[Paleopsych] MRI visualizes gene expression in real time

[Steve Hovland]

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 
in patients.
"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 
reporter.
"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. 
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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.
http://www.eurekalert.org/pub_releases/2005-03/cmu-cms031405.php