bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental characterization of the ISIS technique for volume selected NMR spectroscopy
Authors: Keevil S. F. , Porter D. A. , Smith M. A. 
Published: March 2007

AbstractAs clinical applications of MRS grow in number and complexity, there is a need for standardized methods for characterizing the performance of volume selection techniques. The results are presented of a thorough evaluation of a particular implementation of ISIS performed using a procedure which forms the basis of the method adopted by the European Community Concerted Action on MRS and MRI. We have found that ISIS localization is optimal when the volume of interest is slightly smaller than the region we wish to study. Contamination with extraneous signal has little T1 dependence so long as TR > T1, and the detection pulse angle is 90°. However, a poorly optimized detection pulse results in T1‐weighted contamination unless TR > 3T1. In the clinical context, this corresponds to a different degree of contamination for each peak in the spectrum. Adiabatic detection pulses were used in an attempt to overcome this problem without resorting to unacceptable TR values, but these were found to function less well than properly optimized rectangular pulses, even if the power was increased above the level determined by the system for B1 insensitivity. These detailed results pertain only to our system, but illustrate the importance of performing similar measurements as part of clinical spectroscopy programmes at other centres.
A gating 31P NMR method triggered by pulses for cardiac pacing
Authors: Tanaka Kunio , Honda Hajime , Akita Nobuyuki 
Published: March 2007

AbstractA new gating NMR technique triggered by pulses for the cardiac pacing of isolated, perfused rat heart is described. This technique is suitable for obtaining spectra at the same positions over the cardiac cycle with the same RF pulse repetition time and with constant heart rate. Accordingly, each recovered magnetization level at these positions during the cycle can be kept constant. It also allows a qualitative analysis of the myocardial energy level during the cycle under the condition of the same or different cardiac workload (rate pressure product, HR X LVP). This method was used to observe cyclical changes in the concentration of adenosine triphosphate (ATP), phosphocreatine (PCr), Pi, and in pH during the cardiac cycle, and confirmed that the levels of ATP and PCr showed reversible decreases, and Pi showed an antiphasic increase at the peak systole. On the other hand, no significant changes in pH were noted during the cardiac cycle. This pacing‐gated technique is an improvement over other gated NMR techniques triggered by the blood pressure or by ECG traces.
Localized proton NMR spectroscopy of experimental gliomas in rat brain In Vivo
Authors: Gyngell M. L. , Hoehn‐Berlage M. , Kloiber O. , Michaelis T. , Ernestu R.‐I. , Hörstermann D. , Frahm J. 
Published: March 2007

AbstractExperimental brain tumors produced in rats (n = 10) by stereotactic implantation of cells from the F98 anaplastic glioma clone into the right caudate nucleus were studied in vivo using localized proton NMR and in vitro using high‐resolution proton NMR, bioluminescent imaging of lactate, ATP and glucose distributions, and fluorescent imaging of regional pH. In vivo spectra from normal brain contralateral to the tumor regions showed resonances assignable to N‐acetyl aspartate (NAA), creatines, choline‐containing compounds, myo‐inositol, glutamate and glucose in a pattern similar to those obtained from normal anaesthetized rats. In vivo tumor spectra were characterized by the almost complete absence of NAA, a substantial reduction of total creatine and glucose, and an increase of cholines. Based on the in vitro spectra the increase of the myo‐inositol signal observed in vivo was mainly attributed to glycine. Histological examination as well as bioluminescent and fluorescent imaging indicated two stages of tumor development, i.e., solid vital tumors and tumors with necrosis. However, there was no consistent relationship between proton NMR observations and tumor development.
Absolute quantification of 31P liver metabolites in rat using an external reference and a surface spoiling magnetic field gradient
Authors: De Bisschop Elke , Luypaert Robert , Annaert Guido , Coremans Jean , Osteaux Michel 
Published: March 2007

AbstractA simple method for measuring absolute concentrations of 31P metabolites in rat liver using an external reference is described. It neutralizes systematic errors due to conductive losses by calibration of the matching capacitor and selects liver signals via an electrically driven, surface spoiling magnetic field gradient. The technique avoids the chemical shift problems associated with linear field gradient localization methods at 4.7 T and allows combinaton with the double standard method for absolute metabolite concentration determination. Application of the method to the in vivo measurement of the absolute concentrations of ATP and Pi in eight rat livers yields results that are in good agreement with literature values. Absolute phosphomonoester concentrations were also obtained, but no literature data were available.
A new high sensitivity 19F probe for labeling cysteine groups of proteins
Authors: Kalbitzer Hans Robert , Rohr Gerhard , Nowak Ewa , Goody Roger S. , Kuhn Winfried , Zimmermann Erbert 
Published: March 2007

AbstractA novel iodoacetamide label 4‐perfluoro‐tert‐butyl‐phenyliodoacetamide (PFP) containing nine fluorine atoms in equivalent positions has been synthesized. It provides a homogeneous 19F NMR resonance line which can be detected with high sensitivity when coupled to proteins. As an example, the sulfhydryl groups of actin have been labeled with PFP; <100 nmol of this medium sized protein (corresponding to 2.5 mL of a 40μM solution) can be detected easily in a single scan at 470 MHz.
Comparison of pH measurements made using 31P NMR and a fibreoptic pH meter
Authors: Jayasundar Rama , Hall Laurance D. , Bleehen Norman M. 
Published: March 2007

AbstractThe objective of this study was to compare pH measurements made in biological samples using 31P NMR (pHNMR) with those made with a novel, dye‐based fibreoptic pH measurement system (pHF), which is compatible with use in electromagnetic fields without field perturbation. Using protein‐free model solutions, pHNMR was calibrated against pHF, giving a correlation coefficient of 0.969 and a mean difference (± SD) between pHNMR and pHF of 0.037±0.054 over the pH range 6.8–7.7. Further calibration of pHNMR with pHF was carried out for human red blood lysates and then pHNMR was compared with pHF for whole, packed red blood cells over the pH range 7.0–7.8. Values for pHNMR, the intracellular pH, were consistently lower than for pHF, the extracellular pH, by a mean (±SD) of 0.15±0.02 units. A close correlation of extracellular pHNMR with pHF was demonstrated for a blood sample exhibiting two Pi peaks, over the pH range 7.03–7.71. We conclude that concurrent use of NMR and the fibreoptic pH meter provides a reliable method of simultaneous measurement of intracellular and extracellular pH in biological systems.
Chemical exchange in tissue extracts revisited: Bicarbonate and deuterium isotope effects on 31P resonances of phosphoethanolamine and phosphocreatine
Authors: Bezabeh Tedros , Ackerman Joseph J. H. 
Published: March 2007

AbstractIt is not sufficiently appreciated that chemical exchange can markedly affect the appearance of 31P tissue extract NMR spectra. In addition to the commonly recognized 31P chemical shift effects of divalent metal cation (e.g. Mg2+) binding upon ATP resonances, multiple resonances for phosphoethanolamine (PE) and phosphocreatine (PCr) are observed under certain conditions of pH, temperature, and D2O and bicarbonate concentrations. In the presence of bicarbonate ion (commonly used to neutralize acidic extractions) carbamate formation causes a second 31P resonance for PE to appear. This effect has been described previously for 13C and 1H amino acid resonances in tissue extracts [Sherry et al. J. Magn. Reson. 89, 391––398 (1990)]. The observation of a splitting of the PCr 31P resonance in aqueous solutions containing D2O has been recently ascribed to proton scalar coupling but was described earlier in an underappreciated report [Kupriyanov et al. Biochem. Biophys. Res. Comm. 114, 1117–1125 (1983)] as due to a deuterium isotope effect. These effects, carbamate formation and deuterium isotope shift, are verified herein to cause marked shifts in PE and PCr 31P resonances. The dependence upon experimental parameters is explored.
Aqueous shift reagents for high‐resolution cation NMR. VI. Titration curves for in vivo23Na and 1H2O MRS obtained from rat blood
Authors: Albert Mitchell S. , Huang Wei , Lee Jing‐Huei , Balschi James A. , Springer Charles S. 
Published: March 2007

AbstractFrequency shift/concentration calibration curves applicable to the use of shift reagents (SRs) for in vivo 23Na MRS studies can be obtained from experiments with whole blood. Here, they are reported for titrations of rat blood with the SRs DyTTHA3− and TmDOTP5−. There are a number of considerations that must be made in order to derive accurate calibration curves from the experimental data. These include the effects of bulk magnetic susceptibility (BMS, since the SRs are paramagnetic), the effects of water flux (since addition of the SR stock solution to blood renders the plasma hyperosmotic), and the consequences of restricted distribution of the SR anion in the erythrocyte suspension. We give in some detail the BMS shift theory that obtains in this case and show also how it applies to excised perfused organ as well as in vivo studies. Also, we report significant effects of adjuvant Ca2+ additions in the TmDOTP5−titrations. These are very important to the successful use of this SR in vivo. Finally, our considerations of BMS lead naturally to an understanding of its manifestations in the shifts of the 1H2O resonance frequencies of cell suspensions and tissues induced by SRs. Since these are being increasingly reported, and often misinterpreted, we devote an experiment and some discussion to this subject. We show that this phenomenon cannot be used to quantitatively discriminate intra‐ and extracellular 1H2O signals.
In vivo19F nuclear magnetic resonance of a monofluorinated neuroleptic in the rat
Authors: Günther Ulrich , Albert Klaus 
Published: March 2007

AbstractIn vivo 19F NMR measurements of the fluorinated neuroleptic melperone [4′‐fluoro‐4‐(4‐methylpiperidino)‐butyrophenone hydrochloride] in the rat brain were performed using a geometrically optimized surface coil at 4.7 T. It was possible for the first time to detect a signal of a monofluorinated neuroleptic drug with a time resolution of 30 min after i.p. application. The kinetic time course of the investigated neuroleptic melperone was recorded over 6 h and showed that the half‐life in the rat brain is 4.3 h. The total amount of drug and its metabolites in the brain was estimated to be 50 μM. the chemical shift of the 19F NMR signal shows the same upfield shift relative to that in aqueous solution as has been reported for trifluorinated neuroleptic drugs.
Energy cost of twitch and tetanic contractions of rat muscle estimated in situ by gated 31P NMR
Authors: Foley Jeanne M. , Meyer Ronald A. 
Published: March 2007

AbstractThe phosphagen cost of maximal isometric twitch and tetanic contractions in rat gastrocnemius muscle was measured in situ by 31P NMR with acquisitions gated to precise time points after a brief (< 10 s) burst of contractions. Alteration of twitch stimulation frequency did not affect the energy cost per contraction. Pooled results of four twitch rates from 1 to 8 Hz produced an average cost of 0.257±0.012 μmol ATP/g/twitch. This value was compared with the initial twitch cost estimated from the time zero derivative of an exponential fit of averaged scan phosphocreatine (PCr) data from a previous study of 8 min of contraction in situ at 0.75 Hz. Agreement of the two estimates validates the use of the fitting/derivative method to assess energy cost and confirms the monoexponential character of the PCr time course. Evaluation of muscle pH changes demonstrated that all ATP use during the brief twitch contraction bouts could be accounted for by PCr hydrolysis. Results also showed a brief delay in onset of PCr recovery, consistent with the response time of oxidative systems. Tetanic contractions of 100 ms duration at 100 Hz required 2.17±0.07 μmol ATP/g muscle/contraction, in general agreement with estimates reported using a variety of other methods.
Quantitative 31P MRS of the normal adult human brain. Assessment of interindividual differences and ageing effects
Authors: Longo R. , Ricci C. , Palma L. Dalla , Vidimari R. , Giorgini A. , den Hollander J. A. , Segebarth C. M. 
Published: March 2007

AbstractThe characteristics of the 31P MR spectra from a large central volume in the brain of 47 healthy adults (aged 25–85 years) were assessed. Spectral parameters were estimated by means of a time‐domain fitting technique. Statistical uncertainties of the estimates were determined by means of the Cramer‐Rao theory and minimized by introducing a priori knowledge into the fitting procedure. Age‐dependency of the spectral parameters was assessed by means of linear regression. Significant differences between individuals were established for some parameters. A significant age‐dependency (p⩽0.001) of ca 20% over the age range considered was found for the intensity of the phosphocreatine resonance line.
Graphic‐aided study of metabolic modifications of plasma in cancer using proton magnetic resonance spectroscopy
Authors: Vion‐Dury J. , Favre R. , Sciaky M. , Kriat M. , Confort‐Gouny S. , Harlé J. R. , Grazziani N. , Viout P. , Grisoli F. , Cozzone P. J. 
Published: March 2007

AbstractProton high‐resolution MRS of human plasma allows the rapid detection, on the same spectrum, of many compounds originating from different metabolic pathways. In this paper, we illustrate the modifications of the plasma metabolic profiles recorded by proton NMR spectroscopy in different classes of cancers. These modifications can be easily monitored with graphic aids such as ‘star plots’ which define for each type of cancer a particular pattern describing the most altered metabolic pathways. By using ‘star plots’ three types of metabolic patterns have been distinguished: (i) the ‘inflammatory’ pattern characterized by an increase of glycosylated moieties of glycoproteins; (ii) a ‘lipid modified’ pattern, characterized by various modifications occurring mainly in the lipid moieties detected by MRS; and (iii) a pattern which is often observed in sarcomas and mainly characterized by an alteration in the N‐acetyl glucosamine/N‐acetyl neuraminic acid ratio. This study demonstrates the ability of proton MRS of plasma to rapidly detect the occurrence of metabolic modifications brought about by cancer evolution or therapy.
Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle
Authors: Kemp G. J. , Taylor D. J. , Radda G. K. 
Published: March 2007

AbstractInformation about the control of mitochondrial function in skeletal muscle in vivo can be obtained from the relationship between the rate of mitochondrial oxidation and the intracellular concentrations of phosphorus metabolites, although the analysis is complicated by the constraints imposed by the creatine kinase equilibrium. The rate of phosphocreatine (PCr) recovery after exercise measured by 31P MRS is an estimate of net oxidative ATP synthesis. Analysing such data from normal and abnormal human muscle, we show that the approximately exponential recovery kinetics of ADP and PCr imply that the rate of PCr resynthesis has a hyperbolic dependence on [ADP] but remains approximately linear with respect to the concentration of orthophosphate (Pi) and therefore also [PCr] and [creatine]. Both kinds of relationship are consistent with experimental data from exercising animal muscle and also with data from isolated mitochondria which suggest kinetic control of mitochondrial ATP synthesis of [ADP]. These relationships are altered in proven mitochondrial disease. This analysis offers a way to quantify mitochondrial function and its abnormalities in vivo.
The production, buffering and efflux of protons in human skeletal muscle during exercise and recovery
Authors: Kemp G. J. , Taylor D. J. , Styles P. , Radda G. K. 
Published: March 2007

AbstractWe show how quantitative information about proton handling in human skeletal muscle in exercise and recovery can be obtained by 31P MRS and illustrate this with data from metabolic disorders. Proton production, proton efflux and passive buffering can be distinguished by comparing changes in [phosphocreatine] and pH at the end of exercise and by calculating ATP turnover during ischaemic exercise and in the ‘natural experiment’ of myophosphorylase deficiency (McArdle's disease). We calculate the effective buffer capacity to be 20–30 mmol/L/pH unit (slykes), somewhat lower than published measurements made in vitro but similar to other values obtained in vivo. This analysis is applied to data from normal muscle and a variety of disease states to estimate proton efflux during recovery and ATP production during exercise: (i) proton efflux during recovery is pH‐dependent, reaching a 10 mmol/L/min at pH 6.2, and is increased in some cases of mitochondrial myopathy and in hypertension; (ii) glycogenolytic ATP production during exercise can reach 25 mmol/L/min in normal muscle and correlates approximately with [Pi] at the start of aerobic exercise and throughout ischaemic exercise; (iii) oxidative ATP production can reach 20–25 mmol/L/min and (as during recovery) correlates approximately with [Pi].
Absolute quantification and NMR visibility of glycogen in the isolated, perfused rat heart using 13C NMR spectroscopy
Authors: Garlick Pamela B. , Pritchard Ronald D. 
Published: March 2007

AbstractNMR spectroscopy, possibly, does not detect 100% of large molecules such as glycogen (mol. wt = 107–109). Using both NMR and chemical quantification methods, we have, therefore, determined the NMR visibility of cardiac glycogen (defined as the ratio of the NMR value to the chemical value, expressed as a percentage) in the isolated, perfused heart. Rats (n = 7) were pretreated for 60 min with 0.2mg/kg isoproterenol (s.c.) to deplete their endogenous myocardial glycogen stores (mainly 12C). The hearts were then aerobically perfused (65 cm H2O, at 37 °C) in a double‐walled chamber (the annulus contained a standard), for 70 min with Krebs buffer plus 3.5 mM [13C]1‐glucose and 5 mM sodium acetate (natural abundance). From 70 to 175 min the sole substrate was natural abundance acetate (5 mM). 13C NMR spectra for glycogen quantification were acquired in two different ways; by applying 896, 90° pulses at 0.33 s intervals with 1H decoupling (‘fast’, practical spectra) and by applying 896, 90° pulses at 5 s intervals (‘slow’, impractical spectra). Hearts were then removed from the magnet, freeze‐clamped ( −196 °C) and analysed chemically. Cardiac glycogen, quantified from the ‘fast’ spectra (using conversion factors) and the ‘slow’ spectra was 16.8 ± 1.1 and 16.1 ± 1.8 (mean ± SEM) μmol glucosyl units/heart, respectively. After correction of the chemical value for the residual [12C]glycogen (determined from 1H NMR spectra of the extracted glycogen after hydrolysis), the NMR‐visibilities were calculated to be 101 ± 6 and 109 ± 7%, for the ‘fast’ and ‘slow’ spectra, respectively. We conclude that, despite its size, cardiac glycogen is 100% visible in NMR spectra of isolated rat hearts.
Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference
Authors: Barker Peter B. , Soher Brian J. , Blackband Stephen J. , Chatham John C. , Mathews Vincent P. , Bryan R. Nick 
Published: March 2007

AbstractThe use of cerebral water as an internal intensity standard for the quantitation of spatially localized proton spectra of the human brain is investigated. The method is validated on standard samples of N‐acetyl aspartate (NAA) and lactate, and possible sources of error are discussed. Using the STEAM pulse sequence, concentrations of choline, creatine and NAA in frontal lobe white matter are found to be 1.9±0.5, 10.6±1.3 and 16.6±2.3 μmol/g wet wt, respectively, in 10 normal volunteers. In the thalamus, the concentrations are 2.0±0.4, 11.6±2.0 and 17.2±1.3 μmol/g wet wt, respectively. Choline and creatine concentrations are in good agreement with conventional biochemical values: NAA concentrations are found to be three‐fold higher, suggesting overlap of the NAA signal with other compounds. Quantitation relative to tissue water is a convenient and rapid means of quantitating proton spectra of the human brain.
Design and application of NMR‐compatible bioreactor circuits for extended perfusion of high‐density mammalian cell cultures
Authors: Gillies R. J. , Galons J.‐P. , McGovern K. A. , Scherer P. G. , Lien Y.‐H. , Job C. , Ratcliff R. , Chapa F. , Cerdan S. , Dale B. E. 
Published: March 2007

AbstractMR spectroscopy of cultured cells allows non‐invasive analyses of the metabolism of cells with specific phenotypes under defined conditions. This technique can be used to investigate the intracellular metabolism of cells or extended to critically evaluate phenomena observed by in vivo MRS. In this paper, a cell maintenance system is described which allows MR analyses with unparalleled spectral resolution, S/N and stability. This system consists of a 25 mm diameter hollow fiber bioreactor and a supporting circuit. The hollow fiber reactor was chosen because it yields a large filling factor which can be perfused through defined volumes. The fibers were 300 μm diameter microporous (0.2 μm) cellulose acetate/cellulose nitrate membranes with high porosity, which allow bulk convective flow throughout the extracapillary space. This flow (Starling flow) is necessary to disrupt steady‐state gradients in substrates and waste products. In many respects, the design of the supporting circuit is more important than the bioreactor itself, since it provides the reactor with the proper chemical and physical environment. Hence, this circuit can be applied to a variety of bioreactor configurations. The circuit consists of a hollow fiber oxygenator and a bleed‐and‐feed system housed in a temperature‐controlled cabinet. Culture of mammalian cells in this reactor yields 31P spectra which have excellent spectral and temporal resolution. At confluence, endogenous 31P line widths were typically <10 Hz (at 162 MHz) and well resolved spectra were obtained in <30 s.
Identification of scyllo‐inositol in proton NMR spectra of human brain in vivo
Authors: Michaelis Thomas , Helms Gunther , Merboldt Klaus‐Dietmar , Hänicke Wolfgang , Bruhn Harald , Frahm Jens 
Published: March 2007

AbstractScyllo‐inositol has been identified in proton NMR spectra of mammalian brain in vitro and in vivo. In contrast to myo‐inositol this isomer comprises six equivalent CH protons that yield a singlet resonance at a chemical shift of 3.35 ppm. 1‐D and 2‐D J‐resolved proton NMR studies (7.0 T) of perchloric acid extracts of brain tissues revealed different amounts of scyllo‐inositol in man, sheep, cow and rat. Absolute quantification of localized short‐echo time proton NMR spectra (2.0 T) of human brain in vivo resulted in scyllo‐inositol concentrations of 0.35±0.06 mM for white matter (n = 25), 0.43±0.11 mM for grey matter (n = 23) and 0.57±0.14 mM for cerebellum (n = 10). Evidence for a tight metabolic link to myo‐inositol was supported by a simultaneous variation of myo‐ and scyllo‐inositol in patients with various brain diseases.