Small animal imaging facility is big boon to research

Aug 30 2007

When powerful magnets line up the body's protons before radiofrequency waves can grab their attention away, it's called spin physics.

When signals generated by the movement are mathematically transformed into dramatic images of hearts, lungs and other organs it's called a magnetic resonance image. “Protons normally would be pointing in many different directions,” says Dr. Tom Hu, director of the Small Animal Imaging Program at the Medical College of Georgia. “But if you put an object in the MRI, the magnet will line up the protons and what that does is generate the original, steady state. Then, by applying different radio frequencies, pretty much like what you do with a car antenna, you can pursue radio frequencies to perturb the system and you pretty much listen to it.”

When Dr. Hu, a biochemist and biophysicist, tunes in he sees how calcium moves in and out of heart cells as the heart contracts and relaxes and how that movement doesn't work so well in heart failure, a condition resulting in oversized hearts with difficulty beating.

He's looking at whether the metallic manganese ion, which can travel in the same circles as calcium, can enhance the signal and subsequent images he gets of how calcium can't get back into cells after a heart attack. “Once it's disturbed, the cells die and the myocardium dies and you have scar formation,” says Dr. Hu whose ultimate goals include better ways to diagnose and treat heart failure, an increasingly common problem in the United States where improved cardiac treatment means many people are living with their heart disease. “Not only can you look at a living organ, you can also study the molecular aspects of this like the calcium ion,” says Dr. Hu who came to MCG in 2005 to start the Small Imaging Program in support of research initiatives, such as his, that have clinical promise.

The MRI that is the program's centerpiece looks like the human version except the cylinder the patient lies in is obviously much smaller. However it has a stronger magnet than typical clinical grade units primarily because the organs of interest are so much smaller, says Dr. Nathan Yanasak, magnetic resonance scientist.

Many standard MRIs are 1.5 Tesla and high-end clinical units are 3 Tesla, a measure of the density and intensity of a magnetic field. MCG's small animal MRI is 7 Tesla, not the strongest magnet available for research but one that enables good quality images of small organs which are comparable to those obtained by clinical machines. “It's pretty close to clinical grade,” says Dr. Yanasak. “But since you are scanning something smaller you need a larger field of strength to get the animal images to look like a human image,” he says. The smallest heart they've imaged, for example, is that of a 3-gram mice (that's a .105-ounce mouse). “It is better resolution in the sense that you have to have better resolution to see a brain this big,” Dr. Yanasak says, holding his fingers very close together.

The textbook answer for why scientists need high-tech imaging studies" They are noninvasive, says Dr. Hu, which obviously makes them excellent clinical tools as well. “If you have an animal disease model, for pretty much any noninvasive technique, the advantage is it reduces animal use tremendously,” he says.

Like physicians do with patients, basic scientists now use technology to help monitor disease progression over time and even to see if treatments work. In his own work, for example, Dr. Hu watches development of heart failure by monitoring changes in calcium dynamic and heart structure.

Newer technology, on loan to the facility from Xenogen Corp, part of Caliber Life Sciences Corp., has enabled the lab to throw genetic expression into the mix. The optical scanning system uses luciferase, the same enzyme fireflies use to glow, to identify gene expression.

"If you combine (luciferase) with certain genes and the genes are expressed, they glow,” says Dr. Hu. “For example, after a heart attack, you can look and see if certain genes are up-regulated, such as inflammatory genes. Now we take the same animal model back to the MRI machine and track how many cells have moved to the site of injury. So, we can combine the information and say, okay, potentially those cells that have been mobilized are due to the gene expression. We can try and link cause and effect so it becomes more of a valuable image,” says Dr. Hu. Right now he and Dr. Yanasak are fine-tuning how to make MRI and optical scanning work optimally together and how to also quantify gene expression.

The number of MCG scientists using the facility is significant and growing, says its director. Dr. Adviye Ergul, for example, is looking at blood flow in the brain of her diabetes model and Dr. William Hill is looking at stroke event and recovery.

“We are very open to any interesting ideas that generate interesting scientific data or grant funding opportunities,” says Dr. Hu. Goals include becoming an MCG core laboratory facility and adding a small animal PET scanner and ultrasound.