How to investigate oxygen supply, uptake, and utilization simultaneously by interleaved NMR imaging and spectroscopy of the skeletal muscle

Abstract

Human skeletal muscle perfusion, oxygenation, and high-energy phosphate distribution were measured simultaneously by interleaved 1 H and 31 P NMR spectroscopy and 1 H NMR imaging in vivo. From these parameters, arterial oxygen supply (DO 2 ), muscle reoxygenation rate, mitochondrial ATP production, and O 2 consumption (VO 2 ) were deduced at the recovery phase of a short ischemic exercise bout. In addition, by using a reformulation of the mass conservation law, muscle maximum O 2 extraction was calculated from these parameters. Perhaps even more appealing than its non-invasiveness is the ability of NMR to investigate a great many facets of physiology and biochemistry in vivo. In peripheral organs, it is possible to explore by NMR techniques: muscle kinematics, mass and composition, vascularization, regional perfusion, blood and tissue oxygenation, high-energy phosphate distribution, lactate production and intracellular pH, Krebs cycle activity, and mitochondrial oxidative phosphorylation. Regrettably, NMR acquisition schemes rarely explore more than a limited number of parameters, often one at a time, essentially because of the quite specific spectrometer configuration required for each particular examination type. This has been a handicap in the study of tissue regulation in vivo, which ought to be a major target for NMR biomedical applications.This drawback is well illustrated in one study aimed at elucidating the relationship between skeletal muscle perfusion and oxidative phosphorylation (1). Due to technical constraints, post-ischemic reactive hyperemia and creatine rephosphorylation rate were measured during separate experimental sessions. As a consequence, the modest though highly significant correlation between the two parameters did not clarify the question under consideration. Did the observed, relatively weak, degree of dependence of oxidative phosphorylation on perfusion translate a biologic reality, or did it essentially reflect inter-study variability?One possible solution, instigated by a few groups, was the implementation of other techniques inside the magnet bore, to be run in parallel to the NMR data acquisition. Near infrared spectroscopy (NIRS) was combined to 31 P NMR spectroscopy as an elegant way to investigate further the oxygen dependence of high-energy phosphate production (2). If NIRS offers many practical advantages, such as high temporal resolution, clinical applicability, and favorable cost-effectiveness, it also suffers serious limitations, mainly related to ambiguous spatial and molecular origins of the re-emitted signal. Though more challenging, NMR seems to bear a greater potential in terms of discriminating capillary and cell oxygenation (3), and developing multiparametric NMR protocols is a valid, possibly preferable, option.Concurrent heteronuclear NMR was pioneered both in Oxford and in Philadelphia (4,5) and culminated with the demonstration of simultaneous in vivo 1 H, 19 F, 31 P, and 23 Na NMR acquisitions (6). The relationship between intracellular sodium accumulation an...

Muscle blood flow and oxygenation measured by NMR imaging and spectroscopy

“…Indeed, this switch from aerobic to anaerobic respiration is supported by multiple 1 H and 31 P studies showing that the muscle P i :PCr ratio starts to rise at the exact moment Mb desaturation plateaus (23). During ischaemic exercise, due to the high metabolic demand, the same succession of events occurs at an accelerated rate and Mb can become totally desaturated within a minute or so (28,29).…”

“…Time-constants are short, typically less than 10 s during normal reactive hyperemia, but somewhat longer (10-30 s) during exercise recovery, and may even exceed 300 s when tissue perfusion is compromised during recovery (23,28,29,35).…”

“…More recently, leg Mb concentrations measured by NMR were shown to be 25% higher in endurance-trained athletes as compared with sprinters, and to correlate with mitochondrial oxidative production of ATP (29). Muscle O 2 content can also be readily obtained by multiplying the measured percentage of Mb saturation by the Mb concentration and by Mb oxyphoric capacity, the former usually being derived from NMR data under ischaemia and the latter being taken from physiological reference tables (28). Muscle de-or re-oxygenation rates are the first-order derivatives of muscle O 2 content measured in a series of spectra acquired with a high sampling rate.…”

Dynamic MRS and MRI of skeletal muscle function and biomechanics

“…These techniques are increasingly used to study the balance between muscle activity and the delivery and extraction of oxygen, both in normal and diseased muscle. Recently, Carlier et al (199) have presented a comprehensive MR protocol for the simultaneous measurement of oxygen supply, uptake and utilization by interleaved The inherent sensitivity of the relaxation properties of tissue water to its physicochemical environment is one of the main reasons for the remarkable soft tissue contrast in MRI in general and also one of its major strengthts when applied to skeletal muscle. In particular, the T 2 relaxation time has been widely used to study water organization and compartmentation in skeletal muscle and how these change with muscle injury (200)(201)(202) and contraction [for a review, see (197,203)].…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…Une telle approche fait gagner du temps, elle autorise une analyse combinée de variables dynamiques qui n'aurait pas été possible si celles-ci avaient été acquises séparément, ceci du fait de la difficulté pour un sujet à reproduire plusieurs fois le même exercice musculaire. Il a été démontré que l'extraction d'oxygène musculaire pouvait être déduite de tels protocoles fonctionnels d'imagerie et de spectroscopie multi-paramétriques (Carlier et al 2005). C'est à l'aide d'outils multi-paramétriques qu'il a été identifié qu'une perfusion anormale contribuait à une réduction de la capacité des oxydations phosphorylantes mitochondriales chez les patients atteints de glycogénose de type III (Wary et al 2010).…”