Researchers from Massachusetts Institute of Technology have developed a magnetic resonance image(MRI) based sensor that can detect calcium activity within neurons, allowing them to closely track brain activity.
The researchers tested their sensor in rats by injecting it into the striatum, a region deep within the brain that is involved in planning movement and learning new behaviors. They then stimulated electrical activity in neurons of the striatum, and were able to measure the calcium response in those cells.
“This paper describes the first MRI-based detection of intracellular calcium signaling, which is directly analogous to powerful optical approaches used widely in neuroscience but now enables such measurements to be performed in vivo in deep tissue,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering, and an associate member of MIT’s McGovern Institute for Brain Research.
Calcuim is a critical signaling molecule for most cells and is especially important in neurons for their communication. They achieve this by sending electrical signals, which trigger an influx of calcium ions into active cells. Tracking the signaling process inside neurons would help link neural activity with specific behaviours in animals.
Since MRI is a powerful non-invasive imaging technique, detecting calcium activity using it will enable a deeper penetration into the brain unlike the traditional functional MRI (tfMRI) which measures the blood flow in the brain.
MRI works by detecting magnetic interactions between an injected contrast agent and water molecules inside cells. Though scientists had tried creating calcium based sensors to measure the extracellular calcium concentrations, creating a contrast agent was a major obstacle.
Here the researchers developed the contrast agent with building blocks that can pass through the cell membrane. The contrast agent contains a manganese part that interacts weakly with magnetic fields. This metal is bound to an organic compound that can penetrate cell membranes. This complex contains a calcium-binding arm called a chelator.
Once inside the cell, if calcium levels are low, the calcium chelator binds weakly to the manganese atom, shielding the manganese from MRI detection. When calcium flows into the cell, the chelator binds to the calcium and releases the manganese, which makes the contrast agent appear brighter in an MRI image.
“When neurons, or other brain cells called glia, become stimulated, they often experience more than tenfold increases in calcium concentration. Our sensor can detect those changes,” Jasanoff says.
With further modification this technique could be developed in future to perform diagnostic imaging of the brain or other organs whose functions rely on calcium.