Feature | January 15, 2014

Tweaking MRI to Track Creatine May Spot Heart Problems Earlier, Penn Medicine Study Suggests

Measuring creatine levels with MRI has benefits over contrast-enhanced MRI, MRS

mri systems clinical trial study university pennsylvania creatine CEST map
January 15, 2014 — A new magnetic resonance imaging (MRI) method to map creatine at higher resolutions in the heart may help clinicians and scientists find abnormalities and disorders earlier than traditional diagnostic methods, suggest researchers at the Perelman School of Medicine at the University of Pennsylvania in a new study published online in Nature Medicine. The preclinical findings show an advantage over less sensitive tests and point to a safer and more cost-effective approach than those with radioactive or contrasting agents.
 
Creatine is a naturally occurring metabolite that helps supply energy to all cells through creatine kinase reaction, including those involved in contraction of the heart. When heart tissue becomes damaged from a loss of blood supply, even in the very early stages, creatine levels drop. Researchers exploited this process in a large animal model with a method known as chemical exchange saturation transfer (CEST), which measures specific molecules in the body, to track the creatine on a regional basis.
 
The team, led by Ravinder Reddy, Ph.D., professor of radiology and director of the Center for Magnetic Resonance and Optical Imaging, Penn Medicine, found that imaging creatine through CEST MRI provides higher resolution compared to standard magnetic resonance spectroscopy (MRS), a commonly used technique for measuring creatine. However, its poor resolution makes it difficult to determine exactly which areas of the heart have been compromised.
 
“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,” said Reddy. “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.”
 
MRI-based stress tests are also used to identify dead heart tissue — which is the warning sign of future problems such as coronary artery disease (CAD) — but its reach is limited. MRI is often coupled with contrast agents to help light up problem areas, but it is often not sensitive enough to find ischemic, but not yet infarcted, regions with deranged metabolism, according to Reddy.
 
“After a heart attack, different regions of the heart are damaged at different rates,” said Robert Gorman, M.D., professor of surgery and director of cardiac surgical research, Penn Medicine. “This new technique will allow us to very precisely study regional changes that occur in the heart after heart attacks, enabling us to identify and treat patients at risk for developing heart failure before symptoms develop.”
 
To demonstrate CEST’s ability to detect heart disease, the researchers applied the creatine CEST method in an MRI scanner in healthy and infarcted myocardium in large animals. In the process, the nuclear magnetization of amine (NH2) creatine protons is saturated by a radiofrequency pulse from the MRI. After the exchange with water, the degree of saturation is observed as the water signal drops, and thus the concentration of creatine becomes 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. However, they found CEST has two orders of magnitude higher sensitivity than MRS. That advantage could help spot smaller damaged areas in the heart missed by traditional methods, the authors said.
 
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.
 
The method can also be used to investigate alterations in normal heart function that are seen in many other types of non-ischemic heart disease, such as abnormal cardiac hypertrophy as well as disorders in the brain, according to Reddy.
 
“Though at much lower levels than in the heart, creatine levels change in the brain when abnormalities arise,” said Reddy. “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.”
 
CEST has been used to image tissue pH, map proteins and specific gene expression, but this is the first time to the authors’ knowledge it has been used to study heart tissue.
 
"The ability to visualize heart muscle viability at high resolution without radiation exposure or the injection of a contrast agent is a significant advancement,” said Christina Liu, Ph.D., who oversees funding for molecular imaging research by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health. “It could allow doctors to detect small areas of damaged heart tissue early in the course of a disease when treatments are most likely to be effective.”
 
Penn Medicine co-authors of the study include Mohammad Haris, Anup Singh, Kejia Cai, Feliks Kogan, Jeremy McGarvey, Catherine DeBrosse, Gerald Zsido, Walter RT Witschey, Kevin Koomalsingh, James Pilla, Julio Chirinos, Victor Ferrari, Joseph Gorman and Hari Hariharan.
 
The study was funded with grants from the NIBIB (P41EB015893S1, P41EB015893, and R21DA0332256-01) and a pilot grant from the Translational Biomedical Imaging Center of the Institute for the Translational Medicine and Therapeutics of the University of Pennsylvania.
 
For more information: www.med.upenn.edu, www.nature.com

Related Content

Hospital Readmissions Analysis Across All Ages, Insurance Types Identifies High-Risk Groups
News | Business| July 20, 2017
July 20, 2017 — Clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC) recently published a first-of-i
3-D Vascular Ultrasound Quantifies Plaque Burden to Estimate Cardiovascular Risk
News | Cardiovascular Ultrasound| July 20, 2017
July 20, 2017 — In a large, first-of-its-kind population, researchers found an experimental technique known as...
More Than 20 Percent of Low-Risk Patients Receive Annual ECG
News | ECG| July 20, 2017
July 20, 2017 — More than one in five Ontario patients receive an ...
Cardiac CT scan showing plaque and calcification in the coronary arteries, from a Toshiba CT scanner
News | Business| July 19, 2017
July 19, 2017 — The Society of Cardiovascular Computed Tomography (SCCT) created a reimbursement fee chart for cardia
Sponsored Content | Videos | CT Angiography (CTA)| July 18, 2017
Matthew Budoff, M.D., FACC, professor of medicine, David Geffen School of Medicine at UCLA, endowed chair of preventi
Low Doses of Radiation Could Harm Cardiovascular Health
News | Radiation Dose Management| July 17, 2017
Ionizing radiation, such as X-rays, has a harmful effect on the cardiovascular system even at doses equivalent to...
First Patient Treated in U.S. Feasibility Study of LimFlow Critical Limb Ischemia Device
News | Peripheral Arterial Disease (PAD)| July 17, 2017
LimFlow SA announced enrollment of the first patient in the U.S. feasibility study of the LimFlow Percutaneous Deep...
FDA Approves Six-Month Primary Endpoint for Tack Endovascular System in Below the Knee Disease
News | Stents Peripheral| July 14, 2017
Intact Vascular Inc. announced the U.S. Food and Drug Administration (FDA) approved an Investigational Device Exemption...
Edwards Sapien 3 TAVR valve will be implanted in asymptomatic aortic stenosis patients in the EARLY TAVR Trial
Feature | Heart Valve Technology| July 14, 2017
July 14, 2017 — Morristown Medical Center, part of Atlantic Health System, has randomized the first patient in the wo
long-duration dual anti-platelet therapy (L-DAPT) compared to short-duration dual antiplatelet (S-DAPT) after DES stent implantation
News | Antiplatelet and Anticoagulation Therapies| July 12, 2017
June 12, 2017 — Researchers have evaluated the long-term efficacy and safety of long-duration dual anti-platelet ther
Overlay Init