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Special histologic picrosirius red (PSR) staining of cheek mucosa specimens was used with subsequent assessing of the result of collagen staining in polarized light. High correlation (<jats:italic>r<\/jats:italic>= 0.692,<jats:italic>p<\/jats:italic>= 0.0001) between OCT signal standard deviation (SD) in cross\u2010polarized images and brightness of PSR stained collagen fibers in cheek mucosa specimens was demonstrated in patients with inflammatory intestine and oral mucosa diseases. We have found that the OCT signal SD in cross\u2010polarized images reflects two boundary conditions of collagen disorganization, namely, loss of fiber properties at active inflammation which attenuates the signal and fibrosis that occurs due to synthesis of a new remodeled collagen which amplifies the OCT signal. (\u00a9 2013 WILEY\u2010VCH Verlag GmbH &amp; Co. 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