NEWS

Imaging Facilities Focus On Small Animal Research

Jennifer Michalowski

Specialized imaging techniques for small animals are providing a way to dramatically reduce the number of animals researchers must commit to a project.

GoImaging modalities such as magnetic resonance imaging, positron emission tomography, single positron emission computed tomography, and optical coherence tomography are being used to generate anatomical and biochemical data on animal tumors. So far, imaging facilities have focused on mice and rats, but the instruments are also used to monitor cats, rabbits, and nonhuman primates.



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In this MRI image of a mouse, the arrow on the right points to a normal kidney, and the arrow on the left points to a kidney tumor.

 
The power of these techniques allows researchers to repeatedly and noninvasively monitor a single animal over time, rather than sacrifice several animals at various points in an experiment, said Jerry Glickson, Ph.D., professor of radiology at the University of Pennsylvania, Philadelphia, who uses magnetic resonance to monitor mice given gene therapy for colon cancer metastases.

This advantage allows each animal to serve as its own control, eliminating complications introduced by variations in age, sex, and genetic background and reducing the number of animals required for statistically significant data. "Without this capability, you would have to sacrifice a large cohort of animals and hope that they are well matched," Glickson said.

Fewer Subjects

GoRobert Gillies, Ph.D., professor of biochemistry, physiology, and radiology and director of the Southwest Small Animal Imaging Resource at the University of Arizona, Tucson, devotes about 250 animals a year to his own research program. For studies on the tumor microenvironment, researchers in Gillies’ group use magnetic resonance spectroscopy to image each animal multiple times. "To do this work with more traditional methods would take thousands of animals," Gillies said.



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These MRI images show hepatic metastases from colorectal cancer in a mouse. In the photo on the right, a, b, and d mark the metastases, and c labels the stomach. (Photos on this page courtesy of Jason Koutcher, Ph.D.)

 
For typical pharmacokinetic studies, he added, "a single imaging session with one animal can yield as much information as dozens of animals [analyzed] in a more traditional fashion."

For studies on potential therapeutic agents for brain cancer, Jason Koutcher, Ph.D., chief of the Imaging and Spectroscopic Physics Service at Memorial Sloan-Kettering Cancer Center, New York, pointed out that MRI allows researchers to select only mice that actually have brain tumors for their experiments. They can then treat as few as six to 12 animals and monitor the effectiveness of the drug by continued MRI imaging.

Without imaging, Koutcher said, death rates could be compared among a treatment and a control group, but such an experiment would require at least a hundred animals for reliable data.

Other Advantages

In addition to the reduction in the number of animals needed for experiments, there are other advantages to applying imaging technology to small animals. Using the same imaging modalities in both animals and humans strengthens the connection between basic and clinical science, Gillies said.

"The value is highest in translational work," he said, and he anticipates that, in the immediate future, institutions will focus on acquiring animal imaging instruments that parallel the techniques they use in the clinic.

Animal data can be collected using instruments designed for human patients, but the sensitivity and resolution are poor. "People do use them," said Michael Welch, Ph.D., professor of radiology and codirector of the Small Animal Imaging Core at Washington University’s Siteman Cancer Center, St. Louis, but these methods are not ideal for the majority of animal experiments being done. "The human instruments out there aren’t bad for rats, but they’re pretty awful for mice. And most of what we do is with mice."

Therefore, researchers are turning to tools designed specifically for animal imaging. In some cases an accessory can be attached to an instrument to make it more suitable for use with small animals, but in most cases the design of the instrument itself is unique.

Specialized Instruments

These specialized instruments for animal imaging were uncommon 10 years ago, but Koutcher estimated they are now being used at 50 to 75 institutions, including five specialized facilities that have been funded by the National Cancer Institute’s Small Animal Imaging Resource Program since 1999.

While experts agreed that small animal imaging is an invaluable tool, the question of whether the associated decrease in animal care expenses outweighs the cost of purchasing and operating the necessary equipment was less clear. According to Gillies, "You can get better information in less time with fewer animals. That doesn’t mean it’s cheaper."

Even with the appropriate equipment and expertise, Glickson, who is overseeing the development of a small animal imaging center at the University of Pennsylvania, cautioned that, as with any animal model for a human disease, researchers must bear in mind the limits of what animal models can teach us about human cancer. While he recognized small animal imaging as a powerful tool, he also noted, "Mouse cancer is not human cancer. You have to keep putting up the mirror to check just how what you see in the mouse reflects what you see in the human. The two have to go hand-in-hand."



             
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