Using ion beams to improve brain microscopy

Improving the method researchers can see the tiny structures of the brain can enhance our understanding of a host of brain illness, like Alzheimer’s or numerous sclerosis. Studying these illness is difficult and has actually been restricted by precision of offered designs.

To see the tiniest parts of cells, researchers typically utilize a strategy called electron microscopyElectron microscopy traditionally includes including chemicals and physically cutting the tissue. This method can alter the method the cells and structures look, alarming their natural state, and can restrict resolution.

An option technique, called cryo-electron tomography (cryo-ET), supplies clearer pictures of the brain’s tiniest parts in a more native state, nevertheless, it needs freezing. Freezing samples to cryogenic temperature levels need to be done thoroughly or ice crystals can form, interrupting the native anatomy.

Brand-new research study by Benjamin Creekmore in Yi-Wei Chang and Edward Lee’s laboratories at the University of Pennsylvania reveals a brand-new strategy to study the human brain’s ultrastructure. They provide their research study at the 68th Biophysical Society Annual Meetingheld February 10– 14, 2024 in Philadelphia, Pennsylvania.

Creekmore and coworkers acquired brain tissue from autopsies, flash froze it straight on unique grids with liquid ethane, and utilized an effective tool called a xenon plasma focused ion beam (FIB) to cut thin pieces for imaging. This technique permitted them to take a look at the brain tissue in its near-natural state without cutting with a knife blade, including chemicals, or slower freezing, all of which can cause modifications in the structures.

“The most typical method to protect tissue at a time of autopsy is to put it in a freezer and after that utilize it later on. Letting it freeze gradually and then warming it up and then refreezing it likewise interrupts the tissue. Membranes break and you can lose the regular architecture,” Creekmore described.

One unexpected part of the brand-new technique is that it lets them more quickly and quickly freeze much thicker samples– in the previous samples were restricted to 10 microns utilizing comparable techniques. “We had the ability to freeze samples as much as 250 microns thick without ice crystals,” Creekmore stated. The procedure of getting thick samples prepared for high-resolution imaging is much faster than with other methods. This speed-up can permit analysis of a larger selection of samples.

By using this technique to brain tissue from people with Alzheimer’s illnessthey had the ability to observe undamaged structures within cells, such as tau fibrils, a trademark of Alzheimer’s illness, and cellular elements that attempt to break down these fibrils. The group likewise pictured and determined myelin, a sheath that’s important for nerve function however that breaks down in specific illness, such as numerous sclerosis.

“Techniques for imaging human tissue traditionally have actually been fairly low resolution and they disrupt the native architecture. We wished to attempt to come up with a manner in which we might design and study brain illness in their natural context,” Creekmore stated.

Their ingenious approach supplies a very first glance into the natural state of human brain tissueusing important insights into its anatomy at a high level of information. This brand-new technique can begin to supply special details to figure out disease-causing systems of a broad variety of brain-related illness.