1356291 - Creatine assessment in acute myocardial infarction using CEST

Creatine metabolism is essential to the proper functioning of myocardial contraction. Adenosine triphosphate (ATP) is generated from the conversion of phosphocreatine (PCr) and adenosine diphosphate (ADP) to creatine (Cr) catalyzed by the creatine kinase enzyme (CK system). Loss of metabolites in the CK system has been linked to cardiac dysfunction.

Chemical exchange saturation transfer (CEST) is a non-contrast imaging technique that indirectly detects exchangeable protons in the water pool by pre-saturation at different frequency offsets. CEST can detect Cr separately from other CK metabolites because Cr protons alone have an intermediate transfer rate with water protons. In a previous study [1], creatine signal was shown to be different between chronic myocardial infarction (MI) and remote regions. The purpose of this work was to assess changes in the Cr level in acute myocardial infarction in an animal model.

Methods:

Pig preparations

In 5 farm pigs reperfused transmural acute MI was induced by closed-chest 90-minute mid left anterior descending (LAD) coronary artery occlusion followed by balloon deflation and reestablishment of blood flow. Late gadolinium enhancement (LGE) and CEST cardiac MR were performed on day 3 post-MI to assess creatine content in the infarcted and normal myocardium.

CEST image acquisition and analysis

CEST CMR scans were performed before the contrast injection using FLASH readout 33 images were collected at saturation frequency offsets ranging from −4.8 ppm to 4.8 ppm with a step size of 0.3 ppm. The CEST preparation module consists of five Gaussian-shaped pulses with B1 power of 3.76 μT. The scan time for each slice was approximately 5 min.
Images were analyzed using CEST multi-pool fitting model in MATLAB. Image registration was done to remove residual motion between the CEST offsets. The acquired Z-spectrum was separated into CEST (creatine peak at +1.8 ppm), direct water saturation (DWS), and conventional magnetization transfer (MT), three major effects in saturation experiments with aqueous solutions. Myocardium pixels were selected from the short axis view for CEST analysis. LGE images were used to identify the scar vs. the remote region.

Results:

Creatine CEST maps were obtained for all five pigs at the acute stage for all three slices (Figure 1). The results were averaged for all three slices. Creatine CEST signal was calculated in the remote and scar regions of the myocardium separately. Two sample t-test was used to compare the distribution of CEST values in remote vs. scar regions (Figure 2). The creatine signal, as measured by CEST CMR is statistically different between acute myocardial infarction and remote region.

Conclusion:

Rapid metabolic changes occur at the cellular level in the early stages of MI when Creatine levels decrease as the tissue is severely damaged. CEST CMR can assess myocardial creatine level changes between healthy and acute infarcted myocardium.