Two repetition time saturation transfer (TwiST) with spill-over correction to measure creatine kinase reaction rates in human hearts

Background: Phosphorus saturation transfer (ST) magnetic resonance spectroscopy can measure the rate of ATP generated from phosphocreatine (PCr) via creatine kinase (CK) in the human heart. Recently, the triple-repetition time ST (TRiST) method was introduced to measure the CK pseudo-first-order rate constant k(f) in three acquisitions. In TRiST, the longitudinal relaxation time of PCr while gamma-ATP is saturated, T-1', is measured for each subject, but suffers from low SNR because the PCr signal is reduced due to exchange with saturated gamma-ATP, and the short repetition time of one of the acquisitions. Here, a two-repetition time ST (TwiST) method is presented. In TwiST, the acquisition with gamma-ATP saturation and short repetition time is dropped. Instead of measuring T-1' an intrinsic relaxation time T-1 for PCr, T-1(intrinsic), is assumed. The objective was to validate TwiST measurements of CK kinetics in healthy subjects and patients with heart failure (HF). Methods: Bloch equation simulations that included the effect of spillover irradiation on PCr were used to derive formulae for T-1(intrinsic) and k(f) measured by both TRiST and TwiST methods. Spillover was quantified from an unsaturated PCr measurement used in the current protocol for determining PCr and ATP concentrations. Cardiac TRiST and TwiST data were acquired at 3 T from 12 healthy and 17 HF patients. Results: Simulations showed that both k(f) measured by TwiST and T-1(intrinsic) require spill-over corrections. In human heart at 3 T, the spill-over corrected T-1(intrinsic) = 8.4 +/- 1.4 s (mean +/- SD) independent of study group. TwiST and TRiST k(f) measurements were the same, but TwiST was 9 min faster. Spill-over corrected TwiST k(f) was 0.33 +/- 0.08 s(-1) vs. 0.20 +/- 0.06 s(-1) in healthy vs HF hearts, respectively (p < 0.0001). Conclusion: TwiST was validated against TRiST in the human heart at 3 T, generating the same results 9 min faster. TwiST detected significant reductions in CK k(f) in HF compared to healthy subjects, consistent with prior 1.5 T studies using different methodology.