Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites.
Ontology highlight
ABSTRACT:
SUBMITTER: Marjanska M
PROVIDER: S-EPMC3357544 | biostudies-other | 2012 Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:A ligand-observed 1H NMR relaxation experiment is introduced for measuring the binding kinetics of low-molecular-weight compounds to their biomolecular targets. We show that this approach, which does not require any isotope labeling, is applicable to ligand-target systems involving proteins and nucleic acids of variable molecular size. The experiment is particularly useful for the systematic investigation of low affinity molecules with residence times in the micro- to millisecond time regime.
| S-EPMC5150660 | biostudies-literature
Project description:The novel concept of NORD (NO relaxation delay) NMR spectroscopy is introduced. The idea is to design concatenated experiments in a way that the magnetization used in the first relaxes toward equilibrium during the second and vice versa, thus saving instrument time. Applications include complete well-resolved 1 H-1 H and 1 H-13 C one-bond and long-range correlation maps of an 80 mM solution of a trisaccharide recorded in less than two minutes and hydrocortisone with extensive spectral overlap.
| S-EPMC8252012 | biostudies-literature
Project description:Articular cartilage lines synovial joints and functions as a low-friction deformable tissue to enable smooth and stable joint articulation. The objective of this study was to determine the relationships between cartilage stress-relaxation properties and the collagen and GAG NMR transverse relaxation times (T(2)) toward understanding mechanisms of cartilage viscoelasticity. Stress-relaxation tests were performed on both cultured and enzymatically digested bovine cartilage, followed by measurements of both the collagen and GAG T(2) using the Call-Purcell-Meiboom-Gill pulse sequence. The peak and equilibrium stresses were correlated with the GAG T(2), and the stress-relaxation time constant was correlated with the collagen T(2). Multiple linear regression models were successful in using the specific T(2) values to predict the stress-relaxation properties. As a model of osteoarthritis, enzymatic digestion with collagenase and testicular hyaluronidase had weak effects on T(2) values. These data present a complex picture of cartilage mechanical behavior, with cartilage stiffness associated with the GAG T(2) values and the stress-relaxation time constant associated with the collagen T(2).
| S-EPMC2766774 | biostudies-literature
Project description:Context3,5-Diiodo-L-thyronine (3,5-T2) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T2 and glucose but not lipid metabolism.ObjectiveThe aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T2 concentrations in healthy individuals.Study design and methodsUrine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by (1)H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T2 concentrations.ResultsSerum 3,5-T2 concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T2 concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels.ConclusionOur findings in humans confirmed the metabolic effects of circulating 3,5-T2 on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T2 exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
| S-EPMC4640298 | biostudies-literature
Project description:Background T2 mapping is an important cardiac MRI technique with applications in various conditions. However, a comprehensive evaluation of the T2 literature for normal values is lacking. Purpose To characterize the ranges of normal values and variability of myocardial T2 relaxation times using a systematic review and meta-analysis of the T2 literature. Materials and Methods PubMed and Cochrane Central were searched from June 2019 to January 2020 for myocardial T2 measurements in healthy adults. Studies quantifying T2 relaxation times conducted at 1.5 T or 3.0 T using gradient and spin-echo (GRASE) or T2-prepared balanced steady-state free precession sequences were included. Summary means were generated using a random-effects model. Subgroup analysis and meta-regression were performed to assess factors causing heterogeneity. Results Of the 2481 articles retrieved, 42 studies were included with 954 healthy adults (mean age, 42.4 years ± 10.5 [standard deviation]; 538 men). The pooled mean of T2 across studies was 52 msec at 1.5 T (95% confidence interval [CI]: 51 msec, 53 msec) and 46 msec at 3.0 T (95% CI: 44 msec, 48 msec) (P ≤ .001). I2 was 98% at 1.5 T and 3.0 T. Meta-regression at 1.5 T and 3.0 T identified vendor (β at 1.5 T = -4 msec [with Philips as reference], P < .001; β at 3.0 T = -5 msec, P = .02) and pulse sequence (β at 1.5 T = -5 msec [with GRASE as reference], P < .001; β at 3.0 T = -6 msec, P = .002) as significant covariates, but it did not identify any association with covariates of age (β at 1.5 T = 0 msec per year, P = .70; β at 3.0 T = 0 msec per year, P = .83) or sex (β at 1.5 T = -1 msec, P = .88; β at 3.0 T = 6 msec, P = .42). Conclusion The pooled mean of T2 relaxation times in healthy adults had marked heterogeneity across studies with field strength, vendor, and pulse sequence identified as covariates associated with T2. T2-prepared measurements were similar between vendors at each field strength. © RSNA, 2020 Online supplemental material is available for this article.
| S-EPMC7605362 | biostudies-literature
Project description:Allosteric transmission of information between distant sites in biological macromolecules often involves collective transitions between active and inactive conformations. Nuclear magnetic resonance (NMR) spectroscopy can yield detailed information on these dynamics. In particular, relaxation dispersion techniques provide structural, dynamic, and mechanistic information on conformational transitions occurring on the millisecond to microsecond timescales. In this review, we provide an overview of the theory and analysis of Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiments and briefly describe their application to the study of allosteric dynamics in the homeodomain from the PBX transcription factor (PBX-HD). CPMG NMR data show that local folding (helix/coil) transitions in one part of PBX-HD help to communicate information between two distant binding sites. Furthermore, the combination of CPMG and other spin relaxation data show that this region can also undergo local misfolding, reminiscent of conformational ensemble models of allostery.
| S-EPMC5425744 | biostudies-literature
Project description:Brain glutamine synthetase (GS) is an integral part of the glutamate-glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. (15)N MRS is an alternative approach to (13)C MRS. Incorporation of labeled (15)N from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate-glutamine cycle. To measure (15)N incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel (15)N pulse sequence to simultaneously detect, for the first time, [5-(15)N]Gln and [2-(15)N]Gln+Glu in vivo in the rat brain. In addition, we also measured for the first time in the same experiment localized (1)H spectra for a direct measurement of the net glutamine accumulation. Mathematical modeling of (1)H and (15)N MRS data allowed to reduce the number of assumptions and provided reliable determination of GS (0.30±0.050 μmol/g per minute), apparent neurotransmission (0.26±0.030 μmol/g per minute), glutamate dehydrogenase (0.029±0.002 μmol/g per minute), and net glutamine accumulation (0.033±0.001 μmol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification.
| S-EPMC3318147 | biostudies-other
Project description:Aromatic side chains are prevalent in protein binding sites, perform functional roles in enzymatic catalysis, and form an integral part of the hydrophobic core of proteins. Thus, it is of great interest to probe the conformational dynamics of aromatic side chains and its response to biologically relevant events. Indeed, measurements of (13)C relaxation rates in aromatic moieties have a long history in biomolecular NMR, primarily in the context of samples without isotope enrichment that avoid complications due to the strong coupling between neighboring (13)C spins present in uniformly enriched proteins. Recently established protocols for specific (13)C labeling of aromatic side chains enable measurement of (13)C relaxation that can be analyzed in a straightforward manner. Here we present longitudinal- and transverse-relaxation optimized pulse sequences for measuring R (1), R (2), and {(1)H}-(13)C NOE in specifically (13)C-labeled aromatic side chains. The optimized R (1) and R (2) experiments offer an increase in sensitivity of up to 35 % for medium-sized proteins, and increasingly greater gains are expected with increasing molecular weight and higher static magnetic field strengths. Our results highlight the importance of controlling the magnetizations of water and aliphatic protons during the relaxation period in order to obtain accurate relaxation rate measurements and achieve full sensitivity enhancement. We further demonstrate that potential complications due to residual two-bond (13)C-(13)C scalar couplings or dipolar interactions with neighboring (1)H spins do not significantly affect the experiments. The approach presented here should serve as a valuable complement to methods developed for other types of protein side chains.
| S-EPMC3405241 | biostudies-literature
Project description:OBJECTIVE:To analyze region-specific T1? and T2 relaxation times of the hip joint cartilage in relation to presence or absence of radiographic hip osteoarthritis (OA) and presence or absence of magnetic resonance imaging (MRI)-detected cartilage defects. METHODS:Weight-bearing radiographs and 3T MRI studies of the hip were obtained from 84 volunteers. Based on Kellgren/Lawrence (K/L) scoring of the radiographs, 54 subjects were classified as healthy controls (K/L grade ?1) and 30 were classified as having mild or moderate radiographic hip OA (K/L grades 2 or 3, respectively). Two-dimensional fat-suppressed fast spin-echo MRI sequences were used for semiquantitative clinical scoring of cartilage defects, and a T1?/T2 sequence was used to quantitatively assess the cartilage matrix. The femoral and acetabular cartilage was then segmented into 8 regions and the mean T1?/T2 values were calculated. Differences in T1? and T2 relaxation times were compared between subjects with and those without radiographic hip OA, and those with and those without femoral or acetabular cartilage defects. RESULTS:Higher T1? and T2 relaxation times in the anterior superior and central regions of the acetabular cartilage were seen in individuals with radiographic hip OA and those with acetabular cartilage defects compared to their respective controls (P?<?0.05). In the femoral cartilage, the differences in T1? and T2 were not significant for any of the comparisons. Significant differences in the T1? and T2 values (each P < 0.05) were found in more subregions of the cartilage and across the whole cartilage when subjects were stratified based on the presence of MRI-detected cartilage defects than when they were stratified based on the presence of radiographic hip OA. CONCLUSION:T1? and T2 relaxation parameters are sensitive to the presence of cartilage degeneration. Both parameters may therefore support MRI evidence of cartilage defects of the hip.
| S-EPMC6348065 | biostudies-other
Project description:An NMR-based approach to characterizing the binding kinetics of ligand molecules to biomolecules, like RNA or proteins, by ligand-detected Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments is described. A (15)N-modified preQ1 ligand is used to acquire relaxation dispersion experiments in the presence of low amounts of the Fsu class?I preQ1 aptamer RNA, and increasing ligand concentrations to probe the RNA small molecule interaction. Our experimental data strongly support the conformational selection mechanism postulated. The approach gives direct access to two parameters of a ligand-receptor interaction: the off rate and the population of the small molecule-receptor complex. A detailed description of the kinetics underlying the ligand binding process is of crucial importance to fully understanding a riboswitch's function and to evaluate potential new antibiotics candidates targeting the noncoding RNA species. Ligand-detected NMR relaxation dispersion experiments represent a valuable diagnostic tool for the characterization of binding mechanisms.
| S-EPMC4353840 | biostudies-literature