Members of the team who contributed to the 6-year long work that resulted in this discovery
An international team led by scientists from Lawson Health Research Institute and Cedars-Sinai Medical Center are the first to show that Magnetic Resonance Imaging (MRI) can be used to measure how the heart uses oxygen for both healthy patients and those with heart disease.
Reduced blood flow to the heart muscle is the leading cause of death in the Western world. Currently, the diagnostic tests available to measure blood flow to the heart require injection of radioactive chemicals or contrast agents that change the MRI signal and detect the presence of disease. There are small but finite associated risks and it is not recommended for a variety of patients including those with poor kidney function.
More than 500,000 of these tests are performed each year in Canada. A patient suspected of coronary heart disease for example may have reasonably normal blood flow at rest but as soon as they exercise they have pain or feel out of breath. They need more oxygen delivered to the heart tissue but due to vessels being compromised that doesn’t happen.
The standard technique is usually done in two days with the goal of seeing if the heart can increase blood flow when more oxygen is needed. The first test studies the patient at rest to see what the blood flow is like in the heart. This is a nuclear medicine imaging test that requires radioactive material to be injected and takes about an hour or more to complete.
They next day, they come for the same test but with the introduction of a stressor. That can be physical exercise but more often they are given an injection of a chemical drug which stimulates the heart and increases blood flow. This is in addition to a second injection of the radioactive material. The heart is imaged to see the level of oxygen getting to different parts of the heart and whether there are obstructions or reduction in size of the surrounding arteries.
A new stress test
“We wanted a non-invasive way to image the heart and replace the stress stimulus, and drastically reduce the amount of time needed for testing,” says Dr. Frank Prato, Lawson Assistant Director for Imaging. “This new method, cardiac functional MRI (cfMRI), does not require needles or chemicals being injected into the body. It eliminates the existing risks and can be used on all patients.”
The team included researchers from Lawson; Cedars-Sinai Medical Center and University of California; King’s College in the United Kingdom; University Health Network and the University of Toronto; Siemens Healthineers; and, University of Edinburgh in the United Kingdom.
“Our discovery shows that we can use MRI to study heart muscle activity,” explains Dr. Prato. “We’ve been successful in using a pre-clinical model and now we are preparing to show this can be used to accurately detect heart disease in patients.”
To replace the stress test, this new technique uses repeat exposure to carbon dioxide to test how well the heart’s blood vessels are working to deliver oxygen to the muscle. A breathing machine changes the concentration of carbon dioxide in the blood. Levels are brought up for three minutes and then back down to normal four times. These changes should result in a change in blood flow to the heart, but does not happen when disease is present.
The cfMRI method reliably detects whether these changes are present and is comparable to the information gathered from the current two-day technique – in much less time and without injections. Dr. Prato notes that “we don’t want to stress the heart. We want to see whether there is capacity in the heart to increase blood flow if the heart needs to work harder.”
A brilliant discovery
Other researchers have explored oxygenation-sensitive MRI but initial results contained a high level of ‘noise’ with blurry images. Project leader and partner Dr. Rohan Dharmakumar, Associate Director of the Biomedical Imaging Research Institute at Cedars-Sinai Medical Center, believed that the noise was actually variation in the heart’s processing of oxygen. He engineered a way to average this variation and through testing at Lawson the team discovered that the noise is actually a new way to study how the heart works.
“We’ve opened the door to a new era and totally novel way of doing cardiac stress testing to identify patients with ischemic heart disease” says Dr. Dharmakumar. “This approach overcomes the limitations of all the current diagnostics – there would no longer be a need for injections or physical stress testing like running on treadmills.”
Through investigating this technique, they learned that the blurry images were showing normal physiological variability. People often think of heart rate as being stable, but in fact a heart that is unable to keep up with stressors indicates that disease is developing. In a healthy heart, the oxygen distribution to the tissue needs to vary.
“It’s a very exciting time. We had to bring all the technologies together to be able to image these kinds of changes in blood flow moment to moment,” says Dr. Prato.
He adds that “using MRI will not only be safer than present methods, but also provide more detailed information and much earlier on in the disease process.” Following initial testing through clinical trials, he sees this being used with patients clinically within a few years.
In addition to studying coronary artery disease, the method could be used in other cases where heart blood flow is affected such as the effects of a heart attack or damages to the heart during cancer treatment. Due to its minimal risk, this new tool could be safely used with the same patient multiple times to better select the right treatment and find out early on if it is working. Dr. Prato notes that “with this new window into how the heart works, we have a lot to explore when it comes to the role of oxygen in health and disease.”
The next steps of the research include a proof of principle study in London, Ontario with 20 patients. Following standard tests using the conventional technique at other sites, the participants will then come in for the experimental test to show that it produces the same result. The research would then move into a multi-centre clinical trial internationally.
The study “Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using Magnetic Resonance Imaging” is published in Science Translational Medicine.