OAK RIDGE, Tenn., Sept. 22, 1998 -- Biologists studying genetic mutations and diseases will soon have a new ultra-high-resolution imaging tool to examine soft tissue and skeletal detail of mice and other laboratory animals -- without killing them.
The MicroCAT system, developed by researchers at the Department of Energy's (DOE) Oak Ridge National Laboratory (ORNL), generates three-dimensional images with 10 times the resolution of conventional imaging systems. With MicroCAT, researchers no longer will have to rely on visible genetic markers and physical examinations to discover the presence of mutations. And, because they don't have to dissect the mice, researchers will be able to study the development of a mutation over several weeks or months.
"This means we can survey many offspring of mutagenized mice for organ or skeletal abnormalities and for changes that occur as a mouse ages or is exposed to different environmental conditions -- and then still breed the mouse for genetic analysis," said Dabney Johnson, a genetics researcher in ORNL's Life Sciences Division.
MicroCAT arose from Johnson and colleagues, quest for a better screening tool to study genetic mutations in the world's largest research colony of 70,000 mice at ORNL. The lab's biologists needed a device to quickly and cost-effectively screen the mouse colony, which represent about 400 mutant strains. That's why Michael Paulus and others in ORNL's Instrumentation and Controls Division became involved.
This new device, Johnson believes, will allow ORNL to be among the leaders in the effort to analyze gene function and identify mouse models of human genetic diseases.
"The imaging technology and the kinds of image analysis and reconstruction software that the Paulus team is integrating are revolutionary," Johnson said. "And this is the kind of thing that national laboratories like ORNL can do best because they have diverse resources and expertise."
Paulus and a team that includes Shaun Gleason and Hamed Sari-Sarraf, also members of the Instrumentation and Controls Division, are developing two versions of the MicroCAT. One uses a digital mammography detector with resolution of less than .05 of a millimeter. It can scan a mouse in a few minutes, or it can provide an X-ray in less than a second.
The second version uses a novel detector to measure the position and energy of each X-ray. Incorporating X-ray energy information into the image data set provides greater sensitivity to small variations in tissue density. It also allows researchers to acquire X-ray and nuclear medicine data.
"The nuclear medicine data tells biologists about metabolic activity in the mouse while the X-ray data provides high-resolution structural information," Paulus said.
Paulus and colleagues have already had success with a single-pixel energy-sensitive detector and are developing a multi-element detector array and associated integrated circuits to process the signals.
Ultimately, Paulus hopes the MicroCAT will allow automated screening of mice, which will enable genetics researchers to quickly scan mice and look at phenotypes using a computer program. This will become increasingly important as the worldwide effort to identify gene function intensifies.
Other potential uses for the MicroCAT include in breast cancer screening and possibly in certain industrial processes where precision imaging is important. Paulus believes the MicroCAT could be on the market within two years.
Funding for the project was provided by the Laboratory Directed Research and Development program. Others involved in development of the MicroCAT are Mike Simpson, Chuck Britton and Steve Hicks of the Instrumentation and Controls Division, Doug Lowndes of the Solid State Division and Russ Knapp of the Life Sciences Division.
ORNL, one of DOE's multiprogram research facilities, is managed by Lockheed Martin Energy Research Corporation.
The above story is based on materials provided by Oak Ridge National Laboratory. Note: Materials may be edited for content and length.
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