Key result
In patients with hypertrophic cardiomyopathy, 7T 31P-CMRS revealed a significantly higher cardiac Pi/PCr ratio (0.24 vs 0.11, p=0.001) compared to healthy volunteers, while intracellular pH remained unchanged.
Why the study?
Cardiac intracellular pH and free energy of ATP hydrolysis measurements via 31P-CMRS are limited because blood signals obscure inorganic phosphate, which suffers from saturation under typical protocols.
Does a 7T 31P-CMRS protocol with adiabatic 90° excitation and long TR allow robust quantification of cardiac inorganic phosphate and intracellular pH in healthy subjects and HCM patients?
Cross-Sectional (n=15)
No
Does a 7T 31P-CMRS protocol with adiabatic 90° excitation and long TR allow robust quantification of cardiac inorganic phosphate and intracellular pH in healthy subjects and HCM patients?
Answers are grounded in this paper and cite their sources.
A 7T 31P-CMRS protocol with adiabatic excitation and long TR enables robust in vivo quantification of cardiac inorganic phosphate and intracellular pH, demonstrating energetic impairment in HCM patients.
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). 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. 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. 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 .
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Valkovič et al. (2019) conducted a cross-sectional in Hypertrophic Cardiomyopathy (n=15). Hypertrophic cardiomyopathy vs. Healthy volunteers was evaluated on Cardiac Pi/PCr ratio (p=0.001). In patients with hypertrophic cardiomyopathy, 7T 31P-CMRS revealed a significantly higher cardiac Pi/PCr ratio (0.24 vs 0.11, p=0.001) compared to healthy volunteers, while intracellular pH remained unchanged.
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