Fast Dissolution Dynamic Nuclear Polarization NMR of 13C-Enriched 89Y-DOTA Complex: Experimental and Theoretical Considerations

The yttrium complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(1′-¹³C-acetic acid) [¹³C]DOTA was synthesized. Fast dissolution dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) studies revealed that the ⁸⁹Y, ¹³C, and ¹⁵N nuclei present in the complex could be co-polarized at the same optimum microwave irradiation frequency. The liquid-state spin–lattice relaxation time T ₁ of these nuclei were found to be reasonably long to preserve some or most of the DNP-enhanced polarization after dissolution. The hyperpolarized ¹³C and ⁸⁹Y NMR signals were optimized in different glassing mixtures. The overall results are discussed in light of the thermal mixing model of DNP.     

Rapid sequential injections of hyperpolarized [1-C]pyruvate in vivo using a sub-kelvin,multi-sample DNP polarizer

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of ¹³C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-¹³C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-¹³C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in ¹³C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.     

Study of synthetic diamonds by dynamic nuclear polarization-enhanced13C nuclear magnetic resonance spectroscopy

Four I_b-type synthetic diamond crystals were studied by dynamic nuclear polarization (DNP)-enhanced high resolution solid state¹³C nuclear magnetic resonance (NMR) spectroscopy. The home built DNP magic-angle-spinning (MAS) NMR spectrometer operates at a field strength of 1.9 T and the highest DNP enhancement factor of synthetic diamonds came near to 10³. Comparing with I_b-type natural diamonds, the¹³C NMR linewidths of synthetic diamonds in static spectra are broader. The¹³C spin-lattice relaxation time and DNP polarization time of synthetic diamond are shorter than those of I_b-type natural diamond. From the hyperfine structure of the DNP enhancement curve, four kinds of nitrogen-centred free radicals could be identified in synthetic diamond.     

Dissolution dynamic nuclear polarization–enhanced magnetic resonance spectroscopy and imaging: Chemical and biochemical reactions in nonequilibrium conditions

Hyperpolarization techniques, in particular dissolution dynamic nuclear polarization (D-DNP), make a contribution to overcoming sensitivity limitations of magnetic resonance (MR) spectroscopy through signal enhancement, leading to the study of new fields of research in real time. Utilizing the large signal enhancement initially produced on small molecules, it has become possible to study systems with low γ nuclei, such as ¹³C, ¹⁵N, and ²⁹Si. This review summarizes recent studies that have extended the applicability of D-DNP into various areas of research, especially for systems in nonequilibrium conditions that involve in vivo metabolic/molecular MR imaging for early stage disease diagnosis and real-time MR analysis of various chemical/biochemical reactions for kinetic and mechanistic studies. This review also deals with the theoretical aspects of DNP mechanisms and experimental arrangements of the dissolution setup.     

Aspects of structural order in 209Bi-containing particles for potential MRI contrast agents based on quadrupole enhanced relaxation

ABSTRACT

Quadrupole relaxation enhancement (QRE) has been suggested as the key mechanism for a novel class of field-selective, potentially responsive magnetic resonance imaging contrast agents. In previous publications, QRE has been confirmed for solid compounds containing ²⁰⁹Bi as the quadrupolar nucleus (QN). For QRE to be effective in aqueous dispersions, several conditions must be met, i.e. high transition probability of the QN at the ¹H Larmor frequency, water exchange with the bulk and comparatively slow motion of the Bi-carrying particles. In this paper, the potential influence of structural order within the compounds (‘crystallinity’) on QRE was studied by nuclear quadrupole resonance (NQR) spectroscopy in one crystalline and two amorphous preparations of Triphenylbismuth (BiPh₃). The amorphous preparations comprised (1) a shock-frozen melt and (2) a granulate of polystyrene which contained homogeneously distributed BiPh₃ after common dissolution in THF and subsequent evaporation of the solvent. In contrast to the crystalline powder which exhibits strong, narrow NQR peaks the amorphous preparations did not reveal any NQR signals above the noise floor. From these findings, we conclude that the amorphous state leads to a significant spectral peak broadening and that for efficient QRE in potential contrast agents structures with a high degree of order (near crystalline) are required.     

Feasibility of using hyperpolarized [1-13C]lactate as a substrate for in vivo metabolic 13C MRSI studies

The development of dynamic nuclear polarization in solution has enabled in vivo 13C MR studies at high signal-to-noise ratio following injection of prepolarized 13C substrates. While prior studies have demonstrated the ability to observe metabolism following injection of hyperpolarized 13C pyruvate, the goal of this study was to develop and test a new hyperpolarized agent for investigating in vivo metabolism, [1-13C]lactate. A preparation for prepolarized 13C lactate and the requisite dissolution media were developed to investigate the feasibility for in vivo 13C MRS/MRSI studies following injection of this hyperpolarized agent. This study demonstrated, for the first time, not only the ability to detect hyperpolarized [1-13C]lactate in vivo but also the metabolic products 13C pyruvate, 13C alanine and 13C bicarbonate following injection in normal rats. The use of 13C lactate as a substrate provided the opportunity to study the conversion of lactate to pyruvate in vivo and to detect the secondary conversions to alanine and bicarbonate through pyruvate. This study also demonstrated the potential value of this hyperpolarized agent to investigate in vivo lactate uptake and metabolism in preclinical animal models.     

Potential contrast agents for magnetic resonance imaging

The development ofmagneto-pharmaceuticals plays an important role in the extension of nuclear magnetic resonance into diagnostic medicine. That is the reason why fundamental investigations leading to new insights into NMR contrast agents are presently being considered. The synthesis and the proton relaxation rates of some new contrast agents are presented. The high values ofR ₁, andR ₂ relaxivities of the compounds studied by us are promising for various and novel applications.     

Cavitation-assisted decontamination of yttria from graphite of different densities

Yttria coated graphite crucibles are widely used to handle molten refractory and radioactive metals like uranium and plutonium. However, the coated layer suffers damages like cracking and peeling off owing to thermal cycles. As a result, removal of the yttria layer from the graphite surface is essential to ensure reuse of the crucible and minimization of radioactive waste. The present work investigates intensified dissolution of yttria from the coated graphite samples using ultrasound as a non-destructive decontamination technique to recycle the graphite substrate. The optimum conditions established for maximum dissolution were 8 M as acid strength, frequency of 30 kHz, temperature of 45 °C and power density of 8 W cm⁻² that resulted in maximum dissolution of 52% in 30 min. Use of an oxidant H₂O₂ to the acid, did not yield any improvement in the dissolution kinetics, instead, increased oxidation of the graphite substrate was observed, leading to the anomalous weight gain of the graphite substrate despite surface erosion. Effect of ultrasound on the dissolution was pronounced, with almost a threefold increase compared to dissolution performed under silent conditions. Rates of dissolution of yttria from the substrate of different densities and pore size distribution were also studied. The dissolution was slowest from graphite of density 1.82 g cm⁻³ as the pore size distribution was conducive to accommodate the yttria particles. The dissolution in nitric acid followed ash layer diffusion controlled kinetics. The study has demonstrated the efficacy of application of ultrasound for accelerated decontamination of graphite substrates.     

Systematic theoretical investigations for contribution of lattice constraint to novel atomic arrangements in alloy semiconductor thin films

The atomic arrangements in zinc blende structured GaN_xAs_1−x thin films coherently grown on V-grooved substrates are theoretically investigated using empirical interatomic potentials and Monte Carlo simulation. The resultant atomic arrangements in GaN_xAs_1−x strongly depend on concentration x and substrate lattice parameter a_sub. Surface segregation of As or N is mainly found in GaN_xAs_1−x with large lattice mismatch to the substrate. On the other hand, the novel atomic arrangements such as layered segregation or ordered structure are found in GaN_xAs_1−x at the specific region such as (x, a_sub) = (0.5, 5.3), (0.3, 5.3), and (0.3, 5.1). This specific region corresponds to that with negative excess energy and with sufficient N and As atoms remaining in thin film layers even after their surface segregation. The formation of the novel atomic arrangements is discussed in terms of bond lengths in the surface layers. These results suggest that various novel atomic arrangements in alloy semiconductor thin films appear depending on x and a_sub which control degree of lattice constraint.     

Reaction and deposition of laser-evaporated iron

Reaction of laser-evaporated iron atom was investigated by Mössbauer spectroscopy and was applied for the production of films. Iron oxide films were produced by laser-deposition of Fe metal and hematite solid onto Al substrates, and the compositions of the films changed depending on the pressure of the O₂ atmosphere and the temperature of the substrates. The spin orientations of α-Fe films deposited by three types of deposition methods were compared. The nuclear spin of iron films produced by deposition of Fe atoms vaporized by resistive heating was perpendicular to the substrate surface, while that of films produced by laser-deposition of Fe was parallel to the substrate surface. The nuclear spins of iron films produced using an arc-plasma-gun were linear orientations along nanometer-sized grooves on the Al substrate surface.     

Transfer of1H and13C dynamic nuclear polarization from immobilized nitroxide radicals to flowing liquids

In this study,¹H and¹³C dynamic nuclear polarization (DNP) was generated at a magnetic field strength of 0.33 T utilizing silica phase immobilized nitroxide (SPIN) samples. The polarization was subsequently transferred to flowing liquids and monitored at a magnetic field strength of 4.7 T. These solid/liquid intermolecular transfer (SLIT) experiments provide efficient polarization transfer without the necessity of the free radical system present in the monitoring fluid. Specifically, ultimate¹H SLIT DNP Overhauser enhancements of ?56 and ?110 have been observed for benzene and chloroform in the presence of SPIN system 2, respectively. The¹³C SLIT DNP enhancement for benzene is dominated by three-spin effects and poor leakage factors (f _c). However, a particularly favorable case is the chloroform/SPIN 2 system which exhibits a scalar dominated enhancement. For this case, positive enhancements 40–60 times the¹³C thermal Boltzmann magnetization at 4.7 T have been observed. The large scalar dominated¹³C DNP enhancement for this system represents one of the largest experimental enhancements reported to date. The¹³C DNP spectra for other samples which exhibit favorable scalar¹³C dominated enhancements (e.g., Freon 113) are also presented. Three different SPIN systems were also prepared and characterized in the present study.     

Dynamic Nuclear Polarization by Thermal Mixing Under Partial Saturation

We describe a low-temperature thermodynamic model for dynamic nuclear polarization (DNP) via continuous-wave partial saturation of electron spin resonance (ESR) lines that are both homogeneously and inhomogeneously broadened. It is a variant of a reasoning proposed by Borghini, which in turn used Redfield’s thermodynamic treatment of saturation. Our variant is furthermore based on Provotorov’s insight that under partial saturation of a coupled-spin system two distinct spin temperatures should appear in a thermodynamical theory. We apply our model to DNP results obtained at a temperature of 1.2?K and in magnetic fields of 3.35 and 5?T on 1-¹³C labeled sodium acetate dissolved in a frozen D₂O/ethanol-d₆ solution doped with the free radical TEMPO.     

High-Frequency EPR and ENDOR Spectroscopy on Semiconductor Quantum Dots

It is shown that high-frequency electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) spectroscopy are excellent tools for the investigation of the electronic properties of semiconductor quantum dots (QDs). The great attractions of these techniques are that, in contrast to optical methods, they allow the identification of the dopants and provide information about the spatial distribution of the electronic wave function. This latter aspect is particularly attractive because it allows for a quantitative measurement of the effect of confinement on the shape and properties of the wave function. In this contribution EPR and ENDOR results are presented on doped ZnO QDs. Shallow donors (SDs), related to interstitial Li and Na and substitutional Al atoms, have been identified in this material by pulsed high-frequency EPR and ENDOR spectroscopy. The shallow character of the wave function of the donors is evidenced by the multitude of ENDOR transitions of the ⁶⁷Zn nuclear spins and by the hyperfine interaction of the ⁷Li, ²³Na and ²⁷Al nuclear spins that are much smaller than for atomic lithium, sodium and aluminium. The EPR signal of an exchange-coupled pair consisting of a shallow donor and a deep Na-related acceptor has been identified in ZnO nanocrystals with radii smaller than 1.5 nm. From ENDOR experiments it is concluded that the deep Na-related acceptor is located at the interface of the ZnO core and the Zn(OH)₂ capping layer, while the shallow donor is in the ZnO core. The spatial distribution of the electronic wave function of a shallow donor in ZnO semiconductor QDs has been determined in the regime of quantum confinement by using the nuclear spins as probes. Hyperfine interactions as monitored by ENDOR spectroscopy quantitatively reveal the transition from semiconductor to molecular properties upon reduction of the size of the nanoparticles. In addition, the effect of confinement on the g-factor of SDs in ZnO as well as in CdS QDs is observed. Finally, it is shown that an almost complete dynamic nuclear polarization (DNP) of the ⁶⁷Zn nuclear spins in the core of ZnO QDs and of the ¹H nuclear spins in the Zn(OH)₂ capping layer can be obtained. This DNP is achieved by saturating the EPR transition of SDs present in the QDs with resonant high-frequency microwaves at low temperatures. This nuclear polarization manifests itself as a hole and an antihole in the EPR absorption line of the SD in the QDs and a shift of the hole (antihole). The enhancement of the nuclear polarization opens the possibility to study semiconductor nanostructures with nuclear magnetic resonance techniques.     

Bio-energetic impairment in human calf muscle in thyroid disorders: a P MRS study

Mitochondrial metabolism particularly oxidative phosphorylation is greatly influenced by thyroid hormones. Earlier studies have described neuromuscular symptoms as well as impaired muscle metabolism in hypothyroid and hyperthyroid patients. In this study, we intend to look in to the muscle bioenergetics including phosphocreatine recovery kinetics based oxidative metabolism in thyroid dysfunction using in vivo ³¹P nuclear magnetic resonance spectroscopy (MRS). ³¹P MRS was carried out at resting state on 32 hypothyroid, 10 hyperthyroid patients and 25 control subjects. Nine out of 32 hypothyroid patients and 17 out of 25 control subjects under went exercise protocol for oxidative metabolism study and performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiesters (PDE) and adenosine triphosphate (ATP) of the calf muscle were acquired during rest, exercise and recovery phase. PCr recovery rate constant (k_PCr) and oxidative capacity were calculated by monoexponential fit of PCr versus time (t) at the beginning of recovery. During resting condition in hypothyroid patients, PCr/Pi ratio was reduced whereas PDE/ATP and Pi/ATP were increased. However, in case of hyperthyroidism, an increased PCr/Pi ratio and reduced PDE/ATP and Pi/ATP were observed. The results confirmed differential energy status of the muscle due to increased or decreased levels of thyroid hormone. Our results also demonstrate reduced oxidative metabolism in hypothyroid patients based on PCr recovery kinetics. PCr recovery kinetics study after exercise revealed decreased PCr recovery rate constant (k_PCr) in hypothyroid patients compared to controls that resulted in decrease in oxidative capacity of muscle by 50% in hypothyroids. These findings are consistent with a defect of high energy phosphate mitochondrial metabolism in thyroid dysfunction.     

Study of diamond film by dynamic nuclear polarization-enhanced13C nuclear magnetic resonance spectroscopy

Three chemical vapor deposited diamond films were studied by dynamic nuclear polarization (DNP)-enhanced high-resolution solid-state¹³C nuclear magnetic resonance (NMR) spectroscopy. Enhanced¹³C direct-polarization spectra of diamond films were obtained by irradiating the samples with microwaves at or near electron spin resonance Larmor frequency of carbon center free radicals. No NMR signal for sp² hybridized carbons could be observed. From the curve of the DNP enhancement as a function of frequency, it is found that the dominant DNP mechanism is the solid-state effect. The¹³C cross-polarization spectrum, which is an evidence for existence of the proton defect in the lattice of diamond films, is much broader than the¹³C single pulse spectrum. The reason is discussed shortly.     

NMR studies of two unusual f-electron metals

We present the results of nuclear magnetic resonance (NMR) studies down to very low temperatures for two U compounds, UCu_3.5Pd_1.5 and U_0.8Y_0.2Pd₃, where the conduction electrons experience strong interactions and for which the temperature dependences of the thermal and transport properties do not obey the expectations of a simple Fermi-liquid model. Also the temperature and field dependences of the nuclear magnetization recovery of UCu_3.5Pd_1.5 in Cu nuclear quadrupole resonance show unusual features that cannot be reconciled with common expectations for a simple metal, but they are well accounted for by the Kondo disorder model. For U_0.8Y_0.2Pd₃, our Y NMR results indicate a distribution of internal static magnetic fields at the Y sites and a small temperature-dependent enhancement of the spin-lattice relaxation rateT ₁ ^? with respect to YPd₃. The NMR spectra are consistent with the presence of very small frozen U moments, but the temperature dependence of the spin-lattice relaxation rate indicates a more complicated situation.     

Nuclear equation of state and compression modes

The nuclear matter (N = Z and no Coulomb interaction) incompressibility coefficient, K _nm , which is directly related to the curvature of the nuclear matter equation of state, is a very important physical quantity in the study of properties of nuclei, supernova collapse, neutron stars and heavy-ion collisions. We review the current status of K _nm and the experimental and theoretical methods used to determine the value of K _nm from the excitation crosssections σ(E) and the transition strength distributions S(E) of compression modes in nuclei. In particular, we will consider the isoscalar giant monopole resonance (ISGMR) and the isoscalar giant dipole resonance (ISGDR) and provide a simple explanation to the long standing problem of the conflicting results obtained for K _nm , deduced from experimental data on excitation cross sections for the ISGMR and data for the ISGDR.     

Nearly 10-fold enhancements in intermolecular H double-quantum NMR experiments by nuclear hyperpolarization

Intermolecular Multiple-Quantum Coherences (iMQCs) can yield interesting NMR information of high potential usefulness in spectroscopy and imaging – provided their associated sensitivity limitations can be overcome. A recent study demonstrated that ex situ dynamic nuclear polarization (DNP) could assist in overcoming sensitivity problems for iMQC-based experiments on ¹³C nuclei. In the present work we show that a similar approach is possible when targeting the protons of a hyperpolarized solvent. It was found that although the DNP procedure enhances single-quantum ¹H signals by about 600, which is significantly less than in optimized low-γ liquid-state counterparts, the non-linear dependence of iMQC-derived signals on polarization can yield very large enhancements approaching 10⁶. Cleary no practical amount of data averaging can match this kind of sensitivity gains. The fact that DNP endows iMQC-based ¹H NMR spectra with a sensitivity that amply exceeds that of their thermally polarized single-quantum counterpart, is confirmed in a number of simple single-scan 2D imaging experiments.     

Application of negative velocity dispersion curves to the distinction between layer and substrate Rayleigh waves

This work concerns the investigation of loading layers/substrate structures in order to determine the critical thickness at which Rayleigh wave characteristics of layers can be completely distinguished from those of the substrates. To do so, we first calculate Rayleigh velocity dispersion curves of several thin film materials (about thirty) deposited on different slow and fast substrates (Be, Al₂O₃, AlN, Si, SiO₂, Mg, SiC, TiN, WC and Pyrex). Then, from the beginning of curve saturation (corresponding to the onset of intrinsic layer characteristics) we deduced normalized thickness transition for all layers/substrates combinations. Thus, we were able to deduce an analytical linear expression relating the critical thickness to combined effects of densities and velocities of both layers and substrates. Such a simple relation can be used, as an alternative method, to predict the transition critical thickness for any layer/substrate combination without the usual lengthy calculation of dispersion curves. To cite this article: Z. Hadjoub et al., C. R. Physique 9 (2008).     

DYNAMIC NUCLEAR POLARIZATION OF ORGANIC COMPOUND DOPED WITH FREE RADICALS

For those organic compounds which lack free radicals, a doping approach named melting-liquid-nitrogen-quench was developed in order to perform dynamic nuclear polarization(DNP)-nuclear magnetic resonance experiments. By using this method, the ¹H, ¹³C, ¹⁵N DNP enhancements were observed with free-radical-doped dibenzofuran and benzamide. The enhancement mechanism and relation between the concentration of unpaired electrons and the maximum DNP enhancement are discussed.