Triple repetition time saturation transfer (TRiST) 31P spectroscopy for measuring human creatine kinase reaction kinetics

Abstract

Human cardiac phosphorus MR saturation transfer experiments to quantify creatine kinase forward rate constants (k(f)) have previously been performed at 1.5 T. Such experiments could benefit from increased signal-to-noise ratio (SNR) and spectral resolution at 3 T. At 1.5 T, the four-angle saturation transfer method was applied with low-angle adiabatic pulses and surface coils. However, low-angle adiabatic pulses are potentially problematic above 1.5 T due to bandwidth limitations, power requirements, power deposition, and intrapulse spin-spin relaxation. For localized metabolite spin-lattice relaxation time (T(1)) measurements, a dual repetition time approach with adiabatic half-passage pulses was recently introduced to solve these problems at 3 T. Because the saturation transfer experiment requires a T(1) measurement performed while one reacting moiety is saturated, we adapt the dual repetition time approach to measure k(f) using a triple repetition time saturation transfer (TRiST) method. A new pulsed saturation scheme with reduced sensitivity to static magnetic field inhomogeneity and compatibility with cardiac triggering is also presented. TRiST measurements of k(f) are validated in human calf muscle against conventional saturation transfer and found to agree within 3%. The first 3-T TRiST measurements of creatine kinase k(f) in the human calf (n = 6), chest muscle, and heart (n = 8) are 0.26 +/- 0.04 s(-1), 0.23 +/- 0.03 s(-1), and 0.32 +/- 0.07 s(-1), respectively, consistent with prior 1.5 T values.

Figure 1

Scheme of the TRiST acquisitions showing the amplitude modulation of the frequency selective RF saturation versus time. A zoomed version is shown in the inset where 100μs sub-pulses are used for real-time interrogation of the R-wave to enable cardiac triggering. The negative sign of the RF amplitude is to be understood as 180° phase shift. AHP and ACQ denote adiabatic half passage excitation and the acquisition window, respectively.

Figure 2

Amplitude modulation of the DANTE pulse train as shown in Figure 1 broadens the saturated frequency span. (a) The calculated normalized longitudinal magnetization of γ-ATP after 20s of saturation around the saturation frequency with m=5 saturation bands δ=9Hz apart (black) as compared to a single band with m=1 (gray). (b) The saturation bands for m=5 DANTE saturation overlaid over the entire cardiac ³¹P spectrum. The DANTE sub-pulse separation of τ=0.91ms leads to aliased saturation bands at 1/τ=1100Hz apart.

Figure 3

Results from the Monte Carlo simulations of the TRiST experiment averaged over the k_f range 0.1 to 0.4s⁻¹ as a function of TR_long (with γ-ATP saturated) and TR_control (control saturation). TR_short was 1.7s (γ-ATP saturated) and NA combinations were chosen for a constant total study time of 38±0.2min. (a) The relative % SD in k_f for NA choices that lead to minimum error at each TR_long and TR_control combination. (b) The average bias error in k_f, corresponding to the TR_long, TR_control and NA combinations in part (a). A positive bias of 4% means that the observed k_f is less than the true k_f by 4%.

Figure 4

Steady-state PCr signal (in arbitrary units, a.u.) measured as a function of TR (diamonds) while γ-ATP is saturated in one volunteer to determine T_1,PCr′. T_1,PCr′ was determined both by the conventional partial saturation by fitting all 7 data points (dotted line, relaxation curve), and by the 2TR method using only the data points acquired at TRs of 1.5s and 10s (arrows; the grey line is the corresponding implied relaxation curve).

Figure 5

Typical image and TRiST data from a human leg. (a) Axial ¹H image annotated with location of the coil center and 1D CSI slice positions. (b–d) ³¹P spectra extracted from a slice at a depth of 4cm from the coil. The spectra were acquired with: (b) control saturation at a TR_control=25.0s to determine M_0,PCr; and with saturation of γ-ATP at (c) TR_short=1.5s and (d) TR_long=10.0s to determine M_0,PCr′ and T_1,PCr′. Note the different vertical scales (arbitrary units, a.u.). Arrows depict the location of the DANTE saturation.

Figure 6

Pseudo-first-order forward rate constants, k_f (means±SD) for the CK reaction measured in-vivo in the leg (n=6) and chest (n=8) at 3T. Values plotted from left to right are non-localized (NL) k_fs measured by conventional partial saturation (PS) and by TRiST in the calf muscle; k_fs measured by 1D CSI localized TRiST as a function of depth in the calf muscle; and k_fs measured in the chest and heart by TRiST 1D CSI, as indicated on the horizontal axis.

Figure 7

Typical image and TRiST data from a human heart. (a) Axial ¹H image acquired at end-systole and annotated with the location of the coil center and 1D CSI slice positions. (b-d) Cardiac-gated ³¹P heart spectra extracted from slice 7cm from the coil. The spectra were acquired with: (b) control saturation at a TR_control=16.1s to determine M_0,PCr; and with saturation of γ-ATP at (c) TR_short=1.7s, and at (d) TR_long=10.0s to determine M_0,PCr′ and T_1,PCr′. Note the different vertical scales (arbitrary units, a.u.). Arrows depict the location of the DANTE saturation.

Figure 8

Q (means±SD) measured in-vivo in human leg (n-6), chest, and heart (n=8). Values plotted from left to right are from non-localized (NL) studies of calf muscle; 1D CSI studies as a function of depth in the calf; and from 1D CSI studies of the chest and heart, as indicated on the horizontal axis. Q is a measure of spillover of the frequency selective saturation of the γ-ATP resonance onto the PCr resonance.