Research in Action: - University of Calgary

Research
in
Action:
Disciplines merge
to improve
health + quality
of life
The University of Calgary is leading innovation in biomedical engineering.
Through the collaborative work of researchers and students in six
faculties and multiple disciplines, we have developed the world’s most
advanced robot to help surgeons improve brain surgery, created
leading-edge imaging technology to let us see what the body is doing—
and why—and produced a whole new calibre of artificial joints and more.
This emerging field will transform the economy, improve the efficiency of
health care and change our lives.
Success through research and innovation.
ucalgary.ca
Issue 4: Fall 2008

Biomedical engineering has the potential to stimulate Alberta’s economy to a level we can’t imagine.
It could very easily become an alternative economy to oil and gas. More importantly, it is through
research in this field that we will make the biggest advances in health—new cures, better treatments
for devastating disease and injury, enhanced prevention and diagnosis. This is an opportunity we must
capitalize on at any cost.
Dr. Harvey Weingarten, President and Vice-Chancellor, University of Calgary
The need for advances in biomedical engineering has never been greater. Our population is aging;
people are living with chronic illnesses. At the University of Calgary, we have the tools and expertise
to improve lives; we have a track record of success and a history of working and learning in
interdisciplinary teams. The potential is almost unlimited. We cannot afford to wait.
Dr. Rose Goldstein, Vice-President (Research), University of Calgary
We have an opportunity to leave an academic, economic and health-and-wellness legacy by serving
humanity and building an industry in Alberta—a national resource—that will improve health and
wellness of all humans. What more can one want than knowing that something that you were
involved in has resulted in a paraplegic child being able to walk?
Dr. Naweed Syed, Head, Department of Cell Biology and Anatomy
Research Director, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary
Advisor to the Vice-President (Research) on Biomedical Engineering
Dr. Harvey Weingarten
President and Vice-Chancellor
Dr. Rose Goldstein
Vice-President (Research)
Dr. Naweed Syed
Advisor to the VP (Research)

Biomedical Engineering
A partnership of engineering + health sciences to improve lives
In Issue 1, Research in Action: Creating Wealth,
we explored how the U of C is strengthening
Canada and building the global economy
by creating new businesses, launching new
technologies and advancing science
and medicine.
In Issue 2, Research in Action: Mobilizing
Knowledge, we showed how the U of C
is collaborating with research partners from
all walks of life to find solutions to
society’s challenges.
In Issue 3, Research in Action: Building a
Great City, we illustrated how our community
partnerships help define university research,
and how the results of this research are
helping our city become a national and
international leader.
In Issue 4, Research in Action: Disciplines
Merge to Improve Health + Quality of Life, we
explore the new world of biomedical engineering
at U of C and its potential to make a difference
to Calgary, Canada and the world.
The best way to improve our quality of life is through prevention, early diagnosis
and medical devices. Biomedical engineering—the application of engineering
principles to the field of medicine—is driving innovation in all these areas.
The University of Calgary has built one of the strongest and most comprehensive biomedical engineering programs
in Canada—for researchers, graduate and undergraduate students. Over the past five years, we have tripled the
number of researchers in the biomedical field. This critical mass of more than 100 researchers are distributed across
six faculties--Medicine, the Schulich School of Engineering, Kinesiology, Science,
Nursing and Veterinary Medicine. They share labs and technology—as well as ideas, concepts and
solutions—working together to develop innovations that will change society.
Learn more. ucalgary.ca
Dr. Nigel Shrive
Schulich School of Engineering
University of Calgary

Imagine a time when a child who loses a leg in an accident or to disease could be outfitted with the most
advanced prosthetic in the world. It would be controlled by a microchip that turns her brain impulses into
radio signals to control her bionic limb as if it were her natural leg. Or imagine a special undershirt that is
capable of monitoring an elderly man’s vital signs, reminds him to take his medication and can call for help
if he falls or suffers a stroke. Now imagine that all the knowledge, technology and procedures involved in
these medical advances were developed by University of Calgary researchers, with their worldwide application
directly benefiting the Canadian economy.
2 UofC Research in Action
Building on a vision
This vision is starting to unfold as U of C scientists, engineers, physicians, kinesiologists and other experts
increasingly join forces to tackle medical problems from many angles. This interdisciplinary approach is
already paying off with world-leading developments in areas such as neurosurgery, joint repair and therapy,
and cardio-respiratory care. It’s just the beginning, however, as the university positions itself as a hotspot in
the emerging field of biomedical engineering. “We cannot miss this opportunity,” says Dr. Naweed Syed, head
of cell biology and anatomy in the Faculty of Medicine, research director of the Hotchkiss Brain Institute and
advisor to the Vice-President (Research) on biomedical engineering.
Brain on a chip
Syed and colleagues made headlines around the world in 2004 when they were the first to connect brain cells
to a silicon chip and show that living cells could communicate directly with an electronic device. The so-called
“brain on a chip” discovery is considered a major step towards successfully integrating computers with the
human brain to potentially control artificial limbs, correct memory loss or impaired vision, and treat a wide
range of neurological conditions. Such an achievement took the combined efforts of biologists, neurologists,
engineers and computer scientists from around the world, all working together on a common problem.
What gets Syed fired up these days is the prospect of similar projects being conducted by teams of U of C
researchers. “If we can develop something like this locally, there could be enormous benefits to Canada,
Alberta and the university,” he says. To that end, Syed is leading the development of a biomedical engineering
enhancement strategy at the U of C, centered around the establishment of a National Biomedical Engineering
and Innovation Centre on the university campus. The goal of such a facility is to encourage co-operation and
cross-pollination of ideas between researchers who might not otherwise be connected by their work.
Dr. Naweed Syed was the first to
connect brain cells to a silicon chip,
a major step in controlling artificial
limbs, correcting memory loss,
impaired vision and more. Now,
he’s leading the U of C biomedical
engineering strategy.

Dr. Naweed Syed’s “brain on a chip”
discovery is a major step towards
integrating computers with human brains
to help people control artificial limbs,
monitor people’s vital signs, correct
memory loss or impaired vision.
“We want to harness the innovation
taking place here by putting people
from different disciplines in a place
where they will bump into each other
on a daily basis and work together
on novel ideas,” Syed says.
Understanding the Brain
3

In the space of seven years—the blink of an eye in the world of research—Calgary neurosurgeon Dr. Garnette
Sutherland took an idea about how to improve the precision of brain surgery and made medical history. The
story illustrates exactly why biomedical engineering has such potential to improve health care and change
lives, and why the University of Calgary is poised to play a leading role in this revolution. In 2002, Sutherland,
a professor of neurosurgery at the University of Calgary’s Faculty of Medicine, assembled a multidisciplinary
team of scientists and engineers to tackle a problem that plagues all surgeons. No matter how skilled, they
are limited by the physical constraints of their own hands.
Making medical history
Sutherland’s vision was to create a surgical robot capable of operating on the brain in a way that is less invasive
and more delicate than a surgeon’s hands. On May 12, 2008, he performed a world’s first—groundbreaking
neurosurgery using the neuroArm surgical robotic system to remove a complex brain tumour from a 21-year-old
Calgary chef and mother. This was the first time a robot has performed surgery of this kind, but not the last.
Similar operations are now being conducted at the Foothills Medical Centre, a major health-care partner of the
University of Calgary.
A revolution in neurosurgery
“This system has exceptional capabilities,” says Sutherland. “This is a turning point in the performance and
teaching of neurosurgery.” Typically, the human hand can steady itself and move in increments of one or two
millimetres. NeuroArm can move in increments of 50 microns—about the width of a human hair.
“NeuroArm allows us to harness the capabilities and advantages of both human and machine,” says Alex Greer,
the project’s robotics engineer. “We enhance the surgeon’s manual skills with tremor filtering. By providing
updated imaging and navigation, the surgeon has the tools to better plan and execute complex neurosurgical
procedures.”
The neuroArm system is controlled by a surgeon from a computer workstation, working in conjunction with
intraoperative magnetic resonance (MRI). Sutherland developed this ground-breaking MRI machine, now
marketed by Winnipeg’s IMRIS Inc., with the NRC Institute for Biodiagnostics in the 1990s. The neuroArm was
produced in collaboration with MacDonald, Dettwiler and Associates Ltd., (MDA) creators of the Canadarm
and Canadarm2 used on the International Space Station. Indeed, bringing neuroArm to life required a unique
partnership between medicine, the Schulich School of Engineering, physics and education, some of Calgary's
most visionary philanthropists, the high-tech sector and research funding organizations. As expected, the
research, and now the reality of a human surgery using neuroArm, has garnered attention from
neuroscientists and specialists across the globe.
hbi.ucalgary.ca
medicine.ucalgary.ca
neuroarm.org
4 UofC Research in Action
Dr. Garnette Sutherland is
leading the world with neuroArm,
a robot that’s revolutionizing
brain surgery by allowing
surgeons to remove more
tumours more effectively.

Dr. Garnette Sutherland was the first in
the world to use a surgical robot to
remove a complex brain tumour, using
U of C expertise in neuroscience,
robotics and medical imaging.
Sutherland believes that this is
just the beginning. “The breakthrough
of robotic technology is happening,
it’s evolving and it will continue
to evolve.”
Biomedical Engineering: Understanding the Brain
5

With a pulse of light and a spark of electricity, a computer stimulates a network of brain cells growing
on a silicon wafer. Dr. Michael Colicos watches intently as the neurons flash with activity. Colicos, a researcher
with the Boone Pickens Centre at the Hotchkiss Brain Institute, is using his bio-computer interface to study
the cause of neurological disorders like epilepsy, autism and stroke and to develop new ways to treat them.
The technology has also allowed him to make fundamental discoveries about how neurons grow and
form connections.
6 UofC Research in Action
“We can interface with a large population of brain cells simultaneously,” he explains, “and at the same time see
the connections between them in great detail.” Colicos co-created the interfacing technology—called photoconductive
stimulation—with Dr. Yukiko Goda at the University of California, San Diego. In his own lab, he uses
the technology to study autism, epilepsy, stroke and spinal cord injury.
The technology is versatile. To study epilepsy, for example, the researchers induce a seizure in the neurons on
the wafer. The computer monitor lights up with a fireworks display of neuronal activity. For Colicos, this work is
not only a challenge of discovery, but it also has personal relevance. While he has been involved in epilepsy
research for more than 10 years, his two-year-old daughter, Alexandra, developed epilepsy as a baby. Although
anti-seizure drugs are currently available, Colicos hopes that this new technology will help epilepsy researchers
pursue new therapies.
Little grey cells spark big ideas
Carolina Gutierrez Herrera, a PhD candidate in Colicos’ lab, is working on another puzzle—trying to understand
how autism affects the way that neurons communicate. Gutierrez has been comparing healthy neurons to those
with a gene mutation linked to autism. As the live images of brain cell activity reveal, the cell populations
communicate in very different ways. There is so much to learn from a single synapse—the point of communication
between neurons, she says. “But when you stand back to take in the big picture, it is interesting to see that
the mutation has such a distinctive effect at the global level.”
She and Colicos speculate that the change in communication between brain cells might explain how the
autistic brain processes information differently, although it will be some time before this idea can be tested.
Another goal for the interface is to create a bio-computational device. By interfacing the immense computational
power of a neuronal network with a computer, scientists could develop a device for performing extremely complex
tasks, such as face recognition.
ucalgary.ca/colicos/
Dr. Michael Colicos is using a
technology that links computers
with brain cells to develop new
treatments for epilepsy, autism,
stroke and spinal injury.

Dr. Michael Colicos is using
bio-computer technology to study
autism, epilepsy, stroke and
spinal cord injury.
“We’re fusing living tissue
with computers,” says Colicos.
It’s the next generation of biomedical
technology that will help find the best
treatment for epilepsy, and help people
walk after stroke or spinal injuries.
Biomedical Engineering: Understanding the Brain
7

Ask any woman who’s had a mammogram and she’ll tell you that the technology is far from perfect. The
compression from the procedure can be painful, and some patients are concerned about the X-ray radiation
involved. Dr. Elise Fear, an associate professor of electrical engineering at the Schulich School of Engineering,
is trying to find a better, safer and more comfortable alternative using low-power radar as a diagnostic tool.
“We’re proposing to create a 3D image of the breast using microwaves,” she says.
Safer breast imaging
The process uses tissue sensing adapting radar, TSAR, for early detection of breast tumours. That’s a serious
concern in a country where one in nine women can expect to develop breast cancer in her lifetime. “We hope
that we can detect tumours three millimetres and greater—that’s similar to mammography,” says Fear, adding
the research team hopes to be able to determine information on the seriousness of each tumour. “Malignant
tumours can be spiky, while benign tumours may be more round or compact.”
The idea of using electrical properties for diagnosis dates back to the 1920s and using microwaves for medical
imaging began in the 1980s. Fear stresses the microwaves are low power, so there is minimal risk of heating
the breast tissue. “TSAR uses much lower power signals than a cellphone emits,” she says. “We’re looking
to develop patient-friendly technology.” The aim is to develop a system that can be used in a hospital setting to
scan patients, as well as ways to translate that scan into a useful diagnostic image.
An innovative approach
The device is now on its third prototype. A woman lies down on a table and places one breast into a bath of
canola oil. The breast is illuminated by short pulses of microwaves, while a specially designed sensor
“listens” for a reflection. Clear oil was chosen because it cuts down on reflection from the skin and allows
for a better image. An antenna moves around, up and down so researchers can scan the entire breast
surface. “We record the reflections, then estimate the surface of the breast so we know what we’re interested
in imaging,” says Fear, a winner of the U of C’s Young Innovator award to recognize outstanding young faculty.
“We then look inside the breast to find reflections from tumours.” Breast models have been created from 12
volunteers—nine breast cancer patients recruited by Dr. Daphne Mew at the Foothills Medical Centre, and
three others without cancer. Clinical trials are just beginning and women aged 20 to 80 are lining up to be
part of the process.
8 UofC Research in Action
Using low-power radar, Dr. Elise Fear
is building a better, safer and more
comfortable way to diagnosis
breast cancer.

Medical Imaging
Using tissue sensing adapting
radar, Dr. Elise Fear is developing
new ways to detect breast
tumours.
“When women find out what we do,
they’re very excited,” says Fear.
“It is satisfying to know that patients
are highly engaged in this research.
We are on the right track to improve
breast health care”
9

Since magnetic resonance imaging (MRI) first gave researchers and physicians a non-invasive peek into
the human brain in 1993, the field has exploded in leaps and bounds as the technology improved. Now, University
of Calgary researcher Dr. Brad Goodyear is leading the next evolution as he uses functional MRI technology
and techniques to study brain function in order to uncover how diseases such as Parkinson’s disease, Multiple
Sclerosis and stroke interfere with the brain’s ability to communicate between its different regions.
10 UofC Research in Action
Mapping the brain
Goodyear’s cutting-edge research, while still in its early stages, will ultimately reveal how communication
between the brain’s grey matter regions—the “thinking” part of the brain—becomes severed when the brain’s
white matter—the connective tissue—becomes diseased. When those connections are lost or impaired, the
brain tries to “re-route” the signals to other parts of the brain, but eventually exhausts its options. The result
can be impairments in movement, speech and cognitive function.
By taking high-tech snapshots of the brain using functional MRI, his research will identify fluctuations in brain
activity over time, producing a kind of “map” of the brain indicating the degree to which brain regions are
communicating. In stroke patients, these snapshots will help predict the chances of a patient’s recovery and
help doctors determine the impact of disease. This “mapping” is also an essential tool in developing new
therapeutic strategies. “What we’re trying to develop is the missing link between the size and severity of a
stroke and the actual behavioural function of the patient,” says Goodyear, an assistant professor of radiology
and clinical neurosciences at the U of C.
The next level
Until recently, imaging was used to assess only the size and location of a stroke. Function was not something
that was measured in the brain directly—until now. Goodyear, who also works in the Hotchkiss Brain Institute,
is “taking it to the next level” by using these MRI snapshots to predict patient outcomes, based on the
strength of the communication he identifies in the patient’s brain.
By measuring how brain signals change in different regions of the brain after a stroke—known as connectivity
analysis—Goodyear will potentially provide patients and doctors with an objective indicator of brain function
and, therefore, predict the likelihood of patients recovering some or all of their brain function. Previous models
relied on patients performing a task and measuring brain function during the task, but because stroke sufferers
often have limited physical control, this left out a large population.
hbi.ucalgary.ca
Dr. Brad Goodyear’s high-tech
“snapshots” of the brain
are helping to learn more
about Parkinson’s disease,
Multiple Sclerosis and stroke.

Dr. Brad Goodyear is
using MRI technology to
measure brain function
after a stroke.
“We’ve come up with
a way to be able
to look at brain function
without the patients
actually having to perform
a task at all,” says
Goodyear. “This takes it a
step further by allowing us
to include the large
population of stroke
sufferers, who often have
limited physical control and
can’t perform tasks.”
Biomedical Engineering: Medical Imaging
11

Deep in the ocean, hydrothermal vents spew out boiling water from inside the Earth, which then spirals
upward and swirls into pockets of eddies. It was while studying this phenomenon in graduate school that
Dr. Kristina Rinker, a University of Calgary biomedical engineering specialist, first drew a connection.
“I realized there were actually some similarities with what’s going on in the human body,” says Rinker, an
associate professor at the Schulich School of Engineering.
12 UofC Research in Action
Targeting blood clots
Still intrigued by this similarity years later, Rinker began studying how flowing blood can impact the way in
which white blood cells stick to artery walls, a normal function of the immune system. For people with
cardiovascular disease, something in this process gets out of balance, and over time, sores or plaques form
in the spots where the white blood cells are concentrated. Eventually, these plaques can rupture, causing the
formation of a clot that blocks the flow of blood and results in either a heart attack or a stroke. Rinker and
her team of researchers in the Cellular and Molecular Bioengineering Research Laboratory have developed
experimental models that mimic the flow in blood vessels, and support cell cultures for long periods of time.
These systems allow specific investigations into cardiovascular disease through a focus on “target cells”—the
cells that line artery walls and act as gatekeepers for the passage of nutrients and biochemicals from the blood
into the vessel tissue.
“Now we can look molecularly inside the cell to investigate how blood flow properties influence plaque formation,
and how new drugs may encourage plaque stabilization or regression [thus preventing blood clots], says Rinker,
associate professor in both the Department of Chemical and Petroleum Engineering and the Centre for
Bioengineering Research and Education. Located in the university’s Calgary Centre for Innovative Technology, the
lab has become an incubator of cutting-edge research that draws on the work of graduate students and worldclass
expertise in multiple disciplines.
Bridging the gaps
“A lot of our work is just now starting to have an impact,” Rinker says. Cardiovascular disease is the leading
cause of death in Canada and costs the health-care system more than $18 billion annually. Rinker hopes her
research will eventually help make new cardiovascular therapies more effective. “We’re starting to get to
some real novel approaches for cardiovascular stent design, testing and surgical procedures. The hope is that
through integrating molecular and applied research approaches, the cardiovascular community will be able to
understand each others’ problems more effectively, and we will achieve some major breakthroughs.”
schulich.ucalgary.ca/biomedical
schulich.ucalgary.ca/node/237
Dr. Kristina Rinker’s research
focuses on mimicking the flow in
blood vessels. This is important
for preventing blood clots that
cause heart attacks and strokes.

Dr. Kristina Rinker is developing models to
better understand how blood flow can impact
the behaviour of white blood cells in arteries.
“I think the real advances are going to
come together by bridging the gaps between
the disciplines—science, engineering and
medicine—and trying to get at health
problems using a multi-pronged approach,”
says Rinker.
Cardio-Respiratory
13

Every good university knows how to play to its strengths. And in its relatively young life, the University of
Calgary has emerged as a leader in biomedical technologies, including everything from surgical robots to
high-tech running shoes. There was only one catch: engineering students had to wait until graduate school
to dig into the subject. Four years ago, that all changed when the Schulich School of Engineering admitted
its first crop of students into a unique undergraduate biomedical engineering program. Taught by instructors
from engineering, science, kinesiology and medicine, this innovative program features a multidisciplinary
curriculum, including anatomy, biology and engineering. Practicums and a senior research project round out
the coursework.
14 UofC Research in Action
Emerging researchers
Doing such meaningful work appealed to Tessa Richardson, one of the program’s first graduates. “I entered
the (engineering) program with the intention of eventually finding a job that would help people,” she says.
“Biomedical engineering seemed to be the perfect fit.” Her research project with Dr. Janet Ronsky looked at a
problem of diagnostics: radiation. She examined the case of children with a chest deformity who require
ongoing CAT scans for evaluation. Richardson developed another, less harmful, method. She surrounded a patient
with four cameras and used light projections to capture a 3D shape of the sternum, then used a computer
method to analyze the findings. “I further analyzed my results to show that the optical imaging system was able
to evaluate pectus deformities as effectively as the traditional CT scan method.”
Beyond oil and gas
For Kogan Lee, 21, the biomedical option was a way to expand his engineering horizons. “Initially when I first
applied to engineering I thought everything would be oil and gas related, but throughout my undergrad I realized
engineers have contributed greatly to health care by designing medical devices.” For his research, Lee worked
with Dr. Clifton Johnston and studied stents, the small wire-meshed tubes that prop open diseased blood
vessels. They are used mainly to treat aneurysms. How the blood flows in and around the stent determines
if tissue stays healthy.
Engineering professor Dr. Kristina Rinker, who oversees the students’ research projects, says entry into the
new degree program is competitive. Students must complete their first year of engineering studies, then
compete for one of the 35 spots in biomedical engineering. Most have top marks, and they are drawn by the
prospect of rewarding work that combines engineering and medicine. “These undergraduate students take on
ambitious projects that can lead to advances in human health,” she says.
The first alumni of an innovative
program for undergraduates
are ready to take on the world.

“The goal of my research is to develop an apparatus
that can test for certain physical properties of heart
stents, so that they can help keep surrounding tissue
healthier. Only at U of C could I have gotten this type
of multi-disciplinary education, which will be a great
help to my future career,” says Kogan Lee.
The Students
15

Whether it’s an aching back or a sore neck, there’s no escaping the fact that our bodies deteriorate as
we grow older. But the next generation of biomedical researchers is offering new hope that it might not
have to be that way. No, they haven’t found a miracle cure to old age, but they are on the leading edge of
research that aims to develop new therapies for conditions such as intervertebral disc degeneration in the
spine, lower back pain and osteoporosis.
16 UofC Research in Action
The next generation
“By the time people reach middle age, hardly anyone has a full set of healthy discs,” says Jana McMillan, who
is pursuing her master’s of science in biomedical engineering at the Schulich School of Engineering. She’s
analyzing the mechanics of how the breakdown of intervertebral discs occurs in the spine which, in some
cases, results in various forms of back pain. “The big picture goal is to be able to develop something to help
diagnose these conditions, because right now if people have a disc problem like a prolapse, they might not
even have pain,” she says. By examining the “communication” between cells of the outer layer of the disc,
she hopes her research will result in better ways to test for and identify small tears that could lead to bigger
problems. Another goal is to develop tissue engineering treatments by manufacturing discs to replace ones that
are injured. “They haven’t had much luck developing a replacement disc that works very well yet,” says McMillan.
Muscle interplay with bone
Over in the Faculty of Kinesiology, graduate student Sarah Manske is exploring the fascinating interplay between
muscle and bone—specifically how low-amplitude, high-frequency vibration created by muscle contraction may
be an important stimulation for increased bone strength. Her hypothesis is that as our activity levels typically
decrease with age, our decreasing muscle mass is a contributing factor to osteoporosis. While working toward
her PhD in kinesiology (biomedical engineering), Manske is using Botox to temporarily paralyze muscles in
mice, causing decreased muscle and bone mass, then adding a high-frequency vibration to stimulate the
pathways and then measure its effects.
Research using a vibration platform that accomplishes this task in humans is already underway in the U.S.
Children with cerebral palsy or elderly adults stand on the platforms each day for 15 minutes and are then
measured to see if they experience increased muscle and bone density and strength as a result. “It could be
implemented on a widespread basis, so we’re trying to find out why it works and how to optimize it for the best
possible result,” says Manske.
For graduate students like
Jana McMillan and Sarah Manske,
researching ways to improve health
is just part of the program.

Graduate students Jana
McMillan and Sarah Manske
are researching ways to help
with back pain, osteoporosis
and cerebral palsy.
Biomedical Engineering: The Students
17

The next generation of antibiotics must be able to target hospital-acquired infections and chronic illness,
says U of C microbiologist Dr. Howard Ceri, a professor in the Faculty of Science and chairman of the
Biofilm Research Group. But traditional methods of testing won’t tell us how to fight bacteria growing on
medical implants or in urinary catheters. All antibiotics on the market today have been tested on bacteria
grown in broth suspensions, explains Ceri. But in the real world, bacteria tend to stick together, forming
organized slime layers called biofilms on metals, plastics, body tissues or any other available surface.
Fighting infection on
medical devices
Biofilms are not just an interesting scientific phenomenon—in developed countries, biofilms cause most
bacterial infections and about 90 percent of infections picked up in hospital. Biofilms are also extremely tenacious,
and are able to withstand concentrations of disinfectants or antibiotics that would wipe out free-living microbes.
Ceri and his colleagues around the world are evaluating the first wave of new therapies to fight these biofilms,
using a device developed by Calgary’s Biofilm Research Group, co-founded by Ceri and other Calgary
researchers in the mid-90s. The device, which is commercialized as the MBEC Assay and licensed to
Innovotech Inc., is a plastic, multi-well tray the size of an outstretched hand. With this tool, researchers can
study 96 miniature biofilms at once, allowing for rapid testing.
Prototype product developed
Recent U of C PhD grad Joe Harrison used the MBEC Assay to test the tolerance of bacterial biofilms to
toxic metals and other antimicrobials. Already the research has led to a prototype product that could be used
to disinfect hard surfaces in hospitals. Harrison has tried to find out what is happening in the biofilm to make
it tolerant to metals. He thinks that the answer lies in the way that the bacterial cells take on specialized roles
in the biofilm population. Like people, the bacteria are community members that communicate and interact
to the benefit of the group.
Ceri is particularly interested in biofilms that grow on medical implants, such as artificial hips and heart
valves. Up to about five percent of recipients develop implant-related infections. Many of these patients must
undergo additional—and typically less successful —replacement surgeries. In some cases, the infection kills.
A focus of Ceri’s current research is antimicrobial coatings for medical implants to keep biofilms at bay. Thus
far the work has generated a patent application for a novel coating.
ucalgary.ca/~ceri/brg/
innovotech.ca/index.php
18 UofC Research in Action
Dr. Howard Ceri’s understanding
of biofilms will help fight infections
on medical implants like artificial
hips and heart valves.

Dr. Howard Ceri is using technology he
developed to help fight biofilms, the highly
resistant communities of bacteria that
can form on medical implants and
devices like catheters.
“All this requires the type of collaborative
research that is happening at the
University of Calgary,” says Ceri, who is
working with orthopaedic surgeons and
infectious disease specialists. “If you’re
going to ask important questions today,
you need a lot of different expertise…
a team approach.”
Medical Devices
19

Dr. Cy Frank has performed countless knee surgeries and helped people get back on their feet after
ligament injuries. All these operations—the majority of which involve using tendons from the knee to repair
torn ligaments—have left him with one inescapable conclusion: “There has to be a better way.” Frank
acknowledges that the current method of arthroscopic surgery is a vast improvement over the
methods of 20 years ago but he adds “it’s still fairly barbaric—drilling holes through the joint, disabling
people for months.”
20 UofC Research in Action
A better way to heal
One aspect of his work toward finding that “better way” focuses on the healing process. “All the ligaments we’ve
studied heal with scar tissue and not ligament regeneration,” says Frank, professor of orthopaedic surgery, an
Alberta Heritage Foundation Medical Research (AHFMR) scientist, executive director of the Alberta Bone and
Joint Health Institute and winner of the U of C’s Distinguished Alumni Award in 2002. “Scar tissue is better than
nothing but it’s not the same as normal ligaments.” Frank says scar tissue is about 30 percent as good as a
normal ligament and that getting injured knees back to normal is the goal. But there are lots of factors to
consider when investigating “how to optimize ligament healing, to make them tighter and stronger.”
One method involves intentionally stimulating the size of ligament scar tissue. “If you use more of an inadequate
material you can compensate,” he says. “For example, if you have a scar that is one-third as good but three
times as big as the normal ligament, it actually can be as strong as normal.” The problem with this method is
that it wouldn’t work for cruciate ligaments, as space within the knee is severely restricted, limiting the amount
of scarring that can be created.
“Growing” ligament tissue
Another new technique being explored by the team in Calgary involves looking for stem cells to create new
ligaments. If successful, this approach could involve “growing” more normal ligament tissue in the lab and then
implanting it. A simpler method of improving ligament healing might be to reduce the amount of inflammation
caused by the surgery.
“We’ve got some evidence that the inflammation caused by drilling through the knee could be a cause of
on-going scar weakness and some of the arthritis that develops,” Frank says. “We now have a Canadian
Institutes for Health Research grant to study how to prevent the inflammation to see if that can prevent some
of the arthritis and improve the quality of the grafts.”
Dr. Cy Frank is focused
on the healing process to
find a better way to treat
knee injuries.

One element of Dr. Cy Frank’s research
involves intentionally stimulating
the size of ligament scar tissue.
With the surgery, the repaired ligament
is about 80 percent as strong as
a normal tendon; this method could get
“that other 20 percent back,” Frank says.
If he can do that, he’ll also improve the
quality of life for many people who
suffer knee ligament injuries.
Bone and Joint
21

As any parent at bedtime knows, getting kids to do something they don’t want to is one of life’s biggest
challenges. In the late 1990s, physicians at the Alberta Children’s Hospital were looking for inspiration
on how to coax young patients with scoliosis to wear the uncomfortable braces that can help slow
the progression of the disease that affects about two percent of the population. What they wanted was
a formula to predict the speed and prognosis of scoliosis, a degenerative curvature of the spine, with the
ultimate goal of a spinal brace design which could better mold to individual bodies.
To each their own
They turned to Dr. Janet Ronsky, director of the Centre for Bioengineering Research and Education in
the Schulich School of Engineering and Canada Research Chair in Biomedical Engineering, whose research
focuses on joints but spans the fields of engineering, medicine and kinesiology. “When [a brace is] not worn,
it can’t correct anything,” she says. So, she and her team created the Eagle Brace. Scoliosis is more
prevalent in girls and often becomes apparent between ages nine and 17. The curvature, which may twist to
a helix shape, can dramatically worsen during the growth spurts of adolescence. If left unchecked, the curve
can progress to where surgery is required to insert rods and screws—a process which can increase the pain
of what is already an excruciating ailment.
Comfort a factor
A common treatment is bracing, which holds the torso in place to stop the curve’s growth. But the corset-like
device is hot, sweaty and uncomfortable, especially for boys and girls with slim hips. Too often, the child doesn’t
want to wear the brace for the upwards of 18 hours a day doctors believe it is necessary to make a difference.
To address this, U of C engineers worked with researchers at Montreal’s Ecole Polytechnique, using special
X-rays to create a three-dimensional image which included the spine’s deformity. A mathematical computation
was then used to generate a 3D image of “beads” outlining the youth’s projected form six months down the
road, similar to the technique seen on forensic reconstruction TV shows such as Bones. It worked. Models
designed by graduate student Hongfa Wu correctly predicted the curvature advancement within five per cent.
This information is then used to design a brace specially built for each patient. The new process also means
“we can reduce the number of X-rays we need for monitoring the progression of scoliosis,” says Ronsky.
22 UofC Research in Action
By understanding the course of
scoliosis, Dr. Janet Ronsky is
developing spinal braces that are
better molded to individual bodies.
This makes the braces more
comfortable, and more likely
to be worn by adolescents.

Dr. Janet Ronsky’s Eagle
Brace is helping slow the
progression of scoliosis
in young patients.
So far, two youths have
used the Eagle Brace and
those numbers will rise as
refinements continue on
the brace design.
The name is in honour
of the Fraternal Order
of Eagles, a service group
which has donated up
to $60,000 a year.
Biomedical Engineering: Bone and Joint
23

Weekend warriors and professional athletes alike might want to pay attention to the work of Dr. Walter
Herzog. That’s because Herzog, the multi-award winning co-director of the U of C’s Human Performance Lab,
is looking at how the things we ask our joints to do when we are young and vigorous might lead to
osteoarthritis later in life. His research group takes a unique approach to studying the problem. Unlike most
people working in biomechanics and bioengineering who remove tissue to study it, Herzog studies the
tissues in living systems.
24 UofC Research in Action
A living laboratory
“If we want to understand the disease, we need to know how these things behave in the joint, not how they
behave in a machine,” says Herzog, a professor in the Faculty of Kinesiology and a Canada Research Chair
in Molecular and Cellular Biomechanics. That is made possible by multiphoton excitation microscopy, which
allows Herzog and his team to observe individual cartilage cells. And the results are truly wondrous.
“Under certain loading conditions we have seen that cells can be strained too much and they die—the cell
membrane ruptures,” Herzog says. This is particularly bad in the case of cartilage that surrounds joints
because the cells are not plentiful to begin with, and they are difficult to regenerate.
Cause and effect
Knowing what causes damage to joint cartilage can lead to ways of preventing it or devising new ways to
respond to common injuries such as those to the anterior cruciate ligament in the knee, a very common injury.
“That has been shown to be a risk factor for osteoarthritis later in life because the mechanics of the joint are
changed,” Herzog says. This risk could be minimized through an exercise program that strengthens the joint
and overcomes the injury. “We’d like to ask, ‘OK someone has had an accident and they have these muscle
inhibitions; how do we get them to use their muscles so that their joints remain healthy’,” Herzog says.
Until that time comes, weekend athletes would be well advised to learn something else from Herzog, who
stays in shape by jogging in the summer and cross-country skiing when the snow flies. “I’m at an age now
where I realize that I’m happy when winter comes because after a summer of running, everything aches a little
bit,” he says. “I’m happy to go back to cross-country skiing and let my joints recover.”
Dr. Walter Herzog is studying how
and when individual cartilage cells
die in order to better prevent and
treat injuries.

Unlike most people
who remove tissue to
study it, Dr. Walter Herzog
studies the tissues in
living systems.
Biomedical Engineering: Bone and Joint
25

Grinding pain. Stiff joints. No cure. About three million Canadians live with osteoarthritis, a degenerative joint
condition that can make everyday tasks such as climbing the stairs an excruciating challenge. Many people
develop osteoarthritis in their 30s, 20s, or earlier, often after a sports injury. By the age of 70, most of us will
have the condition. Osteoarthritis occurs when the shock-absorbing cartilage that protects the ends of the
bones begins to degrade. Like an old sponge, the cartilage at a particular joint breaks up and wears away,
leaving the bones to grind against each other. Dr. Andrea Clark wants to know why this happens.
Osteoarthritis under
the microscope
“We don’t understand the mechanisms that cause it,” says Clark, a biomedical engineer and assistant professor
with the University of Calgary’s Faculties of Kinesiology and Medicine. Age, obesity and genetics can each play a
role, as can a tumble on the ski hill. But Clark wants to find out what signals are telling the chondrocytes—the
cartilage-forming cells—to stop functioning. “(We are) trying to understand how the cell translates the mechanics
into the biology,” she says. Current treatments allow people to manage the pain of osteoarthritis, but do not
reverse the damage done. Eventually, patients may require knee, hip or other joint replacement surgery. Clark
hopes that her work will lead to drug therapies that would target the cellular switches that make cartilage degrade
in the first place.
Tracking cellular reactions
Using a confocal microscope to peer into a living cellular world, Clark is studying how chondrocytes move and
attach to surfaces, and how they respond to conditions that mimic osteoarthritic cartilage. Fluorescent probes
allow her to track, in real time, the chain reaction of signals that pass through the cells. “You watch them on
the microscope flash with their calcium signals…I love it!” Clark, who has a double major in sports science
and physics, laughs when she admits that she had never used a microscope before starting graduate school.
She completed her PhD in Calgary, with Dr. Walter Herzog in the Faculty of Kinesiology. For this research she
used microscopy to examine kneecap cartilage affected by osteoarthritis. Significantly, her work revealed the
progression of osteoarthritis in the weeks and months following a tear in a major ligament. However, Clark
wanted to understand the disease at the cellular level. At Duke University in North Carolina, she developed
a method for studying living chondrocytes in cartilage tissue from a mouse model. Mice typically develop
osteoarthritis by the time they reach old age at 12 to 18 months. In addition, their 1.5 cm thighbone easily
fits under the confocal microscope, making it possible to see the joints in entirety. Back in Calgary, Clark is
applying her new methodology.
26 UofC Research in Action
Dr. Andrea Clark is studying
the cellular events that produce
the most common form of
arthritis in order to prevent
this disabilitating condition.

Dr. Andrea Clark is studying why the
cartilage at a particular joint breaks up
and wears away. It’s all part of the
search for a cure for osteoarthritis.
“I feel very privileged to be able to
use real tissue and live cells, and to
try to keep things as close to reality
as possible,” says Clark.
Biomedical Engineering: Bone and Joint
27

You’ll find Dr. Nigel Shrive’s spectacularly cluttered office—every available surface holds a pile of books or
stack of paper—in the Schulich School of Engineering. But while the Killiam Memorial Chairholder teaches
in the Department of Civil Engineering and conducts research on masonry, he’s also developed an expertise
in biomechanics. These days, it is that work that has Shrive quite excited. He is hopeful that a new model
he has developed with Dr. Cy Frank and Dr. David Hart might help determine the relative influence of
mechanical and biological factors in the development of osteoarthritis.
Unpuzzling joint disease
“The model might be able to tell us what are the primary drivers [of osteoarthritis] and, therefore, what we
have to target with any therapy,” Shrive says. “It would be the first time in the world that mechanical factors
have been isolated from biological factors.” Doing so would give new insights into a complex disease. “We’ve
realized in the last couple of years that, as soon as you injure a joint, everything starts to change—all the
tissues in the joint, including those not injured,” Shrive says. When biological changes, such as inflammation,
give rise to mechanical changes, sorting through the puzzle can get very complicated.
The role of inflammation
In his team’s new model, a biological response can be triggered without changing the operational mechanics
of the joint—by essentially creating and then immediately repairing an injury in a way that restores the original
mechanics. Alternatively, to explore mechanical contributors to osteoarthritis, the joint can be altered and the
level of inflammation kept pretty much constant by using anti-inflammatory drugs.
“We can see if, with the same level of inflammation, but different mechanics, osteoarthritis develops at the same
rate,” Shrive says. While he is excited about the model, he is, of course, an engineer at heart. Everything must
be tested rigorously. “The idea is that specimens given anti-inflammatories will have way less osteoarthritis,”
Shrive says. “Who knows, maybe we’ll find out it’s not the inflammation that’s doing the damage.”
That would be an unexpected result, but it’s the sort of thing that can happen when dealing with a biological
system, which by its nature is complex. And it is outcomes like this that can make Shrive appreciate more
traditional engineering. “If you load a piece of steel, you can make it yield,” he says. “It’s not going to get any
different. It’s not going to repair itself in varying degrees depending on the genetics of the system.”
28 UofC Research in Action
Dr. Nigel Shrive is isolating
the “mechanical” from the
“biological” to understand
more about osteoarthritis.

Dr. Nigel Shrive is sorting out when biological
changes, such as inflammation, give rise to
mechanical changes in the joints.
If the challenges of biomechanics are greater,
so too are the rewards. Just consider how Shrive’s
engineering research has helped build stronger
walls, while his work in biomechanics could
lead to stronger joints. With those, people—and
medicine—just might break through even the
toughest barriers.
Biomedical Engineering: Bone + Joint
29

Sometimes in the study of biomechanics, the emphasis is on the mechanical. “We take a $400,000
research microscope, rip it apart—void the warranty—and build these loading devices that fit on top
of them,” says Dr. John Matyas. “Then we take a piece of tissue and crunch it in a way that allows us
to assess its mechanical function.” Matyas is a self-described “egghead scientist” in the new Faculty of
Veterinary Medicine who investigates the basic mechanisms of arthritis. Degenerative joint diseases have
been a long-term focus of his research. His work is as relevant to veterinary joint health as it is to humans.
Understanding arthritis
He and his team use an atomic force microscope to study joint tissue biomechanics because “it allows you to
measure nanometre-length changes in individual molecules as loads are applied,” he says. This particular project
is being led by PhD student Jane Desrochers, and the information gathered is crucial because scientists now
know that cartilage, far from being “a piece of linoleum,” is full of cells that respond to load. Studying those cell
responses in normal and injured cartilage can give insight into how arthritis is initiated and how it progresses.
Using MRI
Kelsey Mountain is a PhD student studying how magnetic resonance imaging might be used in this investigation.
Because cartilage is 80 percent water it cannot be seen in X-rays, but “shows up beautifully on MRI.” So Matyas
and his lab partners turned their mechanical expertise to building a non-magnetic device that allows them to
subject tissue to loads while in a MRI machine.
The ultimate goal—and it may be five or 10 years down the road—is to be able to assess “the functional quality
of joint cartilages while people are standing in an MRI,” Matyas says. Clinicians would be able to see if patients
have arthritis, how fast it progresses (MRIs can be done repeatedly), and if their treatments are effective.
One of those treatments is the subject of an investigation led by PhD student Jaymi Cormier, who is looking at
how stem cells might be used to promote the healing of fractures. Mouse stem cells are “pushed” into becoming
either bone cells or cartilage cells. Then, using what Matyas calls “genetic sleight of hand” the cells are tagged
with a fluorescent protein so they can be easily tracked. “The idea is to take these cells, put them in a controlled
fracture setting and see whether or not they affect healing,” Matyas says.
30 UofC Research in Action
Dr. John Matyas has lots of irons
in the fire in his quest to improve
the health of joints in both animals
and humans.

Dr. John Matyas uses, among other
things, an atomic force microscope to
study joint tissue biomechanics.
While projects of this complexity satisfy
his cerebral side, Matyas says there
is an element of self-interest involved.
“Having played rugby and football for a
dozen years of my life, there is a certain
likelihood that I will pay the price.”
Biomedical Engineering: Bone and Joint
31

In the world of research, access to the most current and sophisticated technology and laboratories is
critical. U of C scientists and students have access to leading-edge technology and facilities to support
their research and learning. Through its community partnerships, the University of Calgary is home to a number
of world-class research facilities that feature leading-edge technology to support the work of scientists
and students. On these pages, we highlight a few of the outstanding people, facilities and technologies that
help make Calgary a thriving, living laboratory where top talent is working toward breakthroughs that are
changing lives.
Advanced Micro/Nanosystems Integration Facility
Tools of the trade
The future of health care will combine the best of science, engineering, medicine and technology—if Dr. Colin Dalton has anything to say
about it. As the facility manager at the Advanced Micro/Nanosystems Integration Facility (AMIF), he sees the results of multidisciplinary
collaboration every day as researchers bustle about the vibration-free clean room developing the integrated sensors, power systems,
micro-electronics and wireless technologies that represent the next generation of biomedical breakthroughs. “We’re not just trying to
create nice gadgets, but to create the next generation of students that know how to think outside of their field in terms of hybrid devices,”
says Dalton. From the development of a “smart, wireless Band-Aid” that’s being used in the Medical Ward of the 21 st Century—
a temperature measuring system that sends real-time data to a computerized nursing station—to any number of tiny biomedical devices
being created, AMIF’s goal aligns with Alberta’s $130-million nano-strategy to make the province a hotbed of expertise in this field.
The centre also runs a graduate course where students receive 30 hours of training on the high-tech equipment, which is also open to
private industry. “We’re also becoming a facility that will help the next generation of start-up companies,” says Dalton.
amif.ca
Medical Ward of the 21st Century (W21C)
Unit 36 at the Foothills Hospital is where research meets reality. Welcome to the Medical Ward of the 21 st Century (W21C), where the
latest biomedical and technological breakthroughs come alive. Computers buzz around every corner, moveable walls allow staff to
optimize space for medical needs and a negative air pressure system allows them to control infectious disease outbreaks if they occur.
When this teaching unit opened in May 2004, it immediately became a melting pot of doctors and researchers from a wide range of
disciplines at all levels, says Dr. Bill Ghali, who co-leads the initiative’s research and innovation program with Dr. Barry Baylis. Work is
being initiated on “smart cameras” that can monitor patients for falls or other injuries, while body temperature, heart rate and blood
oxygen levels are continuously monitored by micro-electronic devices that stream data wirelessly to nurses. The W21C is truly a model
of health-care delivery for the next generation.
w21c.org
32 UofC Research in Action
Dr. Colin Dalton
Advanced Micro/Nanosystems
Integration Facility

Southern Alberta Cancer Research Institute (SACRI)
Cell Imaging Facility
The mind’s eye has never had so much clarity. At SACRI’s Cell Imaging Facility,
Dr. Dallan Young studies three-dimensional images of cells using “the latest
and greatest on the block.” He’s referring to the laboratory’s $700,000
confocal microscope, a device that easily overcomes the flaws of regular
microscopes and is being used by researchers working toward cures and
new therapies for a wide range of cancers. A confocal microscope has the
unique ability to visually eliminate all of a cell’s material located behind and
in front of the desired slice of the cell, taking pictures at different angles to
produce these highly detailed images. “It gives you a three-dimensional, much
crisper and more precise image of what’s going on in the cell without all the
fuzziness,” says Young, a professor in the University of Calgary’s Faculty of
Medicine. A secondary high-powered microscope supplements the work of the
confocal equipment, which graduate students and cancer researchers use to
get a glimpse of things they could never see before. It’s another valuable tool
on the path to medical progress.
sacri.ucalgary.ca
ucalgary.ca/young/confocal
Microscopy and Imaging Facility
At first glance, it’s hard to tell the difference between all of the complex
microscopes that fill the Microscopy and Imaging Facility in the Health
Sciences building. “The atomic force microscopes are the toys I use the
most,” says Dr. Matthias Amrein, director of the facility, with a laugh. He’s
talking about three microscopes which are so powerful they can scan the
surface of a cell down to about half a nanometre, and hard crystalline
samples even at atomic resolution. The microscopes, together with the
larger suite of transmission and scanning electron microscopes, are being
used to study diseases such as diabetes, multiple sclerosis and cancer,
or to tackle basic questions in immunology to develop more effective
vaccines, to name just one of many examples. Prominent researchers
work side-by-side with graduate students to obtain high-powered threedimensional
images of a cell and its inner workings. Amrein knows the
impact these microscopes have goes far beyond the laboratory. “It’s a
fantastic look at the internal workings of the cell,” he says. “Everybody
here depends on this facility.”
mif.ucalgary.ca/client/
The Cave
The world’s first complete object-oriented computer model of a human
body, a kind of four-dimensional human atlas dubbed the CAVEman, gives
scientists the ability to translate medical and genomic data into 4D
images, and view the graphical representation of this data via the human
form. Right before your eyes in this cube-shaped virtual reality room, the
4D human model floats in space projected from three walls and the floor
below. It allows medical researchers to investigate the genetics of various
diseases and to develop new approaches to targeted treatments. A truly
unique tool, the CAVE can size the data to any scale, says Dr. Christoph
Sensen, director of the Sun Centre of Excellence for Visual Genomics
in the Faculty of Medicine at the U of C. While the CAVE is a continual
work in progress, this is a major breakthrough in medical informatics and
systems biology.
Watch the CAVE live at youtube.com/watch?v=xF_4u-o6yPA
Biomedical Engineering at the U of C: Technology + Facilities
Top: Dr. Dallen Young
Southern Alberta Cancer Research Institute
Bottom: Dr. Matthias Amrein
Microscopy and Imaging Facility
33

Using research leadership + partnership to transform our world
The University of Calgary has developed a highly successful partnership with National Research Council through the NRC-
Institute for Biodiagnostics, which has led to the establishment of the university’s Experimental Imaging Centre.
The university will continue to partner with the NRC, the Alberta and federal governments,
industry and other universities to create the National Biomedical Engineering Innovation
Centre, a world-class institute of biomedical engineering research, health product development
and commercialization.
Canada currently imports close to $3.8 billion in medical devices every year and exports only $1 billion. We need to
reverse this by building our made-in-Canada capacity. The potential is vast: estimates are that Alberta will be a leading
jurisdiction for biomedical engineering research, product development and commercial enterprise by 2020 with an
$8 billion industry employing 50,000 people.
Learn more. ucalgary.ca/vpr
Research at the University of Calgary is attracting
sponsored funding of more than $282 million a year, more
than double that from five years ago. U of C is among the
top 10 universities in sponsored research funding in
Canada. As a member of the G13 group of Canadian
universities, U of C is recognized as a top Canadian
research university.
Research excellence in biomedical engineering at the
University of Calgary is supported by Natural Sciences and
Engineering Research Council (NSERC), Canadian Institutes
for Health Research (CIHR), the Canada Research Chairs
program, Alberta Ingenuity Foundation, Alberta Heritage
Foundation for Medical Research (AHFMR), Informatics
Circle of Research Excellence (iCore), Genome Canada,
Western Diversification, Social Sciences and Humanities
Research Council (SSHRC), National Institutes of Health (NIH)
USA, affiliated hospitals, the City of Calgary and others.