Optical design and simulation of two photon fluorescence imaging microendoscope with aberration correction

Two photon fluorescence imaging microendoscopy is a current research thrust for detailed tissue interrogation and early detection of pre-cancerous lesions. There is a need for miniaturization of endoscopes so that it is minimally invasive for in-vivo optical imaging of cavities in the body inaccessible by existing endoscopes. With the advancements in micro-optics and gradient refractive index (GRIN) lenses, high numerical aperture is achieved at the tissue end with compact lenses. However, GRIN lenses owing to their optical aberrations limit the resolution and thereby image quality. We present the optical design of single fiber microendoscope imaging head with distal beam scanning and diameter of probe optics limited to 1.5mm. We found that positioning of the micro mirror plays a crucial role in controlling the aberrations, diameter of probe and field of view. The effect of gradient constant on aberrations is analyzed with excitation path models at 830 nm. The design is optimized to keep the predominant aberrations such as coma and astigmatism in control when the beam is scanned over the sample by tilting a micro electro mechanical system (MEMS) scan mirror. In addition to the monochromatic aberrations, chromatic focal shift is another major challenge in two photon fluorescence imaging that limits fluorescence collection. The key novelty in this research is the incorporation of phase element in the design for chromatic correction at 830nm and 520nm. A homogenous spot radius of 1.5µm is achieved at multiple tilt angles (±3°) of the scan mirror resulting in a field of view of 142µm.