An approach to the endoscopic diagnosis of cancer which eliminates the need for a biopsy and tissue staining is being advanced by researchers in Germany. A handheld fiber optic probe performs multiple nonlinear imaging techniques and could enable doctors to diagnose cancer on the spot.

The new multimodal imaging probe uses an ultrafast laser to create nonlinear optical effects in tissue that can reveal cancer and other diseases. The device, measuring only 8 mm in diameter, might replace imaging techniques that previously required bulky table-top instruments.

This is the first miniaturized probe for multimodal biological imaging to incorporate a multicore imaging fiber, a type of optical fiber consisting of several thousand light-guiding elements. The special imaging fiber allowed the researchers to keep all moving parts and electric power outside of the probe head, making the probe easy and safe to use in the body.

The handheld device functions as a miniaturized microscope that uses near-infrared lasers to investigate tissue. It can simultaneously acquire several types of images: coherent anti-stokes Raman scattering, second harmonic generation, and two-photon excited auto-fluorescence. These nonlinear imaging techniques have been shown to be useful for clinical diagnostics, including identifying cancerous cells, but it has been difficult to miniaturize the required instrumentation for use inside the body. Handheld fiber optic probe represents an important step toward endoscopic cancer diagnosis. (Credit: Jurgen Popp, Leibniz Institute of Photonic Technology Jena and Institute of Physical Chemistry, Friedrich-Schiller University Jena)

Use of gradient index, or GRIN, lenses to focus the laser light is essential for size reduction. Compared to traditional spherical lenses that use complicated shaped surfaces to focus light, GRIN lenses can be miniaturized because they focus light through continuous refractive index changes within the lens material. Researchers from Friedrich-Schiller University of Jena and Leibniz Institute of Photonic Technology collaborated with scientists from Grintech GmbH to design GRIN lenses only 1.8 mm in diameter, which were incorporated into a small aluminum housing.

Endoscopes designed for nonlinear imaging commonly use moving mirrors and electromechanical devices for point by point laser scanning in the probe head. Using the multicore imaging fiber allowed the researchers to further reduce the device’s size by moving the laser scanning out of the probe head and away from the sample site. Because the fiber’s thousands of light guiding elements, or cores, preserve the spatial relationship of the light between the two ends of the fiber, the scanning can be performed at the opposite end of the fiber, making an endoscopic approach much easier.

The probe was demonstrated to acquire separate coherent anti-stokes Raman scattering, second harmonic generation, and two-photon excited autofluorescence images of healthy human skin tissue samples with a resolution of 2048 by 2048 pixels for a scanned area of 300 by 300 microns. This resolution and field of view is sufficient for identifying tumor borders, and the probe can be moved over the tissue surface to get an overview of the affected area.