MIT researchers have now devised a new way to image calcium activity that is based on magnetic resonance imaging (MRI - see also MRI products in the catalogue of MEDICA 2018) and allows them to peer much deeper into the brain. Using this technique, they can track signaling processes inside the neurons of living animals, enabling them to link neural activity with specific behaviors.
"This paper describes the first MRI-based detection of intracellular calcium signaling, which is directly analogous to powerful optical approaches (like microscopes in the catalogue of MEDICA 2018) 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.
Jasanoff is the senior author of the paper, which appeared in Nature Communications. MIT postdocs Ali Barandov and Benjamin Bartelle are the paper's lead authors. MIT senior Catherine Williamson, recent MIT graduate Emily Loucks, and Arthur Amos Noyes Professor Emeritus of Chemistry Stephen Lippard are also authors of the study.
In their resting state, neurons have very low calcium levels. However, when they fire an electrical impulse, calcium floods into the cell. Over the past several decades, scientists have devised ways to image this activity by labeling calcium with fluorescent molecules. This can be done in cells grown in a lab dish, or in the brains of living animals, but this kind of microscopy imaging can only penetrate a few tenths of a millimeter into the tissue, limiting most studies to the surface of the brain.
"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 says.
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 used potassium ions to stimulate electrical activity in neurons of the striatum, and were able to measure the calcium response in those cells.
Jasanoff hopes to use this technique to identify small clusters of neurons that are involved in specific behaviors or actions. Because this method directly measures signaling within cells, it can offer much more precise information about the location and timing of neuron activity than traditional functional MRI (fMRI), which measures blood flow in the brain.
"This could be useful for figuring out how different structures in the brain work together to process stimuli or coordinate behavior," he says. In addition, this technique could be used to image calcium as it performs many other roles, such as facilitating the activation of immune cells. With further modification, it could also one day be used to perform diagnostic imaging of the brain or other organs whose functions rely on calcium, such as the heart (see also Heart circulation diagnostics equipment in the catalogue of MEDICA 2018).
MEDICA-tradefair.com; Source: Massachusetts Institute of Technology
