The diagnosis of disease and surgical removal of diseased tissue relies on optical imaging that the trained human observer can clearly distinguish between healthy and normal tissue. Currently stains and biomarkers are used that help differentiate both the chemistry and morphology of cellular and tissue structures. However, in vivo use of these stains, biomarkers, and nanoparticles have safety and regulatory concerns for routine clinical practice and disease diagnosis is performed only outside the body. Nonetheless, there is medical need to obtain this molecularly- specific high-resolution imaging inside the living human body. Coherent Raman scattering is a promising technology that offers label-free chemical contrast with sub-cellular image resolution at video rates. This Raman signal is generated by near-infrared laser light that probes the chemical bonds within cells while not appearing to damage living tissue. However, traditional endoscopes are not based on laser scanning and thus not suitable for taking this advanced imaging into the clinic. An alternative endoscope technology, compatible with coherent Raman scattering, such as coherent anti-Stokes Raman scattering (CARS), uses a scanning optical fiber that scans laser light to form images at video rates. This technology produces high-quality laser-based images from an ultrathin and flexible endoscope. In this project, specific design modifications are being made to produce the first ultrathin and flexible endoscope for coherent Raman scattering at image acquisition rates that are clinically acceptable for endoscopic tissue diagnosis and surgery. Specialty illumination optical fiber and micro-optical lens assemblies will be custom designed, fabricated, and tested on tissue. The performance of this new endoscope will be compared against a set of quantitative milestones, and for direct comparison to histology. By the end of this two year project, the ability to image living tissue with sub-cellular spatial and chemical resolution without biomarkers will be established. Future uses of such technology will be the direct and rapid assessment of tumor margins and other diseased tissue without having to take repeated biopsies during surgery and endoscopic examination.

Public Health Relevance

A new type of mini-endoscope will be designed and developed that generated video images with specific molecules highlighted without adding any drug, chemical, or particle into the living system. The technique uses scanned laser light that is not absorbed by the cells, but can help determine the disease state of tissue without taking out any tissue for pathology.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-J (80))
Program Officer
Krosnick, Steven
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University of Washington
Engineering (All Types)
Schools of Engineering
United States
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Deladurantaye, Pascal; Paquet, Alex; Paré, Claude et al. (2014) Advances in engineering of high contrast CARS imaging endoscopes. Opt Express 22:25053-64
Saar, Brian G; Johnston, Richard S; Freudiger, Christian W et al. (2011) Coherent Raman scanning fiber endoscopy. Opt Lett 36:2396-8