Special MRI Method May Track Creatine, Spot Early Cardiac Problems

Chemical exchange transfer (CEST) MRI may detect creatine, a preclinical finding for heart disease, earlier than traditional diagnostic methods, according to a study published in the journal Nature Medicine.

Creatine is a naturally occurring metabolite that helps supply energy to cells through creatine kinase reaction, including cells involved in contractions of the heart. When cardiac tissue is damaged from decreased blood supply, even in the very early stages, creatine levels drop. Using animal models, researchers from the University of Pennsylvania School of Medicine sought to determine if CEST could help track creatine more effectively than the current standard, MR spectroscopy (MRS).

The researchers applied the creatine CEST method in an MRI scanner, in healthy and infarcted myocardium in large animals. The nuclear magnetization of amine (NH2) creatine protons was saturated by a radiofrequency pulse from the MRI. After the water exchange, the degree of saturation was observed as the water signal dropped, and the concentration of creatine became apparent.

The team showed that the creatine CEST method can map changes in creatine levels, and pinpoint infarcted areas in heart muscle tissue, just as MRS methods can, but with two orders of magnitude higher sensitivity than MRS.

In addition, the team used CEST to map increases in creatine over time by imaging human subjects as they flexed their calves while inside an MRI scanner to demonstrate the technology's ability to correctly track the molecule.

"Measuring creatine with CEST is a promising technique that has the potential to improve clinical decision making while treating patients with heart disorders and even other diseases, as well as spotting problems sooner," Ravinder Reddy, PhD, said in a release. "Beyond the sensitivity benefits and its advantage over MRS, CEST doesn't require radioactive or contrast agents used in MRI, which can have adverse effects on patients, particularly those with kidney disease, and add to costs." Reddy is a professor of radiology and director of the Center for Magnetic Resonance and Optical Imaging at the university.

The researchers pointed out that not only was CEST MRI resolution superior to MRS, no radioactive or contrast agents were required for the tests, which adds to the benefits.

There could be other uses for the CEST MRI as well, said the researchers, such as assessment of heart function seen in other types of non-ischemic heart disease, such as abnormal cardiac hypertrophy-as well as disorders in the brain.

"Though at much lower levels than in the heart, creatine levels change in the brain when abnormalities arise," Reddy said. "Given the heightened resolution of this technique, this presents an opportunity for studying brain disorders with deranged creatine metabolism without the use of contrast agents as well."