Utah and Texas researchers combined miniature
medical CT scans with high-tech computer methods to produce detailed
three-dimensional images of mouse embryos - an efficient new method to
test the safety of medicines and learn how mutant genes cause birth
defects or cancer.
"Our method provides a fast, high-quality and inexpensive way to
visually explore the 3-D internal structure of mouse embryos so
scientists can more easily and quickly see the effects of a genetic
defect or chemical damage," says Chris Johnson, a distinguished
professor of computer science at the University of Utah.
A study reporting development of the new method - known as
"microCT-based virtual histology" - was published recently in PLoS
Genetics, an online journal of the Public Library of Science.
The study was led by Charles Keller, a pediatric cancer
specialist who formerly worked as a postdoctoral fellow in the
laboratory of University of Utah geneticist Mario Capecchi. Keller now
is an assistant professor at the Children's Cancer Research Institute at
the University of Texas Health Science Center in San Antonio.
University of Utah co-authors of the study are Johnson - who
directs the university's Scientific Computing and Imaging Institute -
Capecchi, medical student Mark S. Hansen and several members of
Johnson's institute: computer science undergraduate Thomas Johnson III,
research assistant Lindsey Healey and former associate director Greg M.
Jones, who now is state science advisor to Utah Gov. Jon Huntsman Jr.
Scientists often use mouse embryos both to learn what genes do
and to test the safety of new drugs and household chemicals. By
disabling or "knocking out" a gene, researchers can see what goes wrong
in the mouse embryo and thus learn the gene's normal function, or learn
how a mutant gene can cause cancer. Mouse embryos also are sensitive to
toxicity from chemicals, so new medicines and chemicals are tested on
them to see if any defects develop, indicating the safety for humans and
their unborn embryos.
But the traditional method of histology - the anatomical study
of the microscopic structure of living tissues - has been difficult and
time-consuming. Mouse embryos with genetic mutations or damage from
toxic chemicals are killed, embedded in wax, sliced into thin sections,
then stained and placed on slides for examination under a microscope.
The new, faster and inexpensive method is called "virtual
histology" because it uses computer visualization techniques to convert
X-ray CT scans of mouse embryos into detailed 3-D images showing both
the mouse's exterior and interior.
Instead of being sliced up physically, mouse embryos are stained
with special dyes. Traditional CT scans take a series of X-ray images
representing "slices" through the body, and they primarily "see" bone
and other hard tissues such as cartilage. In the new microCT virtual
histology, the special dyes permeate the skin and other membranes, which
are still permeable in an embryo.
"This technique allows us to get at a lot more tissues other
than bone, such as internal organs, which [conventional] CT scans can't
pick up," Johnson says.
Johnson and his team wrote a computer algorithm - a
problem-solving formula in computer software - to take the CT scan data
and automatically distinguish various organs and structures in the mouse
embryo. The "virtual rendering" of the CT scan data also includes a
virtual light source so the 3-D embryo image includes shadows that make
it easier for the human eye to understand and interpret the image.
The embryo images can be made transparent or have cutaways so
that internal organs and body parts are visible. And the detail they
show is exquisite - revealing features as small as one-tenth the
thickness of a human hair.
The idea is to allow geneticists to quickly examine large
numbers of embryos, each with a different gene disabled, so that the
normal function of many genes can be determined faster than with
existing methods.
Keller says the U.S. Food and Drug Administration and
Environmental Protection Agency require drug and chemical manufacturers,
respectively, to test their new products, but that such tests often are
subjective. The new method "allows chemical and drug companies to
conduct these studies in a much more quantitative way, improving upon
the safety of the products we find in our homes," he adds.
Keller and a colleague have founded a company named Numira
Biosciences, which plans to make the virtual histology method available
through the sale of kits and imaging services.
The study was published online in the April 28 issue of PLoS
Genetics.
The complete study, with more images of mouse embryos, is at:
dx.doi/10.1371/journal.pgen.0020061.
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