Calcium is a signaling molecule for most cells, including neurons. Imaging calcium can show how neurons are able to communicate with each other. Current brain imaging techniques are only able to view a few millimeters into the brain.
The new imaging technique could track signaling processes in neurons and connect neural activity with certain behaviors.
“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 not enables such measurements to be performed in vivo in deep tissue,” Alan Jasanoff, the senior author on the study and a professor of biological engineering, brain and cognitive sciences at MIT, said in a press release.
Neurons have very low calcium levels in its resting state, according to the researchers. Calcium starts to flood the cell once they fire an electrical impulse. The calcium is typically labeled using fluorescent molecules and grown in a lab dish. However, this imaging technique is only able to penetrate a few tenths of a millimeter into the tissue.
“There are amazing things being done with these tools, but we wanted something that would allow ourselves and others to look deeper at cellular-level signaling,” Jasanoff said.
The researchers developed an MRI sensor that is able to measure extracellular calcium concentrations, but the concentrations were based on nanoparticles that are too large to enter cells. They developed a new intracellular calcium sensor using building blocks that ate able to pass through cell membrane. The contrast agent the researchers used has manganese, which interacts weakly with magnetic fields. Manganese is bound to an organic compound that can go through cell membranes. The sensor also has a calcium-binding arm known as a chelator.
The calcium chelator can bind weakly to manganese atoms when calcium levels are low, which protects the manganese from MRI detection. Once the calcium flows into the cell, the echelon can bind to the calcium and release the manganese. The contrast agent is then 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 said.
The sensor was tested in rats by injecting it into the striatum, which is a deep region of the brain. The researchers used potassium ions to stimulate electrical activity in striatum neurons and could measure the calcium response in the cells.
Jasanoff and the researchers plan to use the imaging technique to identify small clusters of neurons that are used in specific behaviors and actions. The researchers suggest that the technique can offer more precise information about location and timing.
“This could be useful for figuring out how different structures in the brain work together to process stimuli or cordite behavior,” said Jasanoff.
The researchers say that the technique could also be used to image calcium as it is used in other roles like activating immune cells.
The research was published in the journal Nature Communications and was funded by the National Institutes of Health and the MIT Simons Center for the Social Brain.