bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo magnetic resonance imaging and spectroscopy of humans with a 4 t whole‐body magnet
Authors: Barfuss H. , Fischer H. , Hentschel D. , Ladebeck R. , Oppelt A. , Wittig R. , Duerr W. , Oppelt R.
Published: March 2007

A research‐type 4 T whole‐body magnet, built by Siemens AG, Erlangen, FRG, was used to investigate magnetic resonance at high field strengths. Designs for head and body coils operating at 170 MHz are described. Proton images of the human head and body are degraded by dielectric resonances and penetration effects. The nature of the dielectric resonances was demonstrated in phantoms containing distilled and saline doped water. Radiation damping at 170 MHz generates secondary echoes after a spin echo sequence. This effect was observed in phantoms and with reduced amplitude in the human head. Hydrogen spectra of the human head were selected utilizing stimulated and spin echoes. The latter technique allows the volume size to be reduced to 1 cm3. Examples of brain tumors that have been routinely investigated with volumes of 8 cm3 are given. Natural abundance carbon and phosphorus spectra of muscle and liver demonstrate the expected increase in spectral resolution and signal to noise ratio. Carbon spectra from the liver show the glycogen signal. Fluorine spectroscopy was used to study the time course of the absorption and emptying of a fluorinated antibiotic from the human stomach.
31P and 23Na NMR spectroscopy of normal and ischemic rat skeletal muscle. Use of a shift reagent in vivo
Authors: Balschi James A. , Bittl John A. , Springer Charles S. , Ingwall Joanne S.
Published: March 2007

23Na NMR spectroscopy was used 1, to define the distribution of the shift reagent for cations, triethylenetetraminehexaacetatedysprosium(III), DyTTHA3−, in the living rat; 2, to define the characteristics of the Na resonances reporting intra‐ and extracellular Na+ in skeletal muscle in vivo; and 3, to calculate the Na+ concentrations in the intra‐ and extracellular spaces of the gastrocnemius muscle during well‐perfused and ischemic conditions. The concentration of DyTTHA3− infused intravenously into the jugular vein of the living rat reached a maximum value of 8–9 mM in the extracellular space of the muscle after ca 40 min of infusion. This allowed excellent discrimination of extra‐ and intracellular Na signals (Nao and Nai, respectively) and did not spoil the resolution of concurrent 31P NMR spectra. Infusion of shift reagent changed neither hemodynamic performance of the rat nor the high‐energy phosphate content of skeletal muscle. Shift reagent enters ca 15% (v/w) of the rat body weight; this corresponds to almost all of the “fast” or rapidly permeable extracellular space. It is excreted from the body with a pseudo‐first order rate constant of 0.0158 min−1. In resting muscle, we estimate that [Na+]i is 3–5 mM and, in muscle perfused with the sodium salt of the shift reagent, that [Na+]o in the fast exchangeable extracellular space is 166 mM. During 11 h of ischemia at 37°C, the area of the Nai+ signal area monotonically increased sixfold. Based on estimates for maximum changes in fluid shifts reported by the decrease in the area of the Nao signal area, we calculate that the lower limit for [Na+]i after 11 h of ischemia is 27 mM. The NMR‐visibility factors for the extracellular and intracellular Na+ signals are essentially the same. This study demonstrates that the shift reagent DyTTHA3− is acutely non‐toxic and that the 23Na NMR spectra obtained can be used to quantitate [Na+]o and [Na+]i in tissues in vivo. Using this technique, we found that the transmembrane sodium gradient fell from ca 35 in well‐perfused skeletal muscle to <6 during prolonged ischemia.
Hypophosphite transport in human erythrocytes studied by overdetermined one‐dimensional NMR exchange analysis
Authors: Price William S. , Kuchel Philip W.
Published: March 2007

The membrane transport kinetics of the disubstituted phosphorus oxyacid, hypophosphite, were studied in human red cells under equilibrium exchange conditions. Hypophosphite is an analogue of both the bicarbonate and phosphate ions and is known to be rapidly transported across the human red cell membrane via the anion transport protein, Band 3. The hypophosphite ion is a particularly useful probe of Band 3‐mediated membrane transport as the intracellular and extracellular species occur as distinct resonances in the 31P NMR spectrum; as a result the membrane potential may also be readily inferred. We applied ‘overdetermined’ one‐dimensional exchange analysis to estimate the rates of exchange for influx and efflux. The apparent equilibrium exchange (ee) values K for the hypophosphite efflux and influx were different and while the efflux parameters were not able to be unambiguously defined, the measured apparent influx kinetic transport parameters were V = 1600 ± 190 amol cell−1 s−1, and K = 75±16 mM.
31P Magnetic resonance spectroscopy of the human paediatric liver
Authors: Iles R. A. , Cox I. J. , Bell J. D. , Dubowitz L. M. S. , Cowan F. , Bryant D. J.
Published: March 2007

Localized 31P NMR spectroscopy was used to study the developing human liver in three neonates and one infant, all with neonatal intracranial problems, but normal liver function. A prominent resonance was present in the phosphomonoester (PME) region of the spectrum of the neonates; the PME/ATP ratio was 1.0 ± 0.4 (repetition time 1 s), compared to the mean adult liver value of 0.2 ± 0.1. The saturation factor of PME in the neonates was large, indicating that the increase in PME/ATP reflected an increase in relative PME concentration. The chemical shift of the PME peak in the neonatal liver (6.8 ± 0.1) was similar to that found in neonatal brain, suggesting that phosphorylethanolamine may be a major constituent. The phosphodiester (PDE)/ATP ratio in these patients (0.4 ± 0.1) was decreased compared with the mean adult value (1.3 ± 0.2), and the saturation factor of PDE was small. The results from the infant were different from both the neonates and adults; PME/ATP was decreased compared to the neonates, but increased compared to adults. The saturation factor of PDE was increased compared to neonates. The biochemical implications of the observed changes in PME and PDE in paediatric liver are discussed in relation to membrane turnover.
Lipid characterization in an animal model of atherosclerosis using NMR spectroscopy and imaging
Authors: Booth R. F. G. , Honey A. C. , Martin J. F. , Lindon J. C. , Farrant R. D. , Carpenter T. A. , Hall L. D.
Published: March 2007

High resolution 1H and 13C NMR spectroscopic measurements including 1H/13C 2D correlation and magnetic resonance imaging (MRI) studies, have been carried out on intact rabbit aortic tissues ex vivo using animals fed both normal and high cholesterol diets. The results show that 1H and 13C NMR spectroscopy can distinguish mobile lipids and can differentiate between normal triglyceride content and cholesterol‐enriched lipids, in intact tissue. There were considerable differences in the level of deposition of cholesteryl esters in animals all fed on the same diet. Confirmation is presented of temperature‐dependent differences in mobility and organization between the triglycerides found in control tissue and the cholesteryl esters found in aortas from high lipid diet animals. Water‐suppressed MRI showed evidence of lipid accumulation in the aortas of high cholesterol diet rabbits. It is concluded that the hypercholesterolaemic rabbit model of atherosclerosis, coupled with such NMR methods, may offer a noninvasive method of monitoring disease development, allowing the evaluation of the effect of therapeutic agents on the progress of atherosclerosis.
Spin‐exchange NMR spectroscopy in studies of the kinetics of enzymes and membrane transport
Authors: Kuchel Philip W.
Published: March 2007

Spin‐exchange NMR techniques enable the measurement of the rates of exchange of solutes between chemically or physically distinct sites in reactions taking place at chemical equilibrium. The time scale of the events that are able to be investigated lies in the neighbourhood of 1 s. The earliest studies in this area of NMR spectroscopy involved chemical reactions in vitro but the procedures have been adapted to the study of enzyme‐catalysed reactions both in vitro and in vivo, and more recently to transmembrane exchange processes. The emphasis in this review is on the various types of spin‐exchange experiments, the analysis of data derived from them, estimates of uncertainty in measured rate constants, and their shortcomings. Those methods given special attention are saturation transfer, two‐dimensional exchange spectroscopy (2D EXSY), the ‘accordion’ experiment and ‘overdetermined’ one‐dimensional exchange spectroscopy.
In vivo19F nuclear magnetic resonance spectroscopy of trifluorinated neuroleptics in the rat
Authors: Albert K. , Rembold H. , Kruppa G. , Bayer E. , Bartels M. , Schmalzing G.
Published: March 2007

In vivo 19F NMR measurements of trifluorinated neuroleptics in the rat brain were made using a 13 × 18 mm surface coil at 4.7 T. The signal of fluphenazine was obtained within 8–15 min from brains of living rats treated chronically with drug doses of 5–30 mg/kg. Following the intravenous injection of a single dose of trifluoperazine (30 mg/kg), brain levels could be monitored with a time resolution of 30 min. The data demonstrate the possibility of obtaining in vivo pharmacokinetics of fluorinated agents in the rat brain. 19F NMR is expected to become an important tool in neurochemical research.
Spatially‐localized NMR spectroscopy employing an inhomogeneous surface‐spoiling magnetic field gradient 1. Phase coherence spoiling theory and gradient coil design
Authors: Chen Wei , Ackerman Joseph J. H.
Published: March 2007

The use of a current‐generated, inhomogeneous, surface‐spoiling magnetic field gradient for enhancing magnetic resonance spatial localization, by rapidly inducing spin phase incoherence in surface lying regions of a sample is examined theoretically. A geometrically simple surface‐spoiling magnetic field gradient coil design is presented and its gradient field characterized via computer simulations. Mathematical expressions describing the time dependence of net sample spin phase coherence under influence of the spoiling gradient are developed for application with homogeneous (B1) volume coils. The dependence of spoiling efficiency on the magnetogyric ratio of the nuclide under investigation and on the current driving the gradient field is described. Spoiling periods of ca 1–2 ms with driving currents of ca 0.5–1.0 A are predicted to be adequate for surface‐spoiling experiments with rat, e.g., for noninvasive monitoring of liver. A companion article W. Chen and J. J. H. Ackerman, NMR Biomed., 3, 158–165 (1990)) describes implementation of the surface‐spoiling technique with multicompartment models (phantoms) and with rat in vivo.
Spatially‐localized NMR spectroscopy employing an inhomogeneous surface‐spoiling magnetic field gradient 2. Surface coil experiments with multicompartment phantom and rat in vivo
Authors: Chen Wei , Ackerman Joseph J. H.
Published: March 2007

The use of inhomogeneous surface‐spoiling magnetic field gradients for elimination of signal from surface lying regions of a sample was theoretically examined in the companion article (W. Chen and J. J. H. Ackerman, NMR Biomed. 3, 147–157 (1990)). Using the spoiling gradient coil design described therein, this article presents experimental verification of the feasibility of such an approach to enhanced spatial localization. Single coil mode 31P NMR surface coil interrogation of both a two compartment phantom and rat in vivo are shown to provide excellent suppression of surface lying regions with minimal degradation of signal from the deep lying region of interest. Both pulse‐and‐collect and spin echo sequences were highly efficient in concert with spoiling gradient periods of 0.5–2 ms and driving currents of 0.5–2 A. The use of a current‐generated surface spoiling gradient offers a robust means to remove surface tissue signal contributions and can be implemented with a wide range of localizing pulse sequences and imaging protocols.
Proton and phosphorus magnetic resonance spectroscopy of human astrocytomas in vivo. Preliminary observations on tumor grading
Authors: Arnold D. L. , Shoubridge E. A. , Villemure J.‐G. , Feindel W.
Published: March 2007

We have obtained localized, water‐suppressed proton magnetic resonance spectra from eleven astrocytomas in vivo. Localized phosphorus spectra were also obtained from three of these tumors. All tumors were examined prior to surgery, radiotherapy or chemotherapy. Examinations were performed with a commercially available 1.5 Tesla combined imaging and spectroscopy system using a stimulated echo pulse sequence for protons and an ISIS pulse sequence for phosphorus. A relatively high lactate resonance intensity correlated with a more malignant histological tumor grade and more aggressive behaviour. The resonance intensity of N‐acetylaspartate/creatine was decreased and choline/creatine was increased, but these did not reliably discriminate between tumor grades. Other unidentified resonances not present in spectra of normal brain were sometimes seen. Proton magnetic resonance spectroscopy provides a new method for determining the metabolic behaviour of astrocytomas that may be useful in the clinical assessment of patients with these tumors.
31P chemical shift imaging of the regionally ischemic perfused heart
Authors: Chatham John C. , Blackband Stephen J.
Published: March 2007

The application of one‐dimensional 31P chemical shift imaging to the study of the isolated perfused rat heart is described. Its applicability for the examination of regional ischemia in the isolated perfused rat heart is demonstrated. The data sets show clearly the localization to the ischemic and nonischemic regions of the heart. Such studies will permit the correlation of cardiac metabolism and function in a controlled manner that is not possible in the application of these techniques to the intact animal. In particular, the time resolution of the experiments will enable spatially localized metabolic studies to be performed during the onset of ischemia and during reperfusion.
A system for viably maintaining a stirred suspension of multicellular spheroids during NMR spectroscopy
Authors: Freyer James P. , Fink Nancy H. , Schor Patricia L. , Coulter James R. , Neeman Michal , Sillerud Laurel O.
Published: March 2007

We have developed a system for the perfusion of a stirred suspension of multicellular spheroids during nuclear magnetic resonance spectroscopy. Measurement of the medium temperature, pH, oxygen tension, and glucose and lactate concentrations demonstrated that the macroenvironmental conditions around the spheroids during perfusion matched those in standard spinner culture flasks. Spheroids cultured in the NMR perfusion chamber for up to 48 h were virtually identical to spheroids cultured under standard conditions in terms of volume and cell number growth, the extent of central necrosis, cellular clonogenicity, and proliferative status. To avoid problems in interpreting the NMR spectra, we have used a medium containing 10% of the normal inorganic phosphate concentration; comparative growth and NMR studies showed that this medium had no effect on the results reported. 31P NMR spectroscopic analysis demonstrated that the mean pH, nucleotide triphosphate (NTP) to inorganic phosphate (Pi) ratio, the total amount of NTP, and the total energy charge were essentially constant over 8 h of analysis. Stopping the stirring of the spheroid culture during analysis resulted in depletion of the nucleotide phosphate pool in 30 min, with an accumulation of Pi and a shift to a more acid intracellular pH. This effect could be reversed if stirring was resumed within 30 min. Stopping the perfusion while maintaining stirring resulted in a deterioration of the 31P spectra until no high energy phosphates remained at 120 min and the pH fell to ≈6. This effect was also partially reversible after 30 min of reperfusion, with recovery to a normal 31P spectrum requiring 10 h. The combination of the spheroid model system with 31P NMR spectroscopic analysis will provide a powerful tool for investigating basic questions about the regulation of tumor cell energy metabolism and viability.
Stoichiometry of phosphocreatine and inorganic phosphate changes in rat skeletal muscle
Authors: Meyer Ronald A. , Adams Gregory R.
Published: March 2007

The apparent T1's of phosphate metabolites were measured during and after series of twitch contractions in gastrocnemius muscles of pentobarbital‐anesthetized rats by steady‐state progressive saturation using spatially‐selective composite pulses. There was no significant change in apparent T1's of inorganic phosphate (Pi), phosphocreatine (PCr), or the three phosphates of ATP. There was a 5‐10% decrease in the sum of Pi and PCr integrals, and in the sum of the γ‐ and β‐ phosphates of ATP during stimulation, but no significant change in the ratio (Pi + PCr)/(γ‐ATP + β‐ATP). The results indicate that there is no selective decrease in NMR observable Pi during or after a series of muscle contractions.
Differences in metabolite content between intact pancreases and their perchloric acid extracts. A 2D 1H/31P correlation NMR study
Authors: Askenasy Nadir , Kushnir Tammar , Navon Gil , Kaplan Ofer
Published: March 2007

Perchloric and hydrochloric acid extracts of intact pancreases from healthy rats and from rats with experimental acute pancreatitis were analysed using 2D 1H/31P correlation NMR spectroscopy. Major differences were found in the 2D maps between the extracts and the intact tissues. In the case of the intact diseased pancreas the prominent 31P signal at the phosphodiester region has been assigned in our previous work as lecithin/taurocholate complex. However, the signal found in the same chemical shift region in extracts of diseased pancreases as well as healthy ones, is identified here as the phosphodiester residue of oligoribonucleotides. In these extracts additional 31P signals were found and assigned as phosphomonoester and phosphodiester hydrolysis products of RNA. The amounts of these compounds, as a function of the acid concentrations were determined, and conditions for their minimization were defined.
Metabolic heterogeneity in RIF‐1 tumours detected in vivo by 31P NMR spectroscopy
Authors: Bhujwalla Z. M. , Blackband S. J. , Wehrle J. P. , Grossman S. , Eller S. , Glickson J. D.
Published: March 2007

The spatial distribution of phosphate metabolites and pH within subcutaneously implanted RIF‐1 tumours was determined by 1‐dimensional phosphorus chemical shift imaging. 31P spectra from two to three 4 mm thick cross‐sectional slices were obtained for each tumour. Quantitative morphometry was used to estimate the amount of necrosis within those slices. A spatially heterogeneous distribution of phosphate metabolites and pH was detected in most of the tumours. Levels of necrosis ranged from 0–24% for the tumours in this study. There was no significant correlation between the extent of necrosis over this range and levels of metabolites or pH, suggesting that factors besides necrosis can contribute to spectral heterogeneity.
Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion
Authors: Nioka Shoko , Smith D. , Chance B. , Lockard S.
Published: March 2007

Two metabolically distinct cell populations were detected when two peaks of inorganic phosphate (Pi), corresponding to two pHi values, were recorded by Phosphorus Magnetic Resonance Spectroscopy (31P MRS). One cell population, having intracellular pH (pHi) values less than 6.3, was thought to contain neither PCr (phosphocreatine) nor ATP and was thus considered metabolically unstable or inactive. The second cell population, having normal or near normal pHi, was considered metabolically active with adequate values of ATP and PCr. We can therefore further analyze the bioenergetics in this cell population.

The results were based upon studies of 14 ischemic dogs that were anesthetized with 2% isoflurane and ventilated. The amount of Pi associated with the acidic cell population (low pHi) was used to calculate the fraction of metaboliacally inactive brain tissues. This value correlated well with the ATP depletion of the total cell population. This suggests that in the acidic cell population, PCr and ATP supplies were depleted by dephosphorylation during ischemia, leading to an accumulation of acidic Pi. In addition, ATP synthesis in this population may be inhibited by the low intracellular pH. On the other hand, the bioenergetic state of the metabolically stable cell population having a nearly neutral pHi changed markedly during ischemia. The PCr/Pi dropped to 0.8 and the phosphorylation potential (PP) dropped to 10 mM−1 from 40 mM−1. With reperfusion, two distinct patterns of responses were observed. One group showed the restoration of ATP (recovery group) whereas the second group did not (non‐recovery group). After 3 h of reperfusion, the ATP restored group showed complete recovery of PCr. The non‐recovery group showed no restoration of PCr or phosphorylation potential and no reduction in Pi.
1H NMR Spin‐echo Spectroscopy of Human Erythrocytes. Transformation of Exogenous Compounds
Authors: Skibsted Ulrik , Hansen Poul Erik
Published: March 2007

1H NMR spin‐echo spectroscopy has been used to study the metabolism of exogeneous compounds in human erythrocytes. The non‐invasive nature of the technique and the continuous monitoring makes it ideal to investigate both the conversion of substrates and the occurrence and the nature of the products. Hydrolysis rates may be determined and the hydrolysis of alkyl, vinyl, and aryl acetates are shown to be due to A‐esterase activity. The conversion products are normally observed, but in the case of dimethyl phthalate and methyl acetate only part of the methanol is found. An interesting case is the hydrolysis of vinyl acetate and the consecutive conversion of the vinyl alcohol to acetaldehyde (hydrate). Coupling of glutathione to a variety of vinyl derivatives is also observed. Oxidation of acetaldehyde can also be followed. Styrene and 5‐chloro‐2‐methylaniline are slowly converted in what is believed to be oxidation reactions. Changes in 1H chemical shifts are observed for a number of compounds upon uptake into human erythrocytes, a shift that is suggested to be due to binding to haemoglobin.
A method for rapid evaluation of saturation factors in in vivo surface coil NMR spectroscopy using B1‐insensitive pulse cycles
Authors: Gruetter Rolf , Boesch Chris , Martin Ernst , Wüthrich Kurt
Published: March 2007

For a rapid determination of saturation factors in surface coil NMR spectroscopy, the recently published (90°–τ–180°–τ–90°–τ–) SUFIR sequence was modified with adiabatic pulse cycles. Signals were acquired after each of the two 90° pulses and they were stored in different memory blocks. The deleterious offset‐dependent saturation effects inherent in adiabatic 90° excitation pulses were minimized by suitable combinations of adiabatic pulses that sweep from either side of the spectrum onto resonance, and by setting the carrier frequency in the middle of the spectrum. The practical use of the proposed method is illustrated with the determination of 31P NMR saturation factors in human calf muscle.
Evaluation of 31P NMR spectroscopy as an indicator of chemically induced hepatic toxicity in the rat: Comparison with serum enzyme levels and pathology
Authors: Sandhu G. S. , Gonnella N. C. , Kapeghian J. C. , Plocinski A. F. , Plutchok J. , Schlosser M. J.
Published: March 2007

The progression of carbon tetrachloride‐induced liver damage, determined by 31P NMR spectroscopy, was compared with selected serum enzyme and histological changes in rats. ATP levels declined as early as 8 h post‐CCI4 administration, with partial recovery observed at 168 h. The results show that ATP reduction correlates with necrosis. In addition, early decline in ATP occurring prior to significant hepatocellular necrosis indicates abnormal energy metabolism.
Chronic cardiotoxicity of adriamycin studied in a rat model by 31P NMR
Authors: Dekker T. , van Echteld C. J. A. , Kirkels J. H. , Ruigrok T. J. C. , van Hoesel Q. G. C. M. , de Jong W. H. , Schornagel J. H.
Published: March 2007

Adriamycin induced cardiotoxicity is, among other factors, characterized by an impairment of mitochondrial function and altered energy metabolism. The possible merits of 31P NMR in timely detection of this cardiotoxicity were studied in perfused hearts of chronically treated rats after cumulative doses of 6,8,10,12 and 13 mg adriamycin/kg body wt and compared to histological evaluation. After high cumulative doses the Phosphocreatine (PCr)/ATP ratio was significantly decreased in the hearts of treated animals, compared to the control animals (1.65±0.13 vs. 2.47±0.36 (p < 0.001) at 12 mg/kg and 1.92 ± 0.22 vs. 2.37±0.15 (p < 0.01) at 13 mg/kg adriamycin, respectively). This decrease coincides with a sudden increase in the histological score from 2.0 at 10 mg/kg to 8.0 at 12 mg/kg adriamycin on a scale of 10.0. The Pi/PCr ratio, coronary flow and rate pressure product (RPP) of the isolated hearts of treated animals were not significantly different from controls. When heart rates were increased, parallel changes in PCr/ATP ratio, Pi/PCr ratio, RPP and coronary flow were observed in both control and treated groups, except for the 12 mg/kg adriamycin group in which pacing failed to increase RPP. In addition, in this group the Pi/PCr ratio at higher heart rates was significantly increased (p < 0.001) compared to controls. At 13 mg/kg similar effects were observed but less pronounced. The decreased PCr/ATP ratio may indicate an increased ADP concentration and altered regulation of energy metabolism. Differences between control and treated groups in RPP and Pi/PCr ratio during pacing may also be related to cardiotoxicity. The results of this study show that changes in energy metabolism in the heart during chronic adriamycin treatment may well be observed by 31P NMR. Furthermore, they indicate that clinical 31P NMR may be a suitable tool for monitoring the development of adriamycin induced cardiotoxicity, thereby avoiding the disadvantages of invasive procedures.
Effect of anaerobic metabolic changes on the creatine kinase reaction in frog muscle studied by 31P saturation transfer NMR
Authors: Yoshizaki Kazuo , Nishikawa Hiroyasu , Naruse Shoji
Published: March 2007

The effect of anaerobic metabolic changes on the flux of the creatine kinase reaction in bullfrog skeletal muscle was evaluated by 31P saturation transfer NMR. During an anaerobic time course the reduction ratio (M+/M0) of the phosphocreatine signal and the spin‐lattice relaxation time measured in the presence of saturating irradiation at the ATP γ‐phosphate resonance were decreased; however, the intrinsic spin‐lattice relaxation time of phosphocreatine was constant (4 s). The pseudo‐first‐order rate constant for the forward reaction of creatine kinase (i.e., phosphocreatine to ATP) was increased during the time course, accompanied by a decrease in phosphocreatine concentration and an intracellular acidification. However, the flux was constant (4 mmol . kg−1 wet wt . s−1) over the anaerobic time course. The fluxes analysed in several locations along the fibers, which were simultaneously measured by means of the one‐dimensional chemical shift imaging technique, were almost the same along the entire length of the fibers. These results indicate that the creatine kinase reaction is at equilibrium along the entire length of the frog muscle fibers.
The use of In vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex
Authors: de Graaf A. A. , Deutz N. E. P. , Bosman D. K. , Chamuleau R. A. F. M. , de Haan J. G. , Bovee W. M. M. J.
Published: March 2007

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho) choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N‐acetylaspartate in all the models. These changes agree well with the changes in the post‐mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.
31P and 3‐fluoro‐3‐deoxy‐D‐glucose 19F In vivo NMR spectroscopy of aged rat brain
Authors: Kwee Ingrid L. , Nakada Tsutomu , Suzuki Nobuyuki
Published: March 2007

31P and 3‐fluoro‐3‐deoxy‐D‐glucose (3‐FDG) 19F nuclear magnetic resonance (NMR) spectroscopic investigations were performed on aged rat brain in vivo. Phosphodiester (PDE) was found to be significantly higher (p < 0.05) in aged brain (18 months, n = 10) than adult controls (6 months, n = 10) suggesting accelerated phospholipid catabolism in aged brain. Inorganic phosphate (P,) levels were significantly lower (p < 0.05) in aged brain (n = 5) than in normal adult controls (5 = 5). The sorbitol index, a measure of aldose reductase activities in vivo, determined by the 3‐FDG 19F NMR method, revealed that aldose reductase activities were significantly higher (p < 0.05) in aged brain.
Impairment of muscular metabolism in chronic respiratory failure. A human 31P MRS study
Authors: Payen J.‐F. , Wuyam B. , Reutenauer H. , Laurent D. , Levy P. , Le Bas J.‐F. , Benabid A. L.
Published: March 2007

The calf muscle metabolism of 7 patients with stable chronic respiratory failure (PaO2 below 65 Torr) was studied using 31P NMR spectroscopy. NMR spectra were acquired at rest, during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight normal aged‐matched subjects served as a control group. In resting muscle, no significant differences were observed between both groups as regards intracellular pH, inorganic phosphate/phosphocreatine (Pi/PCr) and β‐ATP/PCr + Pi + phosphomonoester (PME) ratios. Although effective power outputs were similar for both groups at each work level, patients exhibited a higher Pi/PCr ratio than healthy controls (3.19 ± 1.01 vs 0.49 ± 0.05 at 50% MVC; p < 0.01) and a lower pHi (6.65 ± 0.11 vs 7.06 ± 0.02 at 50% MVC; p < 0.01). Moreover, PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr = 1.26 ± 0.30 vs 0.47 ± 0.05 min; p = 0.01). These results suggest impairment of aerobic capacity in a non‐ventilatory working muscle, probably due to hypoxemia in patients with chronic respiratory failure.
A review of chemical issues in 1H NMR spectroscopy: N‐acetyl‐l‐aspartate, creatine and choline
Authors: Miller Bruce L.
Published: March 2007

The structure and function of the chemicals contributing to the three main peaks seen with 1H NMR spectroscopy, N‐acetyl‐L‐aspartate (NAA), creatine/phosphocreatine (Cr), and choline‐containing compounds (Cho) is reviewed and the changes seen with these compounds in various disease states are briefly outlined. NAA is present within neurons although its biological function is largely unknown. NAA is elevated in several degenerative neurological conditions including amyotrophic lateral sclerosis and canavan disease, and in high concentrations it may behave like a neurotoxin. The creatine peak seen with 1H NMR spectroscopy consists of creatine and phosphocreatine which serve as a reserve for high‐energy phosphates in the cytosol of muscle and neurons. They also buffer cellular ATP/ADP. The Cho peak seen with 1H NMR consists of a complex mixture of Cho‐containing compounds. Cho is a precursor for the neurotransmitter acetylcholine and for the membrane constituent phosphatidylcholine. Future studies of changes seen in the Cho peak with stroke, degenerative dementia, drug intake, and infectious and neoplastic brain masses will be of great interest.
The metabolism of lactate
Authors: Veech Richard L.
Published: March 2007

Lactate contents of tissues can vary during normal physiological conditions in mammals from 0.5 to over 5 mM, and higher in pathological states, suitable for measurement by NMR. Lactate itself is a dead‐end metabolite, metabolized only by lactate dehydrogenase. The extent and direction of that reaction is determined by the free [NAD+]/[NADH][H+] ratio of cytoplasm with which lactate and pyruvate are in near‐equilibrium. Pyruvate is a crossroads of most of the major degradative and synthetic pathways, but present in about one‐tenth the amount of lactate. Information on the content of both lactate and its redox partner pyruvate is likely to provide more information on the metabolic state of tissue than are measurements of lactate alone.
Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; Myo‐inositol and related metabolites
Authors: Ross Brian D.
Published: March 2007

Glutamate and glutamine, which can be clearly identified and, in part, quantified in proton spectra of the brain, play important roles in normal and pathological biochemistry. Pathways of glutamate metabolism include transamination, dehydrogenation, deamination and decarboxylation (to GABA). Glutamine is notable in hepatic encephalopathy, but is also a significant metabolic fuel in several other organs and tissues, including neoplasms. Myo‐inositol is a 6‐carbon alcohol which acquires new interest from its detection and quantitation in 1H spectra. Its role, apart from a biochemical relationship to messenger‐inositol polyphosphates, is unclear.
Multiple quantum NMR spectroscopy methods for measuring the apparent self‐diffusion coefficient of In Vivo lactic acid
Authors: Sotak Christopher H.
Published: March 2007

Nuclear magnetic resonance spectroscopy methods are presented for measuring the apparent self‐diffusion coefficient of lactic acid in vivo. These techniques incorporate diffusion‐sensitive gradients into multiple quantum NMR pulse sequences that are employed for spectral editing. Both diffusion‐sensitive zero quantum (ZQ) and double quantum (DQ) spectral editing techniques have been developed and the DQ method has been used to measure the apparent self‐diffusion coefficient of in vivo lactic acid in H‐MESO‐1 human tumor xenografts subcutaneously implanted in athymic mice.
Proton editing and imaging of lactate
Authors: Hurd Ralph E. , Freeman Dominique
Published: March 2007

Highly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor‐sensitizers. The methods (GE‐DQCOSY and GE‐HMQC) may be particularly useful in heteronuclear NMR in vivo.
Quantification of glutamate, glutamine, and other metabolites in In Vivo proton NMR spectroscopy
Authors: Bovée W. M. M. J.
Published: March 2007

A reliable quantification of in vivo 1H MRS spectra is hampered by extensive line overlap, by intensity distortions due to the water suppressing pulse sequence and complex modulation patterns of J‐coupled spins, and by deviations between the experimental and model lineshapes in computer fitting programs. By correcting the experimental lineshape, using a suitable pulse sequence, and incorporating prior knowledge about the spin systems and the intensity distortions, a sufficient quantification is possible. If reliable. T2 values are available absolute concentrations can be determined.
Approaches to editing, assignment and interpretation of proton spectra
Authors: Gadian D. G. , Bates T. E. , Williams S. R. , Bell J. D. , Austin S. J. , Connelly A.
Published: March 2007

Clinical 1H spectroscopy of the brain is complemented by parallel analyses of biopsy specimens and by studies of animal models of disease. 1H spectroscopy has been carried out on perchloric acid extracts of biopsy specimens from patients with intracranial tumours. The data suggest that clinical spectroscopy may be useful in the identification and grading of these tumours. In addition, the spectra from extracts derived from normal white matter add weight to the possibility that acetyl‐containing compounds other than N‐acetylaspartate may make a significant contribution to the signal at 2.0 ppm in vivo. Edited 1H spectra of brain metabolites in rats with acute liver failure demonstrate an elevation of glutamine and of lactate, suggesting a role for 1H spectroscopy in clinical investigations of metabolic encephalopathies. However, the observation and resolution of signals from glutamate and glutamine is more difficult at the lower fields that are available for clinical spectroscopy. Finally, some studies of patients with inborn errors of metabolism are described. It is shown that in a disorder of oxidative metabolism, brain lactate can be detected without the need for complex spectral editing techniques. Investigations of the metabolic abnormalities associated with Canavan's disease have shed further light on a possible role for N‐acetylaspartate.
On the identification of cerebral metabolites in localized 1H NMR spectra of human brain In vivo
Authors: Michaelis Thomas , Merboldt Klaus‐Dietmar , Hänicke Wolfgang , Gyngell Michael L. , Bruhn Harald , Frahm Jens
Published: March 2007

Localized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin‐spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0‐T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N‐acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo‐inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.
What the clinician can learn from MR glutamine/glutamate assays
Authors: Chamuleau R. A. F. M. , Bosman D. K. , Bovée W. M. M. J. , Luyten P. R. , Den Hollander J. A.
Published: March 2007

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.
Localized 1H NMR spectroscopy in patients with chronic hepatic encephalopathy. Analysis of changes in cerebral glutamine, choline and inositols
Authors: Kreis Roland , Farrow Neil , Ross Brian D.
Published: March 2007

Localized, short echo 1H magnetic resonance spectra from an area in the parietal cortex of three patients suffering from chronic hepatic encephalopathy are compared with equivalent spectra obtained from healthy control subjects. Three significant differences are found: elevated glutamine, decreased inositol, and decreased choline peak intensities. The elevation of cerebral glutamine concentration is expected as a consequence of the presumed chronic hyperammonemia in this disease. The finding of a 50% change in the inositol peak is physiologically unexpected and so far unaccounted for.

Data acquisition and processing parameters are described in detail. To further define spectral abnormalities, which were readily detected in untransformed spectra, a simple data analysis scheme has been used that consists of post‐acquisition low‐frequency filtering, a lineshape transformation, and a difference technique to clarify spectral changes.
Time‐dependent effects of anesthetic agents on 31P NMR high‐energy phosphates in KHT and RIF‐1 fibrosarcomas
Authors: Fenton Bruce M. , Raubertas Richard F. , Sutherland Robert M.
Published: March 2007

Previous studies have reported significant radiobiological and hemodynamic effects associated with sodium pentobarbital (PB) anesthetization. The present work contrasts the effects of PB with azaperone‐ketamine (AZ) in RIF‐1 and KHT tumors while animal body core temperature is maintained at 37 °C. The primary aims were to evaluate both agents in terms of: (i) duration of anesthetic; (ii) effect on absolute levels of 31P NMR phosphocreatine (PCr) + β‐nucleoside triphosphate (β‐NTP)/inorganic phosphate (Pi) ratios; and (iii) effect on temporal variability of PCr+β‐NTP/Pi ratios. In terms of overall duration, AZ was the clear preference. Although the maintenance of 37 °C core temperature significantly reduced overall durations for both anesthetics, AZ animals invariably remained immobile for a minimum of 80 min. For PB, durations were highly unpredictable. With AZ, mean PCr + β‐NTP/Pi ratios were constant over the entire 80 min period for both lines. With PB, PCr + β‐NTP/Pi ratios were lower in relation to AZ for KHT at select timepoints, but highly variable among RIF‐1 tumours. Since ratios under PB varied substantially with time for RIF‐1 lines, measurements taken with PB are clearly not representative of the control state. Furthermore, in light of the consistent and reproducible results obtained with AZ, this anesthetic is considered a marked improvement over PB for animal studies of this nature.
Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: Significant variations with extent of breast cancer, duration of pregnancy and aging
Authors: Engan Terje , Krane Jostein , Kvinnsland Stener
Published: March 2007

The composite methylene (chemical shift range 1.2‐1.4 ppm) and methyl (0.8‐0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 °C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p<0.001) was found between the average (mean ±SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 ±5.0 Hz) and the controls matched for age and sex (38.7 ±4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5±3.4 Hz) and their controls matched for age and sex (42.7±4.6 Hz) (p<0.001). The average line width was lower in the late (31.5±3.3) than in the early (34.5±2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women. The observations are consistent with an association between ‘stage’ in a most general sense and the apparent NMR lipid line widths, probably accounted for by a variation in plasma lipids.
Non‐invasive 1H NMR spectroscopy of the rat brain In Vivo using a short echo time STEAM localization sequence
Authors: Gyngell M. L. , Ellermann J. , Michaelis T. , Hänicke W. , Merboldt K. D. , Bruhn H. , Frahm J.
Published: March 2007

Fully localized proton NMR spectra were obtained from the brains of normal anaesthetized rats in vivo using stimulated echo (STEAM) spectroscopy sequences. Investigations were carried out at 2.35 T using a 40 cm bore magnet equipped with an actively shielded gradient system. Localized shimming resulted in water proton linewidths of 6.5‐7.8 Hz permitting excellent water suppression. Thus, high‐quality proton NMR spectra (TE = 20 ms) were acquired within measuring times of 1.5‐6.4 min from 64 to 125 μL volumes‐of‐interest. The spectra show metabolite resonances due to N aspartate, glutamate, creatine and phosphocreatine, cholines, taurine and inositols. The assignments of strongly spin‐coupled resonances were confirmed by comparison with spectra from model solutions obtained under identical experimental conditions to those used in vivo. Tl relaxation times as well as relative metabolite concentrations were evaluated from spectra obtained for repetition times ranging from 900 to 6000 ms. Sequential acquisitions of 1.5 min spectra before, during and after killing the animals exhibited a rapid accumulation of lactate, but did not reveal significant changes in other metabolite levels for several hours post mortem.
Estimating the ATP cost of force production in the human gastrocnemius/soleus muscle group using 31P MRS and 1H MRI
Authors: Boska Michael
Published: March 2007

Net ATP production rates in exercising human muscle were calculated from 31P MRS kinetic data collected with 1‐8 s time resolution. During the exercise, the muscle output was measured using a force transducer. Muscle output (force/unit volume) is then divided by the calculated net ATP used to estimate the ATP cost of force production. These measurements have been performed using an exercise protocol of isometric maximum voluntary contraction of the gastrocnemius/soleus muscle group. Results show that by the end of 30 s of exercise, total ATP production and ATP cost of force production had stabilized and remained constant (within the measurement errors) until the end of the 2‐min period. The results also demonstrate that either the ATP cost of force production in the human gastrocnemius/soleus is lower in the first second than at any other time in the 2‐min window which was investigated, or that the ATP production is being underestimated at the later time points. These data on ATP production rates, and the data relating to ATP cost of force production in muscle will aid in understanding the causes of muscle failure as well as the progression and treatment of muscle disease.