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[Display omitted] • The method is the combination of peak-picking and binning for NMR based untargeted metabonomics studies. • The method takes peak top as bin center. • The method improves the following PCA and OPLS-DA analysis. In NMR-based untargeted metabolomic studies, 1H NMR spectra are usually divided into equal bins/buckets to diminish the effects of peak shift caused by sample status or instrument instability, and to reduce the number of variables used as input for the multivariate statistical analysis. It was noticed that the peaks near bin boundaries may cause significant changes in integral values of adjacent bins, and the weaker peak may be obscured if it is allocated in the same bin with intense peaks. Several efforts have been taken to improve the performance of binning. Here we propose an alternative method, named P-Bin, based on the combination of the classic peak-picking and binning procedures. The location of each peak defined by peak-picking is used as the center of the individual bin. P-Bin is expected to keep all spectral information associated with the peaks and significantly reduce the data size as the spectral regions without peaks are not considered. In addition, both peak-picking and binning are routine procedures, making P-Bin easy to be implemented. To verify the performance, two sets of experimental data from human plasma and Ganoderma lucidum (G. lucidum) extracts were processed using the conventional binning method and the proposed method, before the principal component analysis (PCA) and the orthogonal projection to latent structures discriminant analysis (OPLS-DA). The results indicate that the proposed method has improved both the clustering performance of PCA score plots and the interpretability of OPLS-DA loading plots, and P-Bin could be an improved version of data preparation for metabonomic study. [ABSTRACT FROM AUTHOR]

Measuring 1 H chemical shift anisotropy (CSA) is useful for probing proton environments and dynamics but remains a challenge due to strong homonuclear interaction and relatively small shift anisotropy, especially in proteins with multiple proton sites. Here the extended chemical shift anisotropy amplification (xCSA) method is applied for amide proton CSA measurement in uniformly 2 H enriched proteins under fast magic angle spinning. The xCSA method is capable of distinguishing the sign of the CSA asymmetry parameter, complimenting other multiple-pulse recoupling methods. A three-dimensional xCSA experiment is demonstrated for measuring the proton CSA of amide sites in a GB1 protein sample and the possible correlation of amide proton CSA with protein secondary structure is discussed. [ABSTRACT FROM AUTHOR]

2D diffusion-ordered NMR spectroscopy (DOSY) has been widely recognized as a powerful tool for analyzing mixtures and probing inter-molecular interactions in situ. But it is difficult to differentiate molecules with similar diffusion coefficients in presence of overlapped spectra. Its performance is susceptible to the number of chemical components, and usually gets worse when the number of components increases. Here, to alleviate the problem, numerical simultaneous inversion of Laplace transform (SILT) of many related variables is proposed for reconstructing DOSY spectrum (SILT-DOSY). The advantage of the proposed method in comparison to other methods is that it is capable of estimating the number of analytes more accurately and deriving corresponding component spectra, which in turn leads to the more reliable identification of the components. [ABSTRACT FROM AUTHOR]

The longitudinal magnetization of hyperpolarized media, such as hyperpolarized 129 Xe, 3 He, etc., is nonrenewable. When the MRI data acquisition begins at the k -domain center, a constant flip angle (CFA) results in an image of high signal-to-noise ratio (SNR) but sacrifices the accuracy of spatial information. On the other hand, a variable flip angle (VFA) strategy results in high accuracy but suffers from a low SNR. In this paper, we propose a novel scheme to optimize both the SNR and accuracy, called constant-variable flip angles (CVFA). The proposed scheme suggests that hyperpolarized magnetic resonance signals are firstly acquired through a train of n ∗ CFA excitation pulses, followed by a train of N – n ∗ VFA excitation pulses. We simulate and optimize the flip angle used in the CFA section, the number of CFA excitation pulses, the number of VFA excitation pulses, and the initial and final variable flip angles adopted in the VFA section. Phantom and in vivo experiments demonstrate the good performance of the CVFA designs and their ability to maintain both high SNR and spatial resolution. [ABSTRACT FROM AUTHOR]

Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion is a powerful NMR method to study protein dynamics on the microsecond–millisecond time scale. J -coupling, resonance offset, radio frequency field inhomogeneity, and pulse imperfection often introduce systematic errors into the measured transverse relaxation rates. Here we proposed a modified continuous wave decoupling CPMG experiment, which is more unaffected by resonance offset and pulse imperfection. We found that it is unnecessary to match the decoupling field strength with the delay between CPMG refocusing pulses, provided that decoupling field is strong enough. The performance of the scheme proposed here was shown by simulations and further demonstrated experimentally on a fatty acid binding protein. [ABSTRACT FROM AUTHOR]

Abstract: Detection and quantification of total choline-containing metabolites (CCMs) in tissues by magnetic resonance spectroscopy (MRS) has received considerable attention as a biomarker of cancer. Tissue CCMs are mainly choline (Cho), phosphocholine (PCho), and glycerophosphocholine (GPCho). Because the methyl 1H resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 1D 1H MRS, quantification of individual components is precluded. Development of a MRS method capably of resolving individual components of tissue CCMs would be a significant advance. Herein, a modification of the 2D 1H–14N HSQC technique is targeted on the two methylene 1H in the CH2O group (3 J 1H14N =2.7Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37°C). Specifically, the 1H–14N HSQC technique is modified into a 2D 1H–14N three-bond correlation (HN3BC) experiment, which selectively detects the 1H of CH2O coupled to 14N in CCMs. Separate signals from Cho, PCho, and GPCho components are resolved with high detection sensitivity. A 2D HN3BC spectrum can be recorded from mouse liver in only 1.5min and from human carcinoma liver tissue in less than 3min with effective sample volume of 0.2ml at 14.1T. [Copyright &y& Elsevier]

Abstract: As an effective method for solvent suppression, WATERGATE is widely used in high resolution NMR spectroscopy. It is usually composed of a number of pulses separated by constant intervals. However, theoretical and experimental analyses indicate that narrower bandwidth and lower intensities around the secondary suppression points occur in the excitation profile of the composite WATERGATE. The excitation profile distortion is caused by the chemical shift evolution during the RF pulses. The higher the ratio of pulse duration to the inter-pulse delay is, the severer the profile distorts. Therefore, in high magnetic fields, the effect will be serious when WATERGATE is applied to some biological samples whose resonances distribute over a wide range. As can be seen obviously by applying WATERGATE to detect a RNA–protein mixture sample in an 800MHz spectrometer, the resonances of the imino protons were partially suppressed by showing decreased intensities, though the intended secondary suppression points were set far away from them. In this article, we proposed an optimized WATERGATE that could effectively compensate the chemical shift evolution during the RF pulses, and relieve the excitation profile distortion. The optimized experiment will be a good way to retain the imino signal intensities when WATERGATE is applied to detect the RNA samples in high magnetic field. [ABSTRACT FROM AUTHOR]

Abstract: Choline nitrogen (14N) has a long relaxation time (seconds) which is due to the highly symmetric chemical environments. 14N in choline also has coupling constants with protons (0.6Hz to methyl protons, 2.7Hz to CH2O protons and 0.2Hz to NCH2 protons). Based on these properties, we introduce a two-dimensional NMR method to detect choline and its derivatives in solutions. This method is the 1H–14N hetero-nuclear single-quantum correlation (HSQC) experiment which has been developed in solid-state NMR in recent years. Experiments have demonstrated that the 1H–14N HSQC technique is a sensitive method for detection of choline-containing compounds in solutions. From 1mM choline solution in 16min on a 500MHz NMR spectrometer, a 1H–14N HSQC spectrum has been recorded with a signal-to-noise ratio of 1700. Free choline, phosphocholine and glycerophosphocholine in milk can be well separated in 1H–14N HSQC spectra. This technique would become a promising analytical approach to mixture analyses where choline-containing compounds are of interest, such as tissue extracts, body fluids and food solutions. [ABSTRACT FROM AUTHOR]

Abstract: For multidimensional NMR method, indirect dimensional non-uniform sparse sampling can dramatically shorten acquisition time of the experiments. However, the non-uniformly sampled NMR data cannot be processed directly using fast Fourier transform (FFT). We show that the non-uniformly sampled NMR data can be reconstructed to Cartesian grid with the gridding method that has been wide applied in MRI, and sequentially be processed using FFT. The proposed gridding-FFT (GFFT) method increases the processing speed sharply compared with the previously proposed non-uniform Fourier Transform, and may speed up application of the non-uniform sparse sampling approaches. [Copyright &y& Elsevier]

Abstract: A theoretical approach to quantitatively estimate the spin polarization enhancement via spin polarization-induced nuclear Overhauser effect (SPINOE) in solid state is presented. We show that theoretical estimates from the model are in good agreement with published experimental results. This method provides a straightforward way to predict the enhanced factor of nuclear magnetic resonance signals in solid state experiments. [Copyright &y& Elsevier]

[Display omitted] • A 5T liquid DNP spectrometer has been developed. • The home-made 140 GHz TWT amplifier supplies higher power. • About 150-fold in-situ 13C signal enhancement was observed. Dynamic nuclear polarization (DNP) technology can be utilized to dramatically enhance NMR signal. In this paper, we report on the development of a self-constructed 5 T DNP spectrometer for liquid samples and the 13C DNP enhancement achieved with this spectrometer. The DNP spectrometer is comprised of a wide-bore superconducting magnet, a home-made console, a dual resonance probe and a self-built 140 GHz microwave source for the spectrometer. Specifically, a microwave source of traveling wave tube (TWT) amplifier has been developed, which can provide a maximum power output of 4.4 W and a wide frequency tuning range of 1 GHz. The excellent performance of our built liquid-state DNP spectrometer is verified by the observation of more than 100-fold DNP enhancement of the 13C NMR signal for liquid 13CCl 4 sample. Our result shows the superiority of DNP technology in the liquid-state high-field NMR spectrometer. [ABSTRACT FROM AUTHOR]