Researchers from the Massachusetts Institute of Technology (MIT; MA, USA) have developed an MRI-based calcium sensor, which could allow them to peer much deeper into the brain. The study has been published in Nature communications.
Calcium imaging in brain cells can reveal how neurons communicate with each other; however, current imaging techniques are only able to penetrate a few millimeters into the brain. Using this new MRI technology, it may be possible to 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 used widely in neuroscience but now enables such measurements to be performed in vivo in deep tissue,” commented Alan Jasanoff (MIT), senior author of the paper.
Many researchers have been working on MRI-based calcium sensors, however, one major obstacle of this has been developing a contrast agent that can penetrate inside brain cells. In order to overcome this, the study team used building blocks that can pass through the cell membrane.
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To do this, the researchers used a contrast agent that contains manganese, which is a metal that interacts weakly with magnetic fields, bound to an organic compound that can penetrate cell membranes. This complex also contains a calcium-binding arm called a chelator.
If calcium levels are low inside the cell, then the chelator binds weakly to the manganese atoms, which subsequently shields the manganese from MRI detection. When calcium flows into the cell, the chelator then 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,” explained Jasanoff.
Within their study, the sensors were tested in rats by injecting it into a deep brain structure called the striatum. 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.
In the future, Jasanoff anticipates using this technique to identify small clusters of neurons that are involved in specific behaviors or actions. In addition to this, this technique could be used to image calcium facilitating the activation of immune cells.
Sources: Barandov A, Bartelle BB, Williamson CG, Loucks ES, Lippard SJ, Jasanoff A. Sensing intracellular calcium ions using a manganese-based MRI contrast agent. Nat. Comm. doi:10.1038/s41467-019-08558-7 (2019) (Epub ahead of print); http://news.mit.edu/2019/mri-calcium-sensor-image-brain-0222