Time-Lapse Images as the Living Brain Responds to Experiences

Magnetic resonance imaging (MRI) has transformed the field of neuroscience over the past 40 years, allowing scientists to create clear snapshots of living brain structures and even detect functional changes associated with certain activities.

Unlike X-rays or CT scans, MRIs do not rely on beams of radiation. Instead, powerful magnetic fields and radio waves are used to temporarily align hydrogen atoms in the body’s water molecules, meaning they can create a clear picture of soft tissue, such as the brain. .

But newer technology developed by UNM neuroscientist Elaine Bearer, MD, PhD, and collaborators at the California Institute of Technology and the University of Southern California takes MRI even further.

In an article published in the journal NMR in biomedicinethey report the use of manganese, a trace element found throughout the body, as a contrast agent with MRI that allows a series of “time-lapse” images revealing the brain’s response to specific experiences.

“This report emphasizes the power of manganese-based contrast to study dynamic transitions throughout the brain,” said Bearer, a professor in the Department of Pathology at UNM. “The brain is not a static thing. This MRI technique images the slow consequences of an experience over time. It allows us to look deeper into the incredible complexity of thought and feeling.”

In manganese-assisted MRI (MEMRI), small amounts of manganese enter neurons through the same cellular pathway as calcium, which plays a key role in brain signaling. As manganese ions move through the neuron, they highlight the activities of the cell, highlighting the projections by which it communicates with adjacent neurons.

“This exciting emerging methodology captures brain function during normal behavior that otherwise cannot be known at this scale,” said Taylor Uselman, a PhD student in Bearer’s lab and co-author of the paper. Christopher Medina, MD, a graduate of the UNM School of Medicine, was also a co-author.

“Our publication also provides a critical overview of safety considerations for contrast agent use,” Uselman said. “We give a number of examples of how MEMRI reveals the development of the auditory system, as well as Down syndrome, Alzheimer’s disease and anxiety disorders.”

Standard MRI scans have great diagnostic value for detecting tumors or vascular abnormalities in the brain, and they can reveal that changes in certain brain structures are associated with specific behaviors, such as meditation or learning a second tongue. But they don’t show what the brain is actually doing, Bearer says.

“The MRI that we usually do for human diagnosis is just a picture of your anatomy,” she says. Neuroscientists also use a technique called functional MRI that measures cerebral blood flow, based on the idea that highly active regions of the brain use more oxygen.

However, the blood oxygen level-dependent (BOLD) signal is weaker, requiring computational analysis, and it mixes both vascular and neural activity, Bearer said. “With BOLD, what you detect is a proxy for neural activity.”

Bearer and his partners Harry Gray of Caltech and Russell Jacobs of USC have been exploring the potential of MEMRI technology for some time. In 2020, with Uselman and postdoctoral fellow Daniel Barto, they reported on the use of MEMRI to demonstrate how exposure to a frightening stimulus progresses to chronic anxiety.

“The main things that learned from this technology were the computational analysis I did with my students at UNM,” Bearer said. “This review is going to be a go-to reference for all investigators, especially when using this emerging technology.”

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