CVM historical archive
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At the Texas A&M College of Veterinary Medicine &
Biomedical Sciences (CVM), modern medical imaging technology and
techniques have transformed how researchers and doctors view and
interpret cells and tissues. The CVM has assembled an unparalleled
collection of advanced imaging technologies that are being used in
basic, clinical, and translational research as well as diagnostic
imaging and therapeutic intervention. The high resolution images
generated from these technologies range from single molecules at
the nanometer-size scale to whole organ functional imaging on the
meter scale. These images, in turn, have advanced research and
treatment of a number of diseases and conditions, especially
cancer.
Imaging History
Microscopy started with two pieces of glass in a Dutch
spectacle-maker’s workshop in the 1590s. Hans Jansen and his son,
Zacharias, experimented with lenses in a tube and found their
invention created a magnified image of any object viewed through
it. The invention, a compound microscope, was used by Robert Hooke
to view and draw various life specimens for his book,
“Micrographia,” published in 1665. Inspired by Hooke’s drawings and
observations, Anton van Leeuwenhoek, later known as the father of
Microbiology, improved the microscope to pursue his own studies.
His improvements allowed him to be the first person to see and
write about single-celled organisms, blood vessels, bacteria, and
other microscopic biological entities.
Innovation in microscopy technology stalled for two centuries.
Then, in the 1850s, Carl Zeiss, an engineer who manufactured
microscopes, began tweaking the lenses. He employed glass
specialist Otto Schott to improve the lens quality and Ernst Abbe
to refine the manufacturing process. The collaboration of the three
men produced the modern compound microscope found in labs and
classrooms around the world today.
Other forms of viewing patients and their biological samples
were developed later. X-rays were discovered in 1895, and contrast
agents followed a decade later. By the 1950s, radiation technology
had been sufficiently developed for the initial uses of nuclear
medicine to begin. Computed tomography (CT) and magnetic resonance
imaging (MRI) techniques became available in the 1970s.
Over time, these innovative technologies have revolutionized how
physicians and researchers are able to study, diagnose, and treat
conditions. In the modern era, all of these imaging modalities and
more have found a place at the CVM and continue to improve medical
science and research.
Dr. Robert Burghardt
& Dr. Roula Mouneimne
Image Analysis Laboratory
The Image Analysis Laboratory (IAL) began as an electron
microscope (EM) facility in 1987. EM continues to be an important
tool for research and diagnostics. This aspect of the laboratory is
managed by Dr. Ross Payne, associate research scientist in
veterinary pathobiology, who provides a wide range of EM
techniques, data analysis, and training for CVM scientists.
The first confocal microscope joined the ranks in 1990. “Around
this time, there was a renaissance in light microscopy technology
due to the integration of laser light sources, computers, and
sensitive camera systems with microscopes along, with the new field
of biophotonics,” said Dr. Robert Burghardt, director of the IAL
and associate dean for research and graduate studies.
The development of biophotonics, a set of optical techniques for
studying biological samples, gave the lab even more ways to examine
cells.
“This technology, when it was integrated, allowed us to ask new
questions and look into cells in a noninvasive way to eavesdrop on
a variety of different functions, cell behaviors, and basic
homeostatic mechanisms,” said Burghardt. “We could ask questions
about how cells respond to an incredible number of environmental
factors, such as exposure to hormones, growth factors, mechanical
forces, and environmental chemicals.”
With these advancements in the available technology, Burghardt
realized having someone with an engineering background would bring
much needed scientific knowledge and mathematics expertise and a
fresh viewpoint to IAL. He hired Dr. Roula Mouneimne, associate
director of IAL, in 1990 to bring those attributes to the lab.
“He had a vision,” Mouneimne said of Burghardt hiring her. “In
1990, not many people were looking to integrate engineering
principles in biological applications.”
“With her expertise as an engineer, she can help investigators
from many disciplines to integrate the acquisition and processing
of the data with high-end computational methods and statistical
approaches,” Burghardt said.
IAL grew further. The lab now supports the Texas A&M System
as an Advanced Imaging Core Facility for the Center for
Translational Environmental Health Research (CTEHR). Funding for
the CTEHR is provided by the National Institute of Environmental
Health Science (NIEHS). In this role, the core supports the
center’s goal to “improve human environmental health by integrating
advances in basic, biomedical, and engineering research across
translational boundaries from the laboratory to the clinic and to
the community and back.” In addition, IAL acts as a core for the
Center for Organ and Cell Biotechnology, a joint effort of the
Texas Heart Institute (THI) and the CVM that seeks to create and
eventually market disruptive cell and organ biotechnologies and
molecular tools for the next generation of medicine.
“We also provide services to a large cross-section of the
campus,” said Burghardt. “Our lab has been a core facility for
interdisciplinary grants. There have been people working on
reproductive biology, toxicology, biochemistry, neuroscience,
chemical biology, cell signaling, and cancer biology. We support
scientists with experimental design, data collection, and analysis
that lead to new knowledge in their particular disciplines. Acting
in so many capacities requires the laboratory to have adapted to
the many interdisciplinary needs of the groups that utilize it. The
lab’s imaging capabilities have grown from electron microscopy to
noninvasive live-cell imaging tools that can visualize processes at
the tissue and cell level to the single molecule level. The wide
range of microscopic technologies acquired by the lab are available
to researchers allowing them visualize cells in greater detail and
investigate new research areas.
“Over the last 30 years, we have been able to ask more complex
questions,” said Burghardt. “Neuroscientists, reproductive
biologists, toxicologists, and scientists from other disciplines of
modern biology are realizing that functional imaging is a way to
understand basic biological phenomena and processes.”
One example of a major imaging technique used in IAL is
multiphoton fluorescence microscopy. With the application of a
special laser, select molecules can be illuminated. Based on the
spectral pattern fluoresced by the sample, one class of common
lipid soluble carcinogenic molecules, produced in grilled food and
other products of combustion, can be identified as they are forming
in living cells. Identification of these molecules has led to
development of treatments that eliminate the formation of these
carcinogenic molecules. Besides cellular imaging research support,
graduate training in the theory and practice of optical microscopy
technologies is a major emphasis of the IAL.
For example, students are trained to use different microscopes
while applying techniques such as co-localization of two molecules
or transient protein-protein interactions and image processing.
Students learn how to apply computational approaches to determine
with confidence the outcomes of their experiments. Workshops and
individual consultations provide additional avenues for students
and faculty members to utilize the expertise of the lab as well as
its tools.
Dr. Michael Deveau
Diagnostic Imaging & Cancer Treatment Center
The Diagnostic Imaging & Cancer Treatment Center (DICTC) was
formed in 2011 when the CVM gained a 3-Tesla MRI. This powerful
tool allowed researchers and clinicians at the CVM to quickly
capture detailed images of tissues and cells in small and large
animals.
“When the MRI was commissioned for clinical use, it was one of
three in all of Texas. That includes human facilities,” said Dr.
Michael Deveau, clinical assistant professor in oncology. “We have
a veterinary facility with technology that most of the state of
Texas didn’t have access to at the time, including human patients
and clinicians.”
The center’s capabilities are not limited to MRI. Other imaging
modalities include small and large animal radiology, small animal
ultrasound, CT scans, and nuclear medicine. Utilizing multiple
types of imaging technology improves the ability of the clinicians
to provide an accurate diagnosis and create a treatment plan.
“The literature supports no single modality as superior to any
of the others,” Deveau said of the various imaging options
available at the center. “They all have their strengths and
weaknesses. When you put the information that you acquire from all
of them together, that’s when you see a tremendous benefit, as
compared to any single modality by itself.”
DICTC has two primary goals. First, it aims to advance
veterinary healthcare by providing options and solutions for
conditions that animal patients face. Second, it fulfills part of
the One Health Initiative.
“The facility was built in part to answer the Initiative,” said
Deveau. “It was a huge intellectual and financial investment by
Texas A&M University, the CVM, and the donors. The facility
helps utilize veterinary companion animals as representative
translational models for human conditions.” Both goals are broad
and cover a wide range of fields and research studies.
“I think imaging is quite a large topic. It has its fingers in
practically every aspect in medicine,” said Deveau of the breadth
of the center’s abilities.
One example Deveau gave of how the center’s equipment can be
applied involved creating a 3-D model of a patient’s gut. The
virtual model, constructed from CT scans of the patient’s digestive
system, can be used to understand how a piece of food travels
through and is processed by the patient’s gut. Such a model, of any
system or organ or even a section of tissue, can have multiple
applications for both research and clinical practice.
Additional imaging technologies can also be utilized for the
same patient to add greater depth to the diagnostic picture, but at
a cost. In addition to the financial expense associated with
testing, animal patients also have special considerations, as many
types of imaging require the animal to be under general anesthesia
to ensure they remain motionless.
“When you start talking about doing multi-modality imaging, it
adds up quickly,” explained Deveau. “Even if you combine it all
under one round of anesthesia, you still have the cost that comes
out of pocket for the tests and the anesthesia.”
Still, being able to use multiple tests to develop a
comprehensive understanding of a patient’s unique needs can be
invaluable for conditions such as cancer. Precise imaging is
particularly important when using targeted radiation therapy, as it
is essential to know exactly where the cancer cells are before you
can attack them. In addition to revealing location, imaging also
allows doctors to monitor tumors during therapy. Being aware of
changes in a tumor’s size or the presence of additional tumors can
help doctors know if a therapy is working or if it needs to be
modified.
“The more modalities you use, the more information you get,”
said Deveau. “Having more information will potentially set you up
for a more optimal therapy.”
Texas A&M Institute for Preclinical Studies
Just as the IAL supports researchers who apply imaging
techniques at the cellular and subcellular level, the Texas A&M
Institute for Preclinical Studies (TIPS) performs imaging studies
on whole animals involved in research projects. Established by the
Texas A&M Board of Regents in 2007 and opened in 2009, TIPS is
an administrative unit of the CVM. Research at TIPS is done in
collaboration with Texas A&M faculty and investigators from
private companies who wish to establish efficacy of new drugs or
medical devices before moving them to human use.
From its inception, TIPS has heavily emphasized biomedical
imaging. Indeed, imaging methods and equipment at TIPS—extending
from conventional radiography to a 3-Tesla MRI machine—largely
parallel those used through the DICTC. Dr. Joe Kornegay, TIPS
director, said, “The availability of similar instrumentation in the
hospital and at TIPS provides a remarkable opportunity for
collaboration, whereby studies done in each unit can inform and
complement the other.” One such example is a specialized imaging
technique at TIPS called positron emission tomography–computed
tomography (PET-CT). This combines the anatomical detail gained by
CT with information on organ function provided by PET scans.
Through a collaboration involving Deveau and a veterinary
oncologist, Dr. Heather Wilson-Robles, TIPS is conducting PET-CT
scans on animal cancer patients to determine the extent of tumor
metastasis. This allows oncologists to better plan treatment for
the affected animal and, at the same time, give owners a more
accurate prognosis.
Kornegay has used specialized imaging in his own research
involving a canine model of Duchenne muscular dystrophy. In fact,
when he relocated to Texas A&M from the University of North
Carolina–Chapel Hill three years ago, Kornegay immediately started
working with the TIPS imaging group to conduct MRIs on dystrophic
dogs involved in research studies. A veterinary neurologist by
training, Kornegay began using CT and MRI in the 1980s to diagnose
disease in animal patients while on the faculty at North Carolina
State University. These initial studies were done at Duke
University Medical Center before CT and MRI were widely available
in veterinary schools.
“It’s not an overstatement to say that sophisticated imaging
modalities have truly revolutionized medicine,” Kornegay stressed.
“For the diagnosis of brain disease, much of the guesswork inherent
to other imaging methods is removed by the anatomical detail
provided first by CT and later by MRI.” Kornegay sees many of the
same advantages when these techniques are applied in a research
setting. “By definition, imaging is largely noninvasive and, beyond
the ‘pretty pictures’ themselves, provides quantitative data that
can be collected at multiple time points and compared
statistically,” he said. “This is extremely powerful from a
research perspective.”
The Future
We’ve come a long way since Robert Hooke peered through an early
version of the microscope and observed tiny organisms in detail
previously unavailable to scientific inquiry. How imaging will
continue to evolve and adapt is uncertain, but it will continue to
affect how we view, perceive, and respond to conditions not visible
to the naked eye.
“Imaging serves different purposes depending on whom you speak
to,” said Deveau. “I think the biggest thing from a discovery
perspective is that, with the level of technology we have, it is
bringing to life different changes in the information that we get
from imaging, and that dictates or directs how we manage the
patient.”
From left: Dr. Jack Guo;
Rachel Johnson, TIPS imaging technologist; Dr. Joe Kornegay; and
Mandy Bettis, Veterinary Technician
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Contact Information: Megan Palsa,
mpalsa@cvm.tamu.edu, 979-862-4216, 979-421-3121 (cell)