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The highly scattering nature of nontransparent human tissue limits the imaging depth of optical coherence tomography (OCT) to 1–2 mm. When the longer wavelength of the light source is used; the penetration depth is improved; however, the imaging contrast is decreased, largely because of reduced backscattering at the microscopic scale and reduced refractive heterogeneity of the macroscopic scale. For a more effective diagnosis using OCT, a concurrent improvement of penetration depth and imaging contrast is often needed. We report that the OCT imaging depth and contrast can be enhanced concurrently by the use of osmotic agents. Imaging depth enhancement by application of a chemical agent is not new; however, to our knowledge; imaging contrast enhancement has not been reported in the literature. Our hypothesis is that the latter is due to localized dehydration. We demonstrate experimentally, by …