Total creatine in muscle: Imaging and quantification with proton MR spectroscopy

PURPOSE: To provide a noninvasive method of imaging and quantifying total creatine (phosphorylated plus unphosphorylated) in human muscle with proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Water- suppressed, long echo time, stimulated-echo hydrogen-1 chemical shift imaging and short echo time unsuppressed chemical shift imaging were performed on the lower legs of 10 healthy volunteers at rest. Spatial resolution was 4.5-8.0 cm³. Water signals in unsuppressed data sets were quantified and used as chemical shift and concentration references. Images of the integrated N-CH₃ resonance assigned to total creatine were extracted from the water-suppressed chemical shift image data. Correlations between the total creatine, lipid, and water signals from the same voxels were tested. The concentration of total creatine in skeletal muscle was calculated from the ratio of the relaxation-corrected N-CH₃ and water signals from the same voxels. RESULTS: Total creatine was localized to muscle bundles. Lipid signals contributed less than 6% to the variance of total creatine signal on images and in measurements and did not correlate with total creatine in the same voxels (P > .1). Total creatine and unsuppressed water signals were positively correlated (P < .0001). MR spectroscopy yielded a total creatine value of 36.2 mmol/kg wet weight ± 5.0, consistent with prior biopsy data. CONCLUSION: H-1 MR spectroscopy can be used to image and noninvasively quantify total creatine in human muscle. Its use could improve the understanding of the role of altered creatine metabolism in muscle disease and aid quantification of the response to creatine therapies.