Tissue optical properties, absorption, scattering and fluorescence, reveal important information about health, and holds the potential for non-invasive diagnosis and therefore earlier treatment for many diseases. On the other hand, tissue structure determines its function. Studying tissue structural properties helps us better understand structure-function relationship. Optical imaging is an ideal tool to study these tissue properties. However, conventional optical imaging techniques have limitations, such as not being able to quantitatively evaluate tissue absorption and scattering properties and only providing volumetrically averaged quantities with no depth control capability. To better study tissue properties, we integrated spatial frequency domain imaging (SFDI) with conventional reflectance imaging modalities. SFDI is a non-invasive, non-contact wide-field imaging technique which utilizes structured illumination to probe tissues. SFDI imaging is able to accurately quantify tissue optical properties. By adjusting spatial frequency, the imaging depth can be tuned which allows for depth controlled imaging. Especially at high spatial frequency, SFDI reflectance image is more sensitive to tissue scattering property than absorption property. The imaging capability of SFDI allows for studying tissue properties from a whole new perspective. In our study, we developed both benchtop and handheld SFDI imaging systems to accommodate different applications. By evaluating tissue optical properties, we corrected attenuation in fluorescence imaging using an analytical model; and we quantified optical and physical properties of skin diseases. By imaging at high spatial frequency, we demonstrated that absorption in fluorescence imaging can also be reduced because of a reduced imaging depth. This correction can be performed in real-time at 19 frames/second. Furthermore, fibrous structures orientation from the superficial layer can be accurately quantified in a multi-layered sample by limiting imaging depth. Finally, we color rendered SFDI reflectance image at high spatial frequency to reveal structural changes in skin lesions.

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