Multi-Photon Microscopy for Endoscopes

Multi-photon microendoscopy: The endoscopy objective mounted on the coupling objective. (Source: S. Schürmann, FAU)

Biotech­nologists, physicists, and medical researchers at the Univer­sity Erlangen-Nuremberg FAU have developed a tech­nology for micro­scopic imaging in living organisms. A minia­turised multi-photon micro­scope, which could be used in an endoscope in future, excites the body’s own molecules to illuminate and enables cells and tissue structures to be imaged without the use of synthetic contrast agents.

It is often necessary to examine tissue samples under the microscope to diagnose diseases. This involves taking such samples using colono­scopy, for example, and applying contrast agents to distinguish different types of tissue effectively. Biotech­nologists, physicists and medical researchers at FAU have now developed a process that could greatly simplify exa­minations of the colon and other organs. They have miniaturised multi-photon micro­scopy to such an extent as to enable it to be used in endoscopes. “A multi-photon micro­scope emits focussed laser pulses at very high intensity for an extremely short period of time”, explains Oliver Friedrich from the Chair of Medical Biotech­nology. “During this process, two or more photons interact simul­taneously with certain molecules in the body which then makes the molecules illu­minate.”

Multi-photon micro­scopy offers decisive adva­ntages over conven­tional methods. Patients do not need to take synthetic contrast agents for the imaging of parts of connective tissue as the body’s own markers illu­minate due to the excitation by photons. In addition, the multi-photon laser penetrates deep into cells, for example into the walls of the colon, and provides high-resolution three-dimen­sional images of living tissue, whereas conven­tional colono­scopy is restricted to images of the surface of the colon. The procedure could supplement biopsies or even make them super­fluous in some cases.

Multi-photon microscopes are already in use in medical appli­cations, especially on the surface of the skin. For example, derma­tologists use them to look for malignant melanoma. The challenge for using these microscopes in endoscopic examinations is the size of the technical components. The researchers have now success­fully managed to house the entire micro­scope and femtosecond laser in a compact, portable device. The objective lens is housed in a cannula that is 32 milli­meters long and has a diameter of 1.4 milli­meters. The focal point can be adjusted electroni­cally to vary the optical pene­tration. A prism is located on the point of the needle allowing a sideways view into the colon, which means various rotational images of the tissue can be made from the same position.

In current experiments on small animals, the light emitted from the laser is transmitted via a rigid system. More research is needed to integrate the system into an endoscope. “Special photonic crystal fibres are required to guide the laser pulses”, says Friedrich. “Further­more, in addition to the objective lens, the entire scanning mechanism must be minia­turised to allow it to be integrated into a flexible endoscope.”

Multi-photon micro­endoscopy is not only useful for examining the colon. It could also be used in other areas of the body such as in the mouth and throat or in the bladder. The aim of the new method is to enable the doctor to detect whether organ cells and parts of the cell wall have changed on the micro­meter scale. Complex dyeing processes and time-consuming biopsies can thus be limited. Friedrich’s team aim to provide doctors with an image database providing a multi-photon ‘atlas’ of organs and various diseases. (Source: FAU)

Reference: A. Dilipkumar et al.: Label‐Free Multiphoton Endomicroscopy for Minimally Invasive In Vivo Imaging, Adv. Sc. 6, 1801735 (2019); DOI: 10.1002/advs.201801735

Link:Institute of Medical Biotechnology, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg FAU, Erlangen, Germany

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