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

Abstract

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...

Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

“…1 H NMR of perchloric acid extracts shows that this is the case. Furthermore it had been shown that total creatine is proportional to creatine content in other circumstances [21,25]. Therefore, the conclusion drawn with 31 P NMR on muscle energetics (PCr, PCr:ATP ratio and PCr to γ-ATP flux) appears to be valid.…”

“…In our experiment, the rate constants k a and k b between PCr and γ-ATP and between β-ATP and β-ADP respectively were determined as: Ex vivo 1 H NMR spectroscopy Muscle energetics calculated from 31 P NMR spectroscopy parameters rely on hypotheses, one of which is that total creatine (PCr+creatine) content in muscle is strictly proportional to the NMR signal, regardless the circumstances. To make sure that total creatine content was constant in DEX-treated, PF and CON rats, we have measured this content in perchloric acid extracts with 1 H NMR spectroscopy, which is the reference technique [20,21].…”

Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle

“…In turn, macroscopic compartmentation is better described as partial volume effect and is a very common finding in MR spectroscopy and imaging. Different metabolite levels [55][56][57] and splitting of the resonance of inorganic phosphate 56,[58][59][60][61][62] may be the result of the inclusion of slow-and fast-twitch fibers in the sensitive volume of 31 P-MR spectra acquisition. An interpretation of this effect obviously can lead to physiological knowledge; however, since it does not contain specific information on cellular or subcellular order of tissue, it will not be discussed in detail here.…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…La concentration d'ADP libre cytosolique ainsi que la production d'ATP par les voies oxydatives et non-oxydatives peuvent être déterminées. Conjuguée à la mise en oeuvre relativement simple d'antennes de surface posées directement en regard du segment d'intérêt, la spectroscopie du 31 P a contribué énormément à l'avancée des connaissances sur l'énergétique musculaire, sa régulation à l'exercice et les perturbations introduites par les pathologies (Chance et al 1986 ;Heerschap et al 1999 ;Argov et al 2000). À ce jour, la spectroscopie RMN n'a toutefois pas joué un role significatif comme outil d'évaluation des maladies neuromusculaires.…”