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New Imaging Techniques Unlock Secrets of the At-Work Brain



Researchers shared their advances in brain imaging technology during a press briefing at the AAAS Annual Meeting on 16 February. From left: Elizabeth Hillman, professor of biomedical engineering at Columbia University, Sarah Stanley, professor of medicine at Icahn School of Medicine at Mount Sinai, and Julia Brefczynski-Lewis, professor of research, department of physiology and pharmacology at West Virginia University. | Atlantic Photography

BOSTON – Novel imaging techniques are making it possible to study the brain while it’s at work.

These new, non-invasive tools – representing significant advances related to positron emission tomography (PET), 3-D microscopy and the use of magnetic fields and nanoparticles to remotely control targeted cells – permit the real-time study of neural activity in unprecedented detail.

The breakthroughs were described by three researchers in a press briefing at the 2017 AAAS Annual Meeting in Boston.

All three projects were supported by the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, launched by President Obama in 2013, with the aim of improving understanding of the human brain and developing new techniques and tools for discovering and treating brain disorders.

“The human brain has a hundred billion neurons,” said Elizabeth Hillman, associate professor of biomedical engineering and radiology at Columbia University. “We can only measure activity in less than 500 neurons. The BRAIN initiative recognized this massive problem: that we haven’t had the technologies to be able to understand this incredibly complex organ.”

To help unravel that complexity, Hillman and her lab have developed a new imaging method called SCAPE – Swept, Confocally Aligned Planar Excitation microscopy – that can image ten to 100 times faster than previous 3-D microscopy techniques.

Hillman described how SCAPE, which uses lasers to create sheets of light in tissue, can image every neuron in a fruit fly larvae as it crawls, or illuminate networks of firing dendrites in the brains of mice.

“You can see the way neurons are actually signaling and the way neurons in brain are telling the body to move,” she said, pointing to flashing green areas in the body of the crawling larvae.

Previously researchers have only been able to image these organisms while they are stationary. “The SCAPE technique specifically allows animals to do what they would normally do and observe them in this new way,” said Hillman.

“Moving to these smaller organisms gives us the opportunity to try to understand the rules that govern the behavior of neurons and circuits and brains on a holistic level,” Hillman said. “These organisms can be used as models to understand diseases like Lou Gehrig’s disease. You can look at how those neurons are causing the body to move and do genetic models of those diseases.”

Being able to observe the neural activity of an organism while it’s going about its normal routine – whether it’s a human being talking to a friend, or a fruit fly searching for food – opens up new possibilities for mapping the complexity of the brain and understanding the neurological mechanisms of diseases.

“Just as Elizabeth talked about being able for the first time to image drosophila while they’re moving around, now we can image humans while they’re moving around,” said Julie Brefczynski-Lewis, assistant professor of research in physiology and pharmacology at West Virginia University.

Her team has developed the Ambulatory Micro-dose Positron Emission Tomography – or AMPET – scanner, which can image the entire brain while its wearer is in motion. She donned the helmet-like device, mounted with 12 small camera-sized detectors, to show how light and maneuverable it is.

“There are a lot of important things going on with emotion, memory, behavior that are way deep in the brain, in the basal ganglia, the hippocampus, the amygdala,” Brefczynski-Lewis said. “These are areas that we can now reach with our technology.”

She noted that the AMPET’s ability to access these deep brain structures, which also govern critical functions like walking and balance, in real-time, represents an advance over other partially portable imaging techniques such as electroencephalography (EEG).

The AMPET could have a wide range of clinical and research applications, enabling researchers to image certain brain structures while subjects are engaged in a variety of activities.

“There are all these mysteries that require behavior” to access, Brefczynski-Lewis said. “You can image two people face to face, talking to each other, using their hands, using body language.”

It could also be deployed, she said, to image someone in an emergency room with emergent stroke or an athlete who has sustained a mild traumatic brain injury, to determine treatment options.

Sarah Stanley, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, described her work on a new method for remotely switching neurons on or off.

We can do this remotely with radio waves or magnetic fields,” she explained. “This allows us to study the brain in living animals without disturbing their movements or behavior we are trying to study. We can do it precisely, target it to particular nerve types.”

Her technique involves inserting ion channels into targeted cells and having them interact with iron oxide nanoparticles stored by a cell protein called ferritin. Radio waves interact with those nanoparticles, transferring energy that can open or close the channels.

“When it opens, sodium or potassium or chloride enter the cell, depending on the channel and that can change how the cell behaves,” said Stanley.

This noninvasive technique to remotely activate targeted cells could be used for a range of applications, including drug development.

“If we want to know the particular cell type that is involved in a disease and whether silencing or activating it could help cure the disease, we can use this tool,” added Stanley. “Further down the line, it may be used as an alternative for neuro-stimulation, currently done using electrical implants, such as for deep brain stimulation for treating Parkinson’s disease.”

All three researchers said the support of the BRAIN Initiative was transformative for their work.

Hillman said the grant from BRAIN enabled her and her lab colleagues to take risks to try out new ideas: “It was important to have that freedom to explore.”

“The BRAIN Initiative is driving new technology development,” said Hillman. “These new technologies are revealing previously unknown aspects of the brain. And these discoveries are closely linked to better understanding and detecting and treating human disease.”

[Associated Image: Atlantic Photography]