On the Importance of Exchangeable NH Protons in Creatine for the Magnetic Coupling of Creatine Methyl Protons in Skeletal Muscle

Kruiskamp, Marijn J.; Nicolay, Klaas

doi:10.1006/jmre.2000.2266

Cited by 10 publications

(17 citation statements)

References 15 publications

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“…Nor can the MT effect be explained by chemical exchange, since the observed protons are constituents of methyl groups, which are not subject to this effect. In addition, ex vivo experiments in which muscle was equilibrated in D 2 O suggest that an indirect effect through exchange of the NH protons of Cr is unlikely (15). Therefore, the main effect is likely to be cross‐relaxation, probably mediated in part by water, since strong magnetic coupling between water and Cr is known to occur (16).…”

Section: Discussionmentioning

confidence: 99%

Magnetization transfer effect on human brain metabolites and macromolecules

Simister

Barker

Duncan

2005

Magnetic Resonance in Med

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A pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 T amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point-resolved spectroscopy (PRESS)-localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N-acetylated compounds, choline (Cho), myo-inositol, and lactate (Lac); a trend of an effect on glutamate ؉ glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling. The water signal in vivo is reduced following presaturation of the broad signals at several kHz offset from water resonance, through the magnetization transfer (MT) effect (1). This off-resonance irradiation directly saturates immobile protons bound in large macromolecules, which due to their restricted mobility have a very short T 2 (Ͻ100 s) and a very broad linewidth (Ͼ10 kHz). More freely mobile protons, with longer T 2 and narrow linewidth, are not directly affected by the narrow-bandwidth RF irradiation, but are indirectly affected through MT. When the saturation from the bound pool is transferred, signal from the free pool declines, leading to lower intensities in MR images. The mechanisms for this MT are thought to include chemical exchange of weakly-bound protons (such as amines and hydroxyl groups) with water, dipolar crossrelaxation, and diffusion of water from the surface of macromolecules into the bulk environment.MT effects have also been shown in the brain for creatine (Cr), lactate (Lac), and ethanol (2,3), and one study in animals has shown significant albeit small effects of offresonance MT pulses on most metabolites (4). It is unclear whether the MT effect represents subcellular compartmentation, binding of metabolites to enzymes or other proteins, or some other effect.To date, no MT-MRS studies have focused on brain disease, apart from tumors in rats (5,6). Luo et al. (6) showed a significant MT effect on Lac in the tumor, whereas Roell et al. (5) showed an effect on Lac only postmortem. A new MT effect postmortem was also shown on NAA. Glutamate and glutamine (Glx) showed an effect only in contralateral brain, suggesting that there was normally an MT effect on Glx that was lost in the tumor.The effect of MT pulses on the MRS-visible macromolecule signal has never been explicitly studied in humans. In rats, the macromolecule peaks showed no MT effect in 2D correlation spectroscopy, although inspection of 1D difference spectra at short echo times (TEs) suggests that they may have shown an effect (4).The current study details the implementation of MT-MRS ...

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Section: Discussionmentioning

confidence: 99%

Magnetization transfer effect on human brain metabolites and macromolecules

Simister

Barker

Duncan

2005

Magnetic Resonance in Med

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“…In vivo magnetization transfer (MT) effects from irradiated protons associated with immobile macromolecules and membranes can occur to water (1–3) and to metabolites (4–13). The mechanism of MT during off‐resonance irradiation (i.e., not on water) has been well described for both instances.…”

Section: Pathways Of Magnetization Transfer After Labeling At Water Fmentioning

confidence: 99%

“…For instance, for creatine in excised rat muscle, the off‐resonance saturation effect was found to be pH‐independent in H 2 O and to remain unchanged in D 2 O, interpreted as excluding a contribution of exchangeable NH protons to the transfer process (4, 13). However, on‐resonance water saturation was found to increase the saturation transfer effect to metabolites (4, 12, 13). In addition, selective inversion of the water magnetization caused a transient reduction in the creatine resonance in vivo, but not in vitro, the mechanism of which is also unknown.…”

Section: Pathways Of Magnetization Transfer After Labeling At Water Fmentioning

confidence: 99%

Mechanism of magnetization transfer during on‐resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids

Zijl

Zhou

Mori

et al. 2003

Magnetic Resonance in Med

204

257

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The mechanism of magnetization transfer (MT) between water and components of the proton spectrum was studied ex vivo in a perfused cell system and in vivo in the rat brain (n ‫؍‬ 5). Water was selectively labeled and spectral buildup consequential to transfer of longitudinal magnetization was followed as a function of time. At short mixing time (T m ), nitrogen-bound solventexchangeable protons were observed, predominantly assigned to amide groups of proteins and peptides. At longer T m , intramolecular nuclear Overhauser enhancement (NOE) was observed in the aliphatic proton region, leading to a mobile-macromolecule-weighted spectrum that resembles typical protein spectra described in the literature. This effect on the proton spectrum is distinct from that of classical off-resonance MT, which has been shown to be due to the immobile solid-like proton pool. When studying a solution of major brain metabolites under physiological concentrations and conditions (pH), no transfer effects were observed, in line with expectations based on reduced NOE effects in rapidly tumbling molecules and the fast proton exchange rates of amino, amine, SH, and OH groups. In vivo magnetization transfer (MT) effects from irradiated protons associated with immobile macromolecules and membranes can occur to water (1-3) and to metabolites (4 -13). The mechanism of MT during off-resonance irradiation (i.e., not on water) has been well described for both instances. The semisolid lattice protons are efficiently saturated via intramolecular dipolar transfer over the complete spin system (spin diffusion), which is followed by intermolecular transfer to interacting smaller molecules.This intermolecular saturation transfer can in principle occur both via proton exchange and dipolar cross relaxation to short-lived bound molecules (Fig. 1), the descriptions of which are theoretically equivalent. However, the sequence of events after transfer of saturation to metabolites is not yet well understood. For instance, for creatine in excised rat muscle, the off-resonance saturation effect was found to be pH-independent in H 2 O and to remain unchanged in D 2 O, interpreted as excluding a contribution of exchangeable NH protons to the transfer process (4,13). However, on-resonance water saturation was found to increase the saturation transfer effect to metabolites (4,12,13). In addition, selective inversion of the water magnetization caused a transient reduction in the creatine resonance in vivo, but not in vitro, the mechanism of which is also unknown.In the present article we investigate the effect of water perturbation on ex vivo and in vivo metabolite spectra using a selective water-exchange-filter experiment (WEXfilter) (14,15) in which the path of MT of RF-labeled water protons can be followed as a function of time. Using a detection scheme that does not suppress exchangeable protons, it is possible to follow the interaction between water, exchangeable protons, and other molecular sites on a time scale of a few milliseconds to a second. The present...

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“…Subsequently, De Graaf et al (112) demonstrated that other metabolites in rat brain, including glutamate/glutamine and lactate, also exhibit a significant off-resonance MT effect. When studying mouse, rat and human skeletal muscle, Kruiskamp et al (82,(113)(114)(115) observed a pronounced MT effect for PCr/Cr in skeletal muscle as well. Similar conclusions were reached in a more recent study on human skeletal muscle by Renema et al (116).…”

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confidence: 99%

Dynamic MRS and MRI of skeletal muscle function and biomechanics

et al. 2006

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MR is a powerful technique for studying the biomechanical and functional properties of skeletal muscle in vivo in health and disease. This review focuses on 31 P, 1 H and 13 C MR spectroscopy for assessment of the dynamics of muscle metabolism and on dynamic 1 H MRI methods for non-invasive measurement of the biomechanical and functional properties of skeletal muscle. The information thus obtained ranges from the microscopic level of the metabolism of the myocyte to the macroscopic level of the contractile function of muscle complexes. The MR technology presented plays a vital role in achieving a better understanding of many basic aspects of muscle function, including the regulation of mitochondrial activity and the intricate interplay between muscle fiber organization and contractile function. In addition, these tools are increasingly being employed to establish novel diagnostic procedures as well as to monitor the effects of therapeutic and lifestyle interventions for muscle disorders that have an increasing impact in modern society.

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On the Importance of Exchangeable NH Protons in Creatine for the Magnetic Coupling of Creatine Methyl Protons in Skeletal Muscle

Cited by 10 publications

References 15 publications

Magnetization transfer effect on human brain metabolites and macromolecules

Magnetization transfer effect on human brain metabolites and macromolecules

Mechanism of magnetization transfer during on‐resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids

Dynamic MRS and MRI of skeletal muscle function and biomechanics

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