Using medical imaging for detection

Ask Aaron Fenster why he has spent more than 30 years immersed in the development of medical imaging and he will immediately refer you to the wise words of Harold Johns, the professor he did his PhD under at the University of Toronto in the 1970s.

Johns, whose international reputation had been established by his leadership in the creation of the cobalt-60 cancer radiation treatment, was moving at the end of his career into the domain of medical imaging - particularly as it related to cancer. When questioned why he was doing this, Johns often responded with an imaging mantra, "If you can't see it, you can't hit it. If you can't hit it, you can't cure it."

"I was convinced that we could invent new techniques to be able to see cancer better," says Fenster, who is now director of Imaging Research Laboratories at the University of Western Ontario's Robarts Research Institute and chair of the Imaging Sciences Division of UWO's Department of Medical Imaging.

It was a belief that is justified by what in many ways has been the most extraordinary change in medical diagnosis and treatment to appear in the last few decades. Almost all of the commonplace imaging technologies - magnetic resonance imaging, positron emission tomography CT scans and ultrasound - are no more than 30 years old and, in most cases, much less.

Clinically, these technologies have resulted in doctors being able to detect diseases earlier and researchers understanding conditions better, not to mention dramatic declines in the number of infamously anguish-inspiring exploratory surgeries.

But the technological advances have also created a never-ending expectation of better and better. The seemingly relentless progression of imaging tells today's researchers that they must add a technological change footnote to Johns' mantra when thinking about their students' futures and theirs as well.

"I tell my students if your PhD is in three years, don't think that the technology you are using today will improve by a factor of two. Don't think about something you are studying being made a little bit better. No, think exponential change. Think all-of-a-sudden change. Think that new technology is going to create revolutionary differences in your field of study," says Fenster.

To comprehend how this interaction between improved understanding and an exponentially improving imaging technology plays itself out, one simply has to look at the recent past, the present and the hoped-for future of imaging at two leading research institutions in Ontario. One is Fenster's Robarts. The other is the Rotman Research Institute at Baycrest Hospital in Toronto, where imaging is being used to unveil how the brain - particularly the aging brain - functions and can be made to function better.

In less than a decade, Baycrest has gone from being an imaging technology beggar to an imaging technology leader. Donald Stuss, vice-president of Research and Academic Education at Baycrest, says that until Ontario and Canada's recent injection of infrastructure funding into Baycrest, the institution had very little of its own technology. To conduct their research, Baycrest scientists were required to borrow imaging time at machines in other Toronto hospitals and in the United States.

"We had an external review team come see us and they said, 'Well, you're this big imaging group, but you're smoke and mirrors. You've got nothing here.' And they couldn't believe it," Stuss says about the situation that existed less than a decade ago.

"So what the major federal and provincial infrastructure investments did was change our modus operandi. It made us major world players in the field. We quadrupled our studies afterwards," says Stuss.

What specifically did the new technologies - such as MEGs and MRIs allow Baycrest researchers to do?

Randy McIntosh, a senior scientist at Baycrest, points to the development of the Multiple Auditory STEady-state Response (MASTER) technology. It addresses an extremely vexing problem. How can you tell if people have heard something when they can't tell you they have? This "mute category" includes infants, people who speak only a foreign language, people who are in a coma and those who have hearing problems. MASTER, which includes both hardware and software, is being sold to clinicians and researchers as a way of circumventing the response problems through the use of brain images that indicate when a sound has actually been heard.

Institutionally, the patenting of the process and the success of MASTER, says Stuss, "have changed Baycrest's attitude toward commercialization."

A second, important thrust has seen Baycrest become one of the world's leaders in demonstrating what an individualized organ the brain truly is. One study has shown that as people age, they transfer simple memory operations from one part of their brain to another. This ties together with other Baycrest imaging studies that have shown that people are highly varied in not only what they think, but how they think. "We are finding maybe 30 per cent of brain function is common between people, and 70 per cent is different," says McIntosh.

What this discovery could lead to in the future is doctors taking what is essentially a brain organizational fingerprint of patients and using it to personalize their therapies. As a result, your treatment would be based on how your brain, and not the average brain, organizes itself.

Another thing that lies ahead is better brain games. "The problems with the so-called brain games that are marketed today is that they are not validated well. They may start out based in science, but then someone says 'Let's go to Nintendo and have them make a brain game'. And when they come up with something, their people don't come back to scientists and say, 'Is this what you had in mind?'" says McIntosh.

Together with research translation experts at Toronto's MaRS facility, Baycrest researchers hope that over the next two years they will be able to come up with mental games that actually build up brain "muscle". They would then affix to these games what would amount to a Baycrest seal of brain-bettering approval.

Meanwhile, the work of Fenster and others at Robarts has been aimed at combining imaging with sophisticated disease diagnosis and treatment. Fenster himself has 35 patents, a cluster of which pertain to discoveries that allow for 3-D ultrasound imaging. While the technique can be used to detect diseases anywhere in the body, Fenster and his colleagues have received much acclaim for a 3-D ultrasound technology specifically designed to let doctors more precisely locate and treat prostate cancers.

Right now, if PSA testing suggests the presence of prostate cancer, men can go through two years of repeated biopsies trying to find where a cancer might be located.

The current two-dimensional imaging systems are often unreliable because they see only one slice of the prostate at a time. Equally important, they cannot accurately tell doctors attempting to hone in on a notoriously slow cancer precisely where they are sampling today and, thus, where they should avoid sampling in the future if another biopsy is required.

The new technology Fenster is developing not only allows a biopsy needle to be precisely guided into a potentially cancerous area, it accurately tells a technician exactly where in the prostate the biopsy has been taken.

"So it is sort of a Global Positioning System for prostate biopsies?" Fenster is asked.

"Yes, it is," he replies.

What lies in the future is, Fenster hopes, not an imaging evolution but an imaging technological revolution. The goal: being able to accurately image not just organs but individual molecules.

To that end, he is heading up a $10 million project geared to accelerating development of imaging techniques for screening, early cancer diagnosis, cancer stem cell research and clinical trials.

He is also co-director, with Martin Yaffe of Sunnybrook Research Institute, of what is called the Ontario Institute for Cancer Research - One Millimetre Cancer Challenge. This groundbreaking initiative is looking for ways to screen groups of people at risk of cancer and to identify tumours when they are tiny - only a few millimetres in size.

"If you can image this early-stage cancer before it metastasizes, we can destroy the cancer before it becomes life-threatening. So that's really our vision and a very ambitious vision at that," says Fenster.

The question remains: Does one need different ways of thinking, different machines or a different approach to imaging?

"The simple answer is probably 'yes,'" he says.

And as he does, one can almost hear Harold Johns in the background coming up with a new mantra.

In 21st-century Ontario, one can see better and therefore one can hit better, and that, hopefully, will mean Ontario science will also cure better.