In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism?

Bottomley, Paul A.; Edelstein, William A.; Foster, Thomas H.; Adams, William A.

doi:10.1073/pnas.82.7.2148

Cited by 104 publications

(25 citation statements)

References 28 publications

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“…[203][204][205][206][207][208][209] Using these techniques, signal-to-noise ratio enhancements of more than 10,000:1 have been achieved in vitro. Historically, many metabolic pathways have been probed using either 14 C or (more recently) 11 C as radiolabels. It has also been shown that 13 C MRS studies using enriched 13 C have enormous potential for probing metabolic pathways.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

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Recent Advances in Magnetic Resonance Neurospectroscopy

Rosen

Lenkinski

2007

Neurotherapeutics

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Summary:Over the past two decades, proton magnetic resonance spectroscopy (proton MRS) of the brain has made the transition from research tool to a clinically useful modality. In this review, we first describe the localization methods currently used in MRS studies of the brain and discuss the technical and practical factors that determine the applicability of the methods to particular clinical studies. We also describe each of the resonances detected by localized solvent-suppressed proton MRS of the brain and discuss the metabolic and biochemical information that can be derived from an analysis of their concentrations. We discuss spectral quantitation and summarize the reproducibility of both single-voxel and multivoxel methods at 1.5 and 3-4 T. We have selected three clinical neurologic applications in which there has been a consensus as to the diagnostic value of MRS and summarize the information relevant to clinical applications. Finally, we speculate about some of the potential technical developments, either in progress or in the future, that may lead to improvements in the performance of proton MRS.

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Section: Summary and Future Directionsmentioning

confidence: 99%

“…In 1985, Bottomley et al 14 published the first human in vivo solvent-suppressed proton spectrum of the brain (FIG. 2).…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Magnetic Resonance Neurospectroscopy

Rosen

Lenkinski

2007

Neurotherapeutics

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“…The recent development of human-sized magnets with fields up to 2.1 T along with techniques for obtaining spectra from localized volumes has made it possible to obtain 'H NMR brain spectra from humans (5,6). While human brain spectra have been obtained with coils surrounding the entire head (6), their sensitivity and spectral resolution have been low compared to animal studies.…”

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confidence: 99%

Spatially localized 1H NMR spectra of metabolites in the human brain.

Hanstock

Rothman

Prichard

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

166

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Using a surface coil, we have obtained 'H NMR spectra from metabolites in the human brain. Localization was achieved by combining depth pulses with imageselected in vivo spectroscopy magnetic field gradient methods.'H spectra in which total creatine (3.03 ppm) has a signal/noise ratio of 95:1 were obtained in 4 min from 14 ml of brain. A resonance at 2.02 ppm consisting predominantly of Nacetylaspartate was measured relative to the creatine peak in gray and white matter, and the ratio was lower in the white matter. The spin-spin relaxation times of N-acetylaspartate and creatine were measured in white and gray matter and while creatine relaxation times were the same in both, the N-acetylaspartate relaxation time was longer in white matter.Lactate was detected in the normoxic brain and the average of three measurements was =0.5 mM from comparison with the creatine plus phosphocreatine peak, which was assumed to be 10.5 mM.The ability of in vivo 1H NMR to measure concentrations of compounds noninvasively has been used to study brain metabolism in animals during hypoxia, hypoglycemia, and ischemia as well as under normal conditions (1-4). The recent development of human-sized magnets with fields up to 2.1 T along with techniques for obtaining spectra from localized volumes has made it possible to obtain 'H NMR brain spectra from humans (5, 6). While human brain spectra have been obtained with coils surrounding the entire head (6), their sensitivity and spectral resolution have been low compared to animal studies. In this communication, we show 'H NMR spectra of the human brain at 2.1 T with spectral resolution and sensitivity comparable to that achieved in animals at 8.5 T. High signal/noise spectra have been obtained in 4 min from 3 x 3 x 1.5 cm volumes. This degree of spatial localization, obtained by using a surface coil with a hybrid three-dimensional image-selected in vivo spectroscopy (ISIS)/depth pulse technique, has allowed us to make regional studies of human brain metabolites. The peak at 2.02 ppm that came from N-acetylaspartate with contributions from overlapping resonances (0. A. C. Petroff, personal communication) was consistently lower in white matter than in gray matter, relative to the total creatine peak (the term total creatine is used in this paper to refer to creatine plus phosphocreatine). This showed the ability of the present technique to measure spatial variations of chemical concentrations. We shall describe the peak at 2.02 ppm as N-acetylaspartate throughout this paper, keeping in mind that there are very probably appreciable contributions to its intensity from other resonances. We have previously shown that the C3 protons of glutamate and y-aminobutyrate overlap this peak. In addition, it has been pointed out to us (E. Berman, personal communication) that the N-acetyl peaks of several compounds, including sialic acid, are observed at 2.02 ppm and might be contributing to the observed intensity. The lactate methyl resonance at 1.33 ppm was resolved and positively identified by ...

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“…Recent advances in in vivo NMR have emphasized 31P and 1H and not '3C (6,7). However, the '3C studies of rats at 8.5 T (8,9) and rabbit at 1.9 T (10) indicated that the '3C NMR technique can reveal hepatic glycogen signals in vivo.…”

mentioning

confidence: 99%

Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle.

Jue

Rothman

Tavitian

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Optimizing the surface-coil design and spectral-acquisition parameters has led to the observation of the 13C NMR natural abundance glycogen signal in man at 2.1 T. Both the human muscle and hepatic glycogen signals can be detected definitively with a time resolution of -13 min. A IH/'3C concentric surface coil was used. The 1H outer coil was 11 cm in diameter; the 13C inner coil was 8 cm in diameter. The coils were tuned to 89.3 MHz and 22.4 MHz, respectively. The IH coil was used for optimizing field homogeneity (shimming) the magnet and for single-frequency decoupling of the Cl glycogen signal. Total power'deposition from both the transmitter pulse and the continuous wave decoupling did not exceed the Food and Drug Administration guideline of 8 W/kg of tissue. Experiments were done for which healthy subjects returned to the magnets at different times for '3C NMR measurement. The spectral difference between experiments was within the noise in the C, glycogen region. Because of the spectral reproducibility and the signal sensitivity, hepatic glycogen repletion can be followed. Four hours postprandial, hepatic glycogen increases by 3.8 times from the basal fasted state. The hepatic glycogen data correspond directly to previous biopsy results and support the use of 13C NMR as a noninvasive probe of human metabolism.Mammalian cells store glucose as glycogen and expend the latter to meet energy demands. Despite the key role of glycogen, many questions remain about hepatic and muscle glycogen repletion and utilization in man. Our understanding has relied on animal model studies (1, 2) and has rested heavily on experimental data obtained from needle biopsy of human muscle and, sometimes, liver. Animal metabolism, of course, is quite different from human (3), and the invasive nature of needle-biopsy techniques has probably discouraged studies of human glycogen metabolism (4, 5).Recent advances in in vivo NMR have emphasized 31P and 1H and not '3C (6, 7). However, the '3C studies of rats at 8.5 T (8, 9) and rabbit at 1.9 T (10) indicated that the '3C NMR technique can reveal hepatic glycogen signals in vivo. Sillerud and Shulman (8) had shown that the '3C NMR intensities originate from 100% of the glycogen atoms; the visibility was established by hydrolyzing glycogen to glucose and observing that the gain in the glucose intensities equaled the loss in the glycogen intensities. The unexpected nature of this high visibility, coming from glycogen molecules with molecular mass of :10 Da, has prompted other investigators (11,12) to repeat the experiments in live animals. Hence all glycogen molecules in vivo are visible; consequently, with proper calibration, their 13C intensities can be used to determine concentrations.The first natural-abundance 13C glycogen signal from human muscle and liver was observed at 2.1 T (13, 14). Subsequent natural-abundance '3C spectra at 4.7 T confirmed the human muscle results and monitored the changes in glycogen levels with exercise (15). However, the initial '3C spectra at 2.1 T lac...

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In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism?

Cited by 104 publications

References 28 publications

Recent Advances in Magnetic Resonance Neurospectroscopy

Recent Advances in Magnetic Resonance Neurospectroscopy

Spatially localized 1H NMR spectra of metabolites in the human brain.

Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle.

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