Research in Action: - University of Calgary

ucalgary.ca

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.