[Paleopsych] MRI visualizes gene expression in real time
shovland at mindspring.com
Mon Mar 21 13:56:25 UTC 2005
Carnegie Mellon scientists develop tool that uses MRI to visualize gene
expression in living animals
PITTSBURGH--In a first, Carnegie Mellon University scientists have
"programmed" cells to make their own contrast agents, enabling
unprecedented high-resolution, deep-tissue imaging of gene expression. The
results, appearing in the April issue of Nature Medicine, hold considerable
promise for conducting preclinical studies in the emerging field of
molecular therapeutics and for monitoring the delivery of therapeutic genes
"For 20 years it has been the chemist's job to develop agents that can be
used to enhance MRI contrast," said Eric Ahrens, assistant professor of
biological sciences in the Mellon College of Science at Carnegie Mellon.
"Now, with our approach, we have put this job into the hands of the
molecular biologist. Using off-the-shelf molecular biology tools we can now
enable living cells to change their MRI contrast via genetic instructions."
"The new imaging method is a platform technology that can be adapted for
many tissue types and for a range of preclinical uses in conjunction with
emerging molecular therapeutic strategies," Ahrens said.
Ahrens' new approach uses magnetic resonance imaging (MRI) to monitor gene
expression in real-time. Because MRI images deep tissues non-invasively and
at high resolution, investigators don't need to sacrifice animals and
perform laborious and costly analysis.
To trigger living cells into producing their own contrast agent, Ahrens
gave them a gene that produces a form of ferritin, a protein that normally
stores iron in a non-toxic form. This metalloprotein acts like a
nano-magnet and a potent MRI "reporter."
A typical MRI scan detects and analyzes signals given off by hydrogen
protons in water molecules after they are exposed to a magnetic field and
radiofrequency pulses. These signals are then converted into an image.
Ahrens' new MRI reporter alters the magnetic field in its proximity, cau
sing nearby protons to give off a distinctly different signal. The
resulting image reveals dark areas that indicate the presence of the MRI
"Our technology is adaptable to monitor gene expression in many tissue
types. You could link this MRI reporter gene to any other gene of interest,
including therapeutic genes for diseases like cancer and arthritis, to
detect where and when they are being expressed," Ahrens said.
Existing methods used to image gene expression have limitations, according
to Ahrens. Some methods cannot be used in living subjects, fail to image
cells deep inside the body or don't provide high-resolution images. Other
approaches using MRI are not practical for a wide range of applications.
Ahrens and his colleagues constructed a gene carrier, or vector, that
contained a gene for the MRI reporter. They used a widely studied vector
called a replication-defective adenovirus that readily enters cells but
doesn't reproduce itself. Ahrens injected the vector carrying the MRI
reporter gene into brains of living mice and imaged the MRI reporter
expression periodically for over a month in the same cohort of animals. The
research showed no overt toxicity in the mouse brain from the MRI reporter.
Ahrens consulted on aspects of the research with William Goins, a research
assistant professor at the University of Pittsburgh. The work was funded by
the Pittsburgh Life Sciences Greenhouse and the National Institute of
Biomedical Imaging and Bioengineering.
Ahrens is a member of the Pittsburgh NMR Center for Biomedical Research, a
joint endeavor sponsored by Carnegie Mellon University and the University
of Pittsburgh. Established in 1986 and funded continuously since 1988 by
the National Institutes of Health, the Pittsburgh NMR Center is dedicated
to advancing molecular, cellular and functional imaging in animals.
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