(G-264) Assessment of myocardial phosphocreatine: a pilot study with chemical exchange saturation transfer magnetic resonance imaging technique

Myocardial contractions are primarily fueled by cellular energy via the creatine kinase system from adenosine triphosphate (ATP).  The ATP is generated when phosphocreatine (PCr) donates its inorganic phosphate to ADP when ATP is in high demand, while creatine (Cr) accepts an inorganic phosphate from ATP when it is at a surplus.  Therefore, PCr acts as an energy reserve, buffering short-term energy supply and demand changes.

In various cardiac diseases, both ATP and PCr supply decreases.  Cardiac metabolic impairment is suggested as a cause, not a result, of cardiac diseases. Thus, PCr can serve as a biomarker for metabolic changes in the heart.

³¹P-magnetic resonance spectroscopy (MRS) is currently the gold standard to measure myocardial PCr content. However, this method is not readily available in most medical centers due to the need for additional hardware for ³¹P signal acquisitions.  The spectroscopy method also has limitations such as low spatial resolution and signal-to-noise ratio.  Chemical exchange saturation transfer (CEST) is a proton-based magnetic resonance imaging (MRI) technology that detects metabolites with exchangeable solute protons that resonate at a different frequency from water.  This method does not require modifications to proton MRI scanners that are commonly used in clinical settings.  This study aims to develop a new cardiac CEST MRI technique for non-invasive assessment of myocardial PCr in vivo, potentially aiding to the diagnosis and treatment cardiovascular diseases.

MRI scan protocol

            This is an ongoing pilot study for technical development. Ten healthy volunteers ages 18-30, 5 male / 5 females, have been recruited for assessing feasibility and reproducibility of this new technique. All subjects provided signed consent forms prior to the MRI sessions. They are being scanned in the same MRI protocol at two different days, with at least one week separation. Each session consists of localization scans and multiple CEST MRI scans at three short-axis view locations (basal, mid, apex) with different imaging parameters for the optimization purpose.

Cardiac PCr MRI      

            The new cardiac CEST MRI sequence for PCr measurements was composed of saturation and data acquisition modules, along with electrocardiogram (ECG) triggering. The saturation modules had 5 gaussian radio frequency (RF) pulses with a magnitude of 2.4 mT and varied frequency offsets around PCr (319 Hz). The data acquisition module is a single-shot balanced steady-state-free-precession (TrueFISP) technique. The image spatial resolution was 1.7 x 1.7 mm² with a slice thickness of 8 mm. A trigger delay was inserted after the ECG trigger to ensure the data acquisition time to occur at the quiescent period of the heart to minimize cardiac motion. A WAter Saturation Shift Referencing (WASSR) scan was first obtained prior to any CEST scan to correct magnetic field inhomogeneity.  The CEST MRI scans were acquired either with breath-hold or free-breathing. A motion-correction software was used to correct any respiratory motion.

The new cardiac CEST images exhibited proper image quality, adequate WASSR curve, and correct Z-spectra of the CEST images. Figure 1 shows a few representative cardiac CEST images, WASSR, and Z-spectra curves. An algorithm is currently under development for extracting PCr contents based on conventional Bloch Equation.  

The current results demonstrated very promising feasibility for this new cardiac metabolic MRI technique. The ongoing post-processing methods and reproducibility study will be completed within next two months and will be reported in the upcoming conference.

PCr is an important metabolite in the heart which is a biomarker for cardiac health. Gaining the ability to measure absolute cardiac PCr content in vivo through this new MRI method CEST would be valuable. Because the deprivation of PCr in the heart precedes heart disease, measuring this metabolite could be a predictor of metabolic cardiac issues including myocardial ischemia, arrhythmia, hypertensive cardiomyopathy, etc. The proton based CEST MRI is easily accessible to most clinical scanners, making it highly convenient in clinical settings.  Future knowledge about the role of PCr metabolism in hearts will greatly enhance our capability in the understanding of cardiac metabolism and facilitate cellular intervention for early treatment of a variety of cardiac diseases.