Multinuclear MRS at 7T Uncovers Exercise Driven Differences in Skeletal Muscle Energy Metabolism Between Young and Seniors.

Purpose: Aging is associated with changes in muscle energy metabolism. Proton (1H) and phosphorous (31P) magnetic resonance spectroscopy (MRS) has been successfully applied for non-invasive investigation of skeletal muscle metabolism. The aim of this study was to detect differences in adenosine triphosphate (ATP) production in the aging muscle by 31P-MRS and to identify potential changes associated with buffer capacity of muscle carnosine by 1H-MRS. Methods: Fifteen young and nineteen elderly volunteers were examined. 1H and 31P-MRS spectra were acquired at high field (7T). The investigation included carnosine quantification using 1H-MRS and resting and dynamic 31P-MRS, both including saturation transfer measurements of phosphocreatine (PCr), and inorganic phosphate (Pi)-to-ATP metabolic fluxes. Results: Elderly volunteers had higher time constant of PCr recovery (τ PCr ) in comparison to the young volunteers. Exercise was connected with significant decrease in PCr-to-ATP flux in both groups. Moreover, PCr-to-ATP flux was significantly higher in young compared to elderly both at rest and during exercise. Similarly, an increment of Pi-to-ATP flux with exercise was found in both groups but the intergroup difference was only observed during exercise. Elderly had lower muscle carnosine concentration and lower postexercise pH. A strong increase in phosphomonoester (PME) concentration was observed with exercise in elderly, and a faster Pi:PCr kinetics was found in young volunteers compared to elderly during the recovery period. Conclusion: Observations of a massive increment of PME concentration together with high Pi-to-ATP flux during exercise in seniors refer to decreased ability of the muscle to meet the metabolic requirements of exercise and thus a limited ability of seniors to effectively support the exercise load.

Feasibility and repeatability of localized (31) P-MRS four-angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T.

Phosphorus ((31) P) MRS, combined with saturation transfer (ST), provides non-invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T1 (app) measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four-angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra-high-field MR system, to accelerate the measurement of both Pi -to-ATP and PCr-to-ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth-resolved surface coil MRS (DRESS)-localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, Pi -to-ATP and PCr-to-ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS-localized FAST method. The repeatability of PCr-to-ATP and Pi -to-ATP exchange rate constants, determined by the slab-selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr-to-ATP metabolic flux decreased (from FCK = 8.21 ± 1.15 mM s(-1) to FCK = 3.86 ± 1.38 mM s(-1) ) and the Pi -to-ATP flux increased (from FATP = 0.43 ± 0.14 mM s(-1) to FATP = 0.74 ± 0.13 mM s(-1) ). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS-localized FAST method at 7 T.

Depth-resolved surface coil MRS (DRESS)-localized dynamic (31) P-MRS of the exercising human gastrocnemius muscle at 7 T.

Dynamic (31) P-MRS with sufficiently high temporal resolution enables the non-invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single-voxel localized (31) P-MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single-voxel localization scheme with adiabatic pulses limits the quantification of J-coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth-resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic (31) P-MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm/s versus 0.35 ± 0.18 mm/s) and maximum oxidative flux (0.41 ± 0.14 mm/s versus 0.54 ± 0.16 mm/s) were found between the non-localized and DRESS-localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non-localized datasets, but in none of the DRESS-localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle-specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non-echo-based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle.