Realtime Nonlinear Optical-Resolution Photoacoustic Imaging using Novel Fiber-Laser Technology

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We will develop strategies for label-free functional and chemical-bond-specific imaging at a microscale. In the past photoacoustic contrast has primarily been restricted to hemoglobin and exogenous contrast agents. Stimulated Raman and vibrational overtone optical-resolution photoacoustic microscopy (OR-PAM) will be investigated. These nonlinear modes are based on transferring energy directly to molecular vibrations and may provide new opportunities for label-free imaging of new species of molecular targets such as lipids, neuronal myelin sheaths, nucleic acids, etc. This should provide the molecular specificity of CARS-microscopy with improved imaging depth and may offer clinicians and biologists the diagnostic power of histopathology without biopsy samples. By using pump and probe beams tuned so that their wavenumber shift is a Raman peak, we effectively pump energy directly into vibrational modes of specific chemical bonds. In the case of vibrational overtone imaging, an overtone of a Raman peak will be targeted. We will use a tunable fiber-laser source, illuminating tissues at NIR vibrational overtone-wavelengths of lipids, DNA, and other molecular targets (where haemoglobin absorption is very minimal). Efficiency of vibrational mode excitation will be most efficient at high peak intensities, achievable with ps-lasers. With NIR ps-pulses, our calculations show that Raman lipid signal contrast should be >10x linear absorption signals due to haemoglobin, the dominant sub-surface absorbing chromophore. Some of the proposed advances will only be possible due to novel tunable ps-fiber-laser systems being developed by Genia Photonics, highly novel to the literature and the market. We will develop realtime C-scanning pre-clinical tabletop systems and clinical micro-endoscopy systems for translational and clinical research. We anticipate clinical applications in oral cancer, dermatology, gastro-intestinal applications, and other applications extending those currently served by current endo-microscopy systems.