Multimodal and multispectral microscopy for clinical diagnostics

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Current diagnoses of pathologies such as cancer rely on cellular evaluation of tissue samples excised through biopsy procedures. While this technique allows for evaluation of diseased cells, biopsies are uncomfortable for the patient, often hazardous, sample processing is time-consuming, and only a limited portion of a much larger organ is evaluated, resulting in a number of false-negative diagnoses. Optical imaging technologies such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are non-invasive optical technologies capable of producing high resolution images of cells at different depth through small, fibre-optics based instruments. The recent developments in biophotonics research have led to new smaller, more sensitive instruments having imaging speeds that allow non-invasive investigation of larger areas, reducing the risks associated with biopsies. Within the last decade, both these technologies (RCM and OCT) were shown to yield high quality structural (OCT), cellular and sub-cellular (RCM) images in vivo. However, the lack of specific contrast agents that would reproduce the effect of stains used on biopsy samples, limits their clinical utility to the few organs on which biopsies are impracticable. The objective of the proposed research program is to exploit linear and non-linear photon-tissue interactions to increase contrast and specificity of clinical microscopy images in ways that are compatible with constraints associated with the geometry of imaging endoscopes. The originality of this approach consists in combining tools traditionally used by biologists with newly developed optical diagnostics tools to yield high-resolution non-invasive endoscopic imaging with highly specific contrast. The research program includes the development of photonics tools that will enable the rapid transfer to the clinics, and lead to the development of the next generation of medical imaging endoscopes capable of non-invasively imaging human organs in vivo with cellular sensitivity and molecular specificity. These novel optical diagnostics technologies will provide enhanced diagnostics capability, allowing detection of diseases at earlier stages, where chances of survival and cure are the greatest.