A revolutionary way to peek at neurons deep inside the brain

MIT creates new method for deep, intracellular noninvasive brain imaging

Posted Feb 22, 2019

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A large barrier in neuroscience is the ability for researchers to conduct studies on a live, functioning brain without surgery or implanting probes. Today researchers at the Massachusetts Institute of Technology (MIT) announced a new method to monitor neuron signals deep in a living brain noninvasively and published their scientific findings in Nature Communications.

How do neuroscientists observe neurons?

Modern scientists have been studying neurons using calcium imaging for many years. Calcium is a good indicator because the levels of calcium concentration in neurons are measurably different when at rest than when active. The level of intracellular calcium concentration in mammalian neurons is around 50-100 nanomolar at rest, and anywhere to 10-100 times greater when excited.

Frequently neuroscientists image the activity of neurons for research noninvasively in a lab dish with cultured cells. While it’s possible to observe activity in shallow depths of approximately one millimeter in intact tissue, to go any deeper requires more invasive techniques that may involve surgery to install probes.

What makes this discovery a breakthrough?

Alan Jasanoff, MIT professor and senior author of the paper, describes their research discovery the “first MRI-based detection of intracellular calcium signaling” to enable measurements of activity deep inside a living brain.

The other research members include Ali Barandov and Benjamin B. Bartelle (lead authors), together with contributors Catherine G. Williamson, Emily S. Loucks, and Stephen J. Lippard.

The team created an original way to image neuron activity in live animals deeply and noninvasively. The key differentiator is that this noninvasive magnetic resonance imaging (MRI) based sensor works intracellular, inside the neurons, versus outside the cell. Now neuroscientists have a method to not only study neurons widely but also deeply in the brains of living animals without the need for surgery nor invasive probes.

How did the MIT team do it?

Here is where chemistry, physics and an understanding of magnetic MRI technology play a critical role in the discovery.

Magnetic resonance imaging works by manipulating the protons (positively charged subatomic particles) in the body. The human body is mostly water, which the chemical formula is H20 (two hydrogen atoms bound to one oxygen atom). The average adult’s body is around 60-70 percent water, and 75 percent in children. When the human body is placed in a powerful magnetic field, the protons at the center of each of the body’s hydrogen atoms line up in the same direction.

Short bursts of radio waves are delivered to target areas of the body, disrupting the protons’ alignment in the process. After the radio waves are halted, the protons that realign transmit radio signals that contain information on the proton’s location and tissue type—protons in various types of tissues realign at varying velocities with distinctive signals. The proton signals from the image.

To improve the quality of the image requires greater contrast. Chemical contrast agents of metallic elements are used with a chelator to enhance MRI images. Chelators serve as a binder to keep the metal from settling in the human body as a safety measure.

The key to the MIT researchers’ solution is that they created an indicator that can penetrate the cell walls of a neuron, and create a signal that can be picked up by magnetic resonance imaging based on the concentration of calcium inside the cells.

The MIT researchers created a cell permeable calcium sensor for calcium-dependent molecular MRI using a combination of a contrast agent made of manganese (a metal) with an organic compound and a calcium chelator which can form bonds to a metal ion.

When neurons are at rest and the calcium concentration inside is relatively low, the calcium chelator will form chemical bonds with the manganese.

But when the neuron is excited and the calcium concentration inside the cell is significantly greater, the calcium chelator’s bond with the manganese will release to form bonds with the calcium instead.

Increased manganese inside the cell will increase the contrast, and therefore the brightness of the MRI image. The team’s sensors are able to identify and monitor those changes.

Why this discovery matters

The researchers have created a useful to enable precision neuroscientific studies. Instead of tracking the changes in blood flow in the brain through functional MRI (fMRI), scientists can now measure the signaling that occurs inside the cells, which is orders of magnitude more precise.

The exact mechanisms of how the brain functions remain in large part, a black box. Having a method to look into the inner workings deep inside the brain is vital.

Neuroscience is a critical area of scientific research that impacts many other disciplines. It is a multidisciplinary branch of biology that integrates psychology, biochemistry pharmacology, cytology, molecular biology, mathematical modeling, developmental biology, and anatomy.

Discoveries in neuroscience lead to advancement in medicine, biotechnology, pharmaceuticals, and even technology. For example, the recent boom in artificial intelligence (AI) is largely due to deep learning, which is a machine learning method consisting of structural elements such as neural network layers and nodes (analogous to neurons) that were somewhat inspired by the biological brain.

The world’s demographics are changing, placing a greater emphasis on neuroscience—the study of the brain and nervous system. By 2050, people aged 60 and older will account for nearly 25 percent or more of the population in every region in the world except Africa, according to United Nations estimates.

Age-related diseases and disorders are an increasing problem as the average age of the world’s population increases. Mental health issues common to older adults include dementia, Alzheimer’s, Parkinson’s, seizures, bipolar disorder, schizophrenia, depression, anxiety, ALS (Lou Gehrig’s disease), and cognitive impairment. This underscores a greater need for neuroscientific studies to address this growing problem.

There are many unanswered questions regarding the brain. What goes on in our brain when we sleep, dream, or undergo general anesthesia? What is the neural basis of perception? How does the brain form a single conscious experience from various distributed sensory input? What is the very nature of consciousness itself? Understanding the inside workings of neurons in a living brain may lead to future solutions that improve the human condition, and help answer some of the largest mysteries that perplex humankind.

And that’s how having the ability to peer deeply into the intracellular activity of neurons in the brain noninvasively may lead to scientific advancements that have a profound impact on the future of humanity itself.

Copyright © 2019 Cami Rosso All rights reserved.


Barandov, Ali, Bartelle, Benjamin B., Williamson, Catherine G., Loucks, Emily S., Lippard, Stephen J., Jasanoff, Alan. “Sensing intracellular calcium ions using a manganese-based MRI contrast agent.” Nature Communications. 22 February 2019.

Trafton, Anne (2019, Feb. 22). “New MRI sensor can image activity deep within the brain.” Retrieved 2-22-20109 from http://news.mit.edu/2019/mri-calcium-sensor-image-brain-0222

Grienberger, Christine, Konnerth, Arthur. “Imaging Calcium in Neurons.” Neuron. 8 March 2012.

NHS. “MRI scan—Overview.” Retrieved 2-22-2019 from https://www.nhs.uk/conditions/mri-scan/

Richter, Brian. “Walking Water. H20 and the Human Body.” National Geographic. March 6, 2012.

NIH (2018, Feb. 9). ”Alternative MRI contrast agent performs well in NIH study.” Retrieved 2-22-2019 from https://www.nibib.nih.gov/news-events/newsroom/alternative-mri-contrast-agent-performs-well-nih-study

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