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.   Significance:  Assessment of disease using optical coherence tomography is an actively investigated problem, owing to many unresolved challenges in early disease detection, diagnosis, and treatment response monitoring. The early manifestation of disease or precancer is typically associated with subtle alterations in the tissue dielectric and ultrastructural morphology. In addition, biological tissue is known to have ultrastructural multifractality.   Aim:  Detection and characterization of nanosensitive structural morphology and multifractality in the tissue submicron structure. Quantification of nanosensitive multifractality and its alteration in progression of tumor.   Approach:  We have developed a label free nanosensitive multifractal detrended fluctuation analysis(nsMFDFA) technique in combination with multifractal analysis and nanosensitive optical coherence tomography (nsOCT). The proposed method deployed for extraction and quantification of nanosensitive multifractal parameters in mammary fat pad (MFP).   Results:  Initially, the nsOCT approach is numerically validated on synthetic submicron axial structures. The nsOCT technique was applied to pathologically characterized MFP of murine breast tissue to extract depth-resolved nanosensitive submicron structures. Subsequently, two-dimensional MFDFA were deployed on submicron structural  en face  images to extract nanosensitive tissue multifractality. We found that nanosensitive multifractality increases in transition from healthy to tumor.   Conclusions:  This method for extraction of nanosensitive tissue multifractality promises to provide a noninvasive diagnostic tool for early disease detection and monitoring treatment response. The novel ability to delineate the dominant submicron scale nanosensitive multifractal properties may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin.

Characterization of nanosensitive multifractality in submicron scale tissue morphology and its alteration in tumor progression