Looking inside your brain... without hurting you

Researchers at Stanford University have developed a portable device that captures pictures beneath the living brain's surface with minimal invasive effects.

Researchers at Stanford University have developed a portable device that captures pictures beneath the living brain's surface with minimal invasive effects. This new 3.9 gram two-photon fluorescence microendoscope can fit in the palm of your hand. It combines optical and mechanical techniques to image brain cells up to a millimeter beneath the brain surface of the mice used for the experiments. These new devices could be used to discover how individual living cells participate to mental processes such as learning and memory.

As the American Institute of Physics news release mentions, "imaging living cells below the surface has been difficult to accomplish using conventional techniques."

This is why the Stanford researchers have decided to use two-photon fluorescence imaging instead of conventional "one-photon" fluorescence imaging.

Instead of one higher-energy photon, researchers bombard the molecule with two photons of lower energy. Their combined energies total the energy required to excite the fluorescent-dye molecules used to mark the tissue. The technique gets rid of the background haze and reduces scattering, because molecules outside the area of interest are much less likely to absorb a pair of photons simultaneously and fluoresce in response.

Below is an optical schematic of the two-photon microendoscope used last year (Credit: Stanford University).

Optical schematic of the two-photon microendoscope

A laser beam is steered in two angular dimensions by a pair of galvanometer-driven deflector mirrors and is then focused by a microscope objective to a focal spot just above the external face of the endoscope probe. The probe refocuses the lateral scan pattern within the specimen. Then fluorescence emissions (dashed lines) returning from the sample are sent back to a computer which reconstructs the image of the sample.

But the researchers decided that this technology could not help to perform deep brain imaging.

To get at the deep structures, the Stanford researchers turned to microendoscopy, tiny, minimally invasive optical probes that could be inserted deep into living brain tissue. To make one group of images, the researchers inserted the microendoscope into the hippocampus, about a millimeter below the mouse brain surface, to image this part of the brain.

This research work has been published by Optics Letters under the name "In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope" (Volume 30, Issue 17, 2272-2274, September 2005). Here is a link to abstract.

Mark Schnitzer was the team leader for this paper. For more information, you can look at the web site of his research group at Stanford University.

Finally, you should read a previous paper published by the Journal of Neuropsychology under the name "In Vivo Mammalian Brain Imaging Using One- and Two-Photon Fluorescence Microendoscopy" (92: 3121–3133, May 2004).

Here are two links to the abstract and to the full paper (PDF format, 13 pages, 761 KB). The image above comes from this paper.

Will this new technique help neuropsychologists to know more about how our brains are working? This is possible, but first, they have to use this portable device with humans. So stay tuned...

Sources: American Institute of Physics, via EurekAlert!, Aufust 24, 2005; and various web sites

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