•Metabolic responses of abalone induced by tributyltin/triphenyltin were studied.•Obvious gender-, tissue- and compound-specific responses were found.•Tributyltin/triphenyltin disturbs energy metabolism and osmotic regulation.•Immune and oxidative stress was induced by tributyltin/triphenyltin exposure.•Metabolomics is useful to elucidate organotin compound-induced toxic effects.Organotin compounds, especially tributyltin (TBT) and triphenyltin (TPT), are a group of hazardous pollutants in marine environments. Haliotis diversicolor is an important marine model organism for environmental science. In this study, 1H NMR spectroscopy together with pattern recognition methods was used to investigate the responses of hepatopancreas and gill of Haliotis diversicolor to TBT and TPT exposure. It was found that obvious gender-, tissue- and compound-specific metabolomic alterations were induced after a 28-day exposure. TBT and TPT exposure not only caused the disturbance in energy metabolism and osmotic balance in hepatopancreas and gill tissues with different mechanisms, but also induced oxidative stresses. These metabolic alterations were highlighted in the accumulation of aspartate, uridine diphosphate-N-acetylglucosamine, uridine diphosphate glucose, guanosine and the depletion of leucine, isoleucine, valine, malonate, homarine, trigonelline in all exposure gills, as well as in the depletion of ATP, AMP, betaine in male exposure gills and pantothenate in male exposure hepatopancreases. The significant decreased aromatic amino acids (AAAs), lysine and glutamate in gills and increased betaine in hepatopancreases for TPT exposure together with increased glutamate and decreased betaine in gills and increased glutamate and glycine in hepatopancreases for TBT exposure demonstrated their specific metabolic characteristics. Among these characteristic metabolites, AAAs, lysine and glutamate in the gill as well as pantothenate in the hepatopancreas might be identified as potential biomarkers for TPT or TBT exposure in Haliotis diversicolor. The results provide a useful insight into the toxicological mechanisms of organotin compounds on Haliotis diversicolor.Download high-res image (375KB)Download full-size image

•Sucrose presents in a certain infant formula.•Infant formulas examined contained more formate than bovine milk.•The ratio of creatine to creatinine in infant formulas was low.•Higher contents of branched-chain amino acids were found in an infant formula.Infant formulas (IFs), most of which are bovine milk-based, are important for normal growth and development. However, information regarding the ingredients in IFs is often limited in detail, and chemical changes during production and storage appear common. Therefore, it is important to understand in detail the composition of IFs. In this study, a wide range of low-molecular-weight organic components in commercial IFs were determined using the 1H nuclear magnetic resonance (NMR) technique. The components emerging after multivariate data analysis could be used to discriminate certain infant formulas from each other. Particular attention was given to the components with potentially beneficial bioactivities. Our study indicates that NMR spectroscopy in combination with multivariate data analysis constitutes an efficient tool for the comprehensive characterization of various IFs and the in-depth understanding of the nutritional value of IFs for infants.

•Chemical shift-specific T1 values are accurately measured in inhomogeneous fields.•T1 weighted J-resolved spectra are attained making use of measurement results.•Suppression of intense resonances can provide insights into obscured information.•The method is applicable to biological tissues and samples in inhomogeneous fields.The spin-lattice relaxation time (T1) plays a crucial role in the study of spin dynamics, signal optimization and data quantification. However, the measurement of chemical shift-specific T1 constants is hampered by the magnetic field inhomogeneity due to poorly shimmed external magnetic fields or intrinsic magnetic susceptibility heterogeneity in samples. In this study, we present a new protocol to determine chemical shift-specific T1 constants in inhomogeneous fields. Based on intermolecular double-quantum coherences, the new method can resolve overlapped peaks in inhomogeneous fields. The measurement results are in consistent with the measurements in homogeneous fields using the conventional method. Since spatial encoding technique is involved, the experimental time for the new method is very close to that for the conventional method. With the aid of T1 knowledge, some concealed information can be exploited by T1 weighting experiments.Download high-res image (120KB)Download full-size image

•Variable density sampling was proposed for spatiotemporally encoded (SPEN) MRI.•An optimization algorithm was developed for gradient waveforms design.•Non-Cartesian super-resolved reconstruction was developed for SPEN MRI.•The scheme can reduce aliasing artifacts and improve image resolution.•The scheme can facilitate the development of variable density SPEN MRI.Spatiotemporally encoded (SPEN) single-shot MRI is an emerging ultrafast technique, which is capable of spatially selective acquisition and reduced field-of-view imaging. Compared to uniform sampling, variable density sampling has great potential in reducing aliasing artifacts and improving sampling efficiency. In this study, variable density spiral trajectory and non-Cartesian super-resolved (SR) reconstruction method are developed for SPEN MRI. The gradient waveforms design of spiral trajectory is mathematically described as an optimization problem subjected to the limitations of hardware. Non-Cartesian SR reconstruction with specific gridding method is developed to retrieve a resolution enhanced image from raw SPEN data. The robustness and efficiency of the proposed methods are demonstrated by numerical simulation and various experiments. The results indicate that variable density SPEN MRI can provide better spatial resolution and fewer aliasing artifacts compared to Cartesian counterpart. The proposed methods will facilitate the development of variable density SPEN MRI.

•A pulse sequence is proposed for localized high-resolution NMR spectra.•Intermolecular double-quantum coherence and Hadamard encoding are utilized.•High-resolution spectral information can be retrieved in inhomogeneous fields.•The proposed method facilitates analyses of heterogeneous chemical systems.A scheme based on Hadamard encoding and intermolecular double-quantum coherences is designed to obtain localized one-dimensional high-resolution NMR spectra in inhomogeneous fields. Brief theoretical derivation was performed to illuminate its principle. Experiments were carried out on phantom solution and biological tissues to verify its effectiveness in yielding useful spectral information and efficiency in suppressing solvent signal even when the field inhomogeneity is sufficiently severe to erase almost all spectral information. This sequence may provide a promising way for analyzing heterogeneous biological tissues and chemical systems.

•A scheme is proposed for high-resolution J-resolved correlation spectroscopy.•The scheme is applicable in inhomogeneous fields.•Homonuclear correlation and J-resolved spectra can be acquired simultaneously.•The acquisition time is within the time scale for a conventional 2D spectrum.Multi-dimensional NMR spectroscopy alleviates the jam or even overlaps of peaks in one-dimensional spectra of complicated samples, extending the application of NMR spectroscopy. However, the acquisition of high-resolution NMR spectra relies on high homogeneity of magnetic field, which is difficult to achieve in many cases. In this study, we present a fast NMR approach for acquiring high-resolution 3D spectrum in inhomogeneous fields via intermolecular zero-quantum coherence and spatial encoding technique, providing J-resolved spectrum and correlation spectrum information simultaneously within the acquisition time scale for a conventional two-dimensional spectrum.

•A scheme is proposed for ultrafast homonuclear 2D J-resolved spectroscopy.•High-resolution 2D J-resolved spectra can be achieved in inhomogeneous fields.•2H nuclei provide for the dipolar field acting on the observed protons.•The trouble of selective excitation and solvent suppression is avoided.Spatially encoded ultrafast NMR accelerates the acquisition of 2D NMR spectra by orders of magnitude, but it is affected by field inhomogeneity. To circumvent this influence, various approaches have been proposed. Here we propose a new scheme to ultrafast achieve 2D J-resolved spectroscopy in inhomogeneous fields via the distant dipolar field of deuterium nuclei. Compared to the methods via homonuclear distant dipolar field, the trouble of selective excitation and solvent suppression when the peaks of solvent and solute spins are close to each other in inhomogeneous fields will be avoided. Theoretical analyses and experimental results are presented for verification.

1H NMR spectroscopy in combination with multivariate statistical analysis was applied to explore the metabolic variability in urine and serum of high fat-fed rats relative to normal chow-fed ones. Metabolites contributing to intergroup discrimination identified by partial least squares discriminant analysis include 3-hydroxybutyrate, glutamate, glutamine, citrate, choline, hippurate, alanine, lactate, creatinine, taurine, acetate, etc. The aging effect along with long-term feeding was delineated with metabolic trajectory in principal component analysis score plot and age-related differences on metabolic profiling under different dietary intervention were recognised. The identified metabolites responsible for obesity were all imported into a web tool for network-based interpretation of compound lists to interpret their functional context, molecular mechanisms and disturbed signalling pathway globally and systematically. The results are useful for interpreting the pathology of obesity and further probing into the relationship between dietary-induced obesity and type 2 diabetes mellitus.

Statistical two-dimensional correlation spectroscopy combined with pattern recognition is demonstrated for coanalysis of NMR spectroscopic data from different sources. The urine and serum 1H NMR spectra from metabolomics datasets of diabetes and hyperthyroidism are taken as examples. The intrinsic covariance of certain molecules between urine and serum spectra is identified. The highly urine-serum-correlated metabolites are further analyzed by using the projection to latent structure discriminant analysis (PLS-DA) method. To illustrate the applicability of the method, the metabolomics datasets of diabetes and hyperthyroidism are imported separately to calculate the corresponding two-dimensional urine-serum correlation coefficient matrixes. The results show that creatinine (δ 4.08) and succinate (δ 2.45) are found to be highly correlated between urine and serum from diabetes patients, and choline (δ 3.21) and pyruvate (δ 2.33) are highly correlated between urine and serum from hyperthyroidism patients. This study offers a new angle of view for interpreting metabolomics data and demonstrates the potential of the correlation analysis of spectra from different biological sources as a new systems biology tool.Highlights► Urine and serum NMR data were coanalyzed by statistical correlation spectroscopy. ► Intrinsic covariance of molecules between urine and serum spectra was identified. ► The ‘highlighted’ metabolites were analyzed by PLS-DA regression coefficient plot. ► This work provides a new interpretation of metabolomic data.

Intermolecular multiple-quantum coherences (iMQCs) have some intrinsic properties different from conventional single-quantum coherences in solution NMR. In this paper, we extended our study to heteronuclear iMQCs in IS (I = 1/2, S = 3/2) spin systems. A sample of sodium chloride (NaCl) water solution was taken as an example. Heteronuclear COSY revamped by asymmetric Z-gradient echo detection (CRAZED) experiments were performed. One- and two-dimensional heteronuclear iMQC spectra were obtained. The quantum-mechanical treatment was used to deduce the signal expressions. Magic angle experiments validate that the signals are indeed from intermolecular dipolar interaction and insensitive to the imperfection of radio-frequency (RF) flip angles. Both experimental results and theoretical analysis indicate that heteronuclear CRAZED experiment allows coherence transfer from spin-3/2 nuclei to spin-1/2, and vice verse. Furthermore, the dependences of iMQC signal intensities on RF pulse flip angles follow the same rules as those for heteronuclear IS (I = 1/2, S = 1/2 or 1) spin systems.

Recently ultrafast techniques enable 2D NMR spectra to be obtained in a single scan. They have been successfully applied for 2D COSY, TOCSY, DOSY, HMQC, and J-resolved spectra. In this paper, two alternative ultrafast 2D COSY methods (g-COSY and gDQF-COSY) based on continuous constant-time phase-modulated spatial encoding were proposed. Theoretical expressions of the resulting signals were deduced. Experiments were performed to verify our theoretical analysis and the feasibility of the methods. Comparisons between the experimental results of our methods and those of the previous real-time phase-modulated spatial encoding method demonstrate that the signal-to-noise ratio and resolution of the 2D COSY spectra are improved, and a good 2D COSY spectrum is easier to achieve by using our methods.

A vegetarian diet has been demonstrated to have a profound influence on human metabolism as well as to aid the prevention of several chronic diseases relative to an omnivorous diet. However, there have been no systematic metabolomic studies on all of the biochemical changes induced in human subjects by long-term vegetarianism. In this study, 1H NMR spectroscopy in combination with multivariate statistical analysis was applied to explore the variability in the metabolic urinary profiles of healthy populations from four groups: lactovegetarian male (VEGMALE), lactovegetarian female (VEGFEMALE), omnivorous male (OMNMALE), and omnivorous female (OMNFEMALE). Differences in metabolic profiles were examined in relation to diet and gender by principal component analysis (PCA) and spectral integrals. It was found that the most influential low molecular weight metabolites responsible for the differences between the diet groups were N-acetyl glycoprotein (NAG), succinate, citrate, trimethylamine-N-oxide (TMAO), taurine, glycine, hippurate, phenylalanine, methylhistidine and formate, whereas for the differences in gender groups the most discriminatory metabolites were NAG, succinate, creatinine, arginine, TMAO, taurine, hippurate, mannitol, phenylalanine, and methylhistidine. The results from the PCA of all four groups indicated that diet plays a greater role in influencing metabolite differences than gender. As an exploration, this work shows the potential of metabolomics when applied to nutritional and physiological studies, and it will aid further studies.

Intermolecular multiple-quantum coherences (iMQCs) can be utilized to retrieve high-resolution NMR spectra in inhomogeneous magnetic fields. The application of selective pulses in pulse sequences can greatly simplify 2D iMQC spectra. However, so far high-resolution iMQC methods are mainly used in relatively small field inhomogeneities. In this paper, we took the IDEAL-II sequence as an example to study their applicability in moderate inhomogeneous magnetic fields. The experimental and simulation results show that high-resolution NMR spectra can be obtained in moderate inhomogeneous fields if the excitation range of selective pulse is properly set. Once the field inhomogeneity reaches a certain degree, the appearance of undesirable intermolecular cross-peaks due to the distant dipolar field produced by solute spins is inevitable. The spectral quality may vary with sample even in the same moderate inhomogeneous fields, depending on the chemical shift distributions and the J coupling networks of the components under study. The conclusions drawn in this paper are generally applicable to all high-resolution iMQC methods utilizing selective RF pulses.

A novel diperoxovanadate complex NH4[OV(O2)2(picolinamide)]·H2O was synthesized from aqueous solution under physiological conditions. The solution structure of the complex was characterized by multinuclear (1H, 13C, 14N, and 51V), variable temperature as well as two-dimensional (DOSY) NMR techniques in the interaction system of NH4VO3/H2O2/picolinamide at room temperature. The crystal structure of the complex was determined at 223 K by single-crystal X-ray diffraction method. It belongs to the monoclinic space group P21/c with a = 7.323(3) Å, b = 14.255(7) Å, c = 10.022(5) Å, β = 99.524(9)°, V = 1031.7(8) Å3, and Z = 4. The crystal is composed of ammonium ions, picolinamide oxodiperoxovanadate(V) ions, and water molecules, which are held together by ionic and hydrogen bond forces. The species [OV(O2)2(picolinamide)]− is seven-coordinated with a distorted pentagonal bipyramidal geometry both in solution and in crystal.

A metabonomics approach based on high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy was applied to investigate the metabolite composition in intact hepatic tissues and renal cortical tissues from db/db mice of 8 weeks old, an animal model of type 2 diabetes mellitus. Compared to the control group, the hepatic tissues of diabetic mice have elevated levels of triglyceride and bile acid and declined levels of trimethylamine-N-oxide, phosphocholine, glycerophosphocholine, and choline. The biochemical changes are less obvious in renal cortical tissues of diabetic mice. The WET_CPMG pulse sequence was selected for our metabonomics study after the quality and reproducibility of the spectra obtained from the NOEPR, NOEPR_CPMG, and WET_CPMG pulse sequences were analyzed together with principal component analysis. The influence of line-broadening factor of exponential window function for spectral manipulation on class separation was paid attention to for the first time, and an optimal value was obtained under our experimental conditions. These studies show the efficiency of HRMAS 1H NMR spectroscopy for tissue metabonomics study in combination with multivariate statistical analysis, which may help to explore the etiological factor of diabetes mellitus from a new perspective.

In the COSY Revamped with Asymmetric Z-gradient Echo Detection (CRAZED) experiments, magnetization is modulated by the distant dipolar field (DDF) generated by coherence selection gradient (CSG) commonly in sinusoidal wave-form and results in detectable intermolecular multiple-quantum coherence (iMQC) signal. IMQCs have some attractive features, but their intrinsic weak signal intensity prevents their widespread applications. In this paper, a new phase cycling scheme was applied to obtain intermolecular double-quantum coherence (iDQC) signal. It is found that DDF can arise from nonspherical sample geometry or background inhomogeneous field in the absence of CSGs, which is more efficient than that created from CSGs. The experimental results show that the resulting DDF can refocus the ± iDQC signals simultaneously and thus enhance the signal intensity to about two folds of that from the conventional CRAZED sequence. Theoretical prediction and experiments give coincident results.

PurposeWe employ an amplitude-modulated chirp pulse to selectively excite spins in one or more regions of interest (ROIs) to realize reduced field-of-view (rFOV) imaging based on single-shot spatiotemporally encoded (SPEN) sequence and Fourier transform reconstruction.Materials and MethodsThe proposed rFOV imaging method was theoretically analyzed and illustrated with numerical simulation and tested with phantom experiments and in vivo rat experiments. In addition, point spread function was applied to demonstrate the feasibility of the proposed method. To evaluate the proposed method, the rFOV results were compared with those obtained using the EPI method with orthogonal RF excitation.ResultsThe simulation and experimental results show that the proposed method can image one or two separated ROIs along the SPEN dimension in a single shot with higher spatial resolution, less sensitive to field inhomogeneity, and practically no aliasing artifacts. In addition, the proposed method may produce rFOV images with comparable signal-to-noise ratio to the rFOV EPI images.ConclusionThe proposed method is promising for the applications under severe susceptibility heterogeneities and for imaging separate ROIs simultaneously.

•A novel SR reconstruction method is presented for spatiotemporally encoded images.•The resulting image has better resolution than EPI image under similar condition.•Aliasing artifacts are removed without resolution loss.•Prior knowledge of edge ghosts is extracted and used in SR reconstruction.•The proposed method would promote the application of undersampled MRI. Spatiotemporally encoded (SPEN) single-shot MRI is an ultrafast MRI technique proposed recently, which utilizes quadratic rather than linear phase profile to extract the spatial information. Compared to the echo planar imaging (EPI), this technique has great advantages in resisting field inhomogeneity and chemical shift effects. Super-resolved (SR) reconstruction is adopted to compensate the inherent low resolution of SPEN images. Due to insufficient sampling rate, the SR image is challenged by aliasing artifacts and edge ghosts. The existing SR algorithms always compromise in spatial resolution to suppress these undesirable artifacts. In this paper, we proposed a novel SR algorithm termed super-resolved enhancing and edge deghosting (SEED). Different from artifacts suppression methods, our algorithm aims at exploiting the relationship between aliasing artifacts and real signal. Based on this relationship, the aliasing artifacts can be eliminated without spatial resolution loss. According to the trait of edge ghosts, finite differences and high-pass filter are employed to extract the prior knowledge of edge ghosts. By combining the prior knowledge with compressed sensing, our algorithm can efficiently reduce the edge ghosts. The robustness of SEED is demonstrated by experiments under various situations. The results indicate that the SEED can provide better spatial resolution compared to state-of-the-art SR reconstruction algorithms in SPEN MRI. Theoretical analysis and experimental results also show that the SR images reconstructed by SEED have better spatial resolution than the images obtained with conventional k-space encoding methods under similar experimental condition. Download high-res image (276KB)Download full-size image

Chemical exchange saturation transfer (CEST) provides a new type of image contrast in MRI. Due to the intrinsically low CEST effect, new and improved experimental techniques are required to achieve reliable and quantitative CEST images. In the present work, we proposed a novel and more sensitive CEST acquisition approach, based on the intermolecular double-quantum coherence with a module of multiple refocusing pulses (iDQC-MRP). Experiments were performed on creatine and egg white phantoms using a Varian 7 T animal MRI scanner. The iDQC-MRP CEST technique showed a substantial enhancement in CEST and nuclear Overhauser enhancement (NOE) signal intensities, compared to the standard single-quantum coherence approach. In addition, the iDQC-MRP approach increased the signal-to-noise ratio of acquired saturation images, compared to the conventional iDQC approach. The new iDQC-MRP CEST sequence provides a promising way for exploiting in vivo CEST and NOE imaging applications.

•Metabolic profiles of Haliotis diversicolor to Vibrio parahemolyticus were studied.•Obvious gender- & tissue-specific responses are found in gill and hepatopancreas.•Vibrio infection disturbs energy and nucleotide metabolisms and osmotic regulation.•Oxidative and immune stresses are induced by vibrio infection.•This study helps to understand the mechanisms of immune defense of abalone.Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, 1H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection.

•A distortion correction method based on single-shot bi-SPEN sequence is proposed.•The distortion correction is performed without additional field-map scans.•ROI images are further improved after the correction method is applied.Owing to its intrinsic characteristics, spatiotemporally encoded (SPEN) imaging is less sensitive to adverse effects due to field inhomogeneity in comparison with echo planar imaging, a feature highly desired for functional, diffusion, and real-time MRI. However, the quality of images obtained with SPEN MRI is still degraded by geometric distortions when field inhomogeneity exists. In this study, a single-shot biaxial SPEN (bi-SPEN) pulse sequence is implemented, utilizing a 90° and a 180° chirp pulse incorporated with two orthogonal gradients. A referenceless geometric-distortion correction based on the single-shot bi-SPEN sequence is then proposed. The distorted image acquired with the single-shot bi-SPEN sequence is corrected by iterative super-resolved reconstruction involving the field gradients estimated from a field map, which in turn is obtained from its own super-resolved data after a phase-unwrapping procedure without additional scans. In addition, the distortion correction method is applied to improve the quality of the multiple region-of-interest images obtained with single-shot bi-SPEN sequence.

•Changes of brain iron concentration after high-altitude exposure were studied.•Iron in the basal ganglia shows high sensitivity to hypoxia environment.•Brain iron changes after high altitude exposure are hemisphere- and gender-related.•Most brain iron changes are recovered after sea-level re-adaptation for one year.•Iron accumulation keeps close relationship with water diffusion in putamen.Hypoxia can induce physiological changes. This study aims to explore effects of high-altitude (HA) hypoxia on cerebral iron concentration. Twenty-nine healthy sea-level participants were tested shortly before and after approximately 4-week adaptation to the HA environment at fQinghai-Tibet Plateau (4200 m), and were re-investigated after re-adaptation to the sea-level environment one year later. Iron concentration was quantified with quantitative susceptibility mapping (QSM), and the results were compared with transverse relaxation rate (R*2) measurements. The variations of magnetic susceptibility indicate that the iron concentration in gray matter regions, especially in basal ganglia, including caudate nucleus, putamen, globus pallidus and substantia nigra, increases significantly after HA exposure. This increase appears consistent with the conclusion from R*2 value variations. However, unlike QSM, the R*2 value fails to demonstrate the statistical difference of iron content in red nucleus. The re-investigation results show that most variations are recovered after sea-level re-adaptation for one year. Additionally, hemisphere- and gender-related differences in iron concentration changes were analyzed among cerebral regions. The results show greater possibilities in the right hemisphere and females. Further studies based on diffusion tensor imaging (DTI) suggest that the fractional anisotropy increases and the mean diffusivity decreases after HA exposure in six deep gray matter nuclei, with linear dependence on iron concentration only in putamen. In conclusion, the magnetic susceptibility value can serve as a quantitative marker of brain iron, and variations of regional susceptibility reported herein indicate that HA hypoxia can result in significant iron deposition in most deep gray matter regions. Additionally, the linear dependence of DTI metrics on iron concentration in putamen indicates a potential relationship between ferritin and water diffusion.