To make the blood vessels sensitive to light, the researcher engineered them to express a bacterial protein called Beggiatoa photoactivated adenylate cyclase (bPAC). When exposed to light, this enzyme produces a molecule called cAMP, which causes blood vessels to dilate. When blood vessels dilate, it alters the balance of oxygenated and deoxygenated hemoglobin, which have different magnetic properties. This shift in magnetic properties can be detected by MRI.

BPAC responds specifically to blue light, which has a short wavelength, so it detects light generated within close range. The researchers used a viral vector to deliver the gene for bPAC specifically to the smooth muscle cells that make up blood vessels. When this vector was injected in rats, blood vessels throughout a large area of the brain became light-sensitive.


“Blood vessels form a network in the brain that is extremely dense. Every cell in the brain is within a couple dozen microns of a blood vessel,” Jasanoff says. “The way I like to describe our approach is that we essentially turn the vasculature of the brain into a three-dimensional camera.”

Once the blood vessels were sensitized to light, the researchers implanted cells that had been engineered to express luciferase if a substrate called CZT is present. In the rats, the researchers were able to detect luciferase by imaging the brain with MRI, which revealed dilated blood vessels.

Tracking changes in the brain

The researchers then tested whether their technique could detect light produced by the brain’s own cells, if they were engineered to express luciferase. They delivered the gene for a type of luciferase called GLuc to cells in a deep brain region known as the striatum. When the CZT substrate was injected into the animals, MRI imaging revealed the sites where light had been emitted.

This technique, which the researchers dubbed bioluminescence imaging using hemodynamics, or BLUsH, could be used in a variety of ways to help scientists learn more about the brain, Jasanoff says.

For one, it could be used to map changes in gene expression, by linking the expression of luciferase to a specific gene. This could help researchers observe how gene expression changes during embryonic development and cell differentiation, or when new memories form. Luciferase could also be used to map anatomical connections between cells or to reveal how cells communicate with each other.

The researchers now plan to explore some of those applications, as well as adapting the technique for use in mice and other animal models.

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