MIT Team Develops fMRI Probe for Selective Imaging of Neural Populations

Biological engineers at Massachusetts Institute of Technology (MIT) have developed a new probe for functional magnetic resonance imaging (fMRI) that can monitor individual populations of neurons and their interactions with each other. By genetically targeting the probe to specific populations of cells in rats, for example, the researchers were able to identify neural populations involved in a circuit that responds to rewarding stimuli.

“With regular fMRI, we see the action of all the gears at once. But with our new technique, we can pick up individual gears that are defined by their relationship to the other gears, and that's critical for building up a picture of the mechanism of the brain,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

Traditional fMRI imaging measures changes to blood flow in the brain as a proxy for neural activity.  Directly imaging calcium—which is released during neuron activity—can offer a more precise picture of brain activity, but that type of imaging usually requires fluorescent chemicals and invasive procedures. The MIT team wanted to develop a method that could work across the brain without that type of invasiveness.

“If we want to figure out how brain-wide networks of cells and brain-wide mechanisms function, we need something that can be detected deep in tissue and preferably across the entire brain at once,” Jasanoff says. “The way that we chose to do that in this study was to essentially hijack the molecular basis of fMRI itself.”

The researchers created a genetic probe, delivered by viruses, that codes for a protein that sends out a signal whenever the neuron is active. This protein, which the researchers called NOSTIC for Nitric Oxide Synthase for Targeting Image Contrast, can detect elevated calcium levels that arise during neural activity and generate nitric oxide in response. This leads to an artificial fMRI signal that arises only from cells that contain NOSTIC. The probe is delivered by a virus that is injected into a particular site, after which it travels along axons of neurons that connect to that site. That way, the researchers can label every neural population that feeds into a particular location. In rats, the researchers were able to use the probe to determine which neural populations send input to the striatum during or immediately following a rewarding stimulus.

The findings appear in Nature Neuroscience. The researchers now hope to use this approach to study other networks in the brain, beginning with identification of regions that receive input from the striatum following deep brain stimulation.