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 γ-ATP is saturated, T₁', is measured for each subject, but suffers from low SNR because the PCr signal is reduced due to exchange with saturated γ-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 γ-ATP saturation and short repetition time is dropped. Instead of measuring T₁', an intrinsic relaxation time T₁ for PCr, T₁ ^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 T₁ ^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 T₁ ^intrinsic require spill-over corrections. In human heart at 3 T, the spill-over corrected T₁ ^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.