Compact Handheld Probe Helps in Endoscopic Diagnosis of Cancer Without Tissue Staining

An important step toward endoscopic diagnosis of cancer, researchers have come up with a handheld fiber optic probe capable of being used to perform multiple nonlinear imaging techniques without the requirements for tissue staining. An ultrafast laser is used by this new multimodal imaging probe to develop nonlinear optical effects in tissue that can reveal cancer and several other diseases.

Today, cancer is diagnosed by removing a bit of tissue with a biopsy. This is followed by sending that tissue to a specially trained pathologist who looks for cancerous cells by first staining the tissue followed by using a microscope. It is possible to save valuable time with surgeons being able to differentiate between cancerous and healthy tissue during surgery in an easier manner, if doctors have the potential to skip the biopsy and use a multimodal imaging endoscope to diagnose cancer on the spot.

Earlier, imaging techniques needed bulky table-top instruments, however with this new probe these imaging techniques can be carried out with a handheld device measuring only 8 millimeters in diameter, about the same diameter as a ballpoint pen. The probe, if further miniaturized, can be effortlessly incorporated into an endoscope for nonlinear multimodal imaging inside the body.

A detailed report of this new handheld probe has been presented by the researchers in Optica, The Optical Society's journal for high impact research. This handheld probe is considered to be the first miniaturized probe for multimodal biological imaging to integrate a multicore imaging fiber, a type of optical fiber comprising of several thousand light-guiding elements. This special imaging fiber enabled the team to keep electric power and all moving parts outside of the probe head, making the probe safe and easy to use in the body.

We hope that, one day, multimodal endoscopic imaging techniques could help doctors make quick decisions during surgery, without the need for taking biopsies, using staining treatments or performing complex histopathological procedures.

Jürgen Popp, from Leibniz Institute of Photonic Technology in Jena, Germany and the paper’s lead author.

This probe has been tested with different types of tissue samples, but the primary applications of the probe would likely include brain, skin or head and neck surgery as it is currently designed for forward view mode. The researchers are working on implementing a side view mode capable of being used to investigate hollow organs and arteries such as the aorta, bladder or colon.

A mini microscope

The new probe serves as a miniaturized microscope that uses near-infrared lasers to investigate tissue. Different components of biological tissue react differently to the excitation lasers, and their unique response gives us information about the molecular composition and morphology within the tissue.

Popp

The handheld multimodal imaging probe is capable of simultaneously acquiring several types of images: two-photon excited auto-fluorescence, second harmonic generation and coherent anti-stokes Raman scattering. These nonlinear imaging techniques have proved to be useful for clinical diagnostics, including the identification of cancerous cells, however it has been a difficult task to miniaturize the needed instrumentation for use inside the body.  

The reduced size of the probe comes from its use of gradient index, or GRIN, lenses to focus the laser light. Compared to standard spherical lenses that use complex shaped surfaces to focus light, it is possible to make GRIN lenses in very small sizes as they focus light through continuous refractive index changes within the lens material. Popp’s research team worked together with scientists from Grintech Gmbh who designed GRIN lenses only 1.8 millimeters in diameter and helped integrate the robust lens assembly into a small aluminum housing.

Moving mirrors and electromechanical devices are commonly used for point by point laser scanning in the probe head by endoscopes designed for nonlinear imaging. The researchers used the multicore imaging fiber to further reduce the size of the device by moving the laser scanning out of the probe head and away from the sample site. It is possible to perform the scanning at the opposite end of the fiber, making an endoscopic approach much easier, as the fiber’s thousands of light guiding elements, or cores, preserve the spatial relationship of the light between the two ends of the fiber.

Compared to other endoscopic nonlinear imaging approaches, our fiber probe stands out due to its simplicity. Since no moving parts are incorporated in the probe head, possible misalignments in the optics are limited and the probe’s overall lifetime is increased.

Popp.

Multimodal imaging of tissue

The unique capabilities of the multicore imaging fiber were demonstrated by the team by moving one end of the probe across a sample and then transferring the acquired images to the other end.

This is not a trivial task since the cores of the imaging fiber differ in size and shape, hindering efficient and homogeneous coupling of the excitation lasers. Furthermore, we had to deal with unwanted effects like different wavelengths interacting inside the fiber and core-to-core light coupling.

Popp.

The researchers also demonstrated that the probe has the potential to attain 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 ideal for detecting tumor borders, and the probe can be shifted all over the tissue surface in order to obtain an overview of the area that is affected.

Currently, the researchers are focusing on the use of algorithms to enhance the quality of the multimodal images, which appear pixelated because of the structure of the multicore imaging fiber. They next plan to test the probe in animal models and with patients in a clinical setting.