Seeing the shimmer of biology in action  pg. 7

The bioluminescence imaging revealed that the duration of the inflammatory stimulus affected the final outcome, he says. A single bolus injection of endotoxin caused a peak of NF-kappa-B activation, as measured by light output, but no lung injury. The same dose of endotoxin given as an infusion over 24 hours caused a progressive and sustained activation of NF-kappa-B in the lung, and resulted in lung injury.

“That was something that would have been very time consuming to try to figure out without the use of bioluminescence,” Blackwell says, “and it has led us to other studies now trying to understand which cells are activated over this period of time and identify specific injury-provoking gene products.

“The ability to look non-invasively at NF-kappa-B activity over time in a relatively quantitative way is helping us to define the balance of factors that cause either lung injury or effective host defense against infection,” Blackwell says. “Ultimately we might be able to come up with ways to prevent injury and still maintain adequate defenses.”

These inflammation-reporting mice have been useful for Vanderbilt’s Lin as well. Lin is interested in blood vessel formation—angiogenesis—in the context of diseases including cancer, arthritis, and cardiovascular disease.

In the case of arthritis, inflammation appears to trigger excessive angiogenesis, which facilitates tissue growth and eventually causes bone damage, Lin explains. Anti-angiogenic therapies may be effective in preventing the tissue growth. Lin’s group is using multiple imaging technologies—an increasingly common approach known as multi-modality imaging—to probe the arthritic joint: bioluminescence to see the inflammation, x-ray to look at bone damage, and fluorescence techniques to visualize the blood vessels.

“We think this is a very powerful way to study how the blood vessel affects disease progression as well as what kind of therapy we can use to stop this process,” Lin says. “Imaging has really moved from traditional modes of looking at structure into functional imaging, from static into kinetic. We’re no longer satisfied looking at single point snapshots of dynamic processes.”

A cornerstone technology

While bioluminescence imaging offers excellent sensitivity for tracking cells and seeing gene expression in living animals, it suffers from poor spatial resolution. Because light is absorbed and scattered by tissues as it makes its way out of the animal, images become “fuzzy.” Jansen likens it to having a pencil in a glass of water and adding a few drops of milk—you can still make out an image, but it’s no longer clear that it’s a pencil.

“All of the imaging modalities have strengths, and they all have weaknesses,” Jansen says. “Bioluminescence is great at sensitivity, but it’s lousy at resolution. So in many cases we combine it with something like CT or MR, or even fluorescence.”

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