γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter implicated in neuropsychiatric disorders. The best method for quantifying GABA is proton magnetic resonance spectroscopy (
H MRS). ...Considering that accurate measurements of GABA are affected by slight methodological alterations, demonstrating GABA reproducibility in healthy volunteers is essential before implementing the changes in vivo. Thus, our study aimed to evaluate the back-to-back (B2B) and day-to-day (D2D) reproducibility of GABA+ macromolecules (GABA+) using a 3 Tesla MRI scanner, the new 32-channel head coil (CHC), and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) technique with the scan time (approximately 10 min), adequate for psychiatric patients. The dorsomedial pre-frontal cortex/anterior cingulate cortex (dmPFC/ACC) was scanned in 29 and the dorsolateral pre-frontal cortex (dlPFC) in 28 healthy volunteers on two separate days. Gannet 3.1 was used to quantify GABA+. The reproducibility was evaluated by Pearson's r correlation, the interclass-correlation coefficient (ICC), and the coefficient of variation (CV%) (r/ICC/CV%). For Day 1, B2B reproducibility was 0.59/0.60/5.02% in the dmPFC/ACC and 0.74/0.73/5.15% for dlPFC. For Day 2, it was 0.60/0.59/6.26% for the dmPFC/ACC and 0.54/0.54/6.89 for dlPFC. D2D reproducibility of averaged GABA+ was 0.62/0.61/4.95% for the dmPFC/ACC and 0.58/0.58/5.85% for dlPFC. Our study found excellent GABA+ repeatability and reliability in the dmPFC/ACC and dlPFC.
Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. ...Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.
•GABA-edited MEGA-PRESS data from 272 adults were collected from 24 sites.•GABA+ data showed good agreement across vendors and sites.•Variability in MM-suppressed GABA data was attributed in part to B0 field offsets.•Multi-site studies using GABA editing are feasible using a standardized protocol.•These results provide valuable benchmarks for the MRS community.
Purpose
A novel dissolution dynamic nuclear polarization (dDNP) polarizer platform is presented. The polarizer meets a number of key requirements for in vitro, preclinical, and clinical applications.
...Method
It uses no liquid cryogens, operates in continuous mode, accommodates a wide range of sample sizes up to and including those required for human studies, and is fully automated.
Results
It offers a wide operational window both in terms of magnetic field, up to 10.1 T, and temperature, from room temperature down to 1.3 K. The polarizer delivers a 13C liquid state polarization for 1‐13Cpyruvate of 70%. The build‐up time constant in the solid state is approximately 1200 s (20 minutes), allowing a sample throughput of at least one sample per hour including sample loading and dissolution.
Conclusion
We confirm the previously reported strong field dependence in the range 3.35 to 6.7 T, but see no further increase in polarization when increasing the magnetic field strength to 10.1 T for 1‐13Cpyruvate and trityl. Using a custom dry magnet, cold head and recondensing, closed‐cycle cooling system, combined with a modular DNP probe, and automation and fluid handling systems, we have designed a unique dDNP system with unrivalled flexibility and performance.
The structural role of pectins in plant primary cell walls is not yet well understood because of the complex and disordered nature of the cell wall polymers. We recently introduced multidimensional ...solid-state nuclear magnetic resonance spectroscopy to characterize the spatial proximities of wall polysaccharides. The data showed extensive cross peaks between pectins and cellulose in the primary wall of Arabidopsis (Arabidopsis thaliana), indicating subnanometer contacts between the two polysaccharides. This result was unexpected because stable pectin-cellulose interactions are not predicted by in vitro binding assays and prevailing cell wall models. To investigate whether the spatial contacts that give rise to the cross peaks are artifacts of sample preparation, we now compare never-dried Arabidopsis primary walls with dehydrated and rehydrated samples. Onedimensional ¹³C spectra, two-dimensional ¹³C-¹³C correlation spectra, water-polysaccharide correlation spectra, and dynamics data all indicate that the structure, mobility, and intermolecular contacts of the polysaccharides are indistinguishable between never-dried and rehydrated walls. Moreover, a partially depectinated cell wall in which 40% of homogalacturonan is extracted retains cellulose-pectin cross peaks, indicating that the cellulose-pectin contacts are not due to molecular crowding. The cross peaks are observed both at −20°C and at ambient temperature, thus ruling out freezing as a cause of spatial contacts. These results indicate that rhamnogalacturonan I and a portion of homogalacturonan have significant interactions with cellulose microfibrils in the native primary wall. This pectin-cellulose association may be formed during wall biosynthesis and may involve pectin entrapment in or between cellulose microfibrils, which cannot be mimicked by in vitro binding assays.
This work is focused on the characterization of the composition of a COsub.2 supercritical fluid extract of Aquilaria sinensis (Chinese agarwood) collected in the Dongguan area (China) and infected ...by mechanical methods. The constituents of this extract were analyzed by gas chromatography–mass spectrometry (GC-MS) and quantified accurately by gas chromatography with a flame ionization detector (GC-FID), using an internal reference and predicted response factors. Since a significant number of components of this extract remained non-identified after the initial GC-MS analysis of the whole extract, its fractionation by chromatography on silica gel helped to characterize several additional constituents by isolation and structural analysis by NMR spectroscopy. The main components are the classical agarwood chromones (Flindersia chromone and its mono-, di-, and trimethoxylated analogues (respectively, 11.01% and 0.11–4.02%) along with sesquiterpenic constituents typically found in agarwood essential oils, like baimuxinal (1.90%) and kusunol (1.24%), as well as less common selinane dialdehydes (1.58–2.27%) recently described in the literature. Moreover, the structure and stereochemistry of a new sesquiterpenic alcohol, 14β,15β-dimethyl-7αH-eremophila-9,11-dien-8β-ol (0.67%), was determined unambiguously by the combination of structural analysis (NMR, MS), hemisynthesis, and total synthesis, leading to dihydrokaranone and a neopetasane epimer.
Analysis of small molecules is essential to metabolomics, natural products, drug discovery, food technology, and many other areas of interest. Current barriers preclude from identifying the ...constituent molecules in a mixture as overlapping clusters of NMR lines pose a major challenge in resolving signature frequencies for individual molecules. While homonuclear decoupling techniques produce much simplified
spectra, they often affect sensitivity. Conversion of typical NMR spectra to pure shift spectra by signal processing without
knowledge about the coupling patterns is essential for accurate analysis. We developed a super-resolved wavelet packet transform based
H NMR spectroscopy that can be used in high-throughput studies to reliably decouple individual constituents of small molecule mixtures. We demonstrate the efficacy of the method on the model mixtures of saccharides and amino acids in the presence of significant noise.
Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature ...of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (
H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR "magnetic resonance spectroscopy"). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were
H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = -0.38; 95% CI, -0.69 to -0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = -0.50; 95% CI, -0.80 to -0.20), but not in unmedicated patients (SMD = -0.27; 95% CI, -0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.
Degenerate spin-systems consisting of magnetically equivalent nuclear spins, such as a
H
spin-system in selectively
CH
-labeled proteins, present considerable challenges for the design of ...Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiments to characterize chemical exchange on the micro-to-millisecond time-scale. Several approaches have been previously proposed for the elimination of deleterious artifacts observed in methyl
H CPMG relaxation dispersion profiles obtained for (
C)
H
groups. We describe an alternative, experimentally simple solution and design a "steady-state" methyl
H CPMG scheme, where 90° or acute-angle (<90°)
H radiofrequency pulses are applied after each CPMG echo in-phase with methyl
H magnetization, resulting in the establishment of a "steady-state" for effective rates of magnetization decay. A simple computational procedure for quantitative analysis of the "steady-state" CPMG relaxation dispersion profiles is developed. The "steady-state" CPMG methodology is applied to two protein systems where exchange between major and minor species occurs in different regimes on the chemical shift time-scale.
Many developmental processes, such as plasticity and aging, or pathological processes such as neurological diseases are characterized by modulations of specific cellular types and their ...microstructures. Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) is a powerful technique for probing microstructure, yet its information arises from the ubiquitous, non-specific water signal. By contrast, diffusion-weighted Magnetic Resonance Spectroscopy (DW-MRS) allows specific characterizations of tissues such as brain and muscle in vivo by quantifying the diffusion properties of MR-observable metabolites. Many brain metabolites are predominantly intracellular, and some of them are preferentially localized in specific brain cell populations, e.g., neurons and glia. Given the microstructural sensitivity of diffusion-encoding filters, investigation of metabolite diffusion properties using DW-MRS can thus provide exclusive cell and compartment-specific information. Furthermore, since many models and assumptions are used for quantification of water diffusion, metabolite diffusion may serve to generate a-priori information for model selection in DW-MRI. However, DW-MRS measurements are extremely challenging, from the acquisition to the accurate and correct analysis and quantification stages. In this review, we survey the state-of-the-art methods that have been developed for the robust acquisition, quantification and analysis of DW-MRS data and discuss the potential relevance of DW-MRS for elucidating brain microstructure in vivo. The review highlights that when accurate data on the diffusion of multiple metabolites is combined with accurate computational and geometrical modeling, DW-MRS can provide unique cell-specific information on the intracellular structure of brain tissue, in health and disease, which could serve as incentives for further application in vivo in human research and clinical MRI.
•Diffusion-weighted MRS (DW-MRS) allows to investigate brain metabolite diffusion.•Most brain metabolites are predominantly intracellular and cell specific.•Diffusion properties of brain metabolites provide exclusive cell-specific information.•The most recent methods for DW-MRS data acquisition and analysis are reviewed.•The potential relevance of DW-MRS for elucidating brain microstructure is discussed.
Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have ...emerged as a promising tool for improving prognosis.
Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality.
Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (Δ
) show good prediction of mortality. These results suggest that NMR-based metabolomic analysis is useful for a better overall assessment of septic shock patients.
Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes.
All human serum samples were collected and stored, provided by the "center of biologic resources for liver disease", in Jean Verdier Hospital, Bondy, France (BB-0033-00027).
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