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 tests are performed each year in Canada.
“This new method, cardiac functional MRI (cfMRI), does not require needles or chemicals being injected into the body,” says Dr. Frank Prato, Lawson Assistant Director for Imaging. “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.”
Repeat exposure to carbon dioxide is used 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.
This change 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.
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.”
“Using MRI will not only be safer than present methods, but also provide more detailed information and much earlier on in the disease process,” adds Dr. Prato. 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 study “Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using Magnetic Resonance Imaging” is being published in Science Translational Medicine.
As an aerobic organ in a living body, the beating heart relies almost exclusively on the oxidation of energy-providing substrates such as free fatty acids (60-90%) for its primary contractile function.
Specifically, chemical energy is generally produced in aerobic metabolic pathways through oxidative phosphorylation of ADP to ATP.
Myocytes utilize the chemical energy stored in ATP molecules and transform it into mechanical energy.
Accordingly, cardiac cells have to consume large amounts of O2 for the contraction process, which accounts for over 80% of oxygen cost.
The remaining <20% is consumed by other physiological processes not directly associated with contraction, i.e., membrane depolarization and repolarization.
For this reason, the heart can only develop a small oxygen debt. Oxygen supply and demand has to match to maintain normal myocardial contractility.
Myocardial ischemia exists when the supply of oxygen to the myocardial tissue is inadequate for the metabolic oxygen demand of myocardium.
This is usually caused by upstream coronary artery stenosis that reduces blood supply (coronary artery disease or CAD).
Clinically, myocardial hypoxemia results in arrhythmia, angina, and regional or global impairment of ventricular function (1).
Severe and prolonged imbalance between oxygen supply and demand will eventually lead to myocardial infarction.
In addition, ischemia may still present even though the coronary artery flow is maintained due to an imbalance between oxygen supply and demand secondary to the increased myocardial metabolic requirements.
As with severe systemic hypertension, the whole heart becomes ischemic. Measuring and quantifying the balance of myocardial oxygenation would provide direct assessment of the status of myocardial oxidative metabolism and ischemic status.
In current clinical practice, X-ray angiography is considered the gold standard for diagnosis of coronary artery stenosis.
However, measurement of coronary artery stenosis by angiography is not always a reliable indication of the functional consequence of stenosis in CAD patients.
Any variations, e.g., irregular atherosclerotic plaque, variable collateral flow, preexisting ventricle remodeling, etc. will alter the effect of coronary artery stenosis. Currently, cardiac PET has been the major image modality for absolute quantification of regional myocardial perfusion and oxygen metabolism (2).
Investigators have shown that PET permits accurate quantification of regional myocardial blood flow (MBF) (3–5) with 15O-water, and of myocardial oxygen consumption rate (MVO2) (6–9) with 11carbon-acetate.
Perfusion-MVO2 (supply-demand) mismatches were found in CAD patients with significant single-vessel left anterior descending (LAD) stenosis (>70%) using 11C-acetate PET, despite normal regional left ventricular contractile function at rest (10).
Of note, quantitative measurements of MVO2 and oxygen extraction fraction (OEF) using 15O2-labeled oxygen gas were also reported in animals and healthy volunteers (11), and evaluated in patients (12).
However, low spatial resolution (not suitable for the detection of subendocardial perfusion defects), relatively long acquisition time, limited availability, relative high cost, and ionizing radiation discourage the widespread use of PET for these purposes.
MRI is a non-invasive imaging modality that provides excellent image spatial resolution and soft tissue contrast, does not require iodinated contrast media or ionizing radiation, and is widely available.
Cardiac functional MRI demonstrated myocardial blood oxygenation qualitatively evaluated in animals and humans using the BOLD (Blood Oxygen Level Dependence) effect (13–19), which is the fundamental mechanism for detecting tissue and blood oxygenation in MRI (20–23).
Thulborn et al. (24) first recognized the BOLD effect: that the presence of paramagnetic deoxyhemoglobin in red blood cell affects blood T2 relaxation rate in vitro.
Early studies in the heart indicated myocardial relaxation time T2* (1/T2* = 1/T2 + 1/T2‘ and T2‘ is related to the magnetic field inhomogeneity) changes with alterations in total tissue deoxyhemoglobin concentration.
Since then, myocardial T2* or T2*-weighted imaging, which is usually acquired by gradient-echo (GE) sequences, has been explored by many investigators to assess the change in myocardial oxygenation in cardiac MRI (31–35).
More information: Hsin-Jung Yang et al, Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging, Science Translational Medicine (2019). DOI: 10.1126/scitranslmed.aat4407
Journal information: Science Translational Medicine
Provided by Lawson Health Research Institute