CAMBRIDGE, MA -- Scientists often label cells with proteins that glow, allowing them to track the growth of a tumor, or measure changes in gene expression that occur as cells differentiate.

While this technique works well in cells and some tissues of the body, it has been difficult to apply this technique to image structures deep within the brain, because the light scatters too much before it can be detected.

MIT engineers have now come up with a novel way to detect this type of light, known as bioluminescence, in the brain: They engineered blood vessels of the brain to express a protein that causes them to dilate in the presence of light. That dilation can then be observed with magnetic resonance imaging (MRI), allowing researchers to pinpoint the source of light.
“A well-known problem that we face in neuroscience, as well as other fields, is that it’s very difficult to use optical tools in deep tissue. One of the core objectives of our study was to come up with a way to image bioluminescent molecules in deep tissue with reasonably high resolution,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

The new technique developed by Jasanoff and his colleagues could enable researchers to explore the inner workings of the brain in more detail than has previously been possible.

Jasanoff, who is also an associate investigator at MIT’s McGovern Institute for Brain Research, is the senior author of the study, which appears today in Nature Biomedical Engineering. Former MIT postdocs Robert Ohlendorf and Nan Li are the lead authors of the paper.

Detecting light

Bioluminescent proteins are found in many organisms, including jellyfish and fireflies. Scientists use these proteins to label specific proteins or cells, whose glow can be detected by a luminometer. One of the proteins often used for this purpose is luciferase, which comes in a variety of forms that glow in different colors.

Jasanoff’s lab, which specializes in developing new ways to image the brain using MRI, wanted to find a way to detect luciferase deep within the brain. To achieve that, they came up with a method for transforming the blood vessels of the brain into light detectors. A popular form of MRI works by imaging changes in blood flow in the brain, so the researchers engineered the blood vessels themselves to respond to light by dilating.

“Blood vessels are a dominant source of imaging contrast in functional MRI and other non-invasive imaging techniques, so we thought we could convert the intrinsic ability of these techniques to image blood vessels into a means for imaging light, by photosensitizing the blood vessels themselves,” Jasanoff says.

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