Quantification of creatine kinase reaction rate in mouse hindlimb using phosphorus-31 magnetic resonance spectroscopic fingerprinting

NMR Biomed. 2021 Feb;34(2):e4435. doi: 10.1002/nbm.4435. Epub 2020 Oct 27.

Abstract

The goal of this study was to evaluate the accuracy, reproducibility, and efficiency of a 31 P magnetic resonance spectroscopic fingerprinting (31 P-MRSF) method for fast quantification of the forward rate constant of creatine kinase (CK) in mouse hindlimb. The 31 P-MRSF method acquired spectroscopic fingerprints using interleaved acquisition of phosphocreatine (PCr) and γATP with ramped flip angles and a saturation scheme sensitive to chemical exchange between PCr and γATP. Parameter estimation was performed by matching the acquired fingerprints to a dictionary of simulated fingerprints generated from the Bloch-McConnell model. The accuracy of 31 P-MRSF measurements was compared with the magnetization transfer (MT-MRS) method in mouse hindlimb at 9.4 T (n = 8). The reproducibility of 31 P-MRSF was also assessed by repeated measurements. Estimation of the CK rate constant using 31 P-MRSF (0.39 ± 0.03 s-1 ) showed a strong agreement with that using MT-MRS measurements (0.40 ± 0.05 s-1 ). Variations less than 10% were achieved with 2 min acquisition of 31 P-MRSF data. Application of the 31 P-MRSF method to mice subjected to an electrical stimulation protocol detected an increase in CK rate constant in response to stimulation-induced muscle contraction. These results demonstrated the potential of the 31 P-MRSF framework for rapid, accurate, and reproducible quantification of the chemical exchange rate of CK in vivo.

Keywords: 31P spectroscopy; creatine kinase activity; magnetic resonance fingerprinting; magnetization transfer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Creatine Kinase, MM Form / metabolism*
  • Hindlimb / diagnostic imaging*
  • Hindlimb / enzymology
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Phosphorus
  • Reproducibility of Results

Substances

  • Muscle Proteins
  • Phosphorus
  • Adenosine Triphosphate
  • Creatine Kinase, MM Form