Researchers funded by the National Institutes of Health have developed a high-resolution MRI technique to visualize disruptions in energy metabolism in the heart, often a sign of disease. The technique could help doctors identify damaged heart tissue earlier in patients with coronary artery disease or other heart disorders.
“This imaging technique is a significant advancement over current imaging tests, which are low-resolution and can’t reveal areas of tissue damage with precision,” said Christina Liu, Ph.D., a program director at the National Institute of Biomedical Imaging and Bioengineering, which funded the development of the new technology. “It also provides a safer alternative to current imaging techniques, which require the injection of a contrast dye or radioactive tracers that either exposes patients to radioactivity or can be harmful to some patients with kidney disease.”
Coronary artery disease (CAD) is the most common type of heart disease and occurs when the arteries that supply the heart with blood become occluded, preventing the flow of oxygen and nutrients to various areas of the heart. Over time, these areas—referred to as ischemic—lose their ability to contract, and the overall function of the heart is compromised. Alterations in normal heart function are also seen in many other types of non-ischemic heart disease such as cardiac hypertrophy, an inherited condition in which a region of the heart muscle becomes thick, making it harder for the heart to pump blood.
Identifying damaged heart tissue is a primary goal in the treatment of heart disease. Once located, doctors can perform therapeutic interventions to redirect blood flow to these areas. In addition, the ability to distinguish damaged—but still living—heart tissue from heart tissue that has died is important when making decisions about treatment, as only living tissue can be salvaged. Reporting in an article published online January 12, 2014 in Nature Medicine, a team of researchers led by Ravinder Reddy, Ph.D., director of the Center for Magnetic Resonance and Optical Imaging at the University of Pennsylvania’s Perelman School of Medicine, described a high-resolution MRI technique that can reveal local tissue damage in the heart with high precision and without the use of radioactive tracers or contrast dyes.
The technique measures levels of the metabolite creatine, a byproduct of a biochemical reaction that fuels the contraction of the heart. Creatine levels fluctuate naturally in the heart depending on how hard the heart is working, increasing with exercise and returning to base levels at rest. However, very low levels of creatine at rest or failure to increase creatine during exercise are signs of tissue damage.
In their study, the researchers adopted a known MRI technique called Chemical Exchange Saturation Transfer (CEST)—used to image specific molecules in the body with high-resolution—in order to visualize creatine in the heart. The team showed that CEST was up to two orders of magnitude more sensitive than magnetic resonance spectroscopy, a commonly used technique for measuring creatine, and demonstrated that it could be used to locate areas of cell death in the hearts of swine and sheep.
Liu says the ability to identify dead heart tissue without the use of a contrast dye has important clinical implications: “There is currently no good way to detect dead heart tissue in patients who have kidney disease, because they can’t be given an injection of the necessary contrast dye. CEST could provide an alternative method for imaging damaged or dead tissue that would be safe for all patients.”
The team also used CEST to map exercise-induced increases in creatine over time by imaging human subjects as they flexed their calf muscles while inside an MRI scanner. According to the researchers, this experiment showed that CEST could be used to visualize stress-induced metabolic changes, which currently requires the injection of a radioactive tracer.
“As the heart pumps harder, creatine levels increase,” said Reddy. “So, if we don’t see an increase in creatine during a stress test, we know there is something wrong with that tissue.”
Reddy envisions using CEST to assess heart health, both at the beginning stages of heart disease and following treatment: “When a patient first comes in, CEST could be used to identify ischemic tissue during a stress test. Then, the patient is given a treatment, and as that patient’s heart returns to a normal state, we should be able to see the accompanying changes in creatine.”
He also emphasized that the MRI technique could be used to provide insights about metabolic abnormalities present in other types of heart disease.
“Although in this work, CEST MRI was used to measure creatine metabolism in ischemic heart disease, the method can also be used to investigate alterations in heart function that are seen in many other types of non-ischemic heart disease such as cardiac hypertrophy,” said Reddy.
Reddy’s group is currently working to further optimize the creatine CEST MRI technique so that it can be implemented in cardiac imaging in humans.