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Microscopic brain imaging in the palm of your hand

scence 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.

While two-photon microscopy offers an alternative to traditional one-photon fluorescence microscopy, it still only penetrates brain tissue down to about 500-600 microns barely scratching the surface. 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 (figures 1c-1e), the researchers inserted the microendoscope into the hippocampus, about a millimeter below the mouse brain surface, to image this part of the brain. The two-photon imaging provided an additional 80 microns of depth, below the hippocampal surface.

When combined with two-photon fluorescence, the result is a system that brings the power of a cutting-edge imaging technique to the deep tissues of the brain. By creating a handheld device based on some of the latest advances in micromotors, lensing and fiber optics (see accompanying article for more information), the researchers were able to establish a new technique that enables them to obtain microscopic images deeper in the living brain than was possible before microendoscopy.

"We're bringing two-photon imaging to endoscopy and we're putting it all into a miniaturized package," says Mark Schnitzer, the team leader on the Optics Letters paper.

The Stanford researchers have used their two-photon microendoscopy technique to glean the detailed images of the blood vessels in the hippocampus sections of the brains of live mice. T
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Contact: Ben Stein
bstein@aip.org
301-209-3091
American Institute of Physics
24-Aug-2005


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