Creatine kinase rate constant in the human heart at 7T with 1D-ISIS/2D CSI localization

• Published in: PloS one Vol. 15; no. 3; p. e0229933
• Main Authors: Bashir, Adil, Zhang, Jianyi, Denney, Thomas S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2020; Public Library of Science (PLoS)
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Adult; Bandwidths; Biology and Life Sciences; Chemical equilibrium; Computer engineering; Computer simulation; Creatine; Creatine - metabolism; Creatine kinase; Creatine Kinase - isolation & purification; Creatine Kinase - metabolism; Energy; Energy metabolism; Energy Metabolism - physiology; Female; Heart - diagnostic imaging; Heart - physiology; Heart failure; Heart rate; Humans; In vivo methods and tests; Kinases; Kinetics; Livestock; Localization; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy; Male; Mathematical models; Medicine and Health Sciences; Metabolism; Metabolites; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscles; Myocardium; Myocardium - enzymology; Myocardium - pathology; Numerical simulations; Organs; Parameter estimation; Phosphorus Isotopes - chemistry; Physical Sciences; Research and Analysis Methods; Saturation; Skeletal muscle; Spatial discrimination; Spectroscopy; Spectrum analysis; Swine; Alabama; United States > US; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229933

Creatine Kinase (CK) reaction plays an important role in energy metabolism and estimate of its reaction rate constant in heart provides important insight into cardiac energetics. Fast saturation transfer method ([Formula: see text] nominal) to measure CK reaction rate constant (kf) was previously demonstrated in open chest swine hearts. The goal of this work is to further develop this method for measuring the kf in human myocardium at 7T. [Formula: see text] approach is combined with 1D-ISIS/2D-CSI for in vivo spatial localization and myocardial CK forward rate constant was then measured in 7 volunteers at 7T. [Formula: see text] method uses two partially relaxed saturation transfer (ST) spectra and correction factor to determine CK rate constant. Correction factor is determined by numerical simulation of Bloch McConnell equations using known spin and experimental parameters. Optimal parameters and error estimate in calculation of CK reaction rate constant were determined by simulations. The technique was validated in calf muscles by direct comparison with saturation transfer measurements. [Formula: see text] pulse sequence was incorporated with 1D-image selected in vivo spectroscopy, combined with 2D-chemical shift spectroscopic imaging (1D-ISIS/2D-CSI) for studies in heart. The myocardial CK reaction rate constant was then measured in 7 volunteers. Skeletal muscle kf determined by conventional approach and [Formula: see text] approach were the same 0.31 ± 0.02 s-1 and 0.30 ± 0.04 s-1 demonstrating the validity of the technique. Results are reported as mean ± SD. Myocardial CK reaction rate constant was 0.29 ± 0.05 s-1, consistent with previously reported studies. [Formula: see text] method enables acquisition of 31P saturation transfer MRS under partially relaxed conditions and enables 2D-CSI of kf in myocardium. This work enables applications for in vivo CSI imaging of energetics in heart and other organs in clinically relevant acquisition time.