustment of the spacing of the windings of the RF coil. The present results should prove useful in optimizing the coupling of microwave power to the sample in future DNP experiments. Finally, the results of the simulation were used to predict the cross effect DNP enhancement ([epsilon]) vs. [omega]1S/(2[pi]) for a sample of 13C-urea dissolved in a 60:40 glycerol/water mixture containing the polarizing agent TOTAPOL; very good agreement was obtained between theory and experiment.

Relaxometry of insensitive nuclei: Optimizing dissolution dynamic nuclear polarization

MiEville, P., S. Jannin, and G. Bodenhausen, Relaxometry of insensitive nuclei: Optimizing dissolution dynamic nuclear polarization. J. Magn. Reson., 2011. 210(1): p. 137-140

http://dx.doi.org/10.1016/j.jmr.2011.02.006

We report measurements of spin-lattice relaxation of carbon-13 as a function of the magnetic field ('relaxometry') in view of optimizing dissolution-DNP. The sample is temporarily lifted into the stray field above a high-resolution magnet using a simple and inexpensive 'shuttle'. The signals of arbitrary molecules can be observed at high field with high-resolution and sensitivity. During the dissolution process and subsequent 'voyage' from the polarizer to the NMR magnet, relaxation is accelerated by paramagnetic polarizing agents, but it can be quenched by using scavengers.

Application of double spin echo spiral chemical shift imaging to rapid metabolic mapping of hyperpolarized [1-13C]-pyruvate

Josan, S., et al., Application of double spin echo spiral chemical shift imaging to rapid metabolic mapping of hyperpolarized [1-13C]-pyruvate. J. Magn. Reson., 2011. 209(2): p. 332-336


Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows sub-second metabolic imaging of hyperpolarized 13C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B1-homogeneous sensitive volume of the RF coil.

A Dynamic Nuclear Polarization spectrometer at 95 GHz/144 MHz with EPR and NMR excitation and detection capabilities

Feintuch, A., et al., A Dynamic Nuclear Polarization spectrometer at 95†GHz/144†MHz with EPR and NMR excitation and detection capabilities. J. Magn. Reson., 2011. 209(2): p. 136-141


A spectrometer specifically designed for systematic studies of the spin dynamics underlying Dynamic Nuclear Polarization (DNP) in solids at low temperatures is described. The spectrometer functions as a fully operational NMR spectrometer (144 MHz) and pulse EPR spectrometer (95 GHz) with a microwave (MW) power of up to 300 mW at the sample position, generating a MW B1 field as high as 800 KHz. The combined NMR/EPR probe comprises of an open-structure horn-reflector configuration that functions as a low Q EPR cavity and an RF coil that can accommodate a 30-50 micro liter sample tube. The performance of the spectrometer is demonstrated through some basic pulsed EPR experiments, such as echo-detected EPR, saturation recovery and nutation measurements, that enable quantification of the actual intensity of MW irradiation at the position of the sample. In addition, DNP enhanced NMR signals of samples containing TEMPO and trityl are followed as a function of the MW frequency. Buildup curves of the nuclear polarization are recorded as a function of the microwave irradiation time period at different temperatures and for different MW powers.