bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple quantum filtered 23Na NMR spectroscopy in the perfused heart
Authors: Payne Geoffrey S. , Seymour Anne‐Marie L. , Styles Peter , Radda George K. 
Published: March 2007

AbstractIt has been proposed that multiple quantum filtered (MQF) 23Na NMR spectroscopy may distinguish between sodium in the intra‐ and extracellular spaces, in vivo, and without the requirement for toxic shift reagents. We have investigated the origin of such signals in perfused rat hearts, using shift reagents to discriminate between NMR signals from the two compartments. We find that the observed MQF signal arises predominantly from the extracellular space in the normal heart, and from the intracellular space in the ischaemic heart. However, the quenching effect of the shift reagent may hide some of the extracellular MQF signal, especially during ischaemia. Estimates of intracellular and extracellular relaxation times are obtained and possible mechanisms of the interaction discussed.
Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data
Authors: Gartland K. P. R. , Sanins S. M. , Nicholson J. K. , Sweatman B. C. , Beddell C. R. , Lindon J. C. 
Published: March 2007

AbstractA computer‐based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi‐dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2‐ and 3‐dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR‐detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly ‘predicted’ the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data.
Renal distribution and metabolism of [2H9]choline. A 2H NMR and MRI study
Authors: Eng John , Berkowitzt Bruce A. , Balaban Robert S. 
Published: March 2007

AbstractTrimethylamines are required as substrates in the biosynthesis of a number of important molecules in the cell. Herein, we describe the use of choline, deuterated in its 9 methyl positions, as an NMR label for following the distribution and metabolism of methyl groups after intravenous choline infusion. Deuterium (2H) NMR spectroscopy of the rabbit kidney in vivo revealed a linear uptake of infused choline that was directly proportional to the rate of infusion. The sensitivity limit for the spectroscopic studies in vivo was in the order of 100 μM for a 2 min data collection. After the infusion, 2H NMR imaging of the kidney in vivo demonstrated high trimethylamine concentrations in both the cortex and inner medulla but not in the outer medulla. The inner medullary fraction, however, was more labile to diuresis induced by furosemide. Companion high resolution 2H NMR studies of extracts revealed a cortex betaine/choline concentration ratio of 0.69 ± 0.05 (mean ± SEM, n = 3) before furosemide administration. Following furosemide infusion, the cortex betaine/choline concentration ratio was 3 ± 1 (n = 6). Thus, 2H renal images following furosemide treatment can be interpreted as metabolic maps of betaine distribution. In addition, extraction studies revealed high concentrations of labelled choline and betaine in the liver. These data demonstrate that 2H‐labelled choline is an effective marker of choline methyl metabolism in vivo and should provide a unique tool for the investigation of this important substrate.
The combined measurement of blood flow and metabolism in RIF‐1 tumours in vivo. A study using H2 flow and 31P NMR spectroscopy
Authors: Bhujwalla Z. M. , Tozer G. M. , Field S. B. , Proctor E. , Busza A. , Williams S. R. 
Published: March 2007

AbstractBlood flow and phosphorus metabolites have been measured simultaneously in the murine RIF‐1 tumour in vivo. Blood flow was measured using the H2 washout technique and 31P NMR spectroscopy was used to measure high energy phosphates, inorganic phosphate and intracellular pH within the tumour. Following NMR and flow measurements, hydralazine was administered and the measurements repeated. There was always a decrease in blood flow, and a fall in nucleoside triphosphate detected by NMR, after administration of hydralazine. At blood flows in excess of 15 mL 100 g−1 min−1 the nucleoside triphosphate/inorganic phosphate ratio was 1.0 or greater, whereas at flows in the range of 5–12 mL 100 g−1 min−1 the ratio fell to below 0.5, and at flows below 5 mL 100 g−1 min−1 there was no detectable resonance from nucleoside triphosphate.
A 31P study of fatigue and metabolism in human skeletal muscle with voluntary, intermittent contractions at different forces
Authors: Newham D. J. , Cady E. B. 
Published: March 2007

AbstractNormal subjects performed voluntary, isometric exercise (1 s contraction, 1 s rest for 10 min) of the first dorsal interosseous (FDI) muscle with a target force of 25, 50 and 100% of the maximal voluntary contraction (MVC) force. 31P NMR spectra were collected continuously before, during and after exercise. Data were also taken from the resting muscles 2‐28 h after the studies at 50% MVC. Calculations were made of the intracellular pH and concentrations of PCr, Pi, ATP, ADP and H2PO. The 25% MVC contractions did not affect the MVC, but those at 50 and 100% MVC reduced the force by 20% and 60%, respectively (p < 0.005). During the highest force contractions, the MVC declined from the first minute but the target forces of 25 and 50% were maintained throughout. All protocols caused significant changes in pH, PCr, Pi, ADP and H2PO. Exercise at 50% MVC caused greater metabolic changes than that at 25%, but there was no overall difference in the pH and phosphorus metabolites between the two higher forces. In parallel studies, electrical stimulation of the muscle indicated that during the voluntary contractions with a target force of 100% MVC in the magnet: (a), additional muscles were being used to generate the recorded force; and (b), the subjects were not fully activating the FDI. There was no obvious causal relationship between any one metabolite and the decline of force. Resting muscle showed an increase in the Pi peak 2–28 h after exercise at 50% MVC force, despite the muscles being of full strength and pain free.
Proton magnetic resonance spectroscopy of small regions (1 mL) localized inside superficial human tumors. A clinical feasibility study
Authors: van Zijl Peter C. M. , Moonen Chrit T. W. , Gillen Joe , Daly Peter F. , Miketic Linda S. , Frank Joseph A. , Delaney Thomas F. , Kaplan Ofer , Cohen Jack S. 
Published: March 2007

AbstractIt is demonstrated that the stimulated echo technique for proton magnetic resonance spectroscopy (MRS) can be used to study metabolites in volumes of interest (VOls) as small as 1 mL localized within superficial human tumors. Access to these small VOls is important for characterization of tissue regions within a tumor, before, during and after treatment. Spectral appearance resembles that from studies on extracts, and cell suspensions and perfused cells of several tumor types. For the first time proton MRS was used to study cancer treatment in vivo in humans, for a case of radiation treatment of squamous cell carcinoma. No spectral evidence of changed metabolism prior to reduction in tumor size was found. However, after the first period of radiation (39 Gy, 4 weeks), complete disappearance of the metabolite resonances from the spectrum was observed, while a considerable mass still remained, suggesting effective cell destruction upon treatment. Needle aspiration cytology of this mass showed absence of malignant cells, supporting this result.
31P spectroscopy in experimental embolic stroke: Correlation with infarct size
Authors: Smith C. D. , Thomas G. S. , Kryscio R. J. , Markesbery W. R. 
Published: March 2007

AbstractSerial 31P nuclear magnetic resonance spectra were acquired from the brain in 19 rats following microsphere embolization of the right internal carotid artery. The brains were sectioned and stained with 2,3,5‐triphenyltetrazoline chloride 6 h post‐embolization to visualize infarcted areas. There was a narrow dosage range for the effect of embolism measured by maximum decline in pH at 20 min, mortality, and infarct size. This narrow range effect may be due to occlusion of collateral channels by the 16 micron microspheres. There was a strong correlation between decline in pH at 20 min post‐embolization and infarct size (r2 = 0.76); this decline was the best early marker for eventual infarct in our study. This animal model for macroscopically heterogenous brain ischemia may be useful for the evaluation of therapeutic interventions in stroke, and as an aid in the interpretation of phosphorus spectra from mixed volumes of ischemic and non‐ischemic brain.
Nuclear magnetic resonance determination of flow, lactate, and phosphate metabolites during amphetamine stimulation of the rat brain
Authors: Detre John A. , Williams Donald S. , Koretsky Alan P. 
Published: March 2007

AbstractThe effects of amphetamine on rat cerebral blood flow, lactate, and phosphate levels were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Proton NMR imaging was used to determine the region of brain being studied. Blood flow was estimated by detecting the washout of trifluoromethane using 19F NMR. A dose of 20 mg/kg D‐amphetamine sulphate stimulated flow fourfold over control values for at least 1 h. Even though amphetamine stimulated a large increase in flow, there were no significant changes in levels of inorganic phosphate, ATP, phosphocreatine, pH or Mg2+ as determined by 31P NMR. This was true for doses of 10 and 20 mg/kg D‐amphetamine sulphate. No significant changes occurred in 1H NMR detected levels of lactate with a 20 mg/kg dose of amphetamines. Lactate levels increased slightly 30min after administration of 10 mg/kg D‐amphetamine sulphate. The results call into question the central role of changes in levels of phosphates in coupling increased cortical activity to increases in metabolism.
A quantitative analysis of the accuracy of In Vivo pH measurements with 31P NMR spectroscopy: Assessment of pH measurement methodology
Authors: Madden A. , Leach M. O. , Sharp J. C. , Collins D. J. , Easton D. 
Published: March 2007

Abstract31P NMR spectroscopy provides a means of monitoring intracellular pH (pHi). In order to determine the significance of observed pH changes, an assessment of the measurement uncertainty is required. This paper considers the possible sources of error involved, firstly in chemical shift assignment and, secondly, in relating chemical shift to pH. A statistical analysis of these errors is presented and an expression for the accuracy of pH measurements obtained using in vivo 31P NMR spectroscopy is derived. Computer simulations and clinical measurements are considered to determine the likely error in clinical measurements. A comparison of pH measurement methodology using a centre‐of‐gravity calculation, Gaussian and Lorentzian fitting is also presented and discussed.
Acquisition and quantitation in proton spectroscopy
Authors: Luyten Peter R. , Mariën Ad J. H. , Den Hollander A. 
Published: March 2007

AbstractLocalized proton NMR spectroscopy in the human brain is one of the more technically advanced applications of human in vivo NMR spectroscopy. Spin/echo techniques introduced reliable localization procedures, whereas the introduction of phase encoding techniques improved the spatial information content considerably. Using the sensitivity of the 1H NMR signal, a spatial resolution of 7 × 7 × 15 mm can be obtained. Chemical shift images can be reconstructed to represent the choline, creatine, N‐acetyl aspartate and lactate distribution in the human brain. These low resolution images may be used as a new functional imaging modality to visualize and derive quantitative biochemical information from focal brain lesions under normal and pathological conditions.
What the clinician can learn from MRS lactate measurements
Authors: Prichard James W. 
Published: March 2007

AbstractLactate is of special importance in brain metabolism. In the 1980s, noninvasive methods for measurement of lactate concentration and turnover rate in living brain by 1H and 13C NMR spectroscopy were implemented in both animals and humans, opening the way to innovative examination of lactate's role in normal and deranged brain function. Early data on elevation of lactate in human visual cortex by physiologic stimulation and turnover of pathologically elevated brain lactate pools in animals and humans suggest that the new methods are likely to benefit clinical practice both directly–by providing information useful in management of individual patients–and indirectly–through improved understanding of disease processes.
31P magnetic resonance spectroscopy is sensitive to tumor hypoxia: Perfusion and oxygenation of rat 9L gliosarcoma after treatment with BCNU
Authors: Grant Steen R. , Graham Michael M. 
Published: March 2007

AbstractThe mechanism behind the relative increase in high‐energy phosphates observed by MRS in many tumors following chemotherapy is poorly understood. To test the hypothesis that this metabolic activation is associated with a decrease in tumor hypoxia, tumor blood flow and oxygenation were measured in tumors that were also analyzed by MRS. 31P MR spectra were acquired with a GE 2T CSI spectrometer from subcutaneous 9L tumors in rats 4 days following treatment with BCNU (10 mg/kg) and from age‐matched sham‐treated control tumors. BCNU‐treated tumors (n = 13) underwent a significant improvement in bioenergetic state compared to control tumors (n = 14), showing a relative increase in high‐energy phosphate (Pi/phosphocreatine) (p<0.01), and a relative decrease in Pi (Pi/a nucleoside biphosphate) (p<0.01). Gamma camera imaging of 133Xe washout, following injection of 133Xe in saline into control and treated 9L tumors 4 days after treatment, was used to measure tumor perfusion. Sham‐treated control tumors (n = 21) were perfused at a rate of 35.4 (±6.4 SE) mL/100g/min, while BCNU‐treated tumors (n = 20) were perfused at a rate of 55.1 (±7.5 SE) mL/100g/min (T = 1.96; p <0.05). The partial pressure of oxygen (pO2), measured with a polarographic electrode was found to be significantly higher in treated 9L than in sham‐treated controls. Mean tumor pO2 of sham‐treated tumors was 18.1 (±1.7 SE) mmHg (n = 00 measurements in six tumors) while mean pO2 of treated tumors was 45.1 (±2.1 SE) mmHg (n = 500 in five tumors) (T = 10.12; p<0.001). If the range 0‐5 mmHg is taken to approximate the hypoxic fraction, then control tumors are ±23% hypoxic, while treated tumors are only 2% hypoxic. These data suggest that metabolic activation of tumors following therapy may be associated with decreased tumor metabolic hypoxia.
Non‐invasive In Vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: Regional differences followed in time
Authors: Van Vaals J. J. , Bergman A. H. , Van Boogert H. J. Den , Heerschap A. , Van Kogel A. J. Der , Ruifrok A. C. C. , Bernsen H. J. J. A. 
Published: March 2007

AbstractHuman astrocytoma cells were cultured and inoculated into the rat brain. From the pre‐clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water‐suppressed 1H spectroscopy (0.12‐0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non‐invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N‐acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation.
13C NMR spectroscopic analysis of phospholipid metabolism in adrenal chromaffin cells
Authors: Rivera Carlos J. , Plishker Gordon A. , Morrisett Joel D. , Moore John , Percy Alan K. 
Published: March 2007

AbstractPhosphatidylcholine (PC) metabolism in bovine adrenal chromaffin cells has been studied in vivo with 100 MHz 13C NMR spectroscopy. The incorporation of 13[CH3]choline was examined in cells embedded in 1% agarose strands and perfused at 37 °C. The pattern of 13C NMR spectroscopy. The incorporation of [13CH3]choline incorporation into PC of suspension cultures of chromaffin cells. The chemical shifts of labelled carbons in [13CH3]choline before and after their incorporation into PC are identical (ca 56.4 ppm). Incorporated [13CH3]choline can be released from the cells by phospholipase D which reduces the cellular PC signal by >85%, indicating that a major fraction of the labelled PC is on the external membrane surface. This application of NMR spectroscopy provides a basis for direct measurement of the in vivo metabolism of PC in functioning adrenal chromaffin cells
Cerebral metabolism of fluorodeoxyglucose measured with 19F NMR spectroscopy
Authors: Pouremad Reza , Wyrwicz Alice M. 
Published: March 2007

AbstractBrain extracts from rats given various doses of 2‐fluoro‐2‐deoxy‐D‐glucose ranging from 20 to 300 mg/kg were examined with 19F NMR spectroscopy for fluorinated metabolic products and compared with the in vivo 19F spectra. Based on the analysis of these spectra and comparison with synthetic reference compounds, 2‐fluoro‐2‐deoxy‐D‐glucose 6‐phosphate and 2‐fluoro‐2‐deoxy‐D‐mannose 6‐phosphate were identified as the major metabolites present. 2‐Fluoro‐2‐deoxy‐D‐6‐phosphogluconate was detected only at high doses of 2‐fluoro‐2‐deoxy‐D‐glucose administered, along with non‐phosphorylated 2‐fluoro‐2‐deoxy‐D‐glucose and 2‐fluoro‐2‐deoxy‐D‐mannose. Small amounts of two other compounds, which were not identified, were also observed. Presence of the 2‐fluoro‐2‐deoxy‐D‐mannose 6‐phosphate is the result of 2‐fluoro‐2‐deoxy‐D‐glucose 6‐phosphate isomerization at the C2 position catalyzed by phosphoglucose isomerase. Results from the in vitro enzymatic reaction provide support for this hypothesis. Presence of 2‐fluoro‐2‐deoxy‐D‐mannose may be the result of 2‐fluoro‐2‐deoxy‐D‐glucose isomerization at the C2 position catalyzed by glucose isomerase or the result of the dephosphorylation of the 2‐fluoro‐2‐deoxy‐D‐glucose 6‐phosphate.
NMR estimation of protective effect of insulin on mouse liver with epinephrine‐induced metabolic lesions
Authors: Yushmanov Victor E. , Khristianovich Darya S. , Rozantseva Tatyana V. , Sibeldina Lili A. 
Published: March 2007

AbstractIn order to study the effects of epinephrine and insulin on liver metabolism, measurements of cellular phosphates and intracellular pH by 31PNMR, of glycogen by 13C NMR and of lactate by 1H NMR were performed in freshly dissected mouse liver at 0‐4 deg.C and in ethanolic liver extracts. The injection of epinephrine hydrochloride (0.1 mL of 0.1% solution i.p. per mouse) caused remarkable changes in liver metabolic profiles which were expressed most distinctly in 15‐30 min and could not be attributed solely to epinephrine‐induced hyperglycemia. Among these metabolic changes are falls in the levels of ATP and uridine diphosphate sugars by 60‐70%, possibly related to glycogen depletion, and intracellular acidification by 0.5 units attributed to the release of protons during hydrolysis of ATP rather than to accumulation of lactate in anaerobic glycolysis. Insulin injected prior to epinephrine (4 units i.p.) markedly suppressed epinephrine‐induced metabolic alterations, although the effect of the combination of insulin and epinephrine was not the sum of the separate effects of these hormones. The maximum protective effect of insulin was reached when insulin was injected 15 min prior to epinephrine. The results obtained demonstrate the applicability of NMR for evaluating the protective activity of modifiers at various extreme exposures.
23Na, 59Co and 2H NMR studies of experimental acute pancreatitis
Authors: Kushnir Tammar , Kaplan Ofer , Askenasy Nadir , Navon Gil 
Published: March 2007

AbstractMultinuclear MR was applied to the study of experimental acute pancreatitis. A continuous increase, up to 700%, of total, NMR visible, sodium content was detected during the development of the disease through the edematous stage to necrosis. The effect of the elevation of sodium content is amplified by an increased 23Na NMR visibility during the disease. Interstitial and total water volume of pancreases were estimated using the distribution of Co(CN)36 and D2O, by 50Co and 2H NMR, respectively. In healthy pancreases the interstitial compartment was found to comprise 35% of the tissue volume. In the diseased pancreases the penetration volume of Co(CN)36 reached 90% of the total tissue volume, indicating extensive membrane injury. The time dependence of the 23Na NMR in the presence of the shift reagent Na7Dy(tripolyphosphate)2.3NaCl provided additional evidence of the increased permeability of the membranes in the diseased organs.
1H NMR characterization of normal human cerebrospinal fluid and the detection of methylmalonic acid in a vitamin B12 deficient patient
Authors: Commodari Fernando , Arnold Douglas L. , Sanctuary Bryan C. , Shoubridge Eric A. 
Published: March 2007

Abstract1H NMR was used to analyze human cerebrospinal fluid (CSF) from a group of neurological disease controls and from a vitamin B12 deficient patient. The spectra were acquired at either 7.06 or 9.40 T at ambient temperature with CSF freeze dried and reconstituted in 2H2O. 3‐Trimethylsilyl propionate was used as an internal chemical shift and concentration reference. All of the CSF samples showed peaks for lactate, L‐alanine, acetate, glutamine, citrate, creatine/creatinine and sugar resonances. There was good agreement between the metabolite concentrations as determined by NMR with those obtained using conventional chemical methods. 1D and 2D 1H NMR techniques along with J‐coupling and T1 analysis were used to confirm the peak assignments. Methylmalonic acid could be detected and quantitated (ca 150 μM) in the CSF from the vitamin B12 deficient patient.