A new device called Fiberscope could help scientists with their searches by giving them a less-invasive look into the brain’s depths.
The brain poses plenty of obstacles form neuroscientists exploring how it works. Outer brain tissue, for example, blocks access to the deepest brain cells, or neurons, so researchers often have to remove swaths of tissue to measure neurons of interest.
A new device called Fiberscope could help scientists with their searches by giving them a less-invasive look into the brain’s depths. It uses a tiny multimode optical fiber - a light-carrying cable 120 microns in diameter - that travels into brain tissue, providing a view of neurons when they fire. It’s like a periscope that records brain activity.
Shay Ohayon, a neuroscientist at Massachusetts Institute of Technology who worked on this device, sees it as a valuable research tool. In particular, it should be useful for studying larger animals, like nonhuman primates, where more brain regions lie farther below the surface, he says.
In initial tests on mice, Ohayon and his team inserted the Fiberscope one millimeter below the brain’s surface and captured full-field, micron-scale resolution images at about 15 Hz. The Fiberscope has a field of view around the size of the fiber tip, so it can monitor about a dozen neurons at a time with fluorescent imaging.
Neurons aren’t naturally fluorescent. Ohayon and his team genetically modify research animals’ neurons for measurements by injecting viruses into each animal subject’s brain. Post-modification, the mouse’s neurons emit light if a specific wavelength of light hits the neurons as they fire.
To monitor neurons, Ohayon guides the optical fiber into a mouse’s brain, steering the device through a hypodermic needle resting above the organ. Once inside, the Fiberscope sends focused light signals to different points in its field of view, then records the light neurons emit to monitor their activity. The same optical fiber ferries light for both tasks.
Other optical imaging devices operate similarly; they send light to genetically modified neurons and measure the cells’ output. So far, most of these approaches use a lens to focus the light they shine on neurons, making the devices much larger.
Instead of using a lens, Ohayon calibrates the optical fiber’s output mathematically. He feeds focused light into the fiber and images the speckled pattern that exits the fiber, then uses that speckle pattern to find input patterns that will exit the fiber as focused dots of light.
He incorporated a digital mirror device, the kind of chip that governs most overhead projectors’ images, into Fiberscope to send input patterns into the fiber quickly. The digital mirror device consists of a tiny array of mirrors that transmits a grid of signals to the optical fiber quickly enough to image neurons, at a 20 kHz scan rate.
Fiberscope is still a bit slower than other imaging options, and the optical calibration requires the device to be straight for all imaging. Other optical fiber endoscopes have used an additional reflector at the fiber tip to compensate for bending, but Ohayon says neural imaging may not require bending. “When we are imaging regions in the brain we try to target a very specific region and we go along a straight trajectory,” he says. The device is also less invasive than other optical imaging while providing more information than electric measurements.
Electrodes in Fibertscope can measure the voltage changes of neurons in deep brain regions, and there are micron-sized needles that minimize tissue damage. Differentiating between individual neurons in electrode measurements is difficult, so optical imaging is an appealing choice for collecting granular data.
Ultimately, Ohayon developed Fiberscope for its specificity. His dream experiment, he says, is to use multiple fluorescent signals to identify different brain cells and watch how information flows from one region of the brain to another, deep below its surface.
Menaka Wilhelm is an independent technical writer.