Localized rest and stress human cardiac creatine kinase reaction kinetics at 3 T

Abstract

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter “stressed saturation transfer” (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (k f CK ) for healthy volunteers and obese patients. TRiST measures k f CK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further k f CK measurement during <20 min of dobutamine stress. We test our TRiST implementation in skeletal muscle and myocardium in both prone and supine positions. We evaluate StreST in the myocardium of six healthy volunteers and 34 obese subjects. We validated MR‐measured k f CK against biopsy assays of CK activity. TRiST k f CK values matched literature values in skeletal muscle (k f CK = 0.25 ± 0.03 s −1 vs 0.27 ± 0.03 s −1 ) and myocardium when measured in the prone position (0.32 ± 0.15 s −1 ), but a significant difference was found for TRiST k f CK measured supine (0.24 ± 0.12 s −1 ). This difference was because of different respiratory‐ and cardiac‐motion‐induced B 0 changes in the two positions. Using supine TRiST, cardiac k f CK values for normal‐weight subjects were 0.15 ± 0.09 s −1 at rest and 0.17 ± 0.15 s −1 during stress. For obese subjects, k f CK was 0.16 ± 0.07 s −1 at rest and 0.17 ± 0.10 s −1 during stress. Rest myocardial k f CK and CK activity from LV biopsies of the same subjects correlated ( R = 0.43, p = 0.03). We present an independent implementation of TRiST on the Siemens platform using a commercially available coil. Our extended StreST protocol enables cardiac k f CK to be measured during dobutamine‐induced stress in the supine position.

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study

“…Signal amplitudes were then corrected for partial saturation using this estimated local flip angle and literature T1 values of the corresponding resonances [ 28 ]. The ratio of the corrected PCr to γ-ATP signal amplitudes was used to generate a PCr/ATP concentration ratio [ 29 , 30 ].…”

Rapid, ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux

“…schemes, such as FAST, 36 TRiST, 2 STReST, 37 and TWiST, 38 and find other applications beyond 31 P MRS. It may also find wider applications in that require selective excitation, including simultaneous multislice imaging with a degree of immunity to B 1 variation; the selective excitation of metabolites in hyperpolarized metabolic imaging; chemical exchange saturation transfer (CEST), and spatial tagging of multiple arteries or planes in the arterial spin labeling experiment.…”

“…The increased temporal resolution potentially afforded by the omission of the control saturation data allows for dynamic experiments and extends the viability of the perfused heart model, wherein cardiac performance slowly deteriorates after a ∼2 hour window. We note that the designed quasi‐adiabatic multiple‐band saturation or excitation pulses could be incorporated into more widely used saturation schemes, such as FAST, 36 TRiST, 2 STReST, 37 and TWiST, 38 and find other applications beyond 31 P MRS. It may also find wider applications in that require selective excitation, including simultaneous multislice imaging with a degree of immunity to variation; the selective excitation of metabolites in hyperpolarized metabolic imaging; chemical exchange saturation transfer (CEST), and spatial tagging of multiple arteries or planes in the arterial spin labeling experiment.…”

Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited

“…Spectral analysis was performed using the OXSA toolbox which uses a MATLAB implementation of the Advanced Method for Accurate, Robust and Efficient Spectral fitting algorithm (Purvis et al, 2017). Measurements of the CK forward rate constant k f were measured using a Triple Repetition Saturation Transfer (Schar et al, 2010) sequence with stress saturation transfer (Clarke et al, 2019) extension, as previously described (Peterzan et al, 2020;Rayner et al, 2020) and validated in human subjects (Clarke et al, 2019). A transmit/receive 31 P MRS coil with 17 cm loop transmit coil and 11 cm loop receive coil (Pulseteq, United Kingdom) was used.…”