Journal of Magnetic Resonance Open最新文献

An electron spin echo in a nitroxide-containing polymer cathode film for organic radical batteries is observed for various states of charge at cryogenic temperatures. The EPR-detected state of charge (ESOC), as inferred from the number of paramagnetic centers in the film, is compared to the results of Coulomb counting based on galvanostatic charging. Spin concentration, longitudinal relaxation times $T_1$ and phase memory times $T_m$ strongly correlate with the ESOC. In the discharged film, the spin concentration reaches $\left(5\pm 3\right)\times 10^{20}$ cm⁻³, causing a phase memory time $T_m\ll$ 100 ns (shorter than the resonator ring-down time) that hinders the detection of the spin echo. In the charged film, the decreased spin concentration results in a longer $T_m$ between 100 ns and 300 ns that enables spin-echo detection, yet limits the length of the microwave pulse sequence. The short, broad-band pulses cause instantaneous diffusion in the unoxidized domains across the oxidized film, affecting the relative peak intensities in the pulsed EPR spectrum. By simulating the spectral distortion caused by instantaneous diffusion, we obtain information on the local spin concentration, which complements the information on the ‘bulk’ spin concentration determined by electrochemistry and continuous-wave EPR spectroscopy.

In this work, several exact and approximate analytical solutions to the quantum master equation are derived using both classical and non-classical coupling models to describe the kinetics of Hartmann-Hahn cross-polarization (HHCP) and multiple-contact CP (MCCP). Moreover, the analytical solution originally obtained by Naito and McDowell [J. Chem. Phys. 84 (1986) 4181.] is shown to be incorrect and the different regimes of spin diffusion and $T_{1\rho }$ relaxation are characterized by the amplitude of the second stage of the HHCP dynamics and the HHCP/MCCP crossing time. The analysis of the ¹H–¹³C HHCP and MCCP dynamics together with (Lee-Goldburg) ¹H $T_{1\rho }$ relaxation experimental data provides a consistent picture of spin dynamics in solid alanine and explains the apparent discrepancies previously observed between $T_{1\rho }$ and $T_1$ relaxation measurements. The CH and CH₃ protons relax as expected via spin diffusion towards the NH₃ protons but the assumption of common proton spin temperature, in which the bottleneck of relaxation is at the NH₃ sites, generally valid for $T_1$ relaxation breaks down for $T_{1\rho }$ relaxation. A diffusion-limited situation in which nuclear Zeeman energy is transferred to the lattice faster than can be supplied by spin diffusion is observed instead.

Parahydrogen-Induced Polarization (PHIP) is NMR hyperpolarization technique that has matured from fundamental science to a biomedical tool for production of hyperpolarized MRI contrast agents. The spin order of nascent parahydrogen-derived protons can be employed directly for enhancement of their NMR signals or for polarization transfer to other nuclei in the hydrogenation product. In this work, we study the process of pairwise parahydrogen addition to propylene, which results in symmetric propane molecule with substantially enhanced methyl and methylene NMR signals. Specifically, we have synthesized site-selectively isotopically labeled 3-d-propylene molecule to study polarization dynamics in the resulting monodeuterated propane after pairwise parahydrogen addition. The deuterium presence in the hyperpolarized propane product results in a minute isotope chemical shift effect allowing to distinguish the proton resonances of CH₃ and CH₂D groups at 600 MHz. Pairwise parahydrogen 1,2-addition to 3-d-propylene was first confirmed by performing the reaction inside a 600 MHz NMR spectrometer, i.e., in the weakly-coupled regime at 14 T, where proton polarization dynamics is restricted to the molecular sites of parahydrogen addition. However, when the pairwise parahydrogen addition is performed in the strongly-coupled regime, i.e., at the Earth's magnetic field, efficient polarization transfer to CH₂D protons is readily observed, leading to polarization redistribution between the three inequivalent sites. This finding is important as it sheds light on polarization dynamics in the strongly coupled symmetric spin systems such as propane studied here—the presented results are expected to be applicable to other spin systems such as butane.

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1–¹³C]pyruvate. Biocompatible formulations of hyperpolarized [1–¹³C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.

Hyperpolarization with the dissolution dynamic nuclear polarization (dDNP) technique yields > 10,000-fold signal increases for NMR-active nuclei (e.g. ¹³C). Hyperpolarized ¹³C-labeled metabolic tracer molecules thus allow real-time observations of biochemical pathways in living cellular systems without interfering background. This methodology lends itself to the direct observation of altered intracellular reaction chemistry imparted for instance by drug treatment, infections, or other diseases. A reoccurring challenge for longitudinal cell studies of mammalian cells with NMR and dDNP-NMR is maintaining cell viability in the NMR spectrometer. 3D cell culture methods are increasing in popularity because they provide a physiologically more relevant environment compared to 2D cell cultures. Based on such strategies a mobile 3D culture system was devised. The clinical drug etoposide was used to treat cancer cells (HeLa) and the resulting altered metabolism was measured using hyperpolarized [1–¹³C]pyruvate. We show that sustaining the cell cultivation in cell incubators and only transferring the cells to the NMR spectrometer for the few minutes required for the dDNP-NMR measurements is an attractive alternative to cell maintenance in the NMR tube. High cell viability is sustained, and experimental throughput is many doubled.

Molecules are dynamic entities, and understanding intra- and inter-molecular reactions and changes in conformation is one of the most fascinating, important and complex subjects in NMR. Conformational changes and chemical reactions result in observed spins exchanging between different magnetic environments, and the sensitivity of NMR spectra to such dynamic processes has been recognised since the earliest days of the field. Careful analysis of such spectra, acquired using one- or two-dimensional experiments, can provide insight into structural, thermodynamic, kinetic and mechanistic aspects of the underlying exchange process. The theoretical principles of these lineshape analysis methods will be introduced in this article, alongside a practical discussion of calculation methods, data acquisition and analysis software.

In-cell NMR spectroscopy has emerged as a powerful tool to evaluate protein conformations and dynamics in the native environment of live cells. Here we extend these studies to a multicellular developing vertebrate. Zebrafish (Danio rerio) embryos are complex organisms with dynamic tissue organization and may be well suited for the high resolution NMR analysis of microinjected, isotopically enriched proteins. We used the intrinsically disordered protein Alpha-synuclein (aSyn) as a test model. aSyn has been thoroughly evaluated inside bacterial and mammalian cells, providing good reference points for NMR comparisons and the critical analysis of the advantages and disadvantages of the zebrafish system. High resolution 2D ¹H-¹⁵N NMR showed that aSyn in zebrafish embryos had the same conformational and biological features previously observed in mammalian cells, including conserved interactions with cellular biomolecules and the establishment of physiological protein post-translational modifications. A direct comparative analysis of gamma-synuclein (gSyn), a naturally occurring homolog of aSyn, in bacteria, mammalian cells and zebrafish embryos confirmed these observations. Our results showed that high resolution in-cell NMR is attainable in embryonic cells within the native environment of a live animal. This system provides more physiological cellular environments for high resolution, in situ protein biophysical studies.

Magnetic resonance imaging is a powerful, non invasive tool for medical diagnosis. The low sensitivity for detecting the nuclear spin signals, typically limits the image resolution to several tens of micrometers in preclinical systems and millimeters in clinical scanners. Other sources of information, derived from diffusion processes of intrinsic molecules such as water in the tissues, allow getting morphological information at micrometric and submicrometric scales as potential biomarkers of several pathologies. Here we consider extracting this morphological information by probing the distribution of internal magnetic field gradients induced by the heterogeneous magnetic susceptibility of the medium. We use a cumulant expansion to derive the dephasing on the spin signal induced by the molecules that explore these internal gradients while diffusing. Based on the cumulant expansion, we define internal gradient distributions tensors (IGDT) and propose modulating gradient spin echo sequences to probe them. These IGDT contain microstructural morphological information that characterize porous media and biological tissues. We evaluate the IGDT effects on the magnetization decay with typical conditions of brain tissue and show that their effects can be experimentally observed. Our results thus provide a framework for exploiting IGDT as quantitative diagnostic tools.

This study investigates the experimental conditions required for magnetic resonance imaging (MRI) of thermally polarized hydrocarbon gas, focusing on ethane. The nuclear magnetic resonance (NMR) spectra and relaxation properties of ethane were analysed at different pressures in the range from 1.5 to 6 bar at 7 T using ¹H NMR spectroscopy. The spin-lattice relaxation time (T₁) and spin-spin relaxation time (T₂) were measured, and their dependence on the pressure was determined, showing that both relaxation times increase with pressure. Using the estimated relaxation times, we adjusted parameters for imaging of static ethane using rapid acquisition with relaxation enhancement (RARE) and fast low-angle shot (FLASH). The signal-to-noise ratio (SNR) of ethane images was evaluated and compared to the calculation for the given range of pressures. Then, we imaged flowing gas using a 2D velocity-encoded pulse sequence, which is usually used for liquid flow studies. The MRI-measured flow rates are compared to those pre-set with a pump, showing good agreement in the slow flow range. Overall, the results provide insights into the feasibility of ¹H MRI for imaging and flow measurements of thermally polarized ethane.

We report several inductively coupled RF coil designs that are very easy to construct, produce high signal-to-noise ratio (SNR) and high spatial resolution while accommodating life support, anesthesia and monitoring in small animals. Inductively coupled surface coils were designed for hyperpolarized ¹³ C MR spectroscopic imaging (MRSI) of mouse brain, with emphases on the simplicity of the circuit design, ease of use, whole-brain coverage, and high SNR. The simplest form was a resonant loop designed to crown the mouse head for a snug fit to achieve full coverage of the brain with high sensitivity when inductively coupled to a broadband pick-up coil. Here, we demonstrated the coil's performance in hyperpolarized ¹³ C MRSI of a normal mouse and a glioblastoma mouse model at 4.7 T. High SNR exceeding 70:1 was obtained in the brain with good spatial resolution (1.53 mm x 1.53 mm). Similar inductively coupled loop for other X-nuclei can be made very easily in a few minutes and achieve high performance, as demonstrated in ³¹ P spectroscopy. Similar design concept was expanded to splitable, inductively coupled volume coils for high-resolution proton MRI of marmoset at 3T and 9.4T, to easily accommodate head restraint, vital-sign monitoring, and anesthesia delivery.