A New Dawn for Cardiac Imaging

Hyperpolarized MRI could help us understand heart disease progression—and how to stop it before our hardest-working muscle wears out

The heart is the hardest-working muscle in the body. It beats 100,000 times each day to pump about 10 tonnes of blood through a complex network of vessels. Our hearts drive us—our actions, thoughts and feelings—but what drives our hearts?

Our bodies contain a multitude of fuel sources derived from the foods we eat. Like gasoline in a car engine, these fuel sources are consumed in chemical reactions to generate energy that in turn power the trillions of cells comprising our tissues and organs.

The heart is an omnivore consuming whatever foods it can, including sugars and fats. “Depending on the availability and how hard it’s working, the heart can use any of those substrates. It’s very flexible in what it can use,” says Dr. Charles Cunningham, a senior scientist in the Schulich Heart Research Program at Sunnybrook Research Institute (SRI). “But in disease, that changes. Under certain conditions, the heart becomes less flexible, and that can contribute to disease progression.”

The failing heart is like an engine that is running out of fuel.

The field of cardiac metabolism centres on the energetics of the heart: which fuel sources it uses and how it converts that fuel to energy. Although the heart can use diverse fuel sources, it prefers some to others. These preferences are purely utilitarian and driven by questions of efficiency like, “How much energy can be generated from the breakdown of this sugar versus that fat? What food source will produce the most energy when oxygen levels are low?”

Helping those patients is a big medical need where hyperpolarized MRI can fit in, because the current imaging methods don’t answer all the questions.

To understand how cardiac metabolism contributes to heart failure, Cunningham is studying hyperpolarized magnetic resonance imaging (MRI), a new technique that allows imaging of the biochemical reactions occurring within cells. Traditional MRI shows features like clogged arteries, swollen tissues or localized bleeding. Together, hyperpolarized and traditional MRI paint a more complete picture: one illustrates the complex network of pipes, valves and pistons in the engine, while the other measures the efficiency of the process that converts gasoline to power.

Hyperpolarized MRI enables researchers to study how a fuel source is broken down and how much of it is converted into useable energy. With traditional MRI, the signals from the energy source and its byproducts are too low to distinguish from background noise. Hyperpolarized MRI amplifies these signals, making it possible for researchers to locate them and track their journey through a cell.

That SRI has one of only seven clinical hyperpolarizers in the world can be credited to Cunningham’s expertise, says Dr. Graham Wright, director of the Schulich Heart Research Program at SRI. “He’s developed methods that allow us to look at these metabolic products very quickly in a way that works in a moving heart. He’s also developed a lot of the tools that makes this approach practical in preclinical studies. Those tools are immediately translatable into patients,” says Wright, who collaborates with Cunningham.

Prior to Cunningham’s work, most research using hyperpolarized MRI focused on tumours and other static tissues, which are much easier to image than a live, beating muscle. “The motion and fast blood flow of the heart makes any kind of contrast imaging really tricky,” says Cunningham. Add to that the transient nature of the hyperpolarized MR signal, which lasts for only 60 to 90 seconds, and the need for fast and accurate cardiac MRI tools becomes obvious. Having overcome the challenges of adapting hyperpolarized MRI to the heart and large preclinical models, he is bringing the technology to patients.

About 500,000 Canadians are living with heart failure, with 50,000 new patients being diagnosed each year. “Heart failure is really the endpoint of a lot of diseases of the heart,” says Cunningham. “Helping those patients is a big medical need where hyperpolarized MRI can fit in, because the current imaging methods don’t answer all the questions.”

The researchers will soon be starting the first human studies of hyperpolarized carbon-13 signals from pyruvate in the heart. They chose pyruvate as the injected substance for its importance as an energy source in several metabolic pathways. As with any new technology, establishing “normal” baseline values and determining the consistency of the methods—how much variability will there be between measurements of the same patients taken on different days?—will be important to future clinical use. Cunningham and Wright will do these studies in collaboration with Dr. Kim Connelly at St. Michael’s Hospital and pharmacists at Sunnybrook, who will prepare the pyruvate mixture in SRI’s good manufacturing practice laboratory to ensure that all products meet Health Canada guidelines.

Cunningham is optimistic about the potential of hyperpolarized MRI to help predict whether patients will develop heart failure. There’s good reason for optimism. In a preclinical study published in the European Journal of Heart Failure, Cunningham used MRI signals derived from hyperpolarized carbon-13 pyruvate to identify changes in cardiac metabolism; he could see how the metabolism changed from early- to late-stage heart disease. These results suggest that hyperpolarized MRI scans of cardiac metabolism could be a useful tool for tracking the progression of heart failure. Next, Cunningham will use the technology to look for metabolic changes in patients with hypertrophic cardiomyopathy, an enlargement of the heart often associated with a later diagnosis of heart failure.

“For the patients who are going to develop heart failure, I hypothesize that you would see a metabolic change prior to other signs and symptoms developing,” says Cunningham. “The idea is to find the people that are going to do worse and give them more aggressive therapy.”

Another area in which hyperpolarized MRI might be useful is in predicting the effectiveness of treatments like revascularization, which aims to revive damaged heart muscles by introducing blood flow back to the heart. “Shortly after a heart attack, there’s a question—is the tissue recoverable?” says Wright. “You may see a region of the heart wall that’s not squeezing properly. It may be dead or it may not be getting enough oxygen to have the energy to squeeze. It’s often hard to tell the difference between those two states.”

While it may be hard to distinguish between dead and live heart tissues visually, metabolically speaking, the differences between them are glaringly obvious. Dead tissues have little to no detectable metabolic activity, whereas live tissues are trying to generate and consume energy. By comparing metabolic activity in different parts of the heart, hyperpolarized MRI can differentiate between tissues that are past the point of recovery versus tissues that would likely benefit from revascularization.

Like Cunningham, Wright is enthusiastic about the promise of hyperpolarized MRI. “It has huge potential to help us understand the basic biochemistry of metabolism in a situation that matters—in a patient,” he says.

This research was supported by the Canadian Breast Cancer Foundation, Canadian Institutes of Health Research, Heart and Stroke Foundation, Ontario Institute for Cancer Research and Prostate Cancer Canada. Infrastructure support comes from the Canada Foundation for Innovation, GE Healthcare and Ontario Ministry of Research and Innovation.