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Background  Cardiovascular phosphorus MR spectroscopy ( 31 P-CMRS) is a powerful tool for probing energetics in the human heart, through quantification of phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. In principle,  31 P-CMRS can also measure cardiac intracellular pH (pH i ) and the free energy of ATP hydrolysis (ΔG ATP ). However, these require determination of the inorganic phosphate (Pi) signal frequency and amplitude that are currently not robustly accessible because blood signals often obscure the Pi resonance.  Typical cardiac  31 P-CMRS protocols use low (e.g. 30°) flip-angles and short repetition time (TR) to maximise signal-to-noise ratio (SNR) within hardware limits. Unfortunately, this causes saturation of Pi with negligible saturation of the flowing blood pool. We aimed to show that an adiabatic 90° excitation, long-TR, 7T  31 P-CMRS protocol will reverse this balance, allowing robust cardiac pH i  measurements in healthy subjects and patients with hypertrophic cardiomyopathy (HCM).    Methods  The cardiac Pi T 1  was first measured by the dual TR technique in seven healthy subjects. Next, ten healthy subjects and three HCM patients were scanned with 7T  31 P-MRS using long (6 s) TR protocol and adiabatic excitation. Spectra were fitted for cardiac metabolites including Pi.    Results  The measured Pi T 1  was 5.0 ± 0.3 s in myocardium and 6.4 ± 0.6 s in skeletal muscle. Myocardial pH was 7.12 ± 0.04 and Pi/PCr ratio was 0.11 ± 0.02. The coefficients of repeatability were 0.052 for pH and 0.027 for Pi/PCr quantification. The pH in HCM patients did not differ ( p  = 0.508) from volunteers. However, Pi/PCr was higher (0.24 ± 0.09 vs. 0.11 ± 0.02;  p  = 0.001); Pi/ATP was higher (0.44 ± 0.14 vs. 0.24 ± 0.05;  p  = 0.002); and PCr/ATP was lower (1.78 ± 0.07 vs. 2.10 ± 0.20;  p  = 0.020), in HCM patients, which is in agreement with previous reports.    Conclusion  A 7T  31 P-CMRS protocol with adiabatic 90° excitation and long (6 s) TR gives sufficient SNR for Pi and low enough blood signal to permit robust quantification of cardiac Pi and hence pH i . Pi was detectable in every subject scanned for this study, both in healthy subjects and HCM patients. Cardiac pH i  was unchanged in HCM patients, but both Pi/PCr and Pi/ATP increased that indicate an energetic impairment in HCM. This work provides a robust technique to quantify cardiac Pi and pH i .

journal of cardiovascular magnetic resonance

Measuring inorganic phosphate and intracellular pH in the healthy and hypertrophic cardiomyopathy hearts by in vivo 7T 31P-cardiovascular magnetic resonance spectroscopy