Optimization of Nonlinear Multimodal Microendoscopy for Optical Biopsy

Linear and nonlinear optical imaging systems are currently being miniaturized to fit endoscopic size requirements for clinical applications. These systems have demonstrated their potential for medical diagnostics of various diseases as a possible alternative to optical biopsy. Our work aims at transferring the abilities of non-linear microscopy into a miniaturized diagnostic tool for discriminating tumorous tissues with sub cellular resolution and different contrast mechanisms. In this context, we report our progress in the development of a multimodal microendoscope based on double clad fiber (DCF) for femtosecond pulse delivery and signal collection and Gradient Index lenses (GRIN). Grism-based stretcher was used to compensate for second and third orders of dispersion in the DCF and GRIN. Four commercial DCFs were identified from the literature and our choice was based on the simulation and experimental results for optimal pulse delivery and maximum fluorescence signal collection as well as two photon resolution. Pulse propagation in the stretcher and the DCFs was simulated by our Home-built Matlab program while collection efficiency was calculated using geometric ray tracing in Zemax. Finally, experiments showed that our GRIN lens broadened the pulses due to nonlinear effects, nonetheless our GRISM-based stretcher was able to compensate efficiently for this broadening as well as for pulse interactions in DCF. This allows the delivery of sub-30 fs pulses at the tissue site that are several folds shorter than those obtained in the literature using the same types of fibers.