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.

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.

One-dimensional image-selected in vivo spectroscopy localized phosphorus saturation transfer at 7T.

PURPOSE: To evaluate the feasibility of a one-dimensional image-selected in vivo spectroscopy (1D-ISIS) saturation transfer (ST) sequence at 7T for localized in vivo measurements of energy metabolism in different tissues in clinically reasonable examination times. METHODS: The performance of a gradient offset independent adiabacity-based 1D-ISIS localization was tested on phantom and the localized ST sequence was compared with the nonlocalized version in vivo. We performed localized measurements of basal metabolism of human liver and different muscle groups of the calf. Localized ST experiments took 15-25 minutes. RESULTS: The selectivity of the 1D-ISIS sequence was 81.63% and the outer volume suppression was 97.57%. The ST parameters acquired with the 1D-ISIS sequence and with the nonlocalized acquisition in the muscle were not statistically different. The forward rate constants for phosphocreatine (PCr)-adenosine triphosphate (ATP) and inorganic phosphate (Pi)-ATP exchange reactions were measured in the soleus (kCK = 0.30 ± 0.06 s(-1) and kATP = 0.11 ± 0.02 s(-1) , respectively) and in the medial gastrocnemius (kCK = 0.27 ± 0.06 s(-1) and kATP = 0.09 ± 0.03s(-1) , respectively) in 15 minutes per muscle group. The corresponding fluxes were FCK = 6.26 ± 1.28 µmol/g/s, FATP = 0.22 ± 0.05 µmol/g/s and FCK = 6.29 ± 1.66 µmol/g/s, FATP = 0.21 ± 0.07 µmol/g/s, for soleus and gastrocnemius, respectively. The hepatic ATP synthesis measurement was feasible in 24 minutes. CONCLUSION: The fast assessment of PCr-ATP and Pi-ATP exchange rates at 7T makes the 1D-ISIS ST sequence a promising tool for examining local resting-state metabolism in clinically acceptable measurement times.

Interrelation of 31P-MRS metabolism measurements in resting and exercised quadriceps muscle of overweight-to-obese sedentary individuals.

Phosphorus magnetic resonance spectroscopy ((31)P-MRS) enables the non-invasive evaluation of muscle metabolism. Resting Pi-to-ATP flux can be assessed through magnetization transfer (MT) techniques, and maximal oxidative flux (Q(max)) can be calculated by monitoring of phosphocreatine (PCr) recovery after exercise. In this study, the muscle metabolism parameters of 13 overweight-to-obese sedentary individuals were measured with both MT and dynamic PCr recovery measurements, and the interrelation between these measurements was investigated. In the dynamic experiments, knee extensions were performed at a workload of 30% of maximal voluntary capacity, and the consecutive PCr recovery was measured in a quadriceps muscle with a time resolution of 2 s with non-localized (31)P-MRS at 3 T. Resting skeletal muscle metabolism was assessed through MT measurements of the same muscle group at 7 T. Significant linear correlations between the Q(max) and the MT parameters k(ATP) (r = 0.77, P = 0.002) and F(ATP) (r = 0.62, P = 0.023) were found in the study population. This would imply that the MT technique can possibly be used as an alternative method to assess muscle metabolism when necessary (e.g. in individuals after stroke or in uncooperative patients).

Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T and 7 T: a feasibility study.

Phosphorous ((31)P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (kATP) and creatine kinase reaction (kCK), as well as corresponding metabolic fluxes (FATP, FCK), were estimated. A comparison of these exchange parameters, apparent T1s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., kATP 2.7 times higher and kCK 3.4 times higher) than at 3 T (p<0.05). The values for kATP (p=0.35) and kCK (p=0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3T. The minimal time-resolution to reliably quantify both FATP and FCK at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T.