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

Abstract

Purpose: 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.

Methods: [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.

Results: 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.

Conclusion: [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.

Fig 1. Pulse sequence for saturation transfer study.

T_sat is the duration of saturation pulse and d1 is the delay for recovery of magnetization. The GOIA-WURST (16, 4) inversion pulse is applied in alternate scans for each phase encoding step. Time axis is not to scale.

Fig 2. Simulated M_o/M_ss (under fully relaxed conditions) and M_c/M_s ratio vs k_f for creatine kinase reaction showing linear relationship and same intercept.

The parameters for simulation were: flip angle = 90°, TR = 2.8 s, T_sat = 1.8 s, PCr:ATP = 2.0, $T_1^{PCr}=4.5\text{s}$ and $T_1^{ATP}=1.8\text{s}$. $T_1^{nom}$ determined for these spin parameters is 1.9 s.

Fig 3. Numeric simulation of percentage error in k_f calculations due to physiological variations in spin parameters.

(A) error due to variation in the PCr/ATP ratio (B) error due to changes in $T_1^{PCr}$ (C) error due to variations in $T_1^{ATP}$ (D) error due to variations in both PCr/ATP ratio and $T_1^{PCr}$, k_f was fixed at 0.3 (s^-1) for this simulation. Parameters used for these numeric simulations were the same as given in Fig 2.

Fig 4. Scout images of the phantom arrangement for T1 measurements.

Large beaker is filled with 75 mM sodium chloride and the vial contains 0.5 M solution of sodium phosphate. Fiducial marking the center of the radiofrequency coil is visible in the images. Sodium phosphate vial was held at 3 cm (a) and 7 cm (b) from the surface of RF coil.

Fig 5. Skeletal muscle k_f determined by conventional saturation transfer approach and T1nom approach with 1D-ISIS/1D-CSI localization.

(A) MR image of calf muscle showing the locations of the 1D-CSI voxels. (B) Series of spectra for conventional saturation transfer approach. The peak localization are as α-ATP at -7.6 ppm, γ-ATP at -2.5 ppm, PCr at 0.0 ppm, phosphodiester (PDE) at 3.2 ppm and inorganic phosphates (Pi) at 5.2 ppm. γ-ATP peak is visible in the top spectrum and is selectively saturated for other spectra. Saturation time was progressively increased and PCr peak intensity decreases with the increasing duration of saturation of γ-ATP. (C) Stack of spectra showing M_c (without ATP saturation, right) and M_s (with ATP saturation, left) using $T_1^{nom}$ method.

Fig 6. Measurement of in vivo 31P MRS saturation transfer in human heart at 7T.

(a) 1H scout image highlighting the typical location of voxel (orange) chosen for analysis. (b) 31P CSI from the slice (b) control and (c) saturation conditions. (d, e, f) Typical 31P magnetization transfer spectra from selected voxels. M_c (control) is shown in blue and M_s (γ-ATP saturation) is in red. The PCr signal is reduced when γ-ATP is saturated.