Broadband proton decoupling in human <sup>31</sup>p NMR spectroscopy

Luyten, Peter R.; Bruntink, Gerard; Sloff, Frenk M.; Vermeulen, Jan W. A. H.; Heijden, Jan I. Van Der; Hollander, Jan A. den; Heerschap, Arend

doi:10.1002/nbm.1940010405

Cited by 163 publications

(83 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using a so-called second radio frequency channel, it is possible to decouple this interaction by irradiation at the 1 H frequency (Luyten et al 1989). The line splittings collapse to give narrower and higher spectral lines, which improves spectral resolution and sensitivity.…”

Section: H Decouplingmentioning

confidence: 99%

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

et al. 1999

View full text Add to dashboard Cite

fax +31 24 3540 866, email a.heerschap@rdiag.azn.nl 31 P magnetic resonance spectroscopy (MRS) offers a unique non-invasive window on energy metabolism in skeletal muscle, with possibilities for longitudinal studies and of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. The present paper provides an introductory overview of the current status of in vivo 31 P MRS of skeletal muscle, focusing on human applications, but with some illustrative examples from studies on transgenic mice. Topics which are described in the present paper are the information content of the 31 P magnetic resonance spectrum of skeletal muscle, some practical issues in the performance of this MRS methodology, related muscle biochemistry and the validity of interpreting results in terms of biochemical processes, the possibility of investigating reaction kinetics in vivo and some indications for fibre-type heterogeneity as seen in spectra obtained during exercise. P magnetic resonance spectroscopy: Skeletal muscle: High-energy phosphates: Energy metabolism: ExerciseFollowing initial experiments on animal tissue (Hoult et al. 1974;Ackerman et al. 1980), magnetic resonance (MR) spectroscopy (MRS) was first applied to human subjects in the early 1980s, using the 31 P nucleus to monitor the levels and fate of high-energy phosphates in skeletal muscle (Chance et al. 1981;Cresshull et al. 1981;Ross et al. 1981). From these first experiments it was clear that 31 P MRS offers a unique non-invasive window on energy metabolism in skeletal muscle. Of particular interest is the possibility of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. Another important aspect is that longitudinal monitoring is possible. Numerous studies applying this technique to human subjects have been published, and several reviews are available addressing specific results obtained in this way (for example, see Barbiroli, 1992;Cozzone & Bendahan, 1994;Kemp & Radda, 1994;McCully et al. 1994;Radda et al. 1995).The present paper provides an introduction to 31 P MRS as applied to skeletal muscle of human subjects, and also gives some illustrative examples from our recent studies on skeletal muscle of transgenic mouse models lacking creatine kinase (EC 2.7.3.2). Information content of the 31 P magnetic resonance spectrum of skeletal muscleTo appreciate the potential of the method, first, the information content of a spectrum obtained from human skeletal muscle at rest should be examined (see Fig. 1(A)).The most dominant signals in the spectrum are from phosphocreatine (PCr) and the three non-equivalent phosphate groups of ATP. Usually also a signal for inorganic phosphate (Pi) can be observed, and under favourable conditions signals for phosphomonoesters and phosphodiesters are observable as well. What is the origin of the distinct resonance frequencies of the 31 P nuclei in these compounds? In a first approximation the resonance frequency of the nuclear spins is...

show abstract

Section: H Decouplingmentioning

confidence: 99%

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Direct in vivo detection of PC and GPC is possible by 31 P MRS, which also enables detection of phosphoethanolamine (PE) and glycerophosphoethanolamine (GPE), thereby providing a more complete picture of in vivo phospholipid metabolism (35). Because 31 P MRS is less sensitive than 1 H MRS and requires dedicated radiofrequency probes, it has been less used to examine phospholipid metabolites in vivo in brain tumors (36,37).…”

Section: Introductionmentioning

confidence: 99%

IDH1 R132H Mutation Generates a Distinct Phospholipid Metabolite Profile in Glioma

et al. 2014

Self Cite

View full text Add to dashboard Cite

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed 31 P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation.31 P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by 31 P highresolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro 31 P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma. Cancer Res; 74(17); 4898-907. Ó2014 AACR.

show abstract

“…Most 13 C NMR applications have relied on WALTZ decoupling of the protons. 80 Recently, it has been demonstrated that using frequency-swept RF pulses as the basic building block, such as the hyperbolic secant pulse, 81 dramatically increase the decoupling bandwidth. These decoupling methods feature only modest increases in peak RF power demand, [82][83][84] while maintaining a favorable ratio of cycling sideband intensity to center peak intensity.…”

mentioning

confidence: 99%

Localized in vivo¹³C NMR spectroscopy of the brain

et al. 2003

View full text Add to dashboard Cite

Localized 13C NMR spectroscopy provides a new investigative tool for studying cerebral metabolism. The application of 13 C NMR spectroscopy to living intact humans and animals presents the investigator with a number of unique challenges. This review provides in the first part a tutorial insight into the ingredients required for achieving a successful implementation of localized 13 C NMR spectroscopy. The difficulties in establishing 13 C NMR are the need for decoupling of the one-bond 13 C-1 H heteronuclear J coupling, the large chemical shift range, the low sensitivity and the need for localization of the signals. The methodological consequences of these technical problems are discussed, particularly with respect to (a) RF front-end considerations, (b) localization methods, (c) the low sensitivity, and (d) quantification methods. Lastly, some achievements of in vivo localized 13 C NMR spectroscopy of the brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and the feasibility of quantifying glutamatergic action in the brain; (b) the demonstration of significant anaplerotic fluxes in the brain; (c) the demonstration of a highly regulated malate-aspartate shuttle in brain energy metabolism and isotope flux; (d) quantification of neuronal and glial energy metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans. We conclude that the unique and novel insights provided by 13 19-24 Most of these studies have involved the administration of a 13 C-enriched precursor. When the enriched 13 C label is transferred to molecules in the metabolic pathway, sensitivity can not only be increased, but important information on metabolic pathways can also be obtained. For example, recent studies showed that the information content of 13 C NMR spectroscopy can be amplified considerably, such as the resolved observation of GABA labeling in the human brain, as well as the first detection of lactate labeling in normal human brain. 8 In addition to its importance in assessing metabolism in intact brain, 13 C NMR spectroscopy has become an important and useful tool in assessing compartmentation of metabolism in brain cells using extracts. 25,26 In addition to its low sensitivity, 13 C NMR spectroscopy is methodologically more challenging than 1 H or even 31 P NMR spectroscopy. However, 13C NMR provides its own unique insight and advantages over 1 H NMR spectroscopy. The uniqueness of 13 C NMR stems mainly from its increased chemical shift dispersion, which can, for example, be used in two-dimensional NMR to increase spectral resolution following specific labeling of the protein. 27 As shall be elaborated further below, 13 C NMR spectroscopy in living tissue provides a unique window on in vivo metabolism as it occurs. In the

show abstract

Broadband proton decoupling in human ³¹p NMR spectroscopy

Cited by 163 publications

References 21 publications

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

IDH1 R132H Mutation Generates a Distinct Phospholipid Metabolite Profile in Glioma

Localized in vivo¹³C NMR spectroscopy of the brain

Contact Info

Product

Resources

About

Broadband proton decoupling in human 31p NMR spectroscopy

Cited by 163 publications

References 21 publications

Introduction toin vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

IDH1 R132H Mutation Generates a Distinct Phospholipid Metabolite Profile in Glioma

Localized in vivo13C NMR spectroscopy of the brain

Contact Info

Product

Resources

About

Broadband proton decoupling in human ³¹p NMR spectroscopy

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Localized in vivo¹³C NMR spectroscopy of the brain