brain

New MRI sensor can image activity deep within the brain

Calcium is a critical signaling molecule for most cells, and it is especially important in neurons. Imaging calcium in brain cells can reveal how neurons communicate with each other; however, current imaging techniques can only penetrate a few millimeters into the brain.

MIT researchers have now devised a new way to image calcium activity that is based on magnetic resonance imaging (MRI) 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 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 appears in the Feb. 22 issue of 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.

Getting into cells

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.

To achieve that, the MIT team turned to MRI, a noninvasive technique that works by detecting magnetic interactions between an injected contrast agent and water molecules inside cells.

Many scientists have been working on MRI-based calcium sensors, but the major obstacle has been developing a contrast agent that can get inside brain cells. Last year, Jasanoff's lab developed an MRI sensor that can measure extracellular calcium concentrations, but these were based on nanoparticles that are too large to enter cells.

To create their new intracellular calcium sensors, the researchers used building blocks that can pass through the cell membrane. The contrast agent contains manganese, 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.

Once inside the cell, if calcium levels are low, the calcium chelator binds weakly to the manganese atom, shielding the manganese from MRI detection. When calcium flows into the cell, the chelator 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," Jasanoff says.

Precise measurements

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.

The research was funded by the National Institutes of Health and the MIT Simons Center for the Social Brain.

Researchers create organoid of a brain region to study cognitive disorders

In a lab dish, Yale researchers modeled two brain structures and their interactions to shed light on the origins of neuropsychiatric diseases.

In-Hyun Park, associate professor of genetics, and his team created an organoid of the thalamus, a major hub that integrates sensory information and relays it to different areas of the brain. Organoids are created from stem cells to mimic brain areas and assess their function. The lab was interested in the thalamus because it has been implicated in several psychiatric disorders.  The thalamic organoid was then fused with an organoid of the frontal cortex, the seat of higher cognitive function.

"Right now we are trying to utilize the thalamic organoid to study epilepsy, autism spectrum disorder, schizophrenia and even depression. With many of these diseases, people have found that there are some defects in the coritco-thalamic connectivity, as well as microstructural changes in the thalamus."

By creating organoids from cells taken directly from patients, the specifics of the structural changes underlying each disease could be discovered and personalized treatments developed.

The research was published in the journal Cell Stem Cell.

More information: hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids. Cell Stem Cell. DOI: doi.org/10.1016/j.stem.2018.12.015 Provided by Yale University

Citation: Researchers create organoid of a brain region to study cognitive disorders (2019, February 22) retrieved 22 February 2019 from https://medicalxpress.com/news/2019-02-organoid-brain-region-cognitive-disorders.html

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Rihanna Has Love and Basketball on the Brain at a Lakers Game With Her Hot Boyfriend

In the sports world, there's a very plausible theory about the "Drake curse" - meaning, whenever he roots for a team, the team loses (the Toronto Raptors, Alabama football, Kentucky basketball, the list goes on). But Rihanna, on the other hand, she's a blessing in sports, or at least for the Los Angeles Lakers on Thursday night. The 31-year-old superstar attended a very critical game versus the Houston Rockets, where the Lakers came back from a 19-point deficit and won the game, coming one step closer to their playoff goals. The MVP of the night was Rihanna, who celebrated her birthday (which was on Feb. 20) in a suite with a group of friends and her smoking-hot boyfriend, Hassan Jameel.

Rihanna and the Saudi billionaire have reportedly been dating since June 2017, and despite a handful of low-key appearances together, they're relatively private about their relationship. With their good luck in the Staples Center, we have a feeling LeBron James might request their presence at a few upcoming games. ICYMI, Rihanna's been a serious LeBron fan for years, even when he was on the Cavaliers!

Rihanna represented the team wearing LeBron's jersey, but it wouldn't be a birthday without a present from the Laker Lords - they gifted her a "BADGALRIRI" jersey! How do we get one of those? Ahead, see Rihanna and her crew at the game, including a few glowing photos of her and Hassan's sweet relationship.

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