Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE: To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE: 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT: By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS: Frequency. RESULTS: The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION: The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

Using optimal controlled singlet spin order to accurately target molecular signal in MRI and MRS.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have made great successes in clinical diagnosis, medical research, and neurological science. MRI provides high resolution anatomical images of tissues/organs, and MRS provides information of the functional molecules related to a specific tissue/organ. However, it is difficult for classic MRI/MRS to selectively image/probe a specific metabolite molecule other than the water or fat in tissues/organs. This greatly limits their applications on the study of the molecular mechanism(s) of metabolism and disease. Herein, we report a series of molecularly targeted MRI/MRS methods to target specific molecules. The optimal control method was used to efficiently prepare the singlet spin orders of varied multi-spin systems and in turn greatly expand the choice of the targeted molecules in the molecularly targeted MRI/MRS. Several molecules, such as N-acetyl-L-aspartic acid (NAA), dopamine (DA), and a tripeptide (alanine-glycine-glycine, AGG), have been used as targeted molecules for molecularly targeted MRI and MRS. We show in vivo NAA-targeted 1H MRS spectrum of a human brain. The high-resolution signal of NAA suggests a promising way to study important issues in molecular biology at the molecular level, e.g., measuring the local pH value of tissue in vivo, demonstrating the high potential of such methods in medicine.

Distinguishing glutamate and glutamine in in vivo 1 H MRS based on nuclear spin singlet order filtering.

PURPOSE: The signals of glutamate (Glu) and glutamine (Gln) are often significantly overlapped in routine 1 H-MR spectra of human brain in vivo. Selectively probing the signals of Glu and Gln in vivo is very important for the study of the metabolisms in which Glu and Gln are involved. METHODS: The Glu-/Gln- targeted pulse sequences are developed to selectively probe the signals of Glu and Gln. The core part of the Glu-/Gln- targeted pulse sequences lies on the preparation of the nuclear spin singlet orders (SSOs) of the five-spin systems of Glu and Gln. The optimal control method is used to prepare the SSOs of Glu and Gln with high efficiency. RESULTS: The Glu-/Gln- targeted pulse sequences have been applied on phantoms to selectively probe the signals of Glu and Gln. Moreover, in the in vivo experiments, the signals of Glu and Gln in human brains of healthy subjects have been successfully probed separately. CONCLUSION: The developed Glu-/Gln- targeted pulse sequences can be used to distinguish the 1 H-MR signals of Glu and Gln in human brains in vivo. The optimal control method provides an effective way to prepare the SSO of a specific spin system with high efficiency and in turn selectively probe the signals of a targeted molecule.

Multiple-targeting NMR signal selection by optimal control of nuclear spin singlet.

Selectively probing specific molecules in complex mixtures with nuclear magnetic resonance promises new insights into molecular structures or molecular interaction. Such a study often can be further facilitated when two or more objects in chemical moieties of interest can be precisely targeted. Herein, we proposed a novel method to implement the multiple-targeting signal selection by optimal control of the spin singlets of two or more targeted spin systems from one or more molecules. This method can endow the conventional nuclear magnetic resonance (NMR), magnetic resonance image (MRI) and magnetic resonance spectrum (MRS) with the multiple-targeting signal selectivity to selectively probe several targeted molecules and/or chemical groups simultaneously.

Rapid Identification of Adulteration in Edible Vegetable Oils Based on Low-Field Nuclear Magnetic Resonance Relaxation Fingerprints.

Most current approaches applied for the essential identification of adulteration in edible vegetable oils are of limited practical benefit because they require long analysis times, professional training, and costly instrumentation. The present work addresses this issue by developing a novel simple, accurate, and rapid identification approach based on the magnetic resonance relaxation fingerprints obtained from low-field nuclear magnetic resonance spectroscopy measurements of edible vegetable oils. The relaxation fingerprints obtained for six types of edible vegetable oil, including flaxseed oil, olive oil, soybean oil, corn oil, peanut oil, and sunflower oil, are demonstrated to have sufficiently unique characteristics to enable the identification of the individual types of oil in a sample. By using principal component analysis, three characteristic regions in the fingerprints were screened out to create a novel three-dimensional characteristic coordination system for oil discrimination and adulteration identification. Univariate analysis and partial least squares regression were used to successfully quantify the oil adulteration in adulterated binary oil samples, indicating the great potential of the present approach on both identification and quantification of edible oil adulteration.

Preparation of Long-Lived States in a Multi-Spin System by Using an Optimal Control Method.

The lifetime Ts of a long-lived nuclear spin state (LLS) could be much longer than the longitudinal order T1 . Many spin systems were used to produce long-lived states, including two or more homonuclear spins that couple to each other. For multiple homonuclear spins with rather small chemical shift difference, normally it is difficult to selectively control the spins and then to prepare a LLS. Herein, we present a scheme that prepares different spin orders in a multi-spin system by using optimal control and numerical calculation. By experimentally measuring the lifetime of the states, we find that for a three-spin physical system, although there are many forms of state combinations with different spin orders, each component has its own lifetime.

Spin-Scenario: A flexible scripting environment for realistic MR simulations.

In this paper we present a new open source package, Spin-Scenario, aimed at developing an intuitive, flexible and unique scripting framework able to cover many aspects of simulations in both MR imaging and MR spectroscopy. For this purpose, we adopted the Liouville space model as the standard computing engine and let the consequent computational burden be afforded by parallel computing techniques. Benefitting from the powerful Lua scripting language, the pulse sequence programming syntax was specially designed to offer an extremely concise way of scripting. Moreover, the built-in dataflow graph based optimal control scheme enables an efficient optimization of shaped pulses or multiple cooperative pulses for real-life experiment evaluations. As the name states, the users are expected to be able to realize their creative ideas like a scenarist that creates a scenario script and looks at the spin actors acting accordingly. The validation of the framework was demonstrated with several examples within MR imaging and MR spectroscopy. Spin-Scenario is available for download at https://github.com/spin-scenario.

Oriented covalent immobilization of recombinant protein A on the glutaraldehyde activated agarose support.

High IgG-binding capacity of protein A affinity chromatography is crucial to its application in the antibody purification and autoantibody-associated disease treatment. An oriented immobilization strategy was used to covalently conjugate the recombinant protein A (rSpA) on the glutaraldehyde activated agarose. By controlling the glutaraldehyde concentration, pH and reactivity time, one or two molecules of glutaraldehyde per primary amino group were anchored on agarose supports. The structure differences of activated supports were evaluated. Moreover, the 3D surface structure of B domain was modeled to explore the distribution of reactive and adsorptive groups. Compared with the monomeric glutaraldehyde agarose (Aga@MG), the dimeric glutaraldehyde agarose (Aga@DG) seems to be involved with more amino acid groups of rSpA during the immobilization. The leaked rSpA of 0.24 ng/mg IgG from Aga@DG@rSpA was slightly lower than that of 0.36 ng/mg IgG from Aga@MG@rSpA. However, Aga@MG is more suitable for oriented immobilization of rSpA which endows the prepared adsorbents to higher IgG-binding capacity. When rSpA was immobilized on Aga@MG at the low and high ionic strength, the maximum capacities from Langmuir model were 56.2 and 59.2 mg/g, respectively. The Aga@MG provided shorter spacer arm compared with the Aga@DG, which contributed to the oriented immobilization of rSpA.

EPR steering of polar molecules in pendular states and their dynamics under intrinsic decoherence.

Einstein-Podolsky-Rosen (EPR) steering gives evidence for the phenomenon called "spooky action at a distance" in quantum mechanics, and provides a useful resource for the implementation of quantum information tasks. In this paper, we consider a pair of ultracold polar molecules trapped in an external electric field as a promising quantum information carrier, and analyze the evolution behavior of EPR steering for the two coupled polar molecules in pendular states. Our results show that the steering of the two linear dipoles is remarkably reliant upon the Stark effect and dipole-dipole interaction. To be specific, the steerability degree is inversely associated with the intensity of the electric field while it is positively correlated with the coupling strength between the two polar molecules. Moreover, it is found that high ambient temperature can lead to a rapid loss of the steerable resource in thermal equilibrium. Further, we put forward an effective strategy to enhance the steerability using the technique of weak measurement reversal (WMR). By taking into account the influence of intrinsic decoherence on the steering dynamics, we found that robust EPR steering preservation can be realized for the initial state being in the Bell state . Our findings may shed some new light on molecular quantum information processing with pendular states.

Operando NMR spectroscopic analysis of proton transfer in heterogeneous photocatalytic reactions.

Proton transfer (PT) processes in solid-liquid phases play central roles throughout chemistry, biology and materials science. Identification of PT routes deep into the realistic catalytic process is experimentally challenging, thus leaving a gap in our understanding. Here we demonstrate an approach using operando nuclear magnetic resonance (NMR) spectroscopy that allows to quantitatively describe the complex species dynamics of generated H2/HD gases and liquid intermediates in pmol resolution during photocatalytic hydrogen evolution reaction (HER). In this system, the effective protons for HER are mainly from H2O, and CH3OH evidently serves as an outstanding sacrificial agent reacting with holes, further supported by our density functional theory calculations. This results rule out controversy about the complicated proton sources for HER. The operando NMR method provides a direct molecular-level insight with the methodology offering exciting possibilities for the quantitative studies of mechanisms of proton-involved catalytic reactions in solid-liquid phases.

Transferring lithium ions in nanochannels: a PEO/Li⁺ solid polymer electrolyte design.

A new category of crystalline polymer electrolyte prepared by the supramolecular self-assembly of polyethylene oxide (PEO), α-cyclodextrin (α-CD), and LiAsF6 is reported. The polymer electrolyte consists of the nanochannels formed by α-CDs in which the PEO/Li(+) complexes are confined. The nanochannels formed by α-CD provide the pathway for the directional motion of Li(+) ions and at the same time prevent the access of the anions by size exclusion, resulting in good separation of the Li(+) ions and the anions. The conductivity of the reported material is 30 times higher than that of the comparable PEO/Li(+) complex crystal at room temperature. By using state-of-art solid-state NMR spectroscopy, the structure and dynamics of the material were investigated in detail. The dynamics of the Li(+) ions was studied and correlated to the ionic conductivity of the material.

Optimal (2)H rf Pulses and (2)H-(13)C Cross-Polarization Methods for Solid-State (2)H MAS NMR of Perdeuterated Proteins.

We present a novel concept for rf pulses and optimal control designed cross-polarization experiments for quadrupolar nuclei. The methods are demonstrated for (2)H CP-MAS and (2)H multiple-pulse NMR of perdeuterated proteins, for which sensitivity enhancements up to an order of magnitude are presented relative to commonly used approaches. The so-called RESPIRATION rf pulses combines the concept of short broad-band pulses with generation of pulses with large flip angles through distribution of the rf pulse over several rotor echoes. This lead to close-to-ideal rf pulses, facilitating implementation of experiments relying on the ability to realize high-performance 90 and 180° pulses, as, for example, in refocused INEPT and double-to-single quantum coherence experiments, or just pulses that provide a true representation of the quadrupolar powder pattern to extract information about the structure or dynamics. The optimal control (2)H → (13)C CP-MAS method demonstrates transfer efficiencies up to around 85% while being extremely robust toward rf inhomogeneity and resonance offsets.

Structure and sodium channel activity of an excitatory I1-superfamily conotoxin.

Conotoxin iota-RXIA, from the fish-hunting species Conus radiatus, is a member of the recently characterized I1-superfamily, which contains eight cysteine residues arranged in a -C-C-CC-CC-C-C- pattern. iota-RXIA (formerly designated r11a) is one of three characterized I1 peptides in which the third last residue is posttranslationally isomerized to the d configuration. Naturally occurring iota-RXIA with d-Phe44 is significantly more active as an excitotoxin than the l-Phe analogue both in vitro and in vivo. We have determined the solution structures of both forms by NMR spectroscopy, the first for an I1-superfamily member. The disulfide connectivities were determined from structure calculations and confirmed chemically as 5-19, 12-22, 18-27, and 21-38, suggesting that iota-RXIA has an ICK structural motif with one additional disulfide (21-38). Indeed, apart from the first few residues, the structure is well defined up to around residue 35 and does adopt an ICK structure. The C-terminal region, including Phe44, is disordered. Comparison of the d-Phe44 and l-Phe44 forms indicates that the switch from one enantiomer to the other has very little effect on the structure, even though it is clearly important for receptor interaction based on activity data. Finally, we identify the target of iota-RXIA as a voltage-gated sodium channel; iota-RXIA is an agonist, shifting the voltage dependence of activation of mouse NaV1.6 expressed in Xenopus oocytes to more hyperpolarized potentials. Thus, there is a convergence of structure and function in iota-RXIA, as its disulfide pairing and structure resemble those of funnel web spider toxins that also target sodium channels.

Realization of a decoherence-free subspace using multiple quantum coherences.

This Letter presents a two-dimensional nuclear magnetic resonance (NMR) approach for constructing a two-logical-qubit decoherence-free subspace (DFS) by using four multiple-quantum coherences of a CH3 spin system as logical qubits. The three protons in this spin system are magnetically equivalent and can only be used as a single qubit in one-dimensional NMR. We have experimentally demonstrated that our DFS can protect against more types of decoherences than those of the one composed of four noisy physical qubits all with different chemical shifts. This idea may provide new insights into extending qubit systems in the sense that it effectively utilizes the magnetically equivalent nuclei.