We introduce new realistic three-dimensional tissue phantoms which can help to understand the optical properties of human epithelium as well as the optical signatures associated with the dysplasia to carcinoma sequence. The phantoms are based on a step by step multilayer reconstitution of the epithelial tissue using main components characteristic for the human epithelium. Each consecutive step is aimed to increase the similarity between real tissue and a phantom. We began by modeling the stromal layer which predominantly consists of a network of collagen bundles. Phantoms consisting of a collagen matrix alone and in the presence of embedded cervical cells were created. Their morphology and fluorescence properties were studied and were compared with those of cervical epithelium. We show that the phantoms resemble the microstructure and the optical properties of the human epithelial tissue. We also demonstrate that the proposed phantoms provide an opportunity to study changes in optical properties of different tissue components as a result of their interactions with each other or exogenous factors.

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In vivo endoscopic optical microscopy provides a tool to assess tissue architecture and morphology with contrast and resolution similar to that provided by standard histopathology – without need for physical tissue removal. In this article, we focus on optical imaging technologies that have the potential to dramatically improve the detection, prevention, and therapy of epithelial cancers. Epithelial pre-cancers and cancers are associated with a variety of morphologic, architectural, and molecular changes, which currently can be assessed only through invasive, painful biopsy. Optical imaging is ideally suited to detecting cancer-related alterations because it can detect biochemical and morphologic alterations with sub-cellular resolution throughout the entire epithelial thickness. Optical techniques can be implemented non-invasively, in real time, and at low cost to survey the tissue surface at risk. Our manuscript focuses primarily on modalities that currently are the most developed: reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). However, recent advances in fluorescence-based endoscopic microscopy also are reviewed briefly. We discuss the basic principles of these emerging technologies and their current and potential applications in early cancer detection. We also present research activities focused on development of exogenous contrast agents that can enhance the morphological features important for cancer detection and that have the potential to allow vital molecular imaging of cancer-related biomarkers. In conclusion, we discuss future improvements to the technology needed to develop robust clinical devices.

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