OCT-Enhanced Confocal Endomicroscopy

Histopathology is today’s gold standard in diagnosis and treatment of tumors. Researches have shown that images acquired with fluorescent confocal microscopy provide comparable information in identifying abnormalities in cell morphology as histological images. The miniaturization of the confocal probe has permitted various application of confocal endomicroscopy in modern microsurgery. With the help of a contrast agent, intraoperative tumor identification and angiography  can be realized. However, very few fluorescent dyes, such as fluorescin sodium (FNa), Indocyanine green (ICG), aminolevulinic acid (5-ALA), can be applied on humans. Moreover, the global approval of a dye can be an extremely time-consuming process, and so is the process of developing a new dye. Usually tumors other than brain tumors are treated by excision of the tumor together with some marginal healthy tissue. Since the brain controls the human function, the excision area must be examined carefully. Hence, a novel imaging device that can intraoperatively differentiate tumorous cells from normal cells without the presence of a dye becomes in demand. An optical contrast method is proposed in this situation. Optical coherence tomography (OCT) employs a broadband light source in a michelson interferometer so that the out-of-phase light is blocked by coherent gating. Combining OCT with a confocal microscope has the advantage of decoupling the dependence of axial resolution upon numerical aperture (NA) in confocal microscope. Thus, comparable cellular axial and lateral resolution can be realized using a objective with smaller NA, which enables the miniaturization of the probe. The aim of this project is to combine this two techniques to have in-vivo real-time cellular imaging of the morphology of brain cells, by adapting the current scanning mechanism of a confocal endomicroscope into an OCT setup. The signal of the system will be analyzed and optimized. The tradeoff between lateral resolution and depth of focus of the system needs to be settled. Also, the theoretical limits of the system are to be investigated. A fluorescent channel is preferred in the prototype to permit fluorescent images of the same region of interest (ROI) as a contrast to OCT-enhanced images. The reliability of the system will be examined.