This paper reports the evolution of scanning spectral imaging techniques using scattered light for minimally invasive detection of early cancerous changes in tissue and cell biology applications. Optical spectroscopic techniques have shown promising results in the diagnosis of disease on a cellular scale. They do not require tissue removal, can be performed in vivo, and allow for real-time diagnoses. Fluorescence and Raman spectroscopy are most effective in revealing molecular properties of tissue. Light scattering spectroscopy (LSS) relates the spectroscopic properties of light elastically scattered by small particles, such as epithelial cell nuclei and organelles, to their size, shape, and refractive index. It is capable of characterizing the structural properties of tissue on cellular and subcellular scales. However, in order to be useful in the detection of early cancerous changes that are otherwise not visible to the naked eye, it must rapidly survey a comparatively large area while simultaneously detecting these cellular changes. Both goals are achieved by combining LSS with spatial scanning imaging. Two examples are described in this paper. The first reviews a clinical system for screening patients with Barrett''s esophagus. The second presents a novel advancement in confocal light absorption and scattering spectroscopic microscopy.
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