A technology whose roots date to the
1800s has the potential to offer an extraordinary new advantage to
modern-day medicine. In findings published this month in Nature Communications,
Case Western Reserve scientists detail how stereomicroscopy can provide
physicians an invaluable diagnostic tool in assessing issues within the
gastrointestinal tract.
Originally used by 19th-century photographers to create the illusion
of depth in their pictures, stereomicroscopy since has evolved to become
a staple of the film and videogame industries. Only recently has it
become more prevalent in medicine, one factor that makes these findings
particularly important.
Using 3D-pattern stereomicroscopy with mouse models, School of
Medicine researchers reported that they able to develop entire
topographical views of the inside of the intestinal system, rather than
two-dimensional visuals of individual sections or tissue or cell
samples. This more expansive and detailed picture allowed them to
identify distinct patterns related both to health and disease within
those structures -- patterns that they could not see using traditional
approaches.
As part of the study, the researchers developed a catalogue of
specific profiles for abnormalities in those with inflammatory bowel
diseases (IBD). Not only do these profiles provide a depth of
information not attainable by other means, but they also can accelerate
the process of determining the condition or illness that is plaguing the
patient.
"This is really exciting for us because for the first time, we have a
technique that provides a better way to examine these lesions," said
senior author Fabio Cominelli, MD, chief of the Division of
Gastroenterology and Liver Disease and the Hermann Menges, Jr. Chair in
Internal Medicine, Case Western Reserve University School of Medicine.
"The traditional, two-dimensional histology views do not tell us what is
going on in the entire tissue. The precision of this 3D technology will
allow us to visualize the location of lesions along the entire
intestinal tract to learn the exact cause of the inflammation."
Cominelli, also director of the Digestive Health Institute at
University Hospitals Case Medical Center, has assembled a team of
investigators to focus research on inflammatory diseases of the
digestive tract, particularly Crohn's disease, inflammatory bowel
disease and ulcerative colitis. One of those team members, Alexander
Rodriguez-Palacios, DVM, PhD, made the breakthrough possible by
identifying a novel way to use a stereomicroscope, a device often used
in microsurgery. Typically physicians have been limited to endoscopy or
histology in studying these diseases; recognizing their shortcomings,
the team sought other means of gaining better understanding of the
nature of different diseases. The more they knew about different
conditions, the thinking went, the more effective they could be in
helping patients.
""Currently, we have treatments that can make the patient feel
better, but we are not able to achieve a sustained positive response in
patients," Cominelli said. "The goal for developing new therapies now is
to have lesions disappear, or possibly prevent lesions from appearing
in the first place."
Cominelli, Rodriguez-Palacios, and their colleagues set out to test
the efficacy of this alternative approach by studying the
inflammatory-diseased intestinal tracts of more than 800 mice from 16
strains of the animals. During the course of their study, the scientists
saw distinct patterns of lesions develop in the different kinds of
mice. These different patterns point to genetic origins for the various
inflammatory intestinal diseases.
"What we saw were unique structural characteristics in inflamed
tissue and in normal tissue," Rodriguez-Palacios said. "Before, a lesion
was just a lesion. We found that these lesions had a particular
configuration. Now we can tell the different kinds of lesions and
patterns of lesions that make a difference in the disease. Nobody has
ever done that before."
Through 3D microscopy, investigators found two mouse models that most
resemble inflammatory bowel disease in humans. The SAMP mouse has
cobblestone lesions typical of human Crohn's disease, and the TNF mouse
has enlarged and distorted intestinal villa typical of inflammatory
bowel disease. (Villa are finger-like projections protruding from the
intestinal wall to aid in nutrient absorption.)
By studying both mouse models using 3D stereoscopy, investigators
hope to make informed predictions about how these inflammatory bowel
diseases develop and progress in humans. They also plan to observe the
natural history of the illness, from early onset through end stages.
They also aim to uncover what causes these intestinal diseases, what
genes are expressed, underexpressed or overexpressed, and what
intricacies are involved in the microbe environment of the gut.
"We will use the 3D stereoscopy to study these mouse models
extensively to understand what causes the disease in mice," Cominelli
said, "[and then] correlate that understanding to human patients and
then develop new therapies."
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The above post is reprinted from
materials provided by
Case Western Reserve University.
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