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In vivo histology using femtosecond laser multiphoton tomograph for the early diagnosis of skin cancer and corneal diseases while simultaneously reducing Europe’s health care costs

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New laser tomograph for non-invasive early detection of cancers and eye diseases

A new diagnostic device offers early warning of eye diseases and cancers. Without the need for physical biopsies, it increases patient wellbeing, as well as speed of diagnosis - leading to more successful therapy.

Health

Each year around 1.3 million Europeans die from cancer according to Eurostat. Additionally, one in 30 Europeans are expected to develop sight loss. Both obviously take a significant toll on the health of the individuals concerned but also present a major burden to Europe’s health infrastructure. Through the EU-supported LASER-HISTO project, the high-tech Germany company JenLab is the only company in the world to have manufactured and tested a non-invasive diagnostic device, based on femtosecond laser radiation, which enables virtual skin and eye biopsies. Immediate early diagnosis The LASER-HISTO device, a novel type of tomograph, produces ultra-high-resolution images from cells inside the skin and the cornea. It does so by rapid optical sectioning based on near infrared femtosecond laser technology. This approach uses two low-energy photons to excite fluorescence deep in the tissue, instead of the more typical employment of one high-energy photon from long-pulse lasers, resulting in less light penetration. In the clinical tomographs, 80 million extremely short laser pulses per second are employed, at an average power of 20 milliwatts and with a beam dwell time of microseonds per tissue voxel. The potential for DNA damage was calculated as similar to 15 minutes’ exposure to the sun's UV light. As these tomographs enable high-resolution autofluorescence microscopy, RAMAN microscopy, Fluorescence Lifetime Imaging (FLIM) microscopy and Second Harmonic Generation (SHG) microscopy, patients will no longer have to provide stained tissue sections resulting in no pain, no scars and less waiting time. Aside from enabling 3D morphological data with submicron resolution, the imaging also provides information on metabolism and chemical intratissue substances, serving as vital clues for clinicians to detect diseases prior to visibility. Another key feature of the technology is that by using endogenous biomarkers, it images each tissue without the need for an externally applied marker. This approach takes advantage of the fact that our cells provide weak light signals when exposed to femtosecond near infrared laser light which can be measured by single photon counting (SPC) and used to calculate the fluorescence lifetime per pixel. The fluorescence lifetimes of cancer cells and of cells affected by inflammation are different from healthy cells. As project coordinator Dr Karsten König summarises, “We achieved our goal of performing skin and eye diagnostics without a knife, without labelling and with a result in minutes. To put this in perspective, the current diagnosis of skin cancer in Europe, using skin biopsies, microscopes and experienced pathodermatologists, takes about one week.” From anti-ageing to astronauts Multiphoton tomograph promises a number of additional opportunities. Dr König cites the objective testing of the efficacy of anti-ageing products, by measuring the elastin/collagen ration and the metabolism of cells, as one. He also mentions that quality checks for human cornea prior to transplantation could also be performed, before going, literally, much further. “A dream is to provide ultracompact multiphoton tomographs for astronauts on their way to Mars,” he adds. “Our recent studies on three astronauts showed an unexpected thinning of the skin when working for six months in the international space lab, so we could monitor that.” Back on Earth, clinical studies for LASER-HISTO’s skin cancer detection are to be conducted later this year, in hospitals in California and Germany. The team are working towards medical approval by the end of 2019 and production is planned to start in 2020.

Keywords

LASER-HISTO, biopsy, cancer, eye disease, tomograph, skin, cells, cornea, high resolution, diagnosis, photon

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