The purpose of this work was to investigate the temporal relationship between intensity changes in T2*-weighted NMR images and tissue oxygen content, measured by myoglobin proton NMR spectroscopy, in the skeletal muscle. During an ischemic stress test, the calf muscles of five healthy volunteers were studied at 3 Tesla. An interleaved NMRI-NMRS sequence was used, which made it possible to record T2*-weighted images and myoglobin spectra simultaneously. During ischemia, rapid changes in muscle signal intensity were observed on T2*-weighted images, which immediately preceded myoglobin desaturation. Bearing in mind the respective P50 of hemoglobin and myoglobin, this observation clearly favored the hypothesis that hemoglobin desaturation was responsible for the changes in T2*. This interpretation was further supported by the temporal coincidence between the experimental NMR data and a model of hemoglobin desaturation solely derived from physiological considerations.

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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...

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