bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting 1h NMR spectra of blood plasma: cancer, diet and freezing
Authors: Bell J. D. , Brown J. C. C. , Norman R. E. , Sadler P. J. , Newell D. R.
Published: March 2007

Single pulse and Hahn spin‐echo 400 and 500 MHz 1H NMR spectra from normal subjects and cancer patients are reported. No significant difference was found between the average —CH3 and —(CH2)n— lipoprotein linewidths of the two groups in contrast to a previous report. Such measurements are shown to be complicated by freezing and thawing of samples which broadens lipoprotein resonances, and by eating which sharpens them. Deconvolution of the composite lipoprotein signals enables these effects to be interpreted. Other notable features of plasma spectra are discussed including resonances for ‘acute‐phase’ glycoproteins, ketone bodies and other small molecules.
The use of immobilized ferrite to enhance the depth selectivity of in vivo surface coil NMR spectroscopy
Authors: Geoffrion Y. , Rydzy M. , Butler K. W. , Smith Ian C. P. , Jarrell Harold C.
Published: March 2007

Ferrite particles immobilized on a flexible support and arranged in a specific pattern will produce localized gradients in the homogeneous B0 magnetic field. The screening gradients are strong enough to cause inhomogeneous broadening of the NMR signals arising from the region of a specimen which is adjacent to the ferrite particles. This technique allows improvement of the depth selectivity in non‐invasive surface coil NMR spectroscopy while optimizing both the signal‐to‐noise ratio and the data acquisition time of in vivo NMR experiments. The ferrite screen method also facilitates the routine application of high resolution NMR pulse sequences to in vivo experiments. The technique is readily implemented without special hardware or software and displays a great versatility in the size, shape and depth of the screening effect.
Direct 19f NMR spectroscopic observation of 5‐fluorouracil metabolism in the isolated perfused mouse liver model
Authors: Cabanac S. , Malet‐Martino M. C. , Bon M. , Martino R. , Nedelec J. F. , Dimicoli J. L.
Published: March 2007

A direct analysis of 5‐fluorouracil (FUra) metabolism in the isolated perfused mouse liver was carried out using 19F NMR spectroscopy. In livers treated with low (30mg/kg body weight (b.w.)) or high (180 mg/kg b.w.) doses of FUra, with (180 mg/kg b.w.) or without thymidine (dThd), FUra was rapidly catabolized to α‐fluoro‐b̃‐ureidopropionic acid (FUPA) and α‐fluoro‐b̃‐alanine (FBAL), the latter usually becoming by far the major catabolite. The first catabolite of FUra, 5,6‐dihydro‐5‐fluorouracil (5FUH2), was never detected. With the high dose of FUra with or without dThd, a signal corresponding to fluoronucleotides was detected both in the liver and in perchloric acid (PCA) extracts. In the latter, it was generally split into three signals, the major one being attributed to 5‐fluorouridine‐5′‐monophosphate. Moreover, when the liver was treated with high doses of FUra and dThd, a signal for fluoronucleoside was observed in the liver, in PCA extracts and in perfusate where it was attributed to 5‐fluoro‐2′‐deoxyuridine (FdUrd). The injection of concurrent dThd with the high dose of FUra led to a marked reduction of catabolism due to competitive inhibition of dihydrouracil dehydrogenase. Moreover, a significant formation of FdUrd was noticed whereas 5‐fluoro‐2′‐deoxyuridine‐5′‐monophosphate (FdUMP) was not detected. dThd therefore inhibits the conversion of FdUrd to FdUMP.
Direct determination of adp in hypoxic porcine carotid artery using 31p nmr
Authors: Fisher M. J. , Dillon P. F.
Published: March 2007

31‐NMR spectroscopy was performed on vascular smooth muscle (VSM; porcine carotid artery) superfused with a substrate‐free high K+‐PSS. Scans were collected before (control), during (hypoxia), and after (post‐control) hypoxia, and chemical measurements of ATP (0.070 ± 0.13 m̈moles/g wet wt.) and creatine (2.04 ± 0.14 m̈mol/g wet wt.) were made. During hypoxia, well‐defined beta‐ADP signals were consistently resolved. Their areas indicated that after 30, 60, and 90 min of hypoxia, free ADP was 0.05 ± 0.01, 0.09 ± 0.01, and 0.12 ± 0.01 m̈mol/g wet wt., respectively. The apparent tissue equilibrium constant (Kck) for creatine kinase (CK) was calculated using 90 min hypoxic data and was 7.6 ± 0.6 × 108 M–1. It was used to compute free ADP levels (m̈mol/g wet wt.) for control (0.028 ± 0.002) and post‐control (0.23 ± 0.003) periods, since ADP signals could not be directly detected, and for the 30 and 60 min hypoxic periods (0.05 ± 0.01 and 0.08 ± 0.01, respectively). The Kck‐dependent ADP values for the 30 and 60 min hypoxic periods were the same as the ADP values determined directly from the beta‐ADP peak areas, suggesting that the CK reaction is in equilibrium in smooth muscle. These data show that 31P‐NMR provides a means of directly measuring free ADP in hypoxic smooth muscle and a more accurate means of computing free ADP levels in normoxic VSM through the use of an in situ tissue Kck vs an assumed or in vitro Kck.
The effect of methotrexate upon tumour ATP as determined by in vivo31P inversion spin transfer
Authors: Haseler Luke J. , Irving Michael G. , Doddrell David M.
Published: March 2007

The effect of methotrexate upon tumour growth in the hind leg muscle of rats containing a transplanted mammary adenocarcinoma was investigated by 31P magnetic resonance spectroscopy. Using inversion‐transfer techniques, ATP resonances arising from the tumour could be distinguished from those arising from surrounding skeletal muscle. Methotrexate was shown to inhibit, but not prevent, tumour growth as evidenced by the tumour ATP resonances of methotrexate treated animals compared to those of control animals. These findings correlated with decreased tumour volume and enhanced life expectancy.
Evaluation of manual methods for integration of in vivo phosphorus NMR spectra
Authors: Meyer R. A. , Fisher M. J. , Nelson S. J. , Brown T. R.
Published: March 2007

Eight human subjects measured peak integrals from a set of simulated 31P NMR spectra by triangulation, by extrapolation of tangents from the baseline of computed integrals, and by cursor demarcation of computed integrals using standard commercial software. The test spectra were qualitatively similar to phosphorus spectra routinely acquired from mammalian skeletal muscle. All three of the above methods were found to underestimate the areas of relatively broad peaks (e.g., ATP peaks were underestimated by 20–40%), even when the peak signal/rms‐noise ratio was better than 8/1. This bias resulted in major errors in calculated metabolite ratios. Of the three methods, triangulation was the least accurate, and showed the greatest variation between subjects. Cursor demarcation of computed integrals was the most accurate manual method. The same test spectra were also integrated by two fully‐automated fitting algorithms. Although not free of bias, these methods were generally superior to the manual methods.
An NMR blood test for cancer: a critical assessment
Authors: Chmurny G. N. , Hilton B. D. , Halverson D. , McGregor G. N. , Klose J. , Issaq H. J. , Muschik G. M. , Urba W. J. , Mellini M. L. , Costello R. , Papadopoulos N. M. , Caporaso N. , Smith I. C. P. , Czuba M. , Kroft T. , Monck M. , Saunders J. K. , Préfontaine M.
Published: March 2007

An evaluation of the reproducibility and accuracy of the NMR human blood test for cancer described by Fossel, E. T., Carr, J. M. and McDonagh, J., (New England Journal of Medicine 315, 1369–1376) in 1986 has been conducted jointly at the National Cancer Institute–Frederick Cancer Research Facility, Frederick, MD (NCI–FCRF) and the National Research Council, Ottawa, Canada (NRC). The influences on the test of the following were studied: (a) subject fasting; (b) sample collection, storage and handling; (c) use of plasma or serum; (d) variations of test results from the same individual with time; (e) NMR observation parameters including field strength and temperature; and (f) variations in obtaining the Fossel Index (FI) (a number defined by Fossel and co‐workers as the average of the widths at half height of the regions in the NMR spectrum of human plasma at 1.3 and 0.88 ppm) by different people from the same plotted spectrum. This test was found to be reproducible but not accurate for screening a general asymptomatic population. The accuracy is defined in terms of the sensitivity, specificity, and predictive values of the test. The accuracy of the test results from our laboratories is compared with the accuracies from other laboratories including Fossel's. The correlation of the Fossel Index with total triglyceride content in the serum has been confirmed by analysing blood components using the following technologies: KBr density gradient centrifugation, high resolution agarose gel electrophoresis, high performance gel permeation chromatography, and chemical analysis.
Spectroscopy and imaging with a 4 tesla whole‐body mr system
Authors: Bomsdorf H. , Helzel T. , Kunz D. , Röschmann P. , Tschendel O. , Wieland J.
Published: March 2007

Magnetic resonance (MR) spectroscopy and imaging experiments on humans were performed with a whole‐body MR system at a static field of 4 tesla. Spectroscopic studies focussed on 1H, 13C, and 31P. Imaging of humans turned out to be possible, although below the optimum at this field. This holds especially for body imaging, since RF penetration effects and dielectric resonances influence the RF field homogeneity. Excellent volume selective proton spectra of the human cerebrum and cerebellum were obtained using the stimulated echo method. Natural abundance carbon spectra of the human calf were acquired both undecoupled and with narrowband decoupling, resolving the various triglyceride resonances. Broadband decoupling, however, would have violated SAR guidelines. Liver glycogen was detected on natural abundance 13C spectra.
Potential artefacts from overlying tissues in 31p NMR spectra of subcutaneously implanted rat tumours
Authors: Stubbs Marion , Rodrigues Loreta M. , Griffiths John R.
Published: March 2007

31P spectra of rat tumours obtained with surface coils are shown to include skin signals of varying intensity. As reported previously by Stubbs, M., Rodrigues L. M., and Griffiths, J. R., (NMR in Biomedicine 1, 50–55, 1988) three hepatomas (rapidly growing Morris heptoma 7777 and slow growing 9618A, and the UA hepatoma) had negligible phosphocreatine (PCr) or creatine (Cr) in acid extracts but frequently had PCr signals in surface coil spectra. Prolactinomas and mammary adenocarcinomas, which had significant PCr and Cr in extracts, showed higher PCr/NTP ratios in spectra taken in vivo than in extracts. A phantom for studying skin signals in vivo is described. A glass sphere of typical tumour size (3–4 mL) is implanted subcutaneously in the rat. Variations in skin signal with pulse duration are demonstrated with this phantom. The factors that could contribute to skin artefact in 31P tumour spectra include: (i) the relative concentrations of metabolites in skin and tumour; (ii) the skin thickness, which depends on the implantation site and rat size; (iii) skin invasion by the tumour; (iv) coil design (solenoid coils and Faraday shields are unlikely to eliminate this problem); (v) pulse repetition times; (vi) pulse duration and other NMR parameters. Careful attention to these factors could reduce skin artefacts.
Characterization of the transport of the nonelectrolyte dimethyl methylphosphonate across the red cell membrane
Authors: Potts Jennifer R. , Kirk Kiaran , Kuchel Philip W.
Published: March 2007

We have refined the method for measuring the equilibrium exchange of the neutral phosphoryl compound dimethyl methylphosphonate across the human red cell membrane using 31P NMR spectroscopy. Using this improved technique we measured a permeability coefficient of dimethyl methylphosphonate of 9.47 ± 1.01 × 10–5cm s–1 at a concentration of 164 mM, at 25 °C. The transport at 25 °C was not saturable up to a concentration of 600 mM and was not inhibited by 4,4′‐diisothiocyano‐2,2′‐disulfonic acid, p‐chloromercuriphenyl sulfonic acid, copper ions or phloretin, or by thiourea or urea at 16 °C. The permeability was enhanced by butanol and phloretin.
31P NMR Study of the Impact of Dietary Manipulation on Tumor Metabolism and Response to Methotrexate
Authors: Sijens P. E. , van Echteld C. J. A. , Neijt J. P. , Schipper J. , Dunki Jacobs P. B. , de Graaf P. W. , Seijkens D.
Published: March 2007

The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty‐four hours after nutritional replenishment the PD rats and continuously well‐fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as ‘ATP/P1 ratio’) in PD rats in contrast to an unchanged ATP/P1 ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 ± 0.03 [SEM] vs 6.95 ± 0.04; p < 0.02). Tumor response in the PD group was significantly (p < 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/P1 ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.
31P and 13C NMR Studies of Isolated Perfused Hematopoietic Cells from Leukemic Mice
Authors: Mégnin F. , Nedelec J. F. , Dimicoli J. L. , Lhoste J. M.
Published: March 2007

The myeloproliferative leukemic virus (MPLV) induces within 2–3 weeks a massive infiltration of the adult mouse liver by hematopoietic leukemic cells. Since the metabolism of the infiltrated organ might be correlated with an interaction of two cell populations, it was decided to study the isolated hematopoietic cells separately. The metabolism of these cells embedded in an agarose gel and perfused with labeled substrates was investigated using 31P and 13C NMR. Using [1‐13C]glucose as precursor, sequential 13C NMR spectra showed that the hematopoietic cells were able to store glucose as [1‐13C]glycogen and to metabolize it through the glycolytic pathway to give [3‐13C]lactate as sole end‐product. The liver neoglucogenic substrates: [2‐13C]pyruvate and [3‐13C]alanine are not metabolized by these cells. This suggests that the tricarboxylic acid cycle was not efficient. To investigate further the glycolytic properties of the cells, 10 mM sodium azide was added to the medium containing [1‐13C]glucose. When compared to the aerobic conditions, a 40% decrease of nucleotides (0.10 vs 0.17 m̈mole NTP/109 cells), a degradation of [1‐13C]glycogen and an increase of ca 35% of the glycolytic rate were observed. The analysis of 13C NMR spectra of the perfusates at the end of the perfusion indicates a total conversion of [1‐13C]glucose into [3‐13C]lactate and [3‐13C]pyruvate under anaerobic conditions. These results permit a better understanding of the metabolism of the perfused leukemic livers which are extensively infiltrated by these hematopoietic cells.
The use of in vivo2H NMR spectroscopy to investigate the effects of obesity and diabetes mellitus upon lipid metabolism in mice
Authors: Brereton I. M. , Doddrell D. M. , Oakenfull S. M. , Moss D. , Irving M. G.
Published: March 2007

In vivo deuterium magnetic resonance spectroscopy was used to measure fat utilization rates in diabetic and non‐diabetic obese and non‐obese mice. Monosodium glutamate‐treated mice were used as a model for obesity, and diabetes was induced by administration of streptozotocin. Deuterium levels were enhanced by addition of D2O to drinking water (10% v/v) for a period of 14 days. The deuterium magnetic resonance signals of the body water and adipose tissue were then monitored to measure the rate of deuterium loss from the body. The rates of fat utilization for obese mice were significantly lower (75%, p<0.05) (halflife, t1/2 = 113 ± 13 days) than the rates for non‐obese mice (t1/2 = 30.0 ± 9.0 days). The induction of diabetes caused a large (90%) but proportionally similar increase in fat utilization for both groups of mice (obese, t1/2 = 11.0 ± 5.2; non‐obese, t1/2 = 3.0 ± 0.9). The results suggest that the induction of diabetes in obese mice does not affect the utilization of fat as a metabolic fuel. These preliminary studies indicate that deuterium magnetic resonance spectroscopy may be a useful technique for non‐invasive determination of the rates of fat utilization in vivo.
1H NMR of plasma for detecting cancer. The effect of trauma on linewidths
Authors: Sutherland Garnette , Peeling James
Published: March 2007

The specificity of detecting cancer using the methyl and methylene linewidths in the 1H NMR spectrum of plasma has been examined for patients with brain tumors. Apparently healthy controls are distinguished from patients with metastatic brain tumors or malignant primary intracranial neoplasms, although the amount of overlap with the latter group precludes the use of the method as a diagnostic tool. Furthermore, patients with benign primary intracranial neoplasms are not distinguished from those with malignant primary brain tumors, and non‐tumor neurological patients with traumatic head injury are not distinguished from cancer patients. Surgical treatment of neurological patients results in a significant narrowing of the 1H NMR bands of interest, particularly for patients initially exhibiting broad lines. The narrowing persists for at least 3 weeks. This effect of surgical or other trauma on the 1H NMR linewidths indicates that the method is unsuitable for assessing the efficacy of surgical treatment of cancer.
The 1H NMR visibility of intracellular lactate in Streptococcus faecalis
Authors: Moxon Leith N. , Rogers Peter J. , Brereton Ian M. , Doddrell David M. , Irving Michael G.
Published: March 2007

1H NMR studies of glycolysis in washed cell suspensions of Streptococcus faecalis indicated that intracellular lactate is not 1H NMR visible. Evidence for this was gained from time course studies of glycolysis at increasing concentrations of glucose. A close correlation existed between the relative increase in the lactate integral and the enzymatically determined extracellular lactate concentration [Lo]. When ionophores which cause the collapse of the positive intracellular/extracellular lactate gradient were added to cell suspensions following fermentation of 5, 10 and 50 mM glucose, the increase in the lactate integral was proportional to the respective increase in [Lo]. A more direct method for determining the origin of the lactate signal involved centrifugation of a cell suspension after fermentation of 50 mM glucose and measurement of lactate in the extracellular and intracellular fluid. 1H spectra of the cell suspension, supernatant and sonicated pellet revealed that the lactate observed in the cell suspension was equivalent to the lactate in the supernatant alone. The intracellular lactate contained in the pellet represented 42% of the total lactate, indicating that only 58% of lactate is detected by in vivo 1H MRS of S. faecalis. This result is in contrast with the high percentage (70–90%) of in vitro lactate which is detected by in vivo 1H MRS of mammalian brain tissue (Williams S. R. et al. Magn. Res. Med. 7, 425–431, 1988). This may be due to a higher proportion of extracellular lactate in mammalian tissue or differences in the intracellular environments of bacterial and mammalian cells.
1H NMR studies on protein binding of histidine, tyrosine and phenylalanine in blood plasma
Authors: Nicholson Jeremy K. , Gartland Kevin P. R.
Published: March 2007

The binding of histidine (His), phenylalanine (Phe) and tyrosine (Tyr) to macromolecules in blood plasma and serum has been investigated by high resolution 1H NMR spectroscopy. In single pulse and spin‐echo spectra of quality control bovine serum and normal human plasma, there are no resonances in the chemical shift range to high frequency of δ = 5.3 ppm when measured in the pH* (meter reading, uncorrected for the presence of 2H2O) range 3 to 8.5. On acidification of the plasma to pH* < 2.5, resonances from His and Phe are observable. In plasma from patients with Wilson's disease, weak signals from His and Tyr are seen in spin‐echo spectra at pH* 7.6, but increase in strength on acidification and signals from Phe appear at pH* 1.8. Addition of standard solutions containing Tyr, His and especially Phe and Trp to plasma at neutral pH* results in poor recovery of their expected signal intensity in spin‐echo spectra. Addition of 2 M urea to bovine plasma at pH* 4.5 results in the appearance of Phe signals. These data are consistent with Phe and Tyr (and to a lesser extent His) being bound in or to a macromolecular structure at neutral pH from which there is relatively slow exchange with the free solution environment. Experiments with model solutions suggest that serum albumin has a high capacity for binding aromatic amino acids (stabilized by hydrophobic interactions) at neutral pH and this is responsible for the NMR‐invisibility of Tyr and Phe in blood plasma.
31P NMR spectroscopic and near infrared spectrophotometric studies of effects of anesthetics on In vivo RIF‐1 tumors. relationship to tumor radiosensitivity
Authors: Steen R. Grant , Wilson David A. , Bowser Cindy , Wehrle Janna P. , Glickson Jerry D. , Rajan S. Sunder
Published: March 2007

Mice with subcutaneous RIF‐1 tumors were anesthetized with sodium pentobarbital (PB) or ketamine plus acepromazine (KA) before acquisition of in vivo 31P nuclear magnetic resonance (NMR) spectra from tumors. The area of the inorganic phosphate resonance was significantly greater (relative to phosphomonoesters or the α‐phosphate resonance of nucleoside triphosphate) in spectra obtained under PB anesthesia, suggesting that the hypoxic fraction of the tumor increased following PB anesthesia. In vivo near‐infrared laser spectroscopy directly demonstrated that tumor oxyhemoglobin was reduced by more than 20% following PB but was not significantly affected by KA. Total hemoglobin (tumor blood volume) was reduced by 11% following PB anesthesia, but was not significantly affected by KA. Tumor growth delay induced by γ‐irradiation was shorter when tumors were irradiated under PB anesthesia than when irradiated under KA, showing that PB anesthesia had a radioprotective effect. These studies demonstrate that both the 31P NMR and near infrared methods can detect metabolic or physiological changes associated with an increase in tumor radioresistance (i.e., an increase in the radiobiological hypoxic fraction).
An interesting syndrome of hemolytic anemia, degeneration of the liver and diabetes associated with a high red cell mg‐atpase, detected by 31p NMR spectroscopy
Authors: Kagimoto Tadashi , Higaki Tsuyoshi , Nagata Kohichi , Morino Yoshimasa , Takatsuki Kiyoshi
Published: March 2007

31P NMR was used to study the erythrocytes of three patients who exhibited a familial multisystem disease characterized by fatty liver, diabetes and nonspherocytic hemolytic anemia of unknown etiology. 31P NMR measurements disclosed an abnormally high level of intracellular inorganic phosphate (Pi) and an abnormally low level of ATP in the erythrocytes 6 h after blood withdrawal from proband (I–1). This finding suggested that ATP was markedly decreased in the red cells of this proband, as compared with those of normal subjects. Time‐dependent changes of 31P NMR spectra of the erythrocytes from the two daughters (II‐1, II‐2) of the proband demonstrated clearly an enhanced decomposition of ATP with a concomitant increment of Pi. Several ATP‐consuming enzymes in erythrocytes, such as those in the Embden‐Meyerhof system, pentose phosphate pathway enzymes, Na+, K+‐ATPase and Ca2+, Mg2+‐ATPase, were within normal limits of activity, but Mg2+‐ATPase was drastically above the normal limit. The Mg2+‐ATPase activity was 3 times higher in the red cell membranes of these patients than in those from normal subjects.
19F MRS studies of fluoropyrimidine chemotherapy. A review
Authors: McSheehy P. M. J. , Griffiths J. R.
Published: March 2007

19F NMR spectroscopy (MRS) has been used to follow the metabolism of the fluoropyrimidine anticancer drug 5‐fluorouracil and its derivatives non‐invasively, both in animals and humans. This review is concerned with the information that has been acquired concerning cytotoxicity and detoxification in relation to studies performed with conventional methods. The potential uses of 19F MRS of fluoropyrimidines in research, particularly concerning combination chemotherapy, and in monitoring therapy, are discussed.
Perturbation of homogeneous magnetic fields by isolated single and confocal spheroids. Implications for NMR spectroscopy of cells
Authors: Kuchel Philip W. , Bulliman Brian T.
Published: March 2007

Analytical expressions for the magnetic potential and the magnetic field strength vector in cells modelled as isolated confocal prolate and oblate spheroids have been derived. The important results which emerged from the analysis are that the magnetic field in the central spheroid, in a series of confocal spheroids, is always uniform; but its magnitude depends upon the orientation of the spheroids relative to the external field. Therefore, the NMR line‐shape derived from an internal solute in a population of sparsely distributed spheroids, with random orientation of the members, is a superposition of Lorentzians; the resulting ‘complicated’ line shape may often appear to be Gaussian. This spectral phenomenon is at least part of the explanation for the non‐Lorentzian character of NMR line‐shapes in the spectra of many biological samples. Quantitative analysis of the NMR line‐shape of an appropriate intracellular solute can in principal yield the orientational distribution of a dilute suspension of cells of uniform size and shape.
Further evidence that the narrow 1H magnetic resonance signals from malignant cells do not arise from intracellular lipid droplets
Authors: Mackinnon Wanda B. , Dyne Marlen , Holmes Kerry T. , Mountford Carolyn E. , Gupta Radhey S.
Published: March 2007

1H magnetic resonance (MR) spectroscopy of intact viable malignant cells yields high resolution spectra from lipid. In previous studies we have provided evidence that these signals are generated by neutral lipid located in the plasma membrane in unique domains. We show that intracellular lipid droplets do not contribute to the MR signal. Two malignant Chinese hamster ovary cell lines, EOT and its parental line WT were studied. The EOT cells have a more highly resolved lipid spectrum than the WT, a result which correlates with slightly increased levels of triglyceride in highly purified plasma membranes. The intracellular lipid droplets of both lines were quantified using both fluorescence and electron microscopy but no significant differences were observed. Together these results provide evidence that narrow 1H MR signals from malignant cells arise from neutral lipid in the plasma membrane, rather than from intracellular lipid droplets.
31P NMR spectroscopic study of bioenergetic changes in radiation‐induced fibrosarcoma‐1 after radiation therapy
Authors: Rajan S. Sunder , Wehrle Janna P. , Li Shi‐Jiang , Steen R. Grant , Glickson Jerry D.
Published: March 2007

The effects of localized γ‐irradiation on the in vivo 31P NMR spectra of RIF‐1 tumors grown subcutaneously in C3H/HeN mice have been examined before and during the week after treatment. Increases in the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) and in tumor pH, and decreases in the ratio of Pi to the b̃ phosphorus resonance of the nucleotide triphosphates (b̃NTP) were observed in irradiated tumors. The time course of changes in the 31P spectrum following treatment was the opposite of the pattern during untreated growth, and the magnitude and duration of the changes increased with increasing radiation dose, decreasing clonogenic cell survival and increasing growth delay. To examine the possibility that nontherapeutic systemic effects of the tumor irradiation were responsible for the changes observed, a number of animals bearing two tumors were examined. One tumor on each mouse was selectively irradiated. Changes in tumor volume, Pi/b̃NTP, PCr/Pi, the ratio of phosphomonoesters to b̃NTP, and tumor pH were all significantly different in the treated compared to the untreated tumor on each animal, indicating that these changes in 31P NMR spectra were a response to radiation therapy and not a systemic response to radiation toxicity.
Characterization of the spleen by In vivo image guided 31P magnetic resonance spectroscopy
Authors: Smith Stephen R. , Martin Peter A. , Davies John M. , Edwards Richard H. T.
Published: March 2007

Image localized 31P magnetic resonance spectroscopy of the spleen was performed in six normal volunteers, 13 patients with splenomegaly due to haematological malignancies, and two patients with benign causes of splenomegaly. The malignant disorders had elevated phosphomonoesters (PME) compared to controls, probably due to increased turnover of membrane phospholipids, with variable alterations in high energy phosphates. There appeared to be no relationship between grade of malignancy and relative PME peak area. An overlap in spectral characteristics between the benign and malignant cases of splenomegaly existed. Serial studies in a patient with high grade lymphoma receiving combination chemotherapy showed changes in phosphorus spectra, with an increase in the phosphodiester/b̃adenosine triphosphate ratio.
Simultaneous multivolume spectroscopy (simuvosp) using local techniques
Authors: Müller S. , Hafner H.‐P. , Beckmann N.
Published: March 2007

MR spectra simultaneously acquired from different locations in the human body may be obtained with the SIMUVOSP technique (Simultaneous Multivolume Spectroscopy). SIMUVOSP is based on multifrequency selective RF pulses which encode positional information of the spins into the phase of the MR signal. This paper describes SIMUVOSP strategies for 1H, 31P and 13C spectroscopy.

For 1H SIMUVOSP the STEAM experiment may be modified by replacing the selective RF pulses with SIMUFREX pulses (Simultaneous Multifrequency Excitation pulses). This modification allows the simultaneous spectroscopic examination of different regions in the human brain. For 31P SIMUVOSP the ISIS method is combined with SIMUFRIN (Simultaneous Multifrequency Inversion) pulses, which generate the inversion of multiple regions during the RF pulse. An application of 31P SIMUVOSP is the study of the metabolic heterogeneity of the high energy phosphates within the human body. For 13C spectroscopy a localized polarization transfer experiment is combined with multivolume excitation. In this way SIMUVOSP on protons is extended to 13C multivolume spectroscopy.
The importance of the voxel size in clinical 1H spectroscopy of the human brain
Authors: Ernst Th. , Hennig J. , Ott D. , Friedburg H.
Published: March 2007

It is demonstrated that it is possible to acquire two volume selective 1H NMR spectra of human brain in vivo, consisting of voxels of 1.5 × 1.5 × 1.5 cm3, within 14 min with a good S/N ratio. This is mainly achieved by the application of a PRESS sequence generating a spin‐echo of the VOI at 135 ms in conjunction with the STABLE technique by which two spectra can be recorded in an interlaced mode. The Bo homogeneity over such small voxels is considerably higher than over larger voxels. With these methodological improvements it is possible to observe morphological heterogeneity of tumors. The results indicate that spectral changes seem to correlate with the metabolic state of the tumor rather than the tumor type. Additionally the spectrum of a patient with multiple sclerosis suggests that even differentiation between tumors and other lesions might not be possible.
Lactate distribution in ischemic rat kidney by 4D spectroscopic imaging
Authors: Lazeyras Francois , Aue Walter P.
Published: March 2007

A lactate map of the rat kidney is presented, using a four‐dimensional spectroscopic imaging technique in connection with a double resonance editing scheme. A voxel size of 12 μL has been obtained, and we show that eddy currents do not affect the line shape of an individual voxel.
Imaging of brain tissue pH and metabolites. A new approach for the validation of volume‐selective NMR spectroscopy
Authors: Höhn‐Berlage M. , Okada Y. , Kloiber O. , Hossmann K.‐A.
Published: March 2007

For the validation of volume‐selective 1H and 31P NMR spectroscopy of the brain methods are required that allow high resolution quantitative mapping of tissue pH and metabolites on intact brain slices. The following techniques are proposed for this purpose. Tissue pH is imaged on cryostat sections of in situ frozen brains, using umbelliferone as a fluorescent pH indicator (Csiba et al, Brain Res 289, 334–337 (1983)). Regional tissue ATP content is measured in adjacent cryostat sections, using the luciferine/luciferase system of fireflies for evoking substrate‐specific bioluminescence (Kogure and Furones Alonso, Brain Res. 154, 273–284 (1978)). Lactate content is imaged in a similar way by inducing substrate‐specific bioluminescence with lactate dehydrogenase and luciferase from vibrio Fischeri (Paschen, J. Cereb. Blood Flow Metab. 5, 609–612 (1985)). The spatial resolution of these techniques is better than 100m̈, as exemplified in experimental brain tumors and brain infarct of cats.

The applicability of biochemical mapping for the validation of NMR spectroscopy was tested in a global brain ischemia model of cat by correlating surface coil 31P and 1H spectra with the corresponding regional biochemical data, measured in the sensitive volume of the coil. Correlation coefficients were r = 0.907, 0.852 and 0.924 for pH, lactate and ATP, respectively. These results demonstrate that the biochemical measurements obtained by bioluminescence and fluoroscopic imaging correlate closely with the NMR data and, therefore, are appropriate for the validation of more complex applications, such as volume‐selective spectroscopy of brain infarcts or tumors.
Rational approaches to the design of NMR selective pulses
Authors: Morris Peter G. , McLntyre Dominick J. O. , Rourke David E. , Ngo J. Thomas
Published: March 2007

The need for NMR selective pulses in magnetic resonance imaging and spectroscopy is reviewed. The shortcomings of the current generation of pulses are discussed and the need for new categories of pulse identified. Strategies for selective pulse design are outlined and two numerical optimization methods, simulated annealing and SPINCALC (a method recently introduced by us: J. T. Ngo and P. G. Morris, Magn. Reson. Med. 5, 217 (1987)), are discussed in detail. Their use is illustrated and compared for the design of π/2 phase‐compensated pulses. Both methods require substantial amounts of CPU time, with simulated annealing the more demanding. Unconstrained, simulated annealing also tends to produce pulses with discontinuous waveforms. A crude two‐dimensional pulse derived from a low flip angle approximation is illustrated.
Localized 13C‐{1H} NMR of rat liver In vivo using surface‐spoiling gradients
Authors: Chen Wei , Ackerman Joseph J. H.
Published: March 2007

An NMR spectroscopy localization method that employs an inhomogeneous surface‐spoiling magnetic field gradient has been applied to detect the 13C‐{1H} signals from deep‐lying liver tissue of rat in vivo. The method requires small gradient driving currents (less than 1 amp) and short gradient periods (˜0.5–1.6 ms). Thus, it is not likely to suffer from induced eddy currents and can detect short T2 resonances. We demonstrate that by employing a pulsed surface‐spoiling gradient one can eliminate “contaminating” signals from the surface‐lying tissues (muscle, fat and skin) while still maintaining the resonance linewidth resolution for the deep‐lying tissue of interest (liver). The feasibility of using this localization approach to trace glucose conversion into glycogen is shown.
19F chemical shift imaging in perfluorocarbons
Authors: Börnert Peter , Dreher Wolfgang , Schneider Wilfried
Published: March 2007

The use of 19F chemical shift sensitive imaging techniques to monitor the biodistribution of perfluorocarbons (PFC) is discussed. For these experiments one has to study the spectroscopic properties of the PFC to be mapped for choosing high performance NMR imaging sequences. Three techniques used in our laboratory, a chemical shift selective approach, a method using spectrum simplification and a chemical shift sensitive NMR imaging method using adjusted phase encoding are discussed and illustrated by experiments.
Problems and expediencies in human 31P spectroscopy. The definition of localized volumes, dealing with saturation and the technique‐dependence of quantification
Authors: Bottomley Paul A. , Hardy Christopher J. , Roemer Peter B. , Weiss Robert G.
Published: March 2007

Several technological problems in in vivo localized spectroscopy of metabolism are discussed in the context of comparing data obtained by different means. Deficiencies in spectroscopy localization methods can produce spectra that are dominated by artefactual signals derived from outside of selected volumes. Such artefacts are not usually correctly accounted for by representations of the profiles of the transverse magnetization alone. Selected sensitive volumes should be defined in terms of the size of tissue contributing the major fraction of signal to an observed spectrum, which is the integrated response from the sample including any phase cancellation effects. Phase cancellation in one‐dimensional localization techniques employing excitation by an RF field with uniform phase distribution and surface coil detection such as depth resolved surface coil spectroscopy, chemical shift imaging (CSI) and rotating frame zeugmatography (RFZ) can significantly alter the effective radius of the sensitive volumes depending on the sample distribution and the extent of the homogeneous region of the magnet. Also, discrete spatial sampling in RFZ and CSI can radiate signal artefacts of around 25% into adjacent elements depending on the location and distribution of signal sources. Acquisition delays between excitation and detection and partial saturation are other major sources of systematic error. Saturation factors for metabolites are not easily obtainable on localized volumes during clinical exams on an individual basis, but may be expediently obtained as larger‐volume tissue‐averages. Better documentation of saturation effects, acquisition delays and localized volume sizes is needed to compare and validate clinical results and performance.
Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach
Authors: Weiner Michael W. , Hetherington Hoby , Hubesch Bruno , Karczmar Greg , Massie Barry , Maudsley Andrew , Meyerhoff Dieter J. , Sappey–Marinier Dominique , Schaefer Saul , Twieg Donald B. , Matson Gerald B.
Published: March 2007

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water‐suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N‐acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 × 2.25 × 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest. The research activities in this laboratory over the past two years demonstrate the wealth of metabolic information that can be obtained clinically with MRS. Technical advances in the area of proton MRS and spectroscopic imaging should improve the ability to detect metabolic alterations produced by human disease.
In vivo1 values of phosphorus metabolites in human liver and muscle determined at 1.5T by chemical shift imaging
Authors: Buchthal S. D. , Thoma W. J. , Taylor J. S. , Nelson S. J. , Brown T. R.
Published: March 2007

A procedure for obtaining T1 values for phosphorous metabolites in localized regions of human subjects, using a standard 1.5 T MR imager, is described. 31P spectra and T1 values localized to the liver, and to abdominal and calf muscle of healthy volunteers were obtained by means of a multi‐slice spectroscopy technique, consisting of a chemical shift imaging (CSI) sequence with a B1‐insensitive excitation and one dimension of phase encoding, used in conjunction with a surface coil. An examination consisting of proton imaging, shimming and collection of 31P progressive saturation spectroscopic data for T1 determination required 1h to perform. Shimming on the signal from the body region detected by the surface coil gave spectra of excellent spectral resolution. Quantification of all peaks in the localized 31P spectra was carried out with the PIQABLE algorithm, and T1 values were calculated for inorganic phosphate (Pi), the phosphodiester region, and the ATP α‐, b̃‐ and γ peaks of liver, and for calf muscle Pi, phosphocreatine (PCr), and the three ATP peaks. The precisions of the measurement and of the entire process for obtaining and quantifying localized spectra by one‐dimensional CSI were determined, and the accuracy of T1 values obtained by this means was verified. The temporal variation in T1 values obtained in a series of examinations of a single normal subject was also assessed. The consistency of the T1 values obtained in this study with in vivo T1 values obtained by other techniques is a stringent test of accuracy of localized spectra obtained with CSI.
Metabolic consequences of coronary stenosis. Transmurally heterogeneous myocardial ischemia studied by spatially localized 31P NMR spectroscopy
Authors: Uǧurbil K. , Merkle H. , Robitaille P.‐M. , Hendrich K. , Yoshiyama M. , Path G. , Zhang J. , Tristani M. , From A. H. L. , Bache R. J. , Garwood M.
Published: March 2007

Coronary stenosis results in transmurally non‐uniform blood flow with the inner layers of the left ventricular wall typically suffering a more severe hypoperfusion relative to the outer layers. Coupled with numerous other transmural non‐uniformities such as systolic tension development and oxygen needs, the heterogeneous blood flow distribution in the presence of coronary stenosis is expected to result in transmurally heterogeneous ischemia. All previous NMR spectroscopy studies of myocardial metabolism and bioenergetics under normal and ischemic conditions treated the organ as a homogeneous tissue. We have utilized spatially localized 31P NMR spectroscopy together with non‐NMR measurements of regional blood flow to study the myocardium with transmural spatial differentiation under normal and flow‐restricted conditions. 31P NMR and blood flow data obtained concurrently on each heart revealed that sustained coronary artery stenosis resulted in transmurally non‐uniform ischemia which largely paralleled the hypoperfusion pattern. The reduction in creatine phosphate content (with consequent elevation of Pi) and hypoperfusion was tightly correlated in the subendocardium for flow rates less than ∼0.7 mL/min per g wet myocardium. The high energy phosphate and Pi content of the epicardium, however, was responsive not only to the flow to this region but also to the extent of ischemia in the subendocardial layers. These results document the utility of localized NMR spectroscopy in physiologic research and suggest potential biomedical applications due to the tight correlation noted between alterations in blood flow and changes in the phosphorylated metabolite levels detected by 31P NMR.
Some considerations concerning susceptibility, longitudinal relaxation time constants and motion artifacts in In vivo human spectroscopy
Authors: Young I. R. , Cox I. J. , Coutts G. A. , Bydder G. M.
Published: March 2007

Artifacts due to localized susceptibility effects, variations in the spin‐lattice relaxation time constants of signals and a mixing of signals arising from tissue motions can contaminate otherwise credible results. The sources and magnitude of some of these are discussed and their likely impact assessed, so that the necessity of incorporating additional measurements in an individual study can be demonstrated.
Amplification or obfuscation: Is localization improving our clinical understanding of phosphorus metabolism?
Authors: Ross Brian , Narasimhan P. T. , Tropp James , Derby Kevin S.
Published: March 2007

Localization techniques are considered an indispensable part of the clinical spectroscopy examination. The results are often a marked improvement in diagnostic information (amplification), but because of the introduction of new artifacts and the more prolonged examination time, some of the undoubted advantage is lost (obfuscation). There is thus an argument for continued development of more rapid methods of clinical spectroscopy and, if necessary, sacrificing some spatial information.
31P NMR of mammalian cells encapsulated in alginate gels utilizing a new phosphate‐free perfusion medium
Authors: Narayan K. Shankar , Moress E. A. , Chatham J. C. , Barker P. B.
Published: March 2007

A simple technique permitting long term 31P magnetic resonance spectroscopy of cultured mammalian cells is described. Cells are encapsulated in calcium alginate gels and perfused with a new phosphate‐free medium designed for maintenance of high cell viability. Intracellular pH and β‐NTP/Pi ratios, studied in three cell types, remained stable over a 16–20 h NMR monitoring period. The techniques described may be useful for monitoring cell metabolism with a variety of cell types.
Decoupling technique for transmit coils in NMR spectroscopy and imaging
Authors: Yoda K.
Published: March 2007

A decoupling structure using an additional LC resonant configuration for NMR transmit coils is analysed and the probe sensitivity of the receive coil with the decoupled transmit coil is calculated using simple circuit models. An adjustment‐free technique for the decoupling circuit under different loading conditions is proposed using the calculated results and demonstrated by experiments. The proposed method can simplify the probe operation.