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Of Life and Limb

Using high-resolution imaging to prevent amputations in patients with peripheral arterial disease

At an early morning interview, Dr. Trisha Roy is bubbling with enthusiasm about her work and the day ahead. Her energy and passion undoubtedly come in handy as she juggles her dual roles as a surgical resident and PhD student.

“I’ve always wanted to do surgery,” says Roy, who completed her first undergraduate degree in material sciences and engineering at U of T. That early experience helped her realize the potential an engineering background could have in creating better surgical devices. She then did a rotation in vascular surgery at Sunnybrook during medical school under the mentorship of Dr. Andrew Dueck and decided that it was the field for her.

“It’s a really exciting time for vascular [surgery] because it’s completely changed in the last 10 years,” she says. “It seems like a very promising field in terms of advanced technologies and their applications.”

As a third-year resident and surgeon-scientist-in-training, Roy receives protected time during which she can focus on her research at Sunnybrook Research Institute (SRI). Under the supervision of Dueck, a vascular surgeon and researcher at SRI, and Dr. Graham Wright, director of the Schulich Heart Research Program at SRI, she is using magnetic resonance imaging (MRI) to understand the plaques that form in the arteries of people with peripheral arterial disease (PAD).

Peripheral arterial disease results when plaque buildup in the arteries restricts circulation to the limbs, most commonly the legs and feet. More than 800,000 Canadians have PAD. Risk factors include older age, smoking and diabetes. “Now that we have an aging population and more diabetes, [PAD] is becoming a growing issue,” says Roy.

Peripheral arterial disease is the leading cause of amputations in patients aged over 50 years and responsible for more than 90% of amputations overall.

In some cases of PAD, prolonged restrictions in blood flow can lead to tissue death, or gangrene. These dead tissues are highly susceptible to infections and often require amputation to minimize the risk of infections spreading to other parts of the body. Peripheral arterial disease is the leading cause of amputations in patients aged over 50 years and responsible for more than 90% of amputations overall.

Until recently, bypass surgery was considered the standard of care for treating patients with PAD. Similar to a bypass procedure in the heart, bypass surgery in the legs involves taking a blood vessel from another part of the body and using it to reroute blood around the blocked artery to restore circulation to the affected leg. Endovascular procedures such as angioplasty offer a less invasive alternative to bypass surgery. In angioplasty, a balloon inserted into the blocked vessel is inflated to force the vessel to widen. A stent can be also inserted into the vessel to act as a scaffold and ensure the vessel remains open.

“One of the limitations of [endovascular surgeries] is that the stents do not tend to last as long as the bypass,” says Dueck. “A primary goal of our research is to determine whether the plaque itself is part of the reason why some angioplasties fail.”

Imaging techniques commonly used to diagnose PAD like ultrasound and computerized tomography (CT) are able to identify blockages in the blood vessels but do not provide information about the type of blockage. Roy is using MRI to see the finer details of the artery-clogging plaques and translating that knowledge into better-informed decisions on what type of treatment a patient should receive.

Knowing whether a plaque is composed of hard materials like calcium and collagen or soft materials like fat is an important consideration when choosing the best procedure. “If you have a really hard, rigid plaque, that’s going to require different wires, stents and devices compared to if you have a soft, malleable plaque,” says Roy. “Right now, these procedures are not durable and maybe that’s because we’re not selecting our devices and approaches based on the actual [plaque] lesions.”

For the first part of her project, Roy studied human arteries donated by patients who underwent a lower limb amputation. She used ultra-high-resolution MRI to map the composition of plaques found in the isolated arteries. “We’re able to see very clearly when [the plaque] has a big chunk of calcium or collagen,” she says. “Fat appears super bright whereas calcium is quite dark.”

Roy validated her results by examining the same arteries under a microscope, where she could directly see deposits of fat or hardened calcium in the tissues. She was heartened to discover that her high-resolution MRI methods were 100% accurate in identifying fat in the plaques. In identifying collagen and calcium, the MRI techniques were about 95% accurate.

“I was surprised by the degree to which we could subdivide the plaques,” says Dueck. “I thought it would be quite crude but the images that she’s producing are really good at differentiating different types of plaque.”

Moving forward, Roy will test the practicality of her approach in patients. Two of the biggest challenges of adapting her techniques to patient studies are resolution and scan time. In her initial work, Roy used a preclinical 7-Tesla (7T) MRI scanner to produce ultra-high-resolution images. Most clinical MRI scanners are 3T (or lower), which means the images will be much lower in resolution. Furthermore, to produce high-resolution images of the isolated arteries, each artery was scanned for four hours, a length of time that most patients would find difficult to tolerate.

This is very complicated work.

“Maintaining resolution with reasonable [scan] times will be one of our biggest challenges,” says Dueck. Roy is already working on adapting and optimizing the methods she developed on the 7T scanner to produce high quality images on a clinical 3T scanner in less time.

Roy hopes that the knowledge obtained from MRI on the specific type of plaque will better equip doctors to select the most personalized treatment for patients with PAD. “We can expand the group of patients we’re treating with endovascular interventions and maybe be able to salvage more limbs and prevent more amputations,” she says.

It’s a tall order, but if anyone can do it, it’s Roy, says Dueck: “This is very complicated work. Only a very small number of people can actually do it. She is uniquely positioned to do this work because she is a surgeon-scientist and she has a background in engineering.”

As for Roy, she sees engineering playing a bigger role in surgery. “It’s an exciting time to be able to ‘speak’ both ‘languages,’” she says. Her experiences at SRI have strengthened her desire to pursue a career in medicine and research and helped her recognize the value of a multidisciplinary environment.

“What’s nice about Sunnybrook is there are a lot of scientists who are innovators and engineers, so we have a good mentorship model,” she says. “I feel really lucky to be here.”

This research is funded by the Canadian Institutes of Health Research, Ontario Ministry of Health and Long-Term Care, and the Chair in Vascular Surgery at Sunnybrook held by Dueck.