Optical Technique Identifies Brain Tumors in Real Time

An optical phenomenon known as third harmonic generation (THG) can now be used to analyze glial brain tumors within seconds, according to a new study.

Researchers at VU University (Amsterdam, Netherlands) tested the THG method on samples of glial brain tumors from humans, finding that the histological detail in the images was as good as that of conventional staining techniques, which can take up to a day to prepare. In contrast, they were able to generate most images in under five minutes, with smaller ones taking less than a second, while larger images of a few square millimeters took five minutes. The technique provides label-free, real-time images with increased cellularity and nuclear pleomorphism.


The researchers are now developing a hand-held device that a surgeon can use to identify the glial tumor's boundary during surgery. At the moment, the incoming laser pulses can only reach a depth of about 100 micrometers into the tissue, but the researchers think that a needle could be used to pierce the tissue, delivering photons deeper. The study describing the application of THG to intraoperative brain pathology was published in the May 2016 issue of Biomedical Optics Express.

“The special thing about our images is that we showed they contain so much information. When I showed these images to the pathologists that we work with, they were amazed,” said senior author Marloes Groot, PhD, of VU University. “With our technique it's potentially possible to diagnose not only during an operation but possibly before surgery.”

THG involves firing short, 200-femtosecond-long laser pulses into glial tissue. When three photons converge at the same time and place, they interact with the nonlinear optical properties of the tissue, resulting in the generation of a single photon. While the incoming photons are at the 1200 nanometer wavelength--long enough to penetrate deep into the tissue--the single photon produced is at 400 nanometers, allowing it to scatter in the tissue. The scattered photon thus contains information about the tissue, which can be interpreted.

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