A technique for in vivo mapping of myocardial creatine kinase metabolism

Abstract

ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to 1H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from 1H and 31P magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders.

Cardio-Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Reveals Molecular Signatures of Endogenous Fibrosis and Exogenous Contrast Media

“…2 In 1 previous study, CESTweighted imaging was performed using an ECG-gated rapid gradient echo technique in the presence of slow heart rates. 23 However, rapid heart rates in small animals on the order of 400 to 700 bpm obstruct the application of either method for cardiac CEST imaging ( Figure I in the Data Supplement). Steadystate cardioCEST imaging as reported here overcomes these limitations and is optimized to enable imaging of multiple targets, including the circulation, matrix targets, or potentially paraCEST labeled or CEST-reporter gene expressing cells.…”

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

“…Water saturation shift referencing (51) maps and B 1 maps were acquired before and after exercise, and used to generate corrected CrCEST images as described for previous studies (14,50). CrCEST contrast was computed by subtracting the normalized magnetization signal at the creatine proton frequency (Δω = +1.8 ppm), from the magnetization at the corresponding reference frequency on the opposite side of the water resonance (-Δω) (52). CrCEST changes in individual muscle groups before and after exercise were determined by overlaying CrCEST maps onto manually segmented anatomic images.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…Cardiac MR imaging can play a significant role in demonstrating 3D ventricular geometry, intraventricular flow, global function, regional strain, and even biochemical changes. 119,139 Angiography can be implemented in large animal models with Rentrop scoring used to evaluate vascular collateralization. 119 Invasive LV e116…”