Journal of Magnetic Resonance Open最新文献

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.

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.

In this work, we describe essential tools of linear algebra necessary for calculating the effect of chemical exchange on spin dynamics and polarization transfer in various nuclear magnetic resonance (NMR) experiments. We show how to construct matrix representations of Hamiltonian, relaxation, and chemical exchange superoperators in both Hilbert and Liouville space, as well as demonstrate corresponding codes in Python. Examples of applying the code are given for problems involving chemical exchange between NH${}_3$ and NH${}_4^{+}$ at zero and high magnetic field and polarization transfer from parahydrogen relevant in SABRE (signal amplification by reversible exchange) at low magnetic field (0-20 mT). The presented methodology finds utility for describing the effect of chemical exchange on NMR spectra and can be extended further by taking into account non-linearities in the master equation.

Magnetic resonance offers an invaluable testbed for observing and studying the fundamental concepts of quantum cavity interactions with two-level systems in the microwave regime. Typically, these experiments are conducted at low cryogenic temperatures, utilizing spin systems embedded within a high-quality (Q-factor) superconducting cavity. Recent studies indicate that under these conditions, especially in a high-cooperativity regime with strong collective coupling between an electron spin system and a microwave cavity, multiple spin echoes can be detected. These echoes are interpreted as manifestations of coherent quantum effects. To put it simply, photons within the cavity can excite the spin system, which subsequently can stimulate the cavity, creating a feedback loop. In our research, we demonstrate that a specially designed moderate-Q cavity, paired with diamond crystals rich in nitrogen vacancy (NV) centers, allows us to observe such nonlinear quantum phenomena, even at ambient temperatures. Crucially, our experimental design necessitates amplifying the net number of spins for a specific, limited spin concentration. This is achieved by lowering the spins' thermodynamic temperature (as opposed to their physical temperature) to a few kelvins. Notably, we find that maintaining high cooperativity or strong coupling is not essential for these observations. The potential to observe significant microwave cavity quantum effects at room temperature could be useful for future applications, such as quantum memories and quantum sensing.

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.

Novel MRI contrast methods, such as Chemical Exchange Saturation Transfer (CEST), rely on previously developed theory and approaches, often introduced first in solidstate NMR. Understanding or at least connecting the basic principles and original works to the modern-day contrast methods in MRI is instructive. The work brings together concepts in relaxation, saturation, and spin lock experiments in the dynamic (exchanging) systems. The work describes how basic principles and theory are translated and being applied to MRI contrast, including MT and CEST. Finally, we review select papers generalizing concepts of relaxation under periodic RF.

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.

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.

Tuberculosis and non-tuberculosis mycobacterial infections are rising each year and often result in chronic incurable disease. Important antibiotics target cell-wall biosynthesis, yet some mycobacteria are alarmingly resistant or tolerant to currently available antibiotics. This resistance is often attributed to assumed differences in composition of the complex cell wall of different mycobacterial strains and species. However, due to the highly crosslinked and insoluble nature of mycobacterial cell walls, direct comparative determinations of cell-wall composition pose a challenge to analysis through conventional biochemical analyses. We introduce an approach to directly observe the chemical composition of mycobacterial cell walls using solid-state NMR spectroscopy. ¹³C CPMAS spectra are provided of individual components (peptidoglycan, arabinogalactan, and mycolic acids) and of in situ cell-wall complexes. We assigned the spectroscopic contributions of each component in the cell-wall spectrum. We uncovered a higher arabinogalactan-to-peptidoglycan ratio in the cell wall of M. abscessus, an organism noted for its antibiotic resistance, relative to M. smegmatis. Furthermore, differentiating influences of different types of cell-wall targeting antibiotics were observed in spectra of antibiotic-treated whole cells. This platform will be of value in evaluating cell-wall composition and antibiotic activity among different mycobacteria and in considering the most effective combination treatment regimens.

Although very effective in decreasing NMR relaxation of large proteins, homogeneous deuteration can be costly, and anyway unsuitable for recombinant production in metazoan systems. We sought to explore other deuteration schemes, which would be adapted to protein expression in mammalian cells. Here, we evaluate the benefits of the deuteration on alpha- and beta-positions of amino acids for a typical middle size protein domain, namely the model 40 kDa-large kinase p38α. We report the position-specific deuteration of free amino acids by using enzyme-assisted H/D exchange, executed by the cystathionine gamma-synthase and a newly designed high-performance mutant E325A. Then, we used cell-free expression in bacterial extracts to avoid any scrambling and back-protonation of the tested isotopically labelled amino acids (Ala, Leu, Lys, Ser, Asp, Glu, Gly). Our results show signal enhancements up to three in ¹H-¹⁵N spectra when these α/β-deuterated amino acids are integrated. Because our approach relies on single ²H_α/β-¹⁵N-amino acid labeling, an additional three-fold increase in sensitivity is obtained by the possible use of moderate resolution SOFAST-HMQC instead of the classical HSQC or TROSY experiments. This allows recording residue-resolved solution ¹H-¹⁵N NMR spectra of 100 μg of p38α in one hour with S/N∼10.