bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo31p mrs: absolute concentrations, signal‐to‐noise and prior knowledge
Authors: Van Boogaart A. Den , Howe F. A. , Rodrigues L. M. , Stubbs M. , Griffiths J. R. 
Published: March 2007

AbstractAbsolute metabolite concentrations have been estimated for nucleoside triphosphate and Pi from in vivo 31P MR measurements using ISIS localization in a rat tumour model, and the results have been compared to those obtained from acid extracts of the tumours. The aim of the experiment was to assess the performance of four different spectral analysis techniques used for absolute quantitation. The spectral analysis techniques used were two frequency domain methods (peak area integration and Lorentzian fitting–FITSPEC) and two time domain methods (VARPRO and HLSVD). The spectra were acquired in blocks so that the degradation in performance of the four spectral analysis methods with decreasing signal‐to‐noise ratio (SNR) could be compared and referenced. This and the inclusion of a sophisticated method incorporating prior knowledge yields a more realistic and comprehensive protocol than previously published comparisons. The results suggest that VARPRO is the method of choice for quantitative analysis of tumour 31P MR spectra, giving the most reliable results at low SNR.
Determination of proton metabolite concentrations and relaxation parameters in normal human brain and intracranial tumours
Authors: Manton D. J. , Lowry M. , Blackband S. J. , Horsman A. 
Published: March 2007

AbstractQuantitative proton spectroscopic studies were performed on 39 volunteers and 16 patients with intracranial tumours. Estimates of T2 were obtained in white matter, grey matter, cerebellum, astrocytomas and meningiomas; T1 was determined in white matter only. White matter values of T2 for trimethylamines, creatine and N‐acetyl aspartate (NAA) were 309±84, 195±41 and 369±124ms, respectively (mean±SD, n = 20). Metabolite concentrations in white matter were 2.0±0.4 m̈mol/g wet weight for trimethylamines, 7.3±1.1 for creatine and 11.4±1.4 for NAA. The mean concentrations of creatine and NAA in grey matter and all of three metabolites in cerebellum were greater than those in white matter. Tumour spectra were characterized by increased trimethylamines, reduced creatine and NAA and occasionally the presence of lactate. Meningiomas were further characterized by the presence of alanine. The mean T2 and concentration of trimethylamines in tumours was significantly greater than in normal brain. Creatine and NAA concentrations were decreased in all tumours. The longer T2 of trimethylamines and presence of alanine in meningiomas indicate that important differences exist in membrane and glucose metabolism within these tumours when compared to either astrocytomas or normal brain tissue.
Application of homonuclear decoupling to measures of diffusion in biological 31P spin echo spectra
Authors: Hubley Mark J. , Moerland Timothy S. 
Published: March 2007

AbstractPulsed field gradient (PFG) spin echo 31P NMR can be used to measure diffusion coefficients of phosphorus‐containing metabolites in vivo. In biological spin echo spectra, the ATP resonances are phase modulated by J‐coupling between the three phosphorus atoms. This phase modulation may severely decrease the apparent signal intensity of the ATP peaks. In this paper, we describe the use of homonuclear decoupling during spin evolution to suppress the effects of J‐coupling in biological spin echo spectra. Phosphorous spectra of ATP and creatine phosphate (PCr) in solution and goldfish (Carassius auratus) skeletal muscle demonstrate the effectiveness of homonuclear decoupling in improving the effective signal‐to‐noise ratio of ATP. In addition, diffusion coefficients of ATP and PCr determined in goldfish skeletal muscle show that PFG homonuclear decoupled spin echo (HDSE) NMR provides accurate measures of diffusion coefficients.
Inhibition of aldose reductase: 13C NMR studies in isolated peripheral nerve
Authors: Waterton John C. , Breen Seáan A. , Mirrlees Don J. , Sennitt Christopher M. , Carey Frank 
Published: March 2007

AbstractWe report 13C NMR measurements of the flux through aldose reductase in isolated rat sciatic nerve, and its inhibition by an aldose reductase inhibitor of the sulphonylnitromethane class. [1‐13C] galactose was used as substrate, and the rate of production of [1‐13C] dulcitol was measured. Quantitation required the use both of internal extracellular, and external, standards. The mean net forward flux (±S.D) was 20±11 nmol/(mL nerve water)/min (n = 10). In the presence of the inhibitor, flux was reduced significantly (p<0.001) to 13% of control. Since dulcitol is symmetrical, an estimate of the backward flux, to [6‐13C] galactose, is also possible; under our conditions, this was negligible.
In vivo and in vitro studies of cyclophosphamide chemotherapy in a mouse mammary carcinoma by 31P NMR spectroscopy
Authors: Street James C. , Mahmood Umar , Koutcher Jason A. , Matei Cornelia 
Published: March 2007

AbstractThe effect of cyclophosphamide on the metabolic profile of a mammary carcinoma implanted on the foot of mouse was studied by 31P NMR spectroscopy both in vivo and in perchloric acid extracts. The ratio nucleotide triphosphate: Pi was significantly elevated in cyclophosphamide treated tumours relative to untreated tumours after 96 h in vivo (p<0.05). Phosphocreatine: Pi was similarly elevated from 48 to 168 h (p<0.01). Resolution of the phosphomonoester peak into two distinct resonances allowed us to estimate the ratio of PME′ to phosphocholine (PC), where PME′ is a composite peak consisting, in part, of phosphoethanolamine (PE). PME′:PC was found to be significantly higher in treated animals relative to control animals in vivo (p<0.01 from 48 to 168h). Perchloric acid extract spectra suggest that the increase in PME′:PC was in part due to a decrease in PC concentration and also due to an increase in a previously unidentified resonance which was coresonant with PE. Extract data show that there was a significant increase in the concentration of the phosphodiesters, glycerophosphocholine (p<0.01) and glycerophosphoethanolamine (p<0.05) in treated relative to control tumours. The changes in the phosphomonoester resonances are qualitatively similar to previously described changes following radiation and suggest that they may be a marker of cell kill or lack of cell growth after antineoplastic therapy.
Gadolinium and dysprosium chelates of DTPA‐amide‐dextran: synthesis, 1H NMR relaxivity, and induced 23Na NMR shift
Authors: Chu Wen‐Jang , Elgavish Gabriel A. 
Published: March 2007

AbstractIn this study the conjugated macromolecular ligand, diethylenetriaminepentaacetic acid (DTPA)‐amide‐dextran, was synthesized by attaching DTPA to the dextran macromolecule (Mr∼6000) by a covalent amide bond. Subsequently, DTPA‐amide‐dextran was complexed with either of the two lanthanide metal ions dysprosium (Dy) or gadolinium (Gd). The paramagnetic 23Na NMR shift induced by Dy(DTPA‐amide‐dextran) and the relaxivity (ρi) induced by Gd(DTPA‐amide‐dextran) were characterized. Dy(DTPA‐amide‐dextran) induced a 25% larger 23Na NMR shift than that induced by Dy(DTPA). Neither the shift induced by Dy(DTPA‐amide‐dextran) nor the shift induced by Dy(DTPA) was affected by increasing levels of calcium ions in the solution. Gd(DTPA‐amide‐dextran) exhibited an in vitro ρi of 8.4 (mM s)−1 at a 0.23 T magnetic field and 9.3 (mM s)−1 at a 0.47 T magnetic field, thus indicating a positive magnetic field dependence.
31P NMR in vivo study of rat brain energy metabolism after frontal cortex injury. a method based on convoluted correlation matrices of the spectral data
Authors: Semenova Nataly A. , Konradov Alexander A. , Dubinsky Vladimir Z. 
Published: March 2007

AbstractDisturbances of energy metabolism in rat brain after frontal lobectomy and post‐traumatic effects of monosialic ganglioside GM1 on brain energy metabolism were studied by 31P NMR in vivo. Frontal lobectomy caused the statistically significant reversible decrease of ATP and increase of ADP during the compensatory period. In a presence of GM, these post‐operational effects were not observed. The mean value of normalized correlation coefficients between NMR‐measured phosphomonoesters, Pi, pH, phosphocreatine, γ‐ATP +β‐ADP, α‐ATP+α‐ADP + NAD/NADH + diphosphodiesters and β‐ATP for a given group of animals (Z‐index) was used to estimate brain energetic status. It has been shown that the variation of the Z‐index correlates with the dynamics of locomotor activity during the compensatory period. The Z‐index increased by more than 100% for the subgroup with an increased moving activity and only by about 20% for the subgroup with a decreased activity. Moreover, the compositions of these subgroups were almost the same as those from the solution of the reverse task, i.e., the studied group was divided into two subgroups by the Z‐index. The Z‐index is proposed as a possible criterion of pathology detection in brain energetics.
Hypoglycemia prevents increase in lactic acidosis during reperfusion after temporary cerebral ischemia in rats
Authors: Sappey‐Marinier Dominique , Chileuitt Laureano , Weinstein Philip R. , Weiner Michael W. , Faden Alan I. 
Published: March 2007

AbstractSequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N‐acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p≤0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p=0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis.
On the use of 133Cs as an NMR active probe of intracellular space in vivo
Authors: Li Yi , Neil Jeff , Joseph Ackerman J. H. 
Published: March 2007

AbstractData are presented from 133Cs NMR studies on both excised and in situ tissues from rats fed a regular diet and administered i.p. CsCl in aqueous solution for 6 to 14 days. Cesium is an NMR‐active potassium analog which accumulates in the intracellular spaces of tissues [Davies et al., Biochemistry 27, 3547 (1988); Shehan, B.P. et al., Magn. Reson. Med. 30, 573 (1993)]. Chemical shifts, relaxation properties, sensitivity and detectability of cesium in tissues were investigated. Consistent with previous reports, two resonances (representing intra‐ and extracellular cesium) were detected in blood. Only one resonance was detected in brain, kidney, and muscle tissue. Efforts to resolve intra‐ and extracellular components by T1 and T2 relaxation discrimination were not successful. Following i.p. administration, cesium accumulates intracellularly with a brain‐to‐cerebrospinal fluid concentration (μmol/g) ratio of 9:1 and a thigh muscle‐to‐plasma concentration ratio of 40:1. Considering the small extracellular volume in these tissues (ca 18% and 10%, respectively), the net content differences between intra‐ and extracellular cesium are approximately 40‐fold in brain and 360‐fold in muscle. The concentration ratio of cesium in brain to cesium in cerebrosinal fluid decreased to 3:1 1 h after death, indicating a relatively slow rate of leakage of cesium from the intra‐ to extracellular space in the face of bioenergetic failure. These data suggest that the cesium signal is dominated by the intracellularly located cesium and, thus, cesium may be useful as a probe of the intracellular environment despite an inability to resolve and directly observe distinct resonances from intra‐ and extracellular spaces.
Detection and quantitation of phosphorus metabolites in crude tissue extracts by 1H and 31P NMR: use of gradient assisted 1H‐31P HMQC experiments, with selective pulses, for the assignment of less abundant metabolites
Authors: Pollesello Piero , Eriksson Ove , Geimonen Erika , Vittur Franco , Paoletti Sergio , Toffanin Renato 
Published: March 2007

AbstractThe analysis of crude tissue extracts by NMR has proven to be of use in the study of metabolism due to the non‐destructive and non‐selective character of the technique. Lists of 1H and 31P NMR assignments of phosphorus metabolites in water solution at specified pH and ionic composition are of large general value but their usefulness may be limited when analysing complex mixtures of metabolites at low concentrations. In this work we report on the use of gradient‐assisted proton detected multiple quantum 1H and 31P coherence experiments with selective pulses for the rapid and unambiguous assignments of some crowded regions in 1H and 31P spectra of crude extracts from rat liver. The amplitudes of the gradient episodes were calibrated to optimize the coherence transfer pathway between proton and phosphorus, and the delay for the evolution of the long‐range coupling was calculated from values of 3JPH and 4JPH ranging from 1.4 to 7.5 Hz. Moreover, a selective 90° Gaussian pulse on the 31P channel was introduced to increase the resolution in the F1‐domain and make the method even faster. The procedure was then applied to unambiguously assign the ID 31P and 1H spectra of perchloric acid extracts of rat livers that had been stimulated with phenylephrine, dBcAMP and glucagon and thus detect changes in the concentration of less abundant metabolites such as phosphoenolpyruvate, UDP‐glucose and AMP. The fact that the quantification of these metabolites by either 31P and 1H methods lead to different results is discussed, and the use of 1H NMR spectroscopy for the quantification of phosphorus metabolites whose signal are too weak or poorly resolved in a 31P spectrum is proposed.
Evolution of acute focal cerebral ischaemia in rats observed by localized 1H MRS, diffusion‐weighted MRI, and electrophysiological monitoring
Authors: Gyngell Michael L. , Busch Elmar , Schmitz Bernd , Kohno Kanehisa , Back Tobias , Hoehn‐Berlage Mathias , Hossmann Konstantin‐Alexander 
Published: March 2007

AbstractFocal cerebral ischaemia was produced in 11 rats by permanent occlusion of the right middle cerebral artery (MCA) using a suture model modified to enable manipulation with the animals in situ in an NMR spectrometer. The development of the ischaemic insults and the resultant infarcts were observed for up to 6 h by localized 1H MRS and diffusion‐weighted MRI while performing continuous monitoring of electroencephalogram and extracellular DC potential. The ischaemic areas were depicted as regions of hyperintensity in the diffusion‐weighted images. Signals due to lactate became visible in the 1H spectra after MCA occlusion indicating the onset of anaerobic glycolysis. A depletion of N‐acetylaspartate was seen in all animals post‐occlusion. Transient or stepwise increases of lactate were observed to occur coincidentally with the events of spontaneous transient peri‐infarct depolarization detected by the electrophysiological measurements. Expansion of the ischaemic area delineated in the diffusion‐weighted images also accompanied peri‐infarct depolarizations. These observations are consistent with transient peri‐infarct depolarization playing a role in the growth of infarcts.
31P magnetic resonance spectroscopy as predictor of clinical response in human extremity sarcomas treated by single dose TNF‐α+ melphalan isolated limb perfusion
Authors: Sijens Paul E. , Dijk Pieter Van , Oudkerk Matthijs , Eggermont Alexander M. M. 
Published: March 2007

AbstractIrresectable extremity sarcomas are large (grade II/III) tumors requiring amputation of the limb for local control. Limb salvage can be achieved by isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF‐α), interferon‐γ and melphalan. To obtain insight into the effects of single dose ILP on extremity tumors, phosphate metabolism was monitored by 31P magnetic resonance spectroscopy (MRS) using the chemical shift imaging (CSI) technique. 2D CSI was used in combination with a slice select gradient in the third dimension to obtain true 3D localization. Spectral maps obtained prior to ILP revealed reductions in phosphocreatine (PCr) level and increases in phosphomonoester (PME) and phosphodiester (PDE) in tumor compared with muscle tissue. ILP treated tumors showed highly divergent changes in Pi while PME decreased in all cases (n = 11). Tumor volume, unchanged on day 8 after ILP, was decreased by 58±29% (mean±SD) at 2 months. Linear regression analysis revealed correlation between the changes in tumor metabolites measured on day 8, with percent volume decrease (Pi: r=‐0.88, p<0.001) and percent necrosis at resection (PME: r=‐0.79, p‐0.01). Correlation between pretreatment spectra and effectiveness of ILP treatment was not found. It is concluded that a single ILP with TNF‐α+melphalan induced changes in tumor metabolite levels (measured on day 8) that reflect treatment efficacy. 31P MRS can thus provide information facilitating the decision as to when to remove tumor (residue) and, in the case where tumor remains inoperable, whether or not to apply additional therapy.
Quantification of biomedical NMR data using artificial neural network analysis: Lipoprotein lipid profiles from 1H NMR data of human plasma
Authors: Ala‐Korpela M. , Hiltunen Y. , Bell J. D. 
Published: March 2007

AbstractArtificial neural network (ANN) analysis is a new technique in NMR spectroscopy. It is very often considered only as an efficient ‘black‐box’ tool for data classification, but we emphasize here that ANN analysis is also powerful for data quantification. The possibility of finding out the biochemical rationale controlling the ANN outputs is presented and discussed. Furthermore, the characteristics of ANN analysis, as applied to plasma lipoprotein lipid quantification, are compared to those of sophisticated lineshape fitting (LF) analysis. The performance of LF in this particular application is shown to be less satisfactory when compared to neural networks. The lipoprotein lipid quantification represents a regular clinical need and serves as a good example of an NMR spectroscopic case of extreme signal overlap. The ANN analysis enables quantification of lipids in very low, intermediate, low and high density lipoprotein (VLDL, IDL, LDL and HDL, respectively) fractions directly from a 1H NMR spectrum of a plasma sample in <1 h. The ANN extension presented is believed to increase the value of the 1H NMR based lipoprotein quantification to the point that it could be the method of choice in some advanced research settings. Furthermore, the excellent quantification performance of the ANN analysis, demonstrated in this study, serves as an indication of the broad potential of neural networks in biomedical NMR.
Dynamic monitoring of cerebral metabolites during and after transient global ischemia in rats by quantitative proton NMR spectroscopy in vivo
Authors: Nagatomo Yasushi , Wick Markus , Prielmeier Franz , Frahm Jens 
Published: March 2007

AbstractLocalized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user‐independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N‐acetyl aspartate (neuronal marker), creatines, cholines, and myo‐inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1± 2.2 mmol/kg wet weight significantly above the basal value of 2.3± 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0±0.6 to 13.5±1.5 mmol/kg wet weight 10‐15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first‐order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7±0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1‐2 hours post ischemia.
Interpretation of DW‐NMR data: Dependence on experimental conditions
Authors: Norris David G. , Niendorf Thoralf 
Published: March 2007

AbstractThis review examines the effect of experimental conditions on the data obtainable from diffusion weighted NMR experiments. The origin and forms of the Stejskal‐Tanner experiment are presented, and the relative merits of bipolar to monopolar diffusion weighting gradient pulses are discussed, as are those of spin‐echo and stimulated‐echo weighting schemes. The short pulse Stejskal‐Tanner experiment as required for q‐space imaging is described. Criteria for successful diffusion weighted imaging are given, and current strategies for diffusion weighted imaging are evaluated against these. The range of biological objects accessible to diffusion weighted NMR is summarized, together with the associated experimental limitations. In the final section the dependence of diffuson weighted NMR data on diffusion time and b‐value range is examined, and the relationship between apparent restricted diffusion and the size of the extracellular space is demonstrated.
Diffusion‐weighted imaging in tissues: Theoretical models
Authors: Szafer A. , Zhong Jianhui , Anderson Adam W. , Gore John C. 
Published: March 2007

AbstractTypical diffusion measurements use Stejskal‐Tanner pulsed gradient spin echo sequences to provide information about the average diffusion and displacement profiles of particles in a sample. To derive structural information, a measured displacement profile has to be related by means of a model to the physical and geometrical properties of the tissue, such as diffusion coefficients and shapes of semi‐permeable membranes of compartments in the system. The behavior of the NMR signal and the measured ADC are greatly affected by the cellular architecture of a tissue, mainly because cellular membranes are relatively impermeable to water. For long diffusion times, and small signal attenuations, ADC is relatively insensitive to how it is measured. In general, however, ADC values are not readily interpreted unless the measuring conditions are specified in detail. For given measuring conditions, ADC depends on intra‐ and extracellular diffusion coefficients, membrane permeabilities, cell sizes and the cellular volume fraction. If intra‐ and extracellular T2relaxation rates are different enough, ADC may also depend on the relaxation properties of the system and the echo time. An improved understanding of the precise influence of these factors has been obtained by detailed consideration of theoretical and computer models that can be related to experimental data in simple systems. Further refinements of such models should advance our understanding of water diffusion in tissues.